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Sample records for long-term potentiation induction

  1. Metabotropic glutamate receptors are required for the induction of long-term potentiation

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    Zheng, F.; Gallagher, J. P.

    1992-01-01

    Recent observations have led to the suggestion that the metabotropic glutamate receptor may play a role in the induction or maintenance of long-term potentiation (LTP). However, experimental evidence supporting a role for this receptor in the induction of LTP is still inconclusive and controversial. Here we report that, in rat dorsolateral septal nucleus (DLSN) neurons, which have the highest density of metabotropic receptors and show functional responses, the induction of LTP is not blocked by the NMDA receptor antagonist 2-amino-5-phosphonovalerate, but is blocked by two putative metabotropic glutamate receptor antagonists, L-2-amino-3-phosphonopropionic acid and L-2-amino-4-phosphonobutyrate. Furthermore, superfusion of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid, a selective metabotropic glutamate agonist, resulted in a long-lasting potentiation of synaptic transmission similar to that induced by tetanic stimuli. Our results demonstrated that activation of postsynaptic metabotropic receptors is both necessary and sufficient for the induction of LTP in the DLSN, and we suggest that such a mechanism may be important at other CNS synapses.

  2. Intracellular domains of NMDA receptor subtypes are determinants for long-term potentiation induction.

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    Köhr, Georg; Jensen, Vidar; Koester, Helmut J; Mihaljevic, Andre L A; Utvik, Jo K; Kvello, Ane; Ottersen, Ole P; Seeburg, Peter H; Sprengel, Rolf; Hvalby, Øivind

    2003-11-26

    NMDA receptors (NMDARs) are essential for modulating synaptic strength at central synapses. At hippocampal CA3-to-CA1 synapses of adult mice, different NMDAR subtypes with distinct functionality assemble from NR1 with NR2A and/or NR2B subunits. Here we investigated the role of these NMDA receptor subtypes in long-term potentiation (LTP) induction. Because of the higher NR2B contribution in the young hippocampus, LTP of extracellular field potentials could be enhanced by repeated tetanic stimulation in young but not in adult mice. Similarly, NR2B-specific antagonists reduced LTP in young but only marginally in adult wild-type mice, further demonstrating that in mature CA3-to-CA1 connections LTP induction results primarily from NR2A-type signaling. This finding is also supported by gene-targeted mutant mice expressing C-terminally truncated NR2A subunits, which participate in synaptic NMDAR channel formation and Ca2+ signaling, as indicated by immunopurified synaptic receptors, postembedding immunogold labeling, and spinous Ca2+ transients in the presence of NR2B blockers. These blockers abolished LTP in the mutant at all ages, revealing that, without the intracellular C-terminal domain, NR2A-type receptors are deficient in LTP signaling. Without NR2B blockade, CA3-to-CA1 LTP was more strongly reduced in adult than young mutant mice but could be restored to wild-type levels by repeated tetanic stimulation. Thus, besides NMDA receptor-mediated Ca2+ influx, subtype-specific signaling is critical for LTP induction, with the intracellular C-terminal domain of the NR2 subunits directing signaling pathways with an age-dependent preference.

  3. Endogenous neurotrophins are required for the induction of GABAergic long-term potentiation in the neonatal rat hippocampus.

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    Gubellini, Paolo; Ben-Ari, Yehezkel; Gaïarsa, Jean-Luc

    2005-06-15

    In the developing rat hippocampus, GABAergic synapses undergo a Ca2+-dependent long-term potentiation (LTP(GABA-A)); this form of synaptic plasticity is induced in CA3 pyramidal neurons by delivering repetitive depolarizing pulses (DPs) to the recorded neuron, and it is expressed as a long-lasting increase in the frequency and amplitude of spontaneous GABA(A) receptor-mediated postsynaptic currents. In the present study, we examined the role of endogenous tropomyosin-related kinase receptor B (TrkB) receptor ligands and associated protein tyrosine kinases (PTKs) in the induction of LTP(GABA-A). The application of Lavendustin A, a broad spectrum PTK inhibitor, blocked the induction of LTP(GABA-A), whereas Lavendustin B, its inactive form, had no effect. Moreover, k-252a and k-252b, two alkaloids that inhibit the kinase activity of the Trk receptor family, also prevented the induction of LTP(GABA-A). On hippocampal slices incubated with the soluble form of TrkB receptor IgG (TrkB-IgG), which prevents the activation of TrkB receptors by endogenous ligands, DPs failed to induce LTP(GABA-A), whereas the incubation with TrkA-IgG or TrkC-IgG had no such effect. Altogether, these data indicate that endogenous TrkB ligands and associated PTK activity are necessary for the induction of GABAergic LTP in the developing rat hippocampus.

  4. Prior Activation of Inositol 1,4,5-Trisphosphate Receptors Suppresses the Subsequent Induction of Long-Term Potentiation in Hippocampal CA1 Neurons

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    Fujii, Satoshi; Yamazaki, Yoshihiko; Goto, Jun-Ichi; Fujiwara, Hiroki; Mikoshiba, Katsuhiko

    2016-01-01

    We investigated the role of inositol 1,4,5-trisphosphate receptors (IP3Rs) activated by preconditioning low-frequency afferent stimulation (LFS) in the subsequent induction of long-term potentiation (LTP) in CA1 neurons in hippocampal slices from mature guinea pigs. Induction of LTP in the field excitatory postsynaptic potential or the population…

  5. Protein Kinase M[Zeta] Is Essential for the Induction and Maintenance of Dopamine-Induced Long-Term Potentiation in Apical CA1 Dendrites

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    Navakkode, Sheeja; Sajikumar, Sreedharan; Sacktor, Todd Charlton; Frey, Julietta U.

    2010-01-01

    Dopaminergic D1/D5-receptor-mediated processes are important for certain forms of memory as well as for a cellular model of memory, hippocampal long-term potentiation (LTP) in the CA1 region of the hippocampus. D1/D5-receptor function is required for the induction of the protein synthesis-dependent maintenance of CA1-LTP (L-LTP) through activation…

  6. Social Isolation During Adolescence Strengthens Retention of Fear Memories and Facilitates Induction of Late-Phase Long-Term Potentiation.

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    Liu, Ji-Hong; You, Qiang-Long; Wei, Mei-Dan; Wang, Qian; Luo, Zheng-Yi; Lin, Song; Huang, Lang; Li, Shu-Ji; Li, Xiao-Wen; Gao, Tian-Ming

    2015-12-01

    Social isolation during the vulnerable period of adolescence produces emotional dysregulation that often manifests as abnormal behavior in adulthood. The enduring consequence of isolation might be caused by a weakened ability to forget unpleasant memories. However, it remains unclear whether isolation affects unpleasant memories. To address this, we used a model of associative learning to induce the fear memories and evaluated the influence of isolation mice during adolescence on the subsequent retention of fear memories and its underlying cellular mechanisms. Following adolescent social isolation, we found that mice decreased their social interaction time and had an increase in anxiety-related behavior. Interestingly, when we assessed memory retention, we found that isolated mice were unable to forget aversive memories when tested 4 weeks after the original event. Consistent with this, we observed that a single train of high-frequency stimulation (HFS) enabled a late-phase long-term potentiation (L-LTP) in the hippocampal CA1 region of isolated mice, whereas only an early-phase LTP was observed with the same stimulation in the control mice. Social isolation during adolescence also increased brain-derived neurotrophic factor (BDNF) expression in the hippocampus, and application of a tropomyosin-related kinase B (TrkB) receptor inhibitor ameliorated the facilitated L-LTP seen after isolation. Together, our results suggest that adolescent isolation may result in mental disorders during adulthood and that this may stem from an inability to forget the unpleasant memories via BDNF-mediated synaptic plasticity. These findings may give us a new strategy to prevent mental disorders caused by persistent unpleasant memories.

  7. Ryanodine receptors contribute to the induction of nociceptive input-evoked long-term potentiation in the rat spinal cord slice

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    Zhao Zhi-Qi

    2010-01-01

    Full Text Available Abstract Background Our previous study demonstrated that nitric oxide (NO contributes to long-term potentiation (LTP of C-fiber-evoked field potentials by tetanic stimulation of the sciatic nerve in the spinal cord in vivo. Ryanodine receptor (RyR is a downstream target for NO. The present study further explored the role of RyR in synaptic plasticity of the spinal pain pathway. Results By means of field potential recordings in the adult male rat in vivo, we showed that RyR antagonist reduced LTP of C-fiber-evoked responses in the spinal dorsal horn by tetanic stimulation of the sciatic nerve. Using spinal cord slice preparations and field potential recordings from superficial dorsal horn, high frequency stimulation of Lissauer's tract (LT stably induced LTP of field excitatory postsynaptic potentials (fEPSPs. Perfusion of RyR antagonists blocked the induction of LT stimulation-evoked spinal LTP, while Ins(1,4,5P3 receptor (IP3R antagonist had no significant effect on LTP induction. Moreover, activation of RyRs by caffeine without high frequency stimulation induced a long-term potentiation in the presence of bicuculline methiodide and strychnine. Further, in patch-clamp recordings from superficial dorsal horn neurons, activation of RyRs resulted in a large increase in the frequency of miniature EPSCs (mEPSCs. Immunohistochemical study showed that RyRs were expressed in the dorsal root ganglion (DRG neurons. Likewise, calcium imaging in small DRG neurons illustrated that activation of RyRs elevated [Ca2+]i in small DRG neurons. Conclusions These data indicate that activation of presynaptic RyRs play a crucial role in the induction of LTP in the spinal pain pathway, probably through enhancement of transmitter release.

  8. 5-HT4-receptors modulate induction of long-term depression but not potentiation at hippocampal output synapses in acute rat brain slices.

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    Matthias Wawra

    Full Text Available The subiculum is the principal target of CA1 pyramidal cells and mediates hippocampal output to various cortical and subcortical regions of the brain. The majority of subicular pyramidal cells are burst-spiking neurons. Previous studies indicated that high frequency stimulation in subicular burst-spiking cells causes presynaptic NMDA-receptor dependent long-term potentiation (LTP whereas low frequency stimulation induces postsynaptic NMDA-receptor-dependent long-term depression (LTD. In the present study, we investigate the effect of 5-hydroxytryptamine type 4 (5-HT4 receptor activation and blockade on both forms of synaptic plasticity in burst-spiking cells. We demonstrate that neither activation nor block of 5-HT4 receptors modulate the induction or expression of LTP. In contrast, activation of 5-HT4 receptors facilitates expression of LTD, and block of the 5-HT4 receptor prevents induction of short-term depression and LTD. As 5-HT4 receptors are positively coupled to adenylate cyclase 1 (AC1, 5-HT4 receptors might modulate PKA activity through AC1. Since LTD is blocked in the presence of 5-HT4 receptor antagonists, our data are consistent with 5-HT4 receptor activation by ambient serotonin or intrinsically active 5-HT4 receptors. Our findings provide new insight into aminergic modulation of hippocampal output.

  9. The role of dendritic action potentials and Ca2+ influx in the induction of homosynaptic long-term depression in hippocampal CA1 pyramidal neurons.

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    Christie, B R; Magee, J C; Johnston, D

    1996-01-01

    Long-term depression (LTD) of synaptic efficacy at CA1 synapses is believed to be a Ca(2+)-dependent process. We used high-speed fluorescence imaging and patch-clamp techniques to quantify the spatial distribution of changes in intracellular Ca2+ accompanying the induction of LTD at Schaffer collateral synapses in CA1 pyramidal neurons. Low-frequency stimulation (3 Hz), which was subthreshold for action potentials, produced small changes in [Ca2+]i and failed to elicit LTD. Increasing the stimulus strength so that action potentials were generated produced both robust LTD and increases in [Ca2+]i. Back-propagating action potentials at 3 Hz in the absence of synaptic stimulation also produced increases in [Ca2+]i, but failed to induce LTD. When subthreshold synaptic stimulation was paired with back-propagating action potentials, however, large increases in [Ca2+]i were observed and robust LTD was induced. The LTD was blocked by the N-methyl-D-aspartate receptor (NMDAr) antagonist APV, and stimulus-induced increases in [Ca2+]i were reduced throughout the neuron under these conditions. The LTD was also dependent on Ca2+ influx via voltage-gated Ca2+ channels (VGCCs), because LTD was severely attenuated or blocked by both nimodipine and Ni2+. These findings suggest that back-propagating action potentials can exert a powerful control over the induction of LTD and that both VGCCs and NMDArs are involved in the induction of this form of plasticity.

  10. Induction of long-term potentiation in single nociceptive dorsal horn neurons is blocked by the CaMKII inhibitor AIP.

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    Pedersen, Linda Margareth; Lien, Guro Flor; Bollerud, Ingunn; Gjerstad, Johannes

    2005-04-11

    Neuronal events leading to development of long-term potentiation (LTP) in the nociceptive pathways may be a cellular mechanism underlying central hyperalgesia. Here, we examine whether induction of LTP in nociceptive dorsal horn neurons at depths of 80-500 microm from the cord surface can be affected by spinal application of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) inhibitor AIP. Extracellular recordings from single neurons in intact urethane anesthetized Sprague-Dawley rats were performed, and the neuronal A-fiber and C-fiber responses after sciatic nerve test pulses were defined according to latencies. A clear LTP of the nociceptive transmission following sciatic nerve high-frequency stimulation (HFS) was observed in single neurons in laminae I-IV of the dorsal horn. The increase in the C-fiber response after HFS was blocked in the presence of 2.0 mM AIP (P fiber response was not affected by 2.0 mM AIP alone or by vehicle. Thus, our data show that the neuronal process leading to the induction of LTP in the dorsal horn induced by HFS is clearly inhibited by the specific CaMKII inhibitor AIP. It is concluded that CaMKII may be important for the induction of LTP in single nociceptive dorsal horn neurons.

  11. Long-term potentiation and long-term depression: a clinical perspective

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    Timothy V.P. Bliss

    2011-01-01

    Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

  12. mGluR1/5 subtype-specific calcium signalling and induction of long-term potentiation in rat hippocampal oriens/alveus interneurones

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    Topolnik, Lisa; Azzi, Mounia; Morin, France; Kougioumoutzakis, André; Lacaille, Jean-Claude

    2006-01-01

    Hippocampal inhibitory interneurones demonstrate pathway- and synapse-specific rules of transmission and plasticity, which are key determinants of their role in controlling pyramidal cell excitability. Mechanisms underlying long-term changes at interneurone excitatory synapses, despite their importance, remain largely unknown. We use two-photon calcium imaging and whole-cell recordings to determine the Ca2+ signalling mechanisms linked specifically to group I metabotropic glutamate receptors (mGluR1α and mGluR5) and their role in hebbian long-term potentiation (LTP) in oriens/alveus (O/A) interneurones. We demonstrate that mGluR1α activation elicits dendritic Ca2+ signals resulting from Ca2+ influx via transient receptor potential (TRP) channels and Ca2+ release from intracellular stores. By contrast, mGluR5 activation produces dendritic Ca2+ transients mediated exclusively by intracellular Ca2+ release. Using Western blot analysis and immunocytochemistry, we show mGluR1α-specific extracellular signal-regulated kinase (ERK1/2) activation via Src in CA1 hippocampus and, in particular, in O/A interneurones. Moreover, we find that mGluR1α/TRP Ca2+ signals in interneurone dendrites are dependent on activation of the Src/ERK cascade. Finally, this mGluR1α-specific Ca2+ signalling controls LTP at interneurone synapses since blocking either TRP channels or Src/ERK and intracellular Ca2+ release prevents LTP induction. Thus, our findings uncover a novel molecular mechanism of interneurone-specific Ca2+ signalling, critical in regulating synaptic excitability in hippocampal networks. PMID:16740609

  13. Involvement of microglia and interleukin-18 in the induction of long-term potentiation of spinal nociceptive responses induced by tetanic sciatic stimulation

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    Yu-Xia Chu; Yu-Qiu Zhang; Zhi-Qi Zhao

    2012-01-01

    Objective The present study aimed to investigate the potential roles of spinal microglia and downstream molecules in the induction of spinal long-term potentiation (LTP) and mechanical allodynia by tetanic stimulation of the sciatic nerve (TSS).Methods Spinal LTP was induced in adult male Sprague-Dawley rats by tetanic stimulation of the sciatic nerve (0.5 ms,100 Hz,40 V,10 trains of 2-s duration at 10-s intervals).Mechanical allodynia was determined using von Frey hairs.Immunohistochemical staining and Westem blot were used to detect changes in glial expression of interleukin- 18 (IL- 18) and IL- 18 receptor (IL- 18R).Results TSS induced LTP of C-fiber-evoked field potentials in the spinal cord.Intrathecal administration of the microglial inhibitor minocycline (200 μg/20 μL) 1 h before TSS completely blocked the induction of spinal LTP.Furthermore,after intrathecal injection of minocycline (200 μg/20 μL) by lumbar puncture 1 h before TSS,administration of minocycline for 7 consecutive days (once per day) partly inhibited bilateral allodynia.Immunohistochemistry showed that minocycline inhibited the sequential activation of microglia and astrocytes,and IL-1 8 was predominantly colocalized with the microglial marker Iba-1 in the spinal superficial dorsal horn.Western blot revealed that repeated intrathecal injection of minocycline significantly inhibited the increased expression of IL-18 and IL-18Rs in microglia induced by TSS.Conclusion The IL-18 signaling pathway in microglia is involved in TSS-induced spinal LTP and mechanical allodynia.

  14. Hippocampal network activity is transiently altered by induction of long-term potentiation in the dentate gyrus of freely behaving rats

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    Arthur Bikbaev

    2007-12-01

    Full Text Available A role for oscillatory activity in hippocampal neuronal networks has been proposed in sensory encoding, cognitive functions and synaptic plasticity. In the hippocampus, theta (5–10 Hz and gamma (30–100 Hz oscillations may provide a mechanism for temporal encoding of information, and the basis for formation and retrieval of memory traces. Long-term potentiation (LTP of synaptic transmission, a candidate cellular model of synaptic information storage, is typically induced by high-frequency tetanisation (HFT of afferent pathways. Taking into account the role of oscillatory activity in the processing of information, dynamic changes may occur in hippocampal network activity in the period during HFT and/or soon after it. These changes in rhythmic activity may determine or, at least, contribute to successful potentiation and, in general, to formation of memory. We have found that short-term potentiation (STP and LTP as well LTPfailure are characterised with different profiles of changes in theta and gamma frequencies. Potentiation of synaptic transmission was associated with a significant increase in the relative theta power and mean amplitude of theta cycles in the period encompassing 300 seconds after HFT. Where LTP or STP, but not failure of potentiation, occurred, this facilitation of theta was accompanied by transient increases in gamma power and in the mean amplitude of gamma oscillations within a single theta cycle. Our data support that specific, correlated changes in these parameters are associated with successful synaptic potentiation. These findings suggest that changes in theta-gamma activity associated with induction of LTP may enable synaptic information storage in the hippocampus.

  15. Brain-derived neurotrophic factor-mediated retrograde signaling required for the induction of long-term potentiation at inhibitory synapses of visual cortical pyramidal neurons.

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    Inagaki, Tsuyoshi; Begum, Tahamina; Reza, Faruque; Horibe, Shoko; Inaba, Mie; Yoshimura, Yumiko; Komatsu, Yukio

    2008-06-01

    High-frequency stimulation (HFS) induces long-term potentiation (LTP) at inhibitory synapses of layer 5 pyramidal neurons in developing rat visual cortex. This LTP requires postsynaptic Ca2+ rise for induction, while the maintenance mechanism is present at the presynaptic site, suggesting presynaptic LTP expression and the necessity of retrograde signaling. We investigated whether the supposed signal is mediated by brain-derived neurotrophic factor (BDNF), which is expressed in pyramidal neurons but not inhibitory interneurons. LTP did not occur when HFS was applied in the presence of the Trk receptor tyrosine kinase inhibitor K252a in the perfusion medium. HFS produced LTP when bath application of K252a was started after HFS or when K252a was loaded into postsynaptic cells. LTP did not occur in the presence of TrkB-IgG scavenging BDNF or function-blocking anti-BDNF antibody in the medium. In cells loaded with the Ca2+ chelator BAPTA, the addition of BDNF to the medium enabled HFS to induce LTP without affecting baseline synaptic transmission. These results suggest that BDNF released from postsynaptic cells activates presynaptic TrkB, leading to LTP. Because BDNF, expressed activity dependently, regulates the maturation of cortical inhibition, inhibitory LTP may contribute to this developmental process, and hence experience-dependent functional maturation of visual cortex.

  16. Protein kinase Mζ is essential for the induction and maintenance of dopamine-induced long-term potentiation in apical CA1 dendrites

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    Navakkode, Sheeja; Sajikumar, Sreedharan; Sacktor, Todd Charlton; Frey, Julietta U.

    2010-01-01

    Dopaminergic D1/D5-receptor-mediated processes are important for certain forms of memory as well as for a cellular model of memory, hippocampal long-term potentiation (LTP) in the CA1 region of the hippocampus. D1/D5-receptor function is required for the induction of the protein synthesis-dependent maintenance of CA1-LTP (L-LTP) through activation of the cAMP/PKA-pathway. In earlier studies we had reported a synergistic interaction of D1/D5-receptor function and N-methyl-D-aspartate (NMDA)-receptors for L-LTP. Furthermore, we have found the requirement of the atypical protein kinase C isoform, protein kinase Mζ (PKMζ) for conventional electrically induced L-LTP, in which PKMζ has been identified as a LTP-specific plasticity-related protein (PRP) in apical CA1-dendrites. Here, we investigated whether the dopaminergic pathway activates PKMζ. We found that application of dopamine (DA) evokes a protein synthesis-dependent LTP that requires synergistic NMDA-receptor activation and protein synthesis in apical CA1-dendrites. We identified PKMζ as a DA-induced PRP, which exerted its action at activated synaptic inputs by processes of synaptic tagging. PMID:21084457

  17. Nutritional deficit and Long Term Potentiation alterations

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    M. Petrosino

    2009-01-01

    Full Text Available In the present work we examined the ability of prenatally malnourished offspring to produce and maintain long-term potentiation (LTP of the perforant path/dentate granule cell synapse in freely moving rats at 15,30, and 90 days of age. Population spike amplitude (PSA was calculated from dentate field potential recordings prior to and at 15, 30, 60 min. and 3, 5, 18 and 24 h following tetanization of the perforant pathway. All animals of both malnourished and well-nourished diet groups at 15 days of age showed potentiation of PSA measures but the measures obtained from 15-day-old prenatally malnourished animals were significantly less than that of age-matched, well-nourished controls. At 30 days of age, remarkable effect of tetanization was likely observed from PSA measures for this age group followed much the same pattern. At 90 days of age, PSA measures obtained from malnourished animals decreased from pretetanization levels immediately following tetanization. At this age, however, at three hours time recordings, this measure growing up to a level which did not differ significantly from that of the control group. These results indicate that the width of tetanization induced enhancement of dentate granule cell response in preweanling rats (15-day-old animals is signifacantly affected fromgestational protein malnutrition and this trend is kept in animals tested at 30 and 90 days of age. The fact, however, that considerable limitation in LTP generation was gained from prenatally malnourished animals at 90 days of age, implying that dietary rehabilitation starting at birth is an intervention strategy not capable to imbrove the effects of the gestational stress.

  18. Quantification of long term emission potential from landfills

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    Heimovaara, T.J.

    2011-01-01

    Novel approaches for the after-care of Municipal Solid Waste (MSW) landfills are based on technological measures to reduce the long term emission potential in a short time period. Biological degradation in landfills is a means to significantly reduce the long term emission potential. Leachate emission to the groundwater is considered to be one of the largest long-term impacts related to landfilling. Currently we are starting up a research program, partly subsidized by the Dutch Technology fou...

  19. Phase dependency of long-term potentiation induction during the intermittent bursts of carbachol-induced β oscillation in rat hippocampal slices.

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    Nishimura, Motoshi; Nakatsuka, Hiroki; Natsume, Kiyohisa

    2012-01-01

    The rodent hippocampus possesses theta (θ) and beta (β) rhythms, which occur intermittently as bursts. Both rhythms are related to spatial memory processing in a novel environment. θ rhythm is related to spatial memory encoding process. β rhythm is related to the match/mismatch process. In the match/mismatch process, rodent hippocampus detects a representation matching sensory inputs of the current place among the retrieved internal representations of places. Long-term synaptic potentiation (LTP) is induced in both processes. The cholinergic agent carbachol induces intermittent θ and β oscillations in in vitro slices similar to in vivo bursts. LTP is facilitated during the generation of θ oscillation, suggesting that the facilitation of LTP is dependent upon the phases of intermittent burst (burst phases) of the oscillation. However, whether this is the case for β oscillation has not yet been studied. In the present study, LTP-inducing θ-burst stimulation was administered at the different burst phases of carbachol-induced β oscillations (CIBO), and the synaptic changes were measured at CA3-CA3 pyramidal cell synapses (CA3 synapse) and at CA3-CA1 pyramidal cell synapses (CA1 synapse). At the CA3 synapse, the largest magnitude of LTP was induced at the late burst phases of CIBO. At the CA1 synapse, LTP was induced only at the late burst phases. Modulation of LTP was suppressed when CIBO was blocked by the application of atropine at both synapses. The results suggest that the bursts of hippocampal β rhythm can determine the optimal temporal period for completing with the match/mismatch process.

  20. Quantification of long term emission potential from landfills

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    Heimovaara, T.J.

    2011-01-01

    Novel approaches for the after-care of Municipal Solid Waste (MSW) landfills are based on technological measures to reduce the long term emission potential in a short time period. Biological degradation in landfills is a means to significantly reduce the long term emission potential. Leachate emissi

  1. Long-term potentiation of intrinsic excitability in trigeminal motoneurons.

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    Okamoto, Reiko; Enomoto, Akifumi; Koizumi, Hidehiko; Tanaka, Susumu; Ishihama, Kohji; Kogo, Mikihiko

    2010-02-02

    Trigeminal motoneurons (TMNs) relay the final output signals generated within the oral-motor pattern-generating circuits to the jaw muscles for execution of various patterns of motor activity. Activity-dependent plasticity, referred to as long-term potentiation (LTP), in the central nervous system has been the subject of many studies. The mechanisms of plasticity in the trigeminal system, an important component of the oral-motor system underlying mastication, swallowing, and other behaviors, remain to be fully elucidated. In the present study, we investigated long-term potentiation of intrinsic excitability (LTP-IE) in TMNs. Experiments were performed using extracellular recording and whole-cell patch-clamp recording to assess the intrinsic excitability of TMNs. Intrinsic response properties were examined using an induction pulse with ionotropic transmission blocked. The output of the trigeminal motor branch exhibited long-lasting potentiation of intrinsic neuronal excitability following induction. Applying brainstem transection techniques to the neonatal rat brainstem in vitro, we found that the activity of the motoneuron population recorded from the motor branch of the trigeminal nerve exhibited LTP-IE. We thus demonstrated the usefulness of this type of preparation for the study of rudimentary oral-motor activity and observed changes in TMN excitability. In addition, on testing with the whole-cell patch-clamp method, TMNs exhibited a significant increase in excitability with a leftward shift in F-I curves generated with depolarizing current injections, whereas resting membrane potential and input resistance exhibited no remarkable changes. These findings indicate that TMNs exhibit LTP of intrinsic excitability.

  2. Mathematical simulation of the induction of long-term depression in cerebellar Purkinje cells.

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    Murzina, G B

    2004-02-01

    The question of the mechanisms underlying the induction of associative and homosynaptic long-term depression in cerebellar Purkinje cells is addressed. Mathematical simulation was used to investigate the possibility that long-term depression, which is associated with a decrease in the efficiency of AMPA receptors, could be induced both by phosphorylation and dephosphorylation of these receptors.

  3. Nuclear translocation of jacob in hippocampal neurons after stimuli inducing long-term potentiation but not long-term depression.

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    Thomas Behnisch

    Full Text Available BACKGROUND: In recent years a number of potential synapto-nuclear protein messengers have been characterized that are thought to be involved in plasticity-related gene expression, and that have the capacity of importin- mediated and activity-dependent nuclear import. However, there is a surprising paucity of data showing the nuclear import of such proteins in cellular models of learning and memory. Only recently it was found that the transcription factor cyclic AMP response element binding protein 2 (CREB2 transits to the nucleus during long-term depression (LTD, but not during long-term potentiation (LTP of synaptic transmission in hippocampal primary neurons. Jacob is another messenger that couples NMDA-receptor-activity to nuclear gene expression. We therefore aimed to study whether Jacob accumulates in the nucleus in physiological relevant models of activity-dependent synaptic plasticity. METHODOLOGY/PRINCIPAL FINDINGS: We have analyzed the dynamics of Jacob's nuclear import following induction of NMDA-receptor dependent LTP or LTD at Schaffer collateral-CA1 synapses in rat hippocampal slices. Using time-lapse imaging of neurons expressing a Jacob-Green-Fluorescent-Protein we found that Jacob rapidly translocates from dendrites to the nucleus already during the tetanization period of LTP, but not after induction of LTD. Immunocytochemical stainings confirmed the nuclear accumulation of endogenous Jacob in comparison to apical dendrites after induction of LTP but not LTD. Complementary findings were obtained after induction of NMDA-receptor dependent chemical LTP and LTD in hippocampal primary neurons. However, in accordance with previous studies, high concentrations of NMDA and glycine as well as specific activation of extrasynaptic NMDA-receptors resembling pathological conditions induce an even more profound increase of nuclear Jacob levels. CONCLUSIONS/SIGNIFICANCE: Taken together, these findings suggest that the two major forms of NMDA

  4. Nuclear Translocation of Jacob in Hippocampal Neurons after Stimuli Inducing Long-Term Potentiation but Not Long-Term Depression

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    Behnisch, Thomas; YuanXiang, PingAn; Bethge, Philipp; Parvez, Suhel; Chen, Ying; Yu, Jin; Karpova, Anna; Frey, Julietta U.; Mikhaylova, Marina; Kreutz, Michael R.

    2011-01-01

    Background In recent years a number of potential synapto-nuclear protein messengers have been characterized that are thought to be involved in plasticity-related gene expression, and that have the capacity of importin- mediated and activity-dependent nuclear import. However, there is a surprising paucity of data showing the nuclear import of such proteins in cellular models of learning and memory. Only recently it was found that the transcription factor cyclic AMP response element binding protein 2 (CREB2) transits to the nucleus during long-term depression (LTD), but not during long-term potentiation (LTP) of synaptic transmission in hippocampal primary neurons. Jacob is another messenger that couples NMDA-receptor-activity to nuclear gene expression. We therefore aimed to study whether Jacob accumulates in the nucleus in physiological relevant models of activity-dependent synaptic plasticity. Methodology/Principal Findings We have analyzed the dynamics of Jacob's nuclear import following induction of NMDA-receptor dependent LTP or LTD at Schaffer collateral-CA1 synapses in rat hippocampal slices. Using time-lapse imaging of neurons expressing a Jacob-Green-Fluorescent-Protein we found that Jacob rapidly translocates from dendrites to the nucleus already during the tetanization period of LTP, but not after induction of LTD. Immunocytochemical stainings confirmed the nuclear accumulation of endogenous Jacob in comparison to apical dendrites after induction of LTP but not LTD. Complementary findings were obtained after induction of NMDA-receptor dependent chemical LTP and LTD in hippocampal primary neurons. However, in accordance with previous studies, high concentrations of NMDA and glycine as well as specific activation of extrasynaptic NMDA-receptors resembling pathological conditions induce an even more profound increase of nuclear Jacob levels. Conclusions/Significance Taken together, these findings suggest that the two major forms of NMDA-receptor dependent

  5. Gating of Long-Term Potentiation by Nicotinic Acetylcholine Receptors at the Cerebellum Input Stage

    NARCIS (Netherlands)

    F. Prestori (Francesca); C. Bonardi (Claudia); L. Mapelli (Lisa); P. Lombardo (Paola); R. Goselink (Rianne); M.E. de Stefano (Maria Egle); D. Gandolfi (Daniela); J. Mapelli (Jonathan); D. Bertrand (Daniel); M. Schonewille (Martijn); C.I. de Zeeuw (Chris); E. D'Angelo (Egidio)

    2013-01-01

    textabstractThe brain needs mechanisms able to correlate plastic changes with local circuit activity and internal functional states. At the cerebellum input stage, uncontrolled induction of long-term potentiation or depression (LTP or LTD) between mossy fibres and granule cells can saturate synaptic

  6. CAN LONG-TERM POTENTIATION BE INGVCED BY ACUPOINT STIMULATION?

    Institute of Scientific and Technical Information of China (English)

    吴定宗; 张煜; 万平

    2000-01-01

    Long-term potentiation (LTP) is usually induced by direct brain stimulation. An attempt has been made to evoke LTP in dentate granule cells of hippocampus by acupoint stimulation in anesthetized rats. Assuming a gradual increasing course, LTP rose to 146% at the end of one hour. After applying such stimulation to the awake rats for six days (once everyday), their discriminative learning capacity in Y maze test markedly improved as compared with that of the control.

  7. Modeling Maintenance of Long-Term Potentiation in Clustered Synapses: Long-Term Memory without Bistability

    Directory of Open Access Journals (Sweden)

    Paul Smolen

    2015-01-01

    Full Text Available Memories are stored, at least partly, as patterns of strong synapses. Given molecular turnover, how can synapses maintain strong for the years that memories can persist? Some models postulate that biochemical bistability maintains strong synapses. However, bistability should give a bimodal distribution of synaptic strength or weight, whereas current data show unimodal distributions for weights and for a correlated variable, dendritic spine volume. Thus it is important for models to simulate both unimodal distributions and long-term memory persistence. Here a model is developed that connects ongoing, competing processes of synaptic growth and weakening to stochastic processes of receptor insertion and removal in dendritic spines. The model simulates long-term (>1 yr persistence of groups of strong synapses. A unimodal weight distribution results. For stability of this distribution it proved essential to incorporate resource competition between synapses organized into small clusters. With competition, these clusters are stable for years. These simulations concur with recent data to support the “clustered plasticity hypothesis” which suggests clusters, rather than single synaptic contacts, may be a fundamental unit for storage of long-term memory. The model makes empirical predictions and may provide a framework to investigate mechanisms maintaining the balance between synaptic plasticity and stability of memory.

  8. Capsaicin-sensitive C- and A-fibre nociceptors control long-term potentiation-like pain amplification in humans.

    Science.gov (United States)

    Henrich, Florian; Magerl, Walter; Klein, Thomas; Greffrath, Wolfgang; Treede, Rolf-Detlef

    2015-09-01

    Long-term potentiation in the spinal dorsal horn requires peptidergic C-fibre activation in animals. Perceptual correlates of long-term potentiation following high-frequency electrical stimulation in humans include increased sensitivity to electrical stimuli at the high frequency stimulation site (homotopic pain-long-term potentiation) and increased sensitivity to pinprick surrounding the high frequency stimulation site (heterotopic pain-long-term potentiation, equivalent to secondary hyperalgaesia). To characterize the peripheral fibre populations involved in induction of pain-long-term potentiation, we performed two selective nerve block experiments in 30 healthy male volunteers. Functional blockade of TRPV1-positive nociceptors by high-concentration capsaicin (verified by loss of heat pain) significantly reduced pain ratings to high frequency stimulation by 47% (P pain-long-term potentiation by 71% (P pain-long-term potentiation by 92% (P pain to pinprick) significantly reduced pain ratings to high frequency stimulation by 37% (P pain-long-term potentiation (-5%). It had a marginal effect on heterotopic pain-long-term potentiation (-35%, P = 0.059), while the area of secondary hyperalgesia remained unchanged (-2%, P = 0.88). In conclusion, all nociceptor subclasses contribute to high frequency stimulation-induced pain (with a relative contribution of C > Aδ fibres, and an equal contribution of TRPV1-positive and TRPV1-negative fibres). TRPV1-positive C-fibres are the main inducers of both homotopic and heterotopic pain-long-term potentiation. TRPV1-positive A-fibres contribute substantially to the induction of heterotopic pain-long-term potentiation. TRPV1-negative C-fibres induce a component of homotopic self-facilitation but not heterotopic pain-long-term potentiation. TRPV1-negative A-fibres are the main afferents mediating pinprick pain and hyperalgesia, however, they do not appear to contribute to the induction of pain-long-term potentiation. These

  9. Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

    Science.gov (United States)

    Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

    2011-01-01

    To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

  10. Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory.

    Science.gov (United States)

    Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

    2011-07-01

    To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories.

  11. Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Pettorossi, V E

    2000-01-01

    In rat brainstem slices, we investigated the role of nitric oxide in long-term potentiation induced in the ventral portion of the medial vestibular nuclei by high-frequency stimulation of the primary vestibular afferents. The nitric oxide scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ] and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester were administered before and after induction of potentiation. Both drugs completely prevented long-term potentiation, whereas they did not impede the potentiation build-up, or affect the already established potentiation. These results demonstrate that the induction, but not the maintenance of vestibular long-term potentiation, depends on the synthesis and release into the extracellular medium of nitric oxide. In addition, we analysed the effect of the nitric oxide donor sodium nitroprusside on vestibular responses. Sodium nitroprusside induced long-term potentiation, as evidenced through the field potential enhancement and unit peak latency decrease. This potentiation was impeded by D, L-2-amino-5-phosphonopentanoic acid, and was reduced under blockade of synaptosomal platelet-activating factor receptors by ginkgolide B and group I metabotropic glutamate receptors by (R,S)-1-aminoindan-1, 5-dicarboxylic acid. When reduced, potentiation fully developed following the washout of antagonist, demonstrating an involvement of platelet-activating factor and group I metabotropic glutamate receptors in its full development. Potentiation induced by sodium nitroprusside was also associated with a decrease in the paired-pulse facilitation ratio, which persisted under ginkgolide B, indicating that nitric oxide increases glutamate release independently of platelet-activating factor-mediated presynaptic events. We suggest that nitric oxide, released after the activation of N-methyl-D-aspartate receptors, acts as a retrograde messenger leading to an enhancement of glutamate release to a

  12. [Mathematical simulation of induction of long-term depression in cerebellar Purkinje cells].

    Science.gov (United States)

    Murzina, G B

    2003-01-01

    Mechanisms of associative and homosynaptic long-term depression (LTD) in cerebellar Purkinje cells are discussed. The possibility of LTD induction related to a decrease in efficacy of AMPA receptors through either their dephosphorylation or phosphorylation is investigated by mathematical simulation.

  13. Laminin degradation by plasmin regulates long-term potentiation.

    Science.gov (United States)

    Nakagami, Y; Abe, K; Nishiyama, N; Matsuki, N

    2000-03-01

    Plasmin is converted from its zymogen plasminogen by tissue type or urokinase type plasminogen activator (PA) and degrades many components of the extracellular matrix (ECM). To explore the possibility that the PA-plasmin system regulates synaptic plasticity, we investigated the effect of plasmin on degradation of ECM and synaptic plasticity by using organotypic hippocampal cultures. High-frequency stimulation produced long-term potentiation (LTP) in control slices, whereas the potentiation was induced but not maintained in slices pretreated with 100 nM plasmin for 6 hr. The baseline synaptic responses were not affected by pretreatment with plasmin. The impairment of LTP maintenance was not observed in slices pretreated with 100 nM plasmin for 6 hr, washed, and then cultured for 24-48 hr in the absence of plasmin. To identify substrates of plasmin, the expression of three major components of ECM, laminin, fibronectin, and type IV collagen, was investigated by immunofluorescence imaging. The three ECM components were widely distributed in the hippocampus, and only laminin was degraded by plasmin pretreatment. The expression level of laminin returned to normal levels when the slices were cultured for 24-48 hr after washout of plasmin. Furthermore, preincubation with anti-laminin antibodies prevented both the degradation of laminin and the impairment of LTP maintenance by plasmin. These results suggest that the laminin-mediated cell-ECM interaction may be necessary for the maintenance of LTP.

  14. Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer.

    Science.gov (United States)

    Speicher, P J; Wang, X; Englum, B R; Ganapathi, A M; Yerokun, B; Hartwig, M G; D'Amico, T A; Berry, M F

    2015-01-01

    The purpose of this study was to examine the role of induction chemoradiation in the treatment of potentially resectable locally advanced (T2-3N0 and T1-3N+) esophageal cancer utilizing a large national database. The National Cancer Data Base (NCDB) was queried for all patients undergoing esophagectomy for clinical T2-3N0 and T1-3N+ esophageal cancer of the mid- or lower esophagus. Patients were stratified by the use of induction chemoradiation therapy versus surgery-first. Trends were assessed with the Cochran-Armitage test. Predictors of receiving induction therapy were evaluated with multivariable logistic regression. A propensity-matched analysis was conducted to compare outcomes between groups, and the Kaplan-Meier method was used to estimate long-term survival. Within the NCDB, 7921 patients were identified, of which 6103 (77.0%) were treated with chemoradiation prior to esophagectomy, while the remaining 1818 (23.0%) were managed with surgery-first. Use of induction therapy increased over time, with an absolute increase of 11.8% from 2003-2011 (P induction therapy was associated with higher rates of negative margins and shorter hospital length of stay, but no differences in unplanned readmission and 30-day mortality rates. In unadjusted survival analysis, induction therapy was associated with better long-term survival compared to a strategy of surgery-first, with 5-year survival rates of 37.2% versus 28.6%, P induction therapy maintained a significant survival advantage over surgery-first (5-year survival: 37.9% vs. 28.7%, P induction chemoradiation therapy prior to surgical resection is associated with significant improvement in long-term survival, even after adjusting for confounders with a propensity model. Induction therapy should be considered in all medically appropriate patients with resectable cT2-3N0 and cT1-3N+ esophageal cancer, prior to esophagectomy.

  15. Long-term enhancement (LTE) of postsynaptic potentials following neural conditioning, in mammalian sympathetic ganglia.

    Science.gov (United States)

    Libet, B; Mochida, S

    1988-11-15

    Orthodromic, preganglionic conditioning stimulation can consistently induce long-term enhancement (LTE) (greater than 3 h) of the muscarinically mediated slow excitatory postsynaptic potential and the slow inhibitory postsynaptic potential. This was shown for superior cervical ganglia of rabbit and rat. Effective conditioning stimuli are in a physiologically observed range (3/s for 7 min, 5/s for 4 min, 10/s for 2 min, 20/s for 1 min). LTE was producible both homosynaptically and heterosynaptically. LTE can thus be associative, with conditioning synaptic input in one line inducing long-term changes in postsynaptic responses to another (heterosynaptic) input. The dopamine antagonist butaclamol depressed LTE, particularly that following the initial postconditioning period of 30 min. Adrenergic antagonists had no effect. This pharmacological evidence, coupled with the heterosynaptic induction of LTE, supports the view that neurally induced LTE may be at least partly mediated by endogenous dopamine. Another non-cholinergic but non-adrenergic transmitter (possibly a peptide) might contribute to the LTE seen in the initial 30 min postconditioning. The present, orthodromically induced LTE is clearly different from the long-term potentiation widely studied in hippocampus, etc., in the modes of induction and synaptic mediation.

  16. Molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model.

    Directory of Open Access Journals (Sweden)

    Paul Smolen

    Full Text Available Protein synthesis-dependent, late long-term potentiation (LTP and depression (LTD at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC and cross capture hypotheses. Only synapses that have been "tagged" by a stimulus sufficient for LTP and learning can "capture" PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.

  17. Molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model.

    Science.gov (United States)

    Smolen, Paul; Baxter, Douglas A; Byrne, John H

    2012-01-01

    Protein synthesis-dependent, late long-term potentiation (LTP) and depression (LTD) at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ) is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC) and cross capture hypotheses. Only synapses that have been "tagged" by a stimulus sufficient for LTP and learning can "capture" PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.

  18. Induction of thermal hyperalgesia and synaptic long-term potentiation in the spinal cord lamina I by TNF-α and IL-1β is mediated by glial cells.

    Science.gov (United States)

    Gruber-Schoffnegger, Doris; Drdla-Schutting, Ruth; Hönigsperger, Christoph; Wunderbaldinger, Gabriele; Gassner, Matthias; Sandkühler, Jürgen

    2013-04-10

    Long-term potentiation (LTP) of synaptic strength in nociceptive pathways is a cellular model of hyperalgesia. The emerging literature suggests a role for cytokines released by spinal glial cells for both LTP and hyperalgesia. However, the underlying mechanisms are still not fully understood. In rat lumbar spinal cord slices, we now demonstrate that conditioning high-frequency stimulation of primary afferents activated spinal microglia within hyperalgesia induced by spinal application of either IL-1β or TNF-α in naive animals also required activation of spinal glial cells. These results reveal a novel, decisive role of spinal glial cells for the synaptic effects of IL-1β and TNF-α and for some forms of hyperalgesia.

  19. Observation of long term potentiation in papain-based memory devices

    KAUST Repository

    Bag, A.

    2014-06-01

    Biological synaptic behavior in terms of long term potentiation has been observed in papain-based (plant protein) memory devices (memristors) for the first time. Improvement in long term potentiation depends on pulse amplitude and width (duration). Continuous/repetitive dc voltage sweep leads to an increase in memristor conductivity leading to a long term memory in the \\'learning\\' processes.

  20. Postsynaptic Signals Mediating Induction of Long-Term Synaptic Depression in the Entorhinal Cortex

    Directory of Open Access Journals (Sweden)

    Saïd Kourrich

    2008-01-01

    Full Text Available The entorhinal cortex receives a large projection from the piriform cortex, and synaptic plasticity in this pathway may affect olfactory processing. In vitro whole cell recordings have been used here to investigate postsynaptic signalling mechanisms that mediate the induction of long-term synaptic depression (LTD in layer II entorhinal cortex cells. To induce LTD, pairs of pulses, using a 30-millisecond interval, were delivered at 1 Hz for 15 minutes. Induction of LTD was blocked by the NMDA receptor antagonist APV and by the calcium chelator BAPTA, consistent with a requirement for calcium influx via NMDA receptors. Induction of LTD was blocked when the FK506 was included in the intracellular solution to block the phosphatase calcineurin. Okadaic acid, which blocks activation of protein phosphatases 1 and 2a, also prevented LTD. Activation of protein phosphatases following calcium influx therefore contributes to induction of LTD in layer II of the entorhinal cortex.

  1. Postsynaptic Signals Mediating Induction of Long-Term Synaptic Depression in the Entorhinal Cortex

    Science.gov (United States)

    Kourrich, Saïd; Glasgow, Stephen D.; Caruana, Douglas A.; Chapman, C. Andrew

    2008-01-01

    The entorhinal cortex receives a large projection from the piriform cortex, and synaptic plasticity in this pathway may affect olfactory processing. In vitro whole cell recordings have been used here to investigate postsynaptic signalling mechanisms that mediate the induction of long-term synaptic depression (LTD) in layer II entorhinal cortex cells. To induce LTD, pairs of pulses, using a 30-millisecond interval, were delivered at 1 Hz for 15 minutes. Induction of LTD was blocked by the NMDA receptor antagonist APV and by the calcium chelator BAPTA, consistent with a requirement for calcium influx via NMDA receptors. Induction of LTD was blocked when the FK506 was included in the intracellular solution to block the phosphatase calcineurin. Okadaic acid, which blocks activation of protein phosphatases 1 and 2a, also prevented LTD. Activation of protein phosphatases following calcium influx therefore contributes to induction of LTD in layer II of the entorhinal cortex. PMID:18670611

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Long-term performance potential of concentrated photovoltaic (CPV) systems

    KAUST Repository

    Burhan, Muhammad

    2017-07-17

    Owing to the diverse photovoltaic (PV) systems’ design and technology, as well as the dynamic nature of insolation data received on the aperture surfaces, the instantaneous output from a PV system fluctuates greatly. For accurate performance estimation of a large PV field, the long term performance as electrical output is a more rational approach over the conventional testing methods, such as at Standard Testing Conditions (STC) and at the Nominal Operating Cell Temperature (NOCT) available hitherto. In this paper, the long-term performances of concentrated PVs (Cassegrain reflectors and Fresnel lens) with 2-axes tracking and a variety of PV systems, namely the stationary flat-plate PV (mono-crystalline, poly-crystalline and thin-films CIS types), is presented over a period of one year for the merit comparison of system design, under the tropical weather conditions of Singapore. From the measured field performances, the total energy output of 240.2 kW h/m/year is recorded for CPV operation in Singapore, which is nearly two folds higher than the stationary PV panels.

  4. A Protein Synthesis and Nitric Oxide-Dependent Presynaptic Enhancement in Persistent Forms of Long-Term Potentiation

    Science.gov (United States)

    Johnstone, Victoria P. A.; Raymond, Clarke R.

    2011-01-01

    Long-term potentiation (LTP) is an important process underlying learning and memory in the brain. At CA3-CA1 synapses in the hippocampus, three discrete forms of LTP (LTP1, 2, and 3) can be differentiated on the basis of maintenance and induction mechanisms. However, the relative roles of pre- and post-synaptic expression mechanisms in LTP1, 2,…

  5. Bryostatin-1 promotes long-term potentiation via activation of PKCα and PKCε in the hippocampus.

    Science.gov (United States)

    Kim, H; Han, S H; Quan, H Y; Jung, Y-J; An, J; Kang, P; Park, J-B; Yoon, B-J; Seol, G H; Min, S S

    2012-12-13

    Activation of protein kinase C (PKC) by bryostatin-1 affects various functions of the central nervous system. We explored whether bryostatin-1 influenced synaptic plasticity via a process involving PKC. Our purpose was to examine whether bryostatin-1 affected the induction of hippocampal long-term potentiation (LTP) in Schaffer-collateral fibers (CA1 fibers) of the hippocampus, and/or influenced the intracellular Ca(2+) level of hippocampal neurons. We also determined the PKC isoforms involved in these processes. We found that bryostatin-1 strongly facilitated LTP induction, in a dose-dependent manner, upon single-theta burst stimulation (TBS). Further, intracellular Ca(2+) levels also increased with increasing concentration of bryostatin-1. The facilitative effects of bryostatin-1 in terms of LTP induction and enhancement of intracellular Ca(2+) levels were blocked by specific inhibitors of PKCα and PKCε, but not of PKCδ. Our results suggest that bryostatin-1 is involved in neuronal functioning and facilitates induction of LTP via activation of PKCα and/or PKCε. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. β-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus.

    Science.gov (United States)

    O'Dell, Thomas J; Connor, Steven A; Guglietta, Ryan; Nguyen, Peter V

    2015-09-01

    Encoding new information in the brain requires changes in synaptic strength. Neuromodulatory transmitters can facilitate synaptic plasticity by modifying the actions and expression of specific signaling cascades, transmitter receptors and their associated signaling complexes, genes, and effector proteins. One critical neuromodulator in the mammalian brain is norepinephrine (NE), which regulates multiple brain functions such as attention, perception, arousal, sleep, learning, and memory. The mammalian hippocampus receives noradrenergic innervation and hippocampal neurons express β-adrenergic receptors, which are known to play important roles in gating the induction of long-lasting forms of synaptic potentiation. These forms of long-term potentiation (LTP) are believed to importantly contribute to long-term storage of spatial and contextual memories in the brain. In this review, we highlight the contributions of noradrenergic signaling in general and β-adrenergic receptors in particular, toward modulating hippocampal LTP. We focus on the roles of NE and β-adrenergic receptors in altering the efficacies of specific signaling molecules such as NMDA and AMPA receptors, protein phosphatases, and translation initiation factors. Also, the roles of β-adrenergic receptors in regulating synaptic "tagging" and "capture" of LTP within synaptic networks of the hippocampus are reviewed. Understanding the molecular and cellular bases of noradrenergic signaling will enrich our grasp of how the brain makes new, enduring memories, and may shed light on credible strategies for improving mental health through treatment of specific disorders linked to perturbed memory processing and dysfunctional noradrenergic synaptic transmission.

  7. Long Term Potentials and Costs of RES - Part I: Potentials, Diffusion and Technological learning

    NARCIS (Netherlands)

    Hoefnagels, E.T.A.; Junginger, H.M.; Panzer, C.; Resch, G.; Held, A.

    2011-01-01

    Europe requires a long term vision for Renewable Energy Sources (RES) in order to pave the way for a successful and in the mid-term stable RES deployment beyond 2020. This encompasses, on the one hand, an assessment of the mid-term potentials and diffusion constraints for the broad basket of RES opt

  8. Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment.

    Science.gov (United States)

    Moreno-Castilla, Perla; Rodriguez-Duran, Luis F; Guzman-Ramos, Kioko; Barcenas-Femat, Alejandro; Escobar, Martha L; Bermudez-Rattoni, Federico

    2016-05-01

    Alzheimer's disease (AD) is a neurodegenerative condition manifested by synaptic dysfunction and memory loss, but the mechanisms underlying synaptic failure are not entirely understood. Although dopamine is a key modulator of synaptic plasticity, dopaminergic neurotransmission dysfunction in AD has mostly been associated to noncognitive symptoms. Thus, we aimed to study the relationship between dopaminergic neurotransmission and synaptic plasticity in AD models. We used a transgenic model of AD (triple-transgenic mouse model of AD) and the administration of exogenous amyloid-β (Aβ) oligomers into wild type mice. We found that Aβ decreased cortical dopamine levels and converted in vivo long-term potentiation (LTP) into long-term depression (LTD) after high-frequency stimulation delivered at basolateral amygdaloid nucleus-insular cortex projection, which led to impaired recognition memory. Remarkably, increasing cortical dopamine and norepinephrine levels rescued both high-frequency stimulation -induced LTP and memory, whereas depletion of catecholaminergic levels mimicked the Aβ-induced shift from LTP to LTD. Our results suggest that Aβ-induced dopamine depletion is a core mechanism underlying the early synaptopathy and memory alterations observed in AD models and acts by modifying the threshold for the induction of cortical LTP and/or LTD. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Hippocampal CA1 Kindling but Not Long-Term Potentiation Disrupts Spatial Memory Performance

    Science.gov (United States)

    Leung, L. Stan; Shen, Bixia

    2006-01-01

    Long-term synaptic enhancement in the hippocampus has been suggested to cause deficits in spatial performance. Synaptic enhancement has been reported after hippocampal kindling that induced repeated electrographic seizures or afterdischarges (ADs) and after long-term potentiation (LTP) defined as synaptic enhancement without ADs. We studied…

  10. Chronic pre-treatment with memantine prevents amyloid-beta protein-mediated long-term potentiation disruption

    Institute of Scientific and Technical Information of China (English)

    Fushun Li; Xiaowei Chen; Feiming Wang; Shujun Xu; Lan Chang; Roger Anwyl; Qinwen Wang

    2013-01-01

    Previous studies indicate that memantine, a low-affinity N-methyl-D-aspartate receptor antagonist, exerted acute protective effects against amyloid-β protein-induced neurotoxicity. In the present study, the chronic effects and mechanisms of memantine were investigated further using electrophysiological methods. The results showed that 7-day intraperitoneal application of memantine, at doses of 5 mg/kg or 20 mg/kg, did not alter hippocampal long-term potentiation induction in rats, while 40 mg/kg memantine presented potent long-term potentiation inhibition. Then further in vitro studys were carried out in 5 mg/kg and 20 mg/kg memantine treated rats. We found that 20 mg/kg memantine attenuated the potent long-term potentiation inhibition caused by exposure to amyloid-β protein in the dentate gyrus in vitro. These findings are the first to demonstrate the antagonizing effect of long-term systematic treatment of memantine against amyloid-β protein triggered long-term potentiation inhibition to improve synaptic plasticity.

  11. Neurabin contributes to hippocampal long-term potentiation and contextual fear memory.

    Directory of Open Access Journals (Sweden)

    Long-Jun Wu

    Full Text Available Neurabin is a scaffolding protein that interacts with actin and protein phosphatase-1. Highly enriched in the dendritic spine, neurabin is important for spine morphogenesis and synaptic formation. However, less is known about the role of neurabin in hippocampal plasticity and its possible effect on behavioral functions. Using neurabin knockout (KO mice, here we studied the function of neurabin in hippocampal synaptic transmission, plasticity and behavioral memory. We demonstrated that neurabin KO mice showed a deficit in contextual fear memory but not auditory fear memory. Whole-cell patch clamp recordings in the hippocampal CA1 neurons showed that long-term potentiation (LTP was significantly reduced, whereas long-term depression (LTD was unaltered in neurabin KO mice. Moreover, increased AMPA receptor but not NMDA receptor-mediated synaptic transmission was found in neurabin KO mice, and is accompanied by decreased phosphorylation of GluR1 at the PKA site (Ser845 but no change at the CaMKII/PKC site (Ser831. Pre-conditioning with LTD induction rescued the following LTP in neurabin KO mice, suggesting the loss of LTP may be due to the saturated synaptic transmission. Our results indicate that neurabin regulates contextual fear memory and LTP in hippocampal CA1 pyramidal neurons.

  12. Neurabin contributes to hippocampal long-term potentiation and contextual fear memory.

    Science.gov (United States)

    Wu, Long-Jun; Ren, Ming; Wang, Hansen; Kim, Susan S; Cao, Xiaoyan; Zhuo, Min

    2008-01-09

    Neurabin is a scaffolding protein that interacts with actin and protein phosphatase-1. Highly enriched in the dendritic spine, neurabin is important for spine morphogenesis and synaptic formation. However, less is known about the role of neurabin in hippocampal plasticity and its possible effect on behavioral functions. Using neurabin knockout (KO) mice, here we studied the function of neurabin in hippocampal synaptic transmission, plasticity and behavioral memory. We demonstrated that neurabin KO mice showed a deficit in contextual fear memory but not auditory fear memory. Whole-cell patch clamp recordings in the hippocampal CA1 neurons showed that long-term potentiation (LTP) was significantly reduced, whereas long-term depression (LTD) was unaltered in neurabin KO mice. Moreover, increased AMPA receptor but not NMDA receptor-mediated synaptic transmission was found in neurabin KO mice, and is accompanied by decreased phosphorylation of GluR1 at the PKA site (Ser845) but no change at the CaMKII/PKC site (Ser831). Pre-conditioning with LTD induction rescued the following LTP in neurabin KO mice, suggesting the loss of LTP may be due to the saturated synaptic transmission. Our results indicate that neurabin regulates contextual fear memory and LTP in hippocampal CA1 pyramidal neurons.

  13. Hippocampal long-term potentiation is not accompanied by presynaptic spike broadening, unlike synaptic potentiation by K+ channel blockers.

    Science.gov (United States)

    Laerum, H; Storm, J F

    1994-02-21

    The expression of hippocampal long-term potentiation (LTP) is thought to be at least partly due to increased transmitter release. To test whether this increase is due to a broadening of the presynaptic action potential, we have compared the presynaptic fibre volley before and after LTP induction, or application of K+ channel blockers, in CA1 of rat hippocampal slices. Tetraethylammonium (TEA; 1 mM) induced a parallel increase in the fibre volley duration of the slope of the field EPSP, indicating that a presynaptic spike broadening underlying synaptic potentiation can be detected. In contrast, induction of LTP did not produce any measurable change in the fibre volley, although the average increase in the EPSP slope was larger than with TEA. These results indicate that LTP expression is not primarily due to a presynaptic spike broadening.

  14. Colorado Plateau Rapid Ecoregion Assessment Change Agents - Climate Change - Long-Term Potential For Change

    Data.gov (United States)

    Bureau of Land Management, Department of the Interior — This map shows long-term potential for climate change, which was calculated using a logic model to integrate the factors of: vegetation change summer & winter...

  15. Short-Term Plasticity and Long-Term Potentiation in Magnetic Tunnel Junctions: Towards Volatile Synapses

    Science.gov (United States)

    Sengupta, Abhronil; Roy, Kaushik

    2016-02-01

    Synaptic memory is considered to be the main element responsible for learning and cognition in humans. Although traditionally nonvolatile long-term plasticity changes are implemented in nanoelectronic synapses for neuromorphic applications, recent studies in neuroscience reveal that biological synapses undergo metastable volatile strengthening followed by a long-term strengthening provided that the frequency of the input stimulus is sufficiently high. Such "memory strengthening" and "memory decay" functionalities can potentially lead to adaptive neuromorphic architectures. In this paper, we demonstrate the close resemblance of the magnetization dynamics of a magnetic tunnel junction (MTJ) to short-term plasticity and long-term potentiation observed in biological synapses. We illustrate that, in addition to the magnitude and duration of the input stimulus, the frequency of the stimulus plays a critical role in determining long-term potentiation of the MTJ. Such MTJ synaptic memory arrays can be utilized to create compact, ultrafast, and low-power intelligent neural systems.

  16. Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy

    Directory of Open Access Journals (Sweden)

    Liu Xian-Guo

    2011-03-01

    Full Text Available Abstract Long-term potentiation (LTP in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents.

  17. Effect of modafinil on learning performance and neocortical long-term potentiation in rats.

    Science.gov (United States)

    Burgos, Héctor; Castillo, Amparo; Flores, Osvaldo; Puentes, Gustavo; Morgan, Carlos; Gatica, Arnaldo; Cofré, Christian; Hernández, Alejandro; Laurido, Claudio; Constandil, Luis

    2010-10-30

    Modafinil is a novel wake-promoting agent whose effects on cognitive performance have begun to be addressed at both preclinical and clinical level. The present study was designed to investigate in rats the effects of chronic modafinil administration on cognitive performance by evaluating: (i) working and reference memories in an Olton 4×4 maze, and (ii) learning of a complex operant conditioning task in a Skinner box. In addition, the effect of modafinil on the ability of the rat frontal cortex to develop long-term potentiation (LTP) was also studied. Chronic modafinil did not significantly modify working memory errors but decreased long-term memory errors on the Olton 4×4 maze, meaning that the drug may have a favourable profile on performance of visuo-spatial tasks (typically, a hippocampus-dependent task) when chronically administered. On the other hand, chronic modafinil resulted in a marked decrease of successful responses in a complex operant conditioning learning, which means that repeated administration of the drug influences negatively problem-solving abilities when confronting the rat to a sequencing task (typically, a prefrontal cortex-dependent task). In addition, in vivo electrophysiology showed that modafinil resulted in impaired capacity of the rat prefrontal cortex to develop LTP following tetanization. It is concluded that modafinil can improve the performance of spatial tasks that depend almost exclusively on hippocampal functioning, but not the performance in tasks including a temporal factor where the prefrontal cortex plays an important role. The fact that modafinil together with preventing operant conditioning learning was also able to block LTP induction in the prefrontal cortex, suggests that the drug could interfere some critical component required for LTP can be developed, thereby altering neuroplastic capabilities of the prefrontal cortex.

  18. Postsynaptic protein synthesis is required for presynaptic enhancement in persistent forms of long-term potentiation.

    Directory of Open Access Journals (Sweden)

    Victoria Philippa Anne Johnstone

    2013-02-01

    Full Text Available Long-term potentiation (LTP in the hippocampus is a fundamental process underlying learning and memory in the brain. At CA3-CA1 synapses, three discrete forms of LTP (LTP1, 2 and 3 have been differentiated on the basis of their persistence, maintenance mechanisms, Ca2+ signaling pathways, expression loci, and electrophysiological requirements. We previously showed that LTP2 and LTP3 involve a presynaptic expression component that is established in a translation-dependent manner. Here we investigate the locus of translation required for presynaptic expression. Neurotransmitter release rate was estimated via FM 1-43 destaining from CA3 terminals in hippocampal slices from male Wistar rats (6-8 weeks. Destaining was measured at sites making putative contact with CA1 dendritic processes in stratum radiatum that had been filled with a membrane impermeable translation inhibitor and a fluorescent indicator. Our results suggest that inhibition of postsynaptic translation eliminates the enhanced release ordinarily observed at 160 min post LTP induction, and that this effect is limited to sites closely apposed to the filled postsynaptic cell. We conclude that postsynaptic translation is required for the presynaptic component of LTP2 and LTP3 expression. These data considerably strengthen the mechanistic separation of LTP1, 2 and 3 and provide evidence for an expanded repertoire of communication between synaptic elements.

  19. Gating of long-term potentiation by nicotinic acetylcholine receptors at the cerebellum input stage.

    Directory of Open Access Journals (Sweden)

    Francesca Prestori

    Full Text Available The brain needs mechanisms able to correlate plastic changes with local circuit activity and internal functional states. At the cerebellum input stage, uncontrolled induction of long-term potentiation or depression (LTP or LTD between mossy fibres and granule cells can saturate synaptic capacity and impair cerebellar functioning, which suggests that neuromodulators are required to gate plasticity processes. Cholinergic systems innervating the cerebellum are thought to enhance procedural learning and memory. Here we show that a specific subtype of acetylcholine receptors, the α7-nAChRs, are distributed both in cerebellar mossy fibre terminals and granule cell dendrites and contribute substantially to synaptic regulation. Selective α7-nAChR activation enhances the postsynaptic calcium increase, allowing weak mossy fibre bursts, which would otherwise cause LTD, to generate robust LTP. The local microperfusion of α7-nAChR agonists could also lead to in vivo switching of LTD to LTP following sensory stimulation of the whisker pad. In the cerebellar flocculus, α7-nAChR pharmacological activation impaired vestibulo-ocular-reflex adaptation, probably because LTP was saturated, preventing the fine adjustment of synaptic weights. These results show that gating mechanisms mediated by specific subtypes of nicotinic receptors are required to control the LTD/LTP balance at the mossy fibre-granule cell relay in order to regulate cerebellar plasticity and behavioural adaptation.

  20. Stimulus Intensity-dependent Modulations of Hippocampal Long-term Potentiation by Basolateral Amygdala Priming

    Directory of Open Access Journals (Sweden)

    Zexuan eLi

    2012-05-01

    Full Text Available There is growing realization that the relationship between memory and stress/emotionality is complicated, and may include both memory enhancing and memory impairing aspects. It has been suggested that the underlying mechanisms involve amygdalar modulation of hippocampal synaptic plasticity, such as long-term potentiation (LTP. We recently reported that while in CA1 basolateral amygdala (BLA priming impaired theta stimulation induced LTP, it enhanced LTP in the dentate gyrus (DG. However, emotional and stressfull experiences were found to activate synaptic plasticity within the BLA, rasing the possibility that BLA modulation of other brain regions may be altered as well, as it may depend on the way the BLA is activated or is responding. In previous studies BLA priming stimulation was relatively weak (1V, 50 µs pulse duration. In the present study we assessed the effects of two stronger levels of BLA priming stimulation (1V or 2V, 100 µs pulse duration on LTP induction in hippocampal DG and CA1, in anesthetized rats. Results show that 1V-BLA priming stimulation enhanced but 2V-BLA priming stimulation impaired DG LTP; however, both levels of BLA priming stimulation impaired CA1 LTP, suggesting that modulation of hippocampal synaptic plasticity by amygdala is dependent on the degree of amygdala activation. These findings suggest that plasticity induced within the amygdala, by stressful experiences induces a form of metaplasticity that would alter the way the amygdala may modulate memory-related processes in other brain areas, such as the hippocampus.

  1. India’s long-term growth potential and the implications for Australia

    OpenAIRE

    Ben Ralston; Wilson Au-Yeung; Bill Brummitt

    2011-01-01

    After 20 years of economic reform this article discusses India’s long-term growth potential and canvasses some of the challenges that Indian policy makers will need to overcome to realise this potential. Some of the consequences of India’s growth for Australia are also explored.

  2. Input-specific long-term potentiation in the rat lateral amygdala of horizontal slices.

    Science.gov (United States)

    Drephal, Christian; Schubert, Manja; Albrecht, Doris

    2006-05-01

    Long-term potentiation (LTP) at input synapses to the lateral nucleus of the amygdala (LA) is a candidate mechanism for memory storage during fear learning. Cellular mechanisms of LTP have been nearly exclusively investigated in coronal brain slices. In our experiments, we used a horizontal brain slice preparation of rats that preserved most of the connections to cortical areas and the hippocampus. The stimulation electrodes were located either within the external capsule (EC) or the LA. The aim of the present study was to investigate the mechanisms of LTP induced either by weak theta burst stimulation (TBS) or strong high frequency stimulation (HFS) using the two different stimulation sites. Whereas both TBS and HFS of afferences running through the LA induced stable LTP, TBS failed to induce LTP of EC-inputs to the LA. The present findings also show that LTP in the LA exhibits vulnerability at different time windows after induction. The time window was dependent on the kind of stimulated afferences. Later LTP becomes resistant to disruption by low frequency stimulation. We could show that both used inputs depended on NMDA receptors for LTP-induction. LTP induced by stimulation of fibers within the LA was not altered by nifedipine (10 microM). In contrast, EC-induced LTP was dependent on L-type voltage-gated calcium channels (VGCC). Finally, we found a higher magnitude of LTP in females using TBS, whereas HFS did not cause gender-specific differences. Our study supports the conclusion that the form of LA-LTP depend on which afferences are activated and what pattern of stimulation is used to induce LTP.

  3. Induction of long-term depression-like plasticity by pairings of motor imagination and peripheral electrical stimulation

    Directory of Open Access Journals (Sweden)

    Mads eJochumsen

    2015-12-01

    Full Text Available Long-term depression (LTD and long-term potentiation (LTP-like plasticity are models of synaptic plasticity which have been associated with memory and learning. The induction of LTD and LTP-like plasticity, using different stimulation protocols, has been proposed as a means of addressing abnormalities in cortical excitability associated with conditions such as focal hand dystonia and stroke. The aim of this study was to investigate whether the excitability of the cortical projections to the tibialis anterior muscle could be decreased when dorsiflexion of the ankle joint was imagined and paired with peripheral electrical stimulation of the nerve supplying the antagonist soleus muscle. The effect of stimulus timing was evaluated by comparing paired stimulation timed to reach the cortex before, at and after the onset of imagined movement. Fourteen healthy subjects participated in six experimental sessions held on non-consecutive days. The timing of stimulation delivery was determined offline based on the contingent negative variation (CNV of electroencephalography (EEG brain data obtained during imagined dorsiflexion. Afferent stimulation was provided via a single pulse electrical stimulation to the peripheral nerve paired, based on the CNV, with motor imagination of ankle dorsiflexion. A significant decrease (P=0.001 in the excitability of the cortical projection of tibialis anterior was observed when the afferent volley from the electrical stimulation of the tibial nerve (TN reached the cortex at the onset of motor imagination based on the CNV. When TN stimulation was delivered before (P=0.62, or after (P=0.23 imagined movement onset there was no significant effect. Nor was a significant effect found when electrical stimulation of the TN was applied independent of imagined movement (P=0.45. Therefore, the excitability of the cortical projection to a muscle can be inhibited when electrical stimulation of the nerve supplying the antagonist muscle

  4. Induction of Long-term Depression-like Plasticity by Pairings of Motor Imagination and Peripheral Electrical Stimulation.

    Science.gov (United States)

    Jochumsen, Mads; Signal, Nada; Nedergaard, Rasmus W; Taylor, Denise; Haavik, Heidi; Niazi, Imran K

    2015-01-01

    Long-term depression (LTD) and long-term potentiation (LTP)-like plasticity are models of synaptic plasticity which have been associated with memory and learning. The induction of LTD and LTP-like plasticity, using different stimulation protocols, has been proposed as a means of addressing abnormalities in cortical excitability associated with conditions such as focal hand dystonia and stroke. The aim of this study was to investigate whether the excitability of the cortical projections to the tibialis anterior (TA) muscle could be decreased when dorsiflexion of the ankle joint was imagined and paired with peripheral electrical stimulation (ES) of the nerve supplying the antagonist soleus muscle. The effect of stimulus timing was evaluated by comparing paired stimulation timed to reach the cortex before, at and after the onset of imagined movement. Fourteen healthy subjects participated in six experimental sessions held on non-consecutive days. The timing of stimulation delivery was determined offline based on the contingent negative variation (CNV) of electroencephalography brain data obtained during imagined dorsiflexion. Afferent stimulation was provided via a single pulse ES to the peripheral nerve paired, based on the CNV, with motor imagination of ankle dorsiflexion. A significant decrease (P = 0.001) in the excitability of the cortical projection of TA was observed when the afferent volley from the ES of the tibial nerve (TN) reached the cortex at the onset of motor imagination based on the CNV. When TN stimulation was delivered before (P = 0.62), or after (P = 0.23) imagined movement onset there was no significant effect. Nor was a significant effect found when ES of the TN was applied independent of imagined movement (P = 0.45). Therefore, the excitability of the cortical projection to a muscle can be inhibited when ES of the nerve supplying the antagonist muscle is precisely paired with the onset of imagined movement.

  5. Long-term natural gas supply to Europe: Import potential, infrastructure needs and investment promotion

    Energy Technology Data Exchange (ETDEWEB)

    Hafner, M.; Karbuz, S.; Esnault, B.; El Andaloussi, H.

    2007-07-01

    This paper assesses the future long term (2010-2020-2030) gas import requirements and external supply potential for Europe, and identifies future gas corridor infrastructure needs taking into account a reserve/resource analysis, production and demand outlooks, export infrastructure and projects, supply costs as well as institutional, strategy and geopolitical issues, etc. Finally, the paper identifies investment barriers for different types of gas corridor infrastructure projects and proposes issues to be addressed by policymakers in order to put in place a favourable environment regarding investment promotion and to create a sustainable gas market for the long term. (auth)

  6. Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy.

    NARCIS (Netherlands)

    Ruscheweyh, R.; Wilder-Smith, O.H.G.; Drdla, R.; Liu, X.G.; Sandkuhler, J.

    2011-01-01

    Long-term potentiation (LTP) in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contr

  7. Synapse Specificity of Long-Term Potentiation Breaks Down with Aging

    Science.gov (United States)

    Ris, Laurence; Godaux, Emile

    2007-01-01

    Memory shows age-related decline. According to the current prevailing theoretical model, encoding of memories relies on modifications in the strength of the synapses connecting the different cells within a neuronal network. The selective increases in synaptic weight are thought to be biologically implemented by long-term potentiation (LTP). Here,…

  8. LONG-TERM POTENTIATION, PROTEIN-KINASE-C, AND GLUTAMATE RECEPTORS

    NARCIS (Netherlands)

    MULLER, D; BUCHS, PA; STOPPINI, L; BODDEKE, H

    1991-01-01

    Among the various molecular events that have been proposed to contribute to the mechanisms of long-term potentiation (LTP), one of the most cited possibilities has been the activation of protein kinase C (PKC). Here we review various aspects of the cellular actions of PKC activationa and inhibition,

  9. BDNF Regains Function in Hippocampal Long-Term Potentiation Deficits Caused by Diencephalic Damage

    Science.gov (United States)

    Vedder, Lindsey C.; Savage, Lisa M.

    2017-01-01

    Thiamine deficiency (TD), commonly associated with chronic alcoholism, leads to diencephalic damage, hippocampal dysfunction, and spatial learning and memory deficits. We show a decrease in the magnitude of long-term potentiation (LTP) and paired-pulse facilitation (PPF) at CA3-CA1 synapses, independent of sex, following diencephalic damage…

  10. Long-term potentiation at temporoammonic path-CA1 synapses in freely moving rats

    Directory of Open Access Journals (Sweden)

    Jossina eGonzalez

    2016-02-01

    Full Text Available Hippocampal area CA1 receives direct entorhinal layer III input via the temporoammonic path (TAP and recent studies implicate TAP-CA1 synapses are important for some aspects of hippocampal memory function. Nonetheless, as few studies have examined TAP-CA1 synaptic plasticity in vivo, the induction and longevity of TAP-CA1 long-term potentiation (LTP has not been fully characterized. We analyzed CA1 responses following stimulation of the medial aspect of the angular bundle and investigated LTP at medial temporoammonic path (mTAP-CA1 synapses in freely moving rats. We demonstrate monosynaptic mTAP-CA1 responses can be isolated in vivo as evidenced by observations of independent current sinks in the stratum lacunosum moleculare of both areas CA1 and CA3 following angular bundle stimulation. Contrasting prior indications that TAP input rarely elicits CA1 discharge, we observed mTAP-CA1 responses that appeared to contain putative population spikes in 40% of our behaving animals. Theta burst high frequency stimulation of mTAP afferents resulted in an input specific and NMDA receptor-dependent LTP of mTAP-CA1 responses in behaving animals. LTP of mTAP-CA1 responses decayed as a function of two exponential decay curves with time constants (τ of 2.7 and 148 days to decay 63.2% of maximal LTP. In contrast, mTAP-CA1 population spike potentiation longevity demonstrated a τ of 9.6 days. To our knowledge, these studies provide the first description of mTAP-CA1 LTP longevity in vivo. These data indicate TAP input to area CA1 is a physiologically relevant afferent system that displays robust synaptic plasticity.

  11. Genetic enhancement of memory and long-term potentiation but not CA1 long-term depression in NR2B transgenic rats.

    Directory of Open Access Journals (Sweden)

    Deheng Wang

    Full Text Available One major theory in learning and memory posits that the NR2B gene is a universal genetic factor that acts as rate-limiting molecule in controlling the optimal NMDA receptor's coincidence-detection property and subsequent learning and memory function across multiple animal species. If so, can memory function be enhanced via transgenic overexpression of NR2B in another species other than the previously reported mouse species? To examine these crucial issues, we generated transgenic rats in which NR2B is overexpressed in the cortex and hippocampus and investigated the role of NR2B gene in NMDA receptor-mediated synaptic plasticity and memory functions by combining electrophysiological technique with behavioral measurements. We found that overexpression of the NR2B subunit had no effect on CA1-LTD, but rather resulted in enhanced CA1-LTP and improved memory performances in novel object recognition test, spatial water maze, and delayed-to-nonmatch working memory test. Our slices recordings using NR2A- and NR2B-selective antagonists further demonstrate that the larger LTP in transgenic hippocampal slices was due to contribution from the increased NR2B-containing NMDARs. Therefore, our genetic experiments suggest that NR2B at CA1 synapses is not designated as a rate-limiting factor for the induction of long-term synaptic depression, but rather plays a crucial role in initiating the synaptic potentiation. Moreover, our studies provide strong evidence that the NR2B subunit represents a universal rate-limiting molecule for gating NMDA receptor's optimal coincidence-detection property and for enhancing memory function in adulthood across multiple mammalian species.

  12. Spacing Effect: SHP2 Phosphatase Regulates Resting Intervals Between Learning Trials in Long-Term Memory Induction

    OpenAIRE

    Pagani, Mario R.; Oishi, Kimihiko; Gelb, Bruce D.; Zhong, Yi

    2009-01-01

    A common property of long-term memory (LTM) induction is the requirement for repeated training sessions spaced over time. The phenomena of better memory being formed with resting intervals between training sessions is called the spacing effect, for which the underlying molecular and neural bases are largely unknown. Our study reveals that the duration of resting intervals required for inducing LTM can be regulated by activity levels of the protein tyrosine phosphatase corkscrew (CSW) in Droso...

  13. Polygalasaponin F induces long-term potentiation in adult rat hippocampus via NMDA receptor activation

    Institute of Scientific and Technical Information of China (English)

    Feng SUN; Jian-dong SUN; Ning HAN; Chuang-jun LI; Yu-he YUAN; Dong-ming ZHANG; Nai-hong CHEN

    2012-01-01

    Aim:To investigate the effect and underlying mechanisms of polygalasaponin F (PGSF),a triterpenoid saponin isolated from Polygala japonica,on long-term potentiation (LTP)in hippocampus dentate gyrus (DG)of anesthetized rats.Methods:Population spike (PS)of hippocampal DG was recorded in anesthetized male Wistar rats.PGSF,the NMDAR inhibitor MK801 and the CaMKll inhibitor KN93 were intracerebroventricularly administered.Western blotting analysis was used to examine the phosphorylation expressions of NMDA receptor subunit 2B (NR2B),Ca2+/calmodulin-dependent kinase Ⅱ (CaMKII),extracellular signalregulated kinase (ERK),and cAMP response element-binding protein (CREB).Results:Intracerebroventricular administration of PGSF (1 and 10 μmol/L)produced long-lasting increase of PS amplitude in hippocampal DG in a dose-dependent manner.Pre-injection of MK801 (100 μmol/L)or KN93 (100 μmol/L)completely blocked PGSFinduced LTP.Furthermore,the phosphorylation of NR2B,CaMKII,ERK,and CREB in hippocampus was significantly increased 5-60min after LTP induction.The up-regulation of p-CaMKII expression could be completely abolished by pre-injection of MK801.The upregulation of p-ERK and p-CREB expressions could be partially blocked by pre-injection of KN93.Conclusion:PGSF could induce LTP in hippocampal DG in anesthetized rats via NMDAR activation mediated by CaMKII,ERK and CREB signaling pathway.

  14. Learning, memory and long-term potentiation are altered in Nedd4 heterozygous mice.

    Science.gov (United States)

    Camera, Daria; Coleman, Harold A; Parkington, Helena C; Jenkins, Trisha A; Pow, David V; Boase, Natasha; Kumar, Sharad; Poronnik, Philip

    2016-04-15

    The consolidation of short-term memory into long-term memory involves changing protein level and activity for the synaptic plasticity required for long-term potentiation (LTP). AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, although the physiological relevance of these findings are yet to be determined. We therefore investigated learning and memory in Nedd4(+/-) mice that have a 50% reduction in levels of Nedd4. These mice showed decreased long-term spatial memory as evidenced by significant increases in the time taken to learn the location of and subsequently find a platform in the Morris water maze. In contrast, there were no significant differences between Nedd4(+/+) and Nedd4(+/-) mice in terms of short-term spatial memory in a Y-maze test. Nedd4(+/-) mice also displayed a significant reduction in post-synaptic LTP measured in hippocampal brain slices. Immunofluorescence of Nedd4 in the hippocampus confirmed its expression in hippocampal neurons of the CA1 region. These findings indicate that reducing Nedd4 protein by 50% significantly impairs LTP and long-term memory thereby demonstrating an important role for Nedd4 in these processes.

  15. Long-term potentiation of GABAergic synaptic transmission in neonatal rat hippocampus.

    Science.gov (United States)

    Caillard, O; Ben-Ari, Y; Gaiarsa, J L

    1999-07-01

    1. The plasticity of GABAergic synapses was investigated in neonatal rat hippocampal slices obtained between postnatal days 3 and 6 using intracellular recording techniques. Ionotropic glutamate receptor antagonists were present throughout the experiments to isolate GABAA receptor-mediated postsynaptic potentials (GABAA PSPs) or currents (GABAA PSCs). 2. Repetitive depolarizing pulses (20 pulses, 0.5 s duration, at 0.1 Hz, each pulse generating 4-6 action potentials) induced a long-term potentiation in the slope and amplitude of the evoked GABAA PSPs and GABAA PSCs. 3. Long-term potentiation was prevented by intracellular injection of the calcium chelator BAPTA (50 mM), or when the voltage-dependent calcium channels blockers Ni2+ (50 microM) and nimodipine (10 microM) were bath applied. 4. Repetitive depolarizing pulses induced a persistent (over 1 h) increase in the frequency of spontaneous GABAA PSCs. 5. Repetitive depolarizing pulses induced a long-lasting increase in the frequency of miniature GABAA PSCs, without altering their amplitude or decay-time constant. 6. It is concluded that the postsynaptic activation of voltage-dependent calcium channels leads to a long-term potentiation of GABAergic synaptic transmission in neonatal rat hippocampus. This form of plasticity is expressed as an increase in the probability of GABA release or in the number of functional synapses, rather than as an upregulation of postsynaptic GABAA receptor numbers or conductance at functional synapses.

  16. D-Serine rescues the deficits of hippocampal long-term potentiation and learning and memory induced by sodium fluoroacetate.

    Science.gov (United States)

    Han, Huili; Peng, Yan; Dong, Zhifang

    2015-06-01

    It is well known that bidirectional glia-neuron interactions play important roles in the neurophysiological and neuropathological processes. It is reported that impairing glial functions with sodium fluoroacetate (FAC) impaired hippocampal long-term depression (LTD) and spatial memory retrieval. However, it remains unknown whether FAC impairs hippocampal long-term potentiation (LTP) and learning and/or memory, and if so, whether pharmacological treatment with exogenous d-serine can recuse the impairment. Here, we reported that systemic administration of FAC (3mg/kg, i.p.) before training resulted in dramatic impairments of spatial learning and memory in water maze and fear memory in contextual fear conditioning. Furthermore, the behavioral deficits were accompanied by impaired LTP induction in the hippocampal CA1 area of brain slices. More importantly, exogenous d-serine treatment succeeded in recusing the deficits of hippocampal LTP and learning and memory induced by FAC. Together, these results suggest that astrocytic d-serine may be essential for hippocampal synaptic plasticity and memory, and that alteration of its levels may be relevant to the induction and potentially treatment of psychiatric and neurological disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Potential Long-Term Complications of Endovascular Stent Grafting for Blunt Thoracic Aortic Injury

    Directory of Open Access Journals (Sweden)

    Larry E. Miller

    2012-01-01

    Full Text Available Blunt thoracic aortic injury (BTAI is a rare, but lethal, consequence of rapid deceleration events. Most victims of BTAI die at the scene of the accident. Of those who arrive to the hospital alive, expedient aortic intervention significantly improves survival. Thoracic endovascular aortic repair (TEVAR has been accepted as the standard of care for BTAI at many centers, primarily due to the convincing evidence of lower mortality and morbidity in comparison to open surgery. However, less attention has been given to potential long-term complications of TEVAR for BTAI. This paper focuses on these complications, which include progressive aortic expansion with aging, inadequate stent graft characteristics, device durability concerns, long-term radiation exposure concerns from follow-up computed tomography scans, and the potential for (Victims of Modern Imaging Technology VOMIT.

  18. Failed stabilization for long-term potentiation in the auditory cortex of FMR1 knockout mice.

    Directory of Open Access Journals (Sweden)

    Sungchil Yang

    Full Text Available Fragile X syndrome is a developmental disorder that affects sensory systems. A null mutation of the Fragile X Mental Retardation protein 1 (Fmr1 gene in mice has varied effects on developmental plasticity in different sensory systems, including normal barrel cortical plasticity, altered ocular dominance plasticity and grossly impaired auditory frequency map plasticity. The mutation also has different effects on long-term synaptic plasticity in somatosensory and visual cortical neurons, providing insights on how it may differentially affect the sensory systems. Here we present evidence that long-term potentiation (LTP is impaired in the developing auditory cortex of the Fmr1 knockout (KO mice. This impairment of synaptic plasticity is consistent with impaired frequency map plasticity in the Fmr1 KO mouse. Together, these results suggest a potential role of LTP in sensory map plasticity during early sensory development.

  19. DEVELOPMENTAL LEAD (PB) EXPOSURE REDUCES THE ABILITY OF THE NNDA ANTAGONIST MK801 TO SUPPRESS LONG-TERM POTENTIATION (LTP) IN THE RAT DENTATE GYRUS, IN VIVO

    Science.gov (United States)

    Chronic developmental lead (Pb) exposure increases the threshold and enhances decay of long-term potentiation (LTP) in the dentate gyrus of the hippocampal formation. MK-801 and other antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor subtype impair induction of LT...

  20. Presynaptic ultrastructural plasticity along CA3→CA1 axons during long-term potentiation in mature hippocampus.

    Science.gov (United States)

    Bourne, Jennifer N; Chirillo, Michael A; Harris, Kristen M

    2013-12-01

    In area CA1 of the mature hippocampus, synaptogenesis occurs within 30 minutes after the induction of long-term potentiation (LTP); however, by 2 hours many small dendritic spines are lost, and those remaining have larger synapses. Little is known, however, about associated changes in presynaptic vesicles and axonal boutons. Axons in CA1 stratum radiatum were evaluated with 3D reconstructions from serial section electron microscopy at 30 minutes and 2 hours after induction of LTP by theta-burst stimulation (TBS). The frequency of axonal boutons with a single postsynaptic partner was decreased by 33% at 2 hours, corresponding perfectly to the 33% loss specifically of small dendritic spines (head diameters complement postsynaptic ultrastructural plasticity during LTP.

  1. Frequency-dependent associative long-term potentiation at the hippocampal mossy fiber-CA3 synapse.

    Science.gov (United States)

    Derrick, B E; Martinez, J L

    1994-10-25

    The mossy fiber-CA3 synapse displays an N-methyl-D-aspartate-receptor-independent mu-opioid-receptor-dependent form of long-term potentiation (LTP) that is thought not to display cooperativity or associativity with coactive afferents. However, because mossy fiber LTP requires repetitive synaptic activity for its induction, we reevaluated cooperativity and associativity at this synapse by using trains of mossy fiber stimulation. Moderate-, but not low-, intensity trains induced mossy fiber LTP, indicating cooperativity. Low-intensity mossy fiber trains that were normally ineffective in inducing LTP could induce mossy fiber LTP when delivered in conjunction with trains delivered to commissural-CA3 afferents. Associative mossy fiber LTP also could be induced with single mossy fiber pulses when delivered with commissural trains in the presence of a mu-opioid-receptor agonist. Our findings suggest a frequency-dependent variation of Hebbian associative LTP induction that is regulated by the release of endogenous opioid peptides.

  2. Expression mechanisms underlying long-term potentiation: a postsynaptic view, 10 years on

    OpenAIRE

    2014-01-01

    This review focuses on the research that has occurred over the past decade which has solidified a postsynaptic expression mechanism for long-term potentiation (LTP). However, experiments that have suggested a presynaptic component are also summarized. It is argued that the pairing of glutamate uncaging onto single spines with postsynaptic depolarization provides the final and most elegant demonstration of a postsynaptic expression mechanism for NMDA receptor-dependent LTP. The fact that the m...

  3. Long-term potentiation in the in vitro perirhinal cortex displays associative properties.

    Science.gov (United States)

    Bilkey, D K

    1996-09-16

    Brief high frequency tetanization trains reliably induced input-specific long-term potentiation (LTP) in slices of rat perirhinal cortex maintained in vitro. Furthermore, associative interactions between inputs were observed following simultaneous tetanization of separate inputs. This associativity may be mediated via NMDA receptors as LTP was blocked in the presence of APV. These results suggest that LTP may underline participation of perirhinal cortex in memory processes.

  4. Correlating learning and memory improvements to long-term potentiation in patients with brain injury

    Institute of Scientific and Technical Information of China (English)

    Xingfu Peng; Qian Yu

    2008-01-01

    BACKGROUND:Brain injury patients often exhibit learning and memory functional deficits.Long-term potentiation(LTP)is a representative index for studying learning and memory cellular models; the LTP index correlates to neural plasticity. OBJECTIVE:This study was designed to investigate correlations of learning and memory functions to LTP in brain injury patients,and to summarize the research advancements in mechanisms underlying brain functional improvements after rehabilitation intervention. RETRIEVAL STRATEGY:Using the terms "brain injuries,rehabilitation,learning and memory,long-term potentiation",manuscripts that were published from 2000-2007 were retrieved from the PubMed database.At the same time,manuscripts published from 2000-2007 were also retrieved from the Database of Chinese Scientific and Technical Periodicals with the same terms in the Chinese language.A total of 64 manuscripts were obtained and primarily screened.Inclusion criteria:studies on learning and memory,as well as LTP in brain injury patients,and studies focused on the effects of rehabilitation intervention on the two indices; studies that were recently published or in high-impact journals.Exclusion criteria:repetitive studies.LITERATURE EVALUATION:The included manuscripts primarily focused on correlations between learning and memory and LTP,the effects of brain injury on learning and memory,as well as LTP,and the effects of rehabilitation intervention on learning and memory after brain injury.The included 39 manuscripts were clinical,basic experimental,or review studies. DATA SYNTHESIS:Learning and memory closely correlates to LTP.The neurobiological basis of learning and memory is central nervous system plasticity,which involves neural networks,neural circuits,and synaptic connections,in particular,synaptic plasticity.LTP is considered to be an ideal model for studying synaptic plasticity,and it is also a classic model for studying neural plasticity of learning and memory.Brain injury

  5. A neuroligin-1-derived peptide stimulates phosphorylation of the NMDA receptor NR1 subunit and rescues MK-801-induced decrease in long-term potentiation and memory impairment

    DEFF Research Database (Denmark)

    Korshunova, Irina; Gjørlund, Michelle D; Jacobsen, Sylwia Owczarek

    2015-01-01

    neurolide-1 effects on short- and long-term social and spatial memory in social recognition, Morris water-maze, and Y-maze tests. We found that subcutaneous neurolide-1 administration, restored hippocampal LTP compromised by NMDA receptor inhibitor MK-801. It counteracted MK-801-induced memory deficit...... in the water-maze and Y-maze tests after long-term treatment (24 h and 1-2 h before the test), but not after short-term exposure (1-2 h). Long-term exposure to neurolide-1 also facilitated social recognition memory. In addition, neurolide-1-induced phosphorylation of the NMDA receptor NR1 subunit on a site...... receptor phosphorylation after treatment with NL1 or a mimetic peptide, neurolide-1, was quantified by immunoblotting. Subsequently, we investigated effects of neurolide-1 on long-term potentiation (LTP) induction in hippocampal slices compromised by NMDA receptor inhibitor MK-801. Finally, we investigated...

  6. Mechanisms of induction and expression of long-term depression at GABAergic synapses in the neonatal rat hippocampus.

    Science.gov (United States)

    Caillard, O; Ben-Ari, Y; Gaïarsa, J L

    1999-09-01

    Synaptic plasticity at excitatory glutamatergic synapses is believed to be instrumental in the maturation of neuronal networks. Using whole-cell patch-clamp recordings, we have studied the mechanisms of induction and expression of long-term depression at excitatory GABAergic synapses in the neonatal rat hippocampus (LTD(GABA-A)). We report that the induction of LTD(GABA-A) requires a GABA(A) receptor-mediated membrane depolarization, which is necessary to remove the Mg(2+) block from postsynaptic NMDA receptors. LTD(GABA-A) is associated with an increase in the coefficient of variation of evoked GABA(A) receptor-mediated synaptic currents and a decrease in the frequency, but not amplitude, of Sr(2+)-induced asynchronous GABA(A) quantal events. We conclude that LTD(GABA-A) induction requires the activation of both GABA(A) and NMDA postsynaptic receptors and that its expression is likely presynaptic.

  7. Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility

    Directory of Open Access Journals (Sweden)

    Eric J. Neuberger

    2017-09-01

    Full Text Available Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.

  8. Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility.

    Science.gov (United States)

    Neuberger, Eric J; Swietek, Bogumila; Corrubia, Lucas; Prasanna, Anagha; Santhakumar, Vijayalakshmi

    2017-09-12

    Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Endocannabinoids Induce Lateral Long-Term Potentiation of Transmitter Release by Stimulation of Gliotransmission.

    Science.gov (United States)

    Gómez-Gonzalo, Marta; Navarrete, Marta; Perea, Gertrudis; Covelo, Ana; Martín-Fernández, Mario; Shigemoto, Ryuichi; Luján, Rafael; Araque, Alfonso

    2015-10-01

    Endocannabinoids (eCBs) play key roles in brain function, acting as modulatory signals in synaptic transmission and plasticity. They are recognized as retrograde messengers that mediate long-term synaptic depression (LTD), but their ability to induce long-term potentiation (LTP) is poorly known. We show that eCBs induce the long-term enhancement of transmitter release at single hippocampal synapses through stimulation of astrocytes when coincident with postsynaptic activity. This LTP requires the coordinated activity of the 3 elements of the tripartite synapse: 1) eCB-evoked astrocyte calcium signal that stimulates glutamate release; 2) postsynaptic nitric oxide production; and 3) activation of protein kinase C and presynaptic group I metabotropic glutamate receptors, whose location at presynaptic sites was confirmed by immunoelectron microscopy. Hence, while eCBs act as retrograde signals to depress homoneuronal synapses, they serve as lateral messengers to induce LTP in distant heteroneuronal synapses through stimulation of astrocytes. Therefore, eCBs can trigger LTP through stimulation of astrocyte-neuron signaling, revealing novel cellular mechanisms of eCB effects on synaptic plasticity.

  10. Potentially inappropriate prescriptions for older patients in long-term care

    Directory of Open Access Journals (Sweden)

    Laurin Danielle

    2004-10-01

    Full Text Available Abstract Background Inappropriate medication use is a major healthcare issue for the elderly population. This study explored the prevalence of potentially inappropriate prescriptions (PIPs in long-term care in metropolitan Quebec. Methods A cross sectional chart review of 2,633 long-term care older patients of the Quebec City area was performed. An explicit criteria list for PIPs was developed based on the literature and validated by a modified Delphi method. Medication orders were reviewed to describe prescribing patterns and to determine the prevalence of PIPs. A multivariate analysis was performed to identify predictors of PIPs. Results Almost all residents (94.0% were receiving one or more prescribed medication; on average patients had 4.8 prescribed medications. A majority (54.7% of treated patients had a potentially inappropriate prescription (PIP. Most common PIPs were drug interactions (33.9% of treated patients, followed by potentially inappropriate duration (23.6%, potentially inappropriate medication (14.7% and potentially inappropriate dosage (9.6%. PIPs were most frequent for medications of the central nervous system (10.8% of prescribed medication. The likelihood of PIP increased significantly as the number of drugs prescribed increased (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 1.33 – 1.43 and with the length of stay (OR: 1.78, CI: 1.43 – 2.20. On the other hand, the risk of receiving a PIP decreased with age. Conclusion Potentially inappropriate prescribing is a serious problem in the highly medicated long-term care population in metropolitan Quebec. Use of explicit criteria lists may help identify the most critical issues and prioritize interventions to improve quality of care and patient safety.

  11. Long term hydrogen production potential of concentrated photovoltaic (CPV) system in tropical weather of Singapore

    KAUST Repository

    Burhan, Muhammad

    2016-08-23

    Concentrated photovoltaic (CPV) system provides highest solar energy conversion efficiency among all the photovoltaic technologies and provides the most suitable option to convert solar energy into hydrogen, as future sustainable energy carrier. So far, only conventional flat plate PV systems are being used for almost all of the commercial applications. However, most of the studies have only shown the maximum efficiency of hydrogen production using CPV. In actual field conditions, the performance of CPV-Hydrogen system is affected by many parameter and it changes continuously during whole day operation. In this paper, the daily average and long term performances are proposed to analyze the real field potential of the CPV-Hydrogen system, which is of main interest for designers and consumers. An experimental setup is developed and a performance model is proposed to investigate the average and long term production potential of CPV-Hydrogen system. The study is carried out in tropical weather of Singapore. The maximum CPV efficiency of 27-28% and solar to hydrogen (STH) efficiency of 18%, were recorded. In addition, the CPV-Hydrogen system showed the long term average efficiency of 15.5%, for period of one year (12-months), with electrolyser rating of 47 kWh/kg and STH production potential of 218 kWh/kg. Based upon the DNI availability, the system showed hydrogen production potential of 0.153-0.553 kg/m/month, with average production of 0.43 kg/m/month. However, CPV-Hydrogen system has shown annual hydrogen production potential of 5.162 kg/m/year in tropical weather of Singapore.

  12. The mechanisms underlying long-term potentiation of C-fiber evoked field potentials in spinal dorsal horn

    Institute of Scientific and Technical Information of China (English)

    LIU Xian-Guo

    2008-01-01

    Long-term potentiation (LTP) of C-fiber evoked feld potentials in spinal dorsal horn is first reported in 1995. Since then, the mechanisms underlying the long-lasting enhancement in synaptic transmission between primary afferent C-fibers and neurons in spinal dorsal horn have been investigated by different laboratories. In this article, the related data were summarized and discussed.

  13. Reward improves long-term retention of a motor memory through induction of offline memory gains.

    Science.gov (United States)

    Abe, Mitsunari; Schambra, Heidi; Wassermann, Eric M; Luckenbaugh, Dave; Schweighofer, Nicolas; Cohen, Leonardo G

    2011-04-12

    In humans, training in which good performance is rewarded or bad performance punished results in transient behavioral improvements. The relative effects of reward and punishment on consolidation and long-term retention, critical behavioral stages for successful learning, are not known. Here, we investigated the effects of reward and punishment on these different stages of human motor skill learning. We studied healthy subjects who trained on a motor task under rewarded, punished, or neutral control conditions. Performance was tested before and immediately, 6 hr, 24 hr, and 30 days after training in the absence of reward or punishment. Performance improvements immediately after training were comparable in the three groups. At 6 hr, the rewarded group maintained performance gains, whereas the other two groups experienced significant forgetting. At 24 hr, the reward group showed significant offline (posttraining) improvements, whereas the other two groups did not. At 30 days, the rewarded group retained the gains identified at 24 hr, whereas the other two groups experienced significant forgetting. We conclude that training under rewarded conditions is more effective than training under punished or neutral conditions in eliciting lasting motor learning, an advantage driven by offline memory gains that persist over time.

  14. Running enhances neurogenesis, learning, and long-term potentiation in mice

    Science.gov (United States)

    van Praag, Henriette; Christie, Brian R.; Sejnowski, Terrence J.; Gage, Fred H.

    1999-01-01

    Running increases neurogenesis in the dentate gyrus of the hippocampus, a brain structure that is important for memory function. Consequently, spatial learning and long-term potentiation (LTP) were tested in groups of mice housed either with a running wheel (runners) or under standard conditions (controls). Mice were injected with bromodeoxyuridine to label dividing cells and trained in the Morris water maze. LTP was studied in the dentate gyrus and area CA1 in hippocampal slices from these mice. Running improved water maze performance, increased bromodeoxyuridine-positive cell numbers, and selectively enhanced dentate gyrus LTP. Our results indicate that physical activity can regulate hippocampal neurogenesis, synaptic plasticity, and learning. PMID:10557337

  15. Rescuing impairment of long-term potentiation in fyn-deficient mice by introducing Fyn transgene

    OpenAIRE

    1997-01-01

    To examine the physiological role of the Fyn tyrosine kinase in neurons, we generated transgenic mice that expressed a fyn cDNA under the control of the calcium/calmodulin-dependent protein kinase IIα promoter. With this promoter, we detected only low expression of Fyn in the neonatal brain. In contrast, there was strong expression of the fyn-transgene in neurons of the adult forebrain. To determine whether the impairment of long-term potentiation (LTP) observed in adult fyn-deficient mice wa...

  16. Long-term changes in pigmentation of arctic Daphnia provide potential for reconstructing aquatic UV exposure

    Science.gov (United States)

    Nevalainen, Liisa; Rantala, Marttiina V.; Luoto, Tomi P.; Ojala, Antti E. K.; Rautio, Milla

    2016-07-01

    Despite the biologically damaging impacts of solar ultraviolet radiation (UV) in nature, little is known about its natural variability, forcing mechanisms, and long-term effects on ecosystems and organisms. Arctic zooplankton, for example the aquatic keystone genus Daphnia (Crustacea, Cladocera) responds to biologically damaging UV by utilizing photoprotective strategies, including pigmentation. We examined the preservation and content of UV-screening pigments in fossil Daphnia remains (ephippia) in two arctic lake sediment cores from Cornwallis Island (Lake R1), Canada, and Spitsbergen (Lake Fugledammen), Svalbard. The aims were to document changes in the degree of UV-protective pigmentation throughout the past centuries, elucidate the adaptive responses of zooplankton to long-term variations in UV exposure, and estimate the potential of fossil zooplankton pigments in reconstructing aquatic UV regimes. The spectroscopic absorbance measurements of fossil Daphnia ephippia under UV (280-400 nm) and visible light (400-700 nm) spectral ranges indicated that melanin (absorbance maxima at UV wavebands 280-350 nm) and carotenoids (absorbance maxima at 400-450 nm) pigments were preserved in the ephippia in both sediment cores. Downcore measurements of the most important UV-protective pigment melanin (absorbance measured at 305 and 340 nm) showed marked long-term variations in the degree of melanisation. These variations likely represented long-term trends in aquatic UV exposure and were positively related with solar radiation intensity. The corresponding trends in melanisation and solar activity were disrupted at the turn of the 20th century in R1, but remained as strong in Fugledammen. The reversed trends in the R1 core were simultaneous with a significant aquatic community reorganization taking place in the lake, suggesting that recent environmental changes, likely related to climate warming had a local effect on pigmentation strategies. This time horizon is also

  17. The age-related attenuation in long-term potentiation is associated with microglial activation.

    Science.gov (United States)

    Griffin, Rebecca; Nally, Rachel; Nolan, Yvonne; McCartney, Yvonne; Linden, James; Lynch, Marina A

    2006-11-01

    It is well established that inflammatory changes contribute to brain ageing, and an increased concentration of proinflammatory cytokine, interleukin-1beta (IL-1beta), has been reported in the aged brain associated with a deficit in long-term potentiation (LTP) in rat hippocampus. The precise age at which changes are initiated is unclear. In this study, we investigate parallel changes in markers of inflammation and LTP in 3-, 9- and 15-month-old rats. We report evidence of increased hippocampal concentrations of the proinflammatory cytokines IL-1alpha, IL-18 and interferon-gamma (IFNgamma), which are accompanied by deficits in LTP in the older rats. We also show an increase in expression of markers of microglial activation, CD86, CD40 and intercellular adhesion molecules (ICAM). Associated with these changes, we observed a significant impairment of hippocampal LTP in the same rats. The importance of microglial activation in the attenuation of long-term potentiation (LTP) was demonstrated using an inhibitor of microglial activation, minocycline; partial restoration of LTP in 15-month-old rats was observed following administration of minocycline. We propose that signs of neuroinflammation are observed in middle age and that these changes, which are characterized by microglial activation, may be triggered by IL-18.

  18. Synapse-specific mGluR1-dependent long-term potentiation in interneurones regulates mouse hippocampal inhibition

    Science.gov (United States)

    Lapointe, Valérie; Morin, France; Ratté, Stéphanie; Croce, Ariane; Conquet, François; Lacaille, Jean-Claude

    2004-01-01

    Hippocampal CA1 inhibitory interneurones control the excitability and synchronization of pyramidal cells, and participate in hippocampal synaptic plasticity. Pairing theta-burst stimulation (TBS) with postsynaptic depolarization, we induced long-term potentiation (LTP) of putative single-fibre excitatory postsynaptic currents (EPSCs) in stratum oriens/alveus (O/A) interneurones of mouse hippocampal slices. LTP induction was absent in metabotropic glutamate receptor 1 (mGluR1) knockout mice, was correlated with the postsynaptic presence of mGluR1a, and required a postsynaptic Ca2+ rise. Changes in paired-pulse facilitation and coefficient of variation indicated that LTP expression involved presynaptic mechanisms. LTP was synapse specific, occurring selectively at synapses modulated by presynaptic group II, but not group III, mGluRs. Furthermore, the TBS protocol applied in O/A induced a long-term increase of polysynaptic inhibitory responses in CA1 pyramidal cells, that was absent in mGluR1 knockout mice. These results uncover the mechanisms of a novel form of interneurone synaptic plasticity that can adaptively regulate inhibition of hippocampal pyramidal cells. PMID:14673190

  19. A model of the mechanism of cooperativity and associativity of long-term potentiation in the hippocampus: a fundamental mechanism of associative memory and learning.

    Science.gov (United States)

    Kitajima, T; Hara, K

    1991-01-01

    Long-Term Potentiation (LTP) has three properties: (1) input specificity, (2) cooperativity and (3) associativity. In a previous paper, we proposed an integrated model of the mechanisms of the induction and maintenance of LTP with input specificity. In this paper, a model of the mechanism of cooperative and associative LTP is described. According to computer simulations of the model, its mechanism is based on the spread of synaptic potentials.

  20. Cholinergic pairing with visual activation results in long-term enhancement of visual evoked potentials.

    Directory of Open Access Journals (Sweden)

    Jun Il Kang

    Full Text Available Acetylcholine (ACh contributes to learning processes by modulating cortical plasticity in terms of intensity of neuronal activity and selectivity properties of cortical neurons. However, it is not known if ACh induces long term effects within the primary visual cortex (V1 that could sustain visual learning mechanisms. In the present study we analyzed visual evoked potentials (VEPs in V1 of rats during a 4-8 h period after coupling visual stimulation to an intracortical injection of ACh analog carbachol or stimulation of basal forebrain. To clarify the action of ACh on VEP activity in V1, we individually pre-injected muscarinic (scopolamine, nicotinic (mecamylamine, alpha7 (methyllycaconitine, and NMDA (CPP receptor antagonists before carbachol infusion. Stimulation of the cholinergic system paired with visual stimulation significantly increased VEP amplitude (56% during a 6 h period. Pre-treatment with scopolamine, mecamylamine and CPP completely abolished this long-term enhancement, while alpha7 inhibition induced an instant increase of VEP amplitude. This suggests a role of ACh in facilitating visual stimuli responsiveness through mechanisms comparable to LTP which involve nicotinic and muscarinic receptors with an interaction of NMDA transmission in the visual cortex.

  1. Treadmill exercise alters ecstasy- induced long- term potentiation disruption in the hippocampus of male rats.

    Science.gov (United States)

    Sajadi, Azam; Amiri, Iraj; Gharebaghi, Alireza; Komaki, Alireza; Asadbeigi, Masoumeh; Shahidi, Siamak; Mehdizadeh, Mehdi; Soleimani Asl, Sara

    2017-06-13

    3, 4-methylenedioxymethamphetamine (MDMA) or ecstasy is a derivative of amphetamine that leads to long term potentiation (LTP) disruption in the hippocampal dentate gyrus (DG). Exercise has been accepted as a treatment for the improvement of neurodegenerative disease. Herein, the effects of exercise on the MDMA- induced neurotoxicity were assessed. Male Wistar rats received intraperitoneal injection of MDMA (10 mg/kg) and exercised for one month on a treadmill (Simultaneously or asynchronously with MDMA). LTP and expression of BDNF were assessed using electrophysiology and western blotting methods, respectively. MDMA attenuated the field excitatory post-synaptic potential (fEPSP) slope in comparison with the control group, whereas treadmill exercise increased this parameter when compared to MDMA group. Furthermore, BDNF expression significantly decreased in MDMA group and treadmill exercise could increase that. In conclusion, results of this study suggest that synchronous exercise is able to improve MDMA-induced LTP changes through increase of BDNF expression in the hippocampus of rats.

  2. Potentiation of muscimol-induced long-term depression by benzodiazepines but not zolpidem.

    Science.gov (United States)

    Akhondzadeh, Shahin; Mohammadi, Mohammad Reza; Kashani, Ladan

    2002-10-01

    Zolpidem is a rapid-onset, short-duration, quickly eliminated imidazopyridine hypnotic. It has been suggested that zolpidem may produce less memory and cognitive impairment than benzodiazepines (BZs) due to its low binding affinity for BZ receptor subtypes found in areas of the brain that are involved in learning and memory, in particular the hippocampus. A novel protocol for inducing long-term synaptic depression through activation of gamma-aminobutyric acid (GABA(A)) receptors in the hippocampal slices has been recently reported. The authors used the CA1 region of rat hippocampal slices to compare the effects of classic BZs, which bind equipotently to BZ1 and BZ2 sites, and of nonbenzodiazepine zolpidem, which binds preferentially to the BZ1 sites of GABA(A) receptors, on the GABA(A)-induced long-term depression (LTD), a possible cellular mechanism for their different cognition-impairment profile. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz). It was observed that diazepam and cholordiazepoxide at concentrations of 10 and 20 microM, which did not have any effect themselves on the population spike, potentiate the ability of muscimol to induce LTD, whereas zolpidem at concentrations of 10 and 20 microM failed to potentiate muscimol-induced LTD. The results suggest that the potentiation of muscimol-induced LTD by diazepam or chlordiazepoxide and the lack of this effect by zolpidem may explain their different cognition impairment profiles.

  3. "Heading" and neck injuries in soccer: a review of biomechanics and potential long-term effects.

    Science.gov (United States)

    Mehnert, Michael J; Agesen, Thomas; Malanga, Gerard A

    2005-10-01

    Although soccer has a lower injury rate than does American football, injuries to the head and neck do occur. Indeed, soccer is classified as a contact sport. The potential for cervical injuries from the maneuver known as "heading" are of particular concern. This review provides a synopsis of soccer-related head and neck injuries, an overview of the biomechanics of trauma, and a rational approach to evaluating patients. This review was conducted to assess and evaluate existing literature on the biomechanics of the act of heading in soccer and the potential for acute and long-term injury to the head and neck. The resulting work is based on literature searches of the PubMed and Medline databases, textbook reviews, and bibliographies of articles and textbooks obtained during the search. Findings from several studies were summarized and critiqued. Biomechanics, anatomy, pathophysiology, and their relation to the act of heading in soccer were also synthesized into the discussion. Relevant studies of athletes in other sports where activity can affect the neck and head in a manner similar to heading were also considered. The act of heading in soccer involves the athlete's entire body, and studies have used electromyography to define the activity of neck musculature during heading. The majority of head and neck injuries in soccer occur secondary to impacts other than those that occur during heading, however, rare case reports of serious injury exist. Degenerative bony changes in the cervical spine of soccer players have been noted in a few studies, but the connection with heading is not well established. Data from research in other sports, particularly American football and rugby, suggest a predisposition to degenerative disease of the neck secondary to axial loading mechanisms; the exact relevance of these studies to heading and soccer is unclear. The complex biomechanics of heading in soccer are not completely defined, especially with regard to long-term effects on the

  4. Potential of "lure and kill" in long-term pest management and eradication of invasive species.

    Science.gov (United States)

    El-Sayed, A M; Suckling, D M; Byers, J A; Jang, E B; Wearing, C H

    2009-06-01

    "Lure and kill" technology has been used for several decades in pest management and eradication of invasive species. In lure and kill, the insect pest attracted by a semiochemical lure is not "entrapped" at the source of the attractant as in mass trapping, but instead the insect is subjected to a killing agent, which eliminates affected individuals from the population after a short period. In past decades, a growing scientific literature has been published on this concept. This article provides the first review on the potential of lure and kill in long-term pest management and eradication of invasive species. We present a summary of lure and kill, either when used as a stand-alone control method or in combination with other methods. We discuss its efficacy in comparison with other control methods. Several case studies in which lure and kill has been used with the aims of long-term pest management (e.g., pink bollworm, Egyptian cotton leafworm, codling moth, apple maggot, biting flies, and bark beetles) or the eradication of invasive species (e.g., tephritid fruit flies and boll weevils) are provided. Subsequently, we identify essential knowledge required for successful lure and kill programs that include lure competitiveness with natural odor source; lure density; lure formulation and release rate; pest population density and risk of immigration; and biology and ecology of the target species. The risks associated with lure and kill, especially when used in the eradication programs, are highlighted. We comment on the cost-effectiveness of this technology and its strengths and weaknesses, and list key reasons for success and failure. We conclude that lure and kill can be highly effective in controlling small, low-density, isolated populations, and thus it has the potential to add value to long-term pest management. In the eradication of invasive species, lure and kill offers a major advantage in effectiveness by its being inverse density dependent and it provides

  5. Post-ischaemic long-term synaptic potentiation in the striatum: a putative mechanism for cell type-specific vulnerability.

    Science.gov (United States)

    Calabresi, Paolo; Saulle, Emilia; Centonze, Diego; Pisani, Antonio; Marfia, Girolama A; Bernardi, Giorgio

    2002-04-01

    In the present in vitro study of rat brain, we report that transient oxygen and glucose deprivation (in vitro ischaemia) induced a post-ischaemic long-term synaptic potentiation (i-LTP) at corticostriatal synapses. We compared the physiological and pharmacological characteristics of this pathological form of synaptic plasticity with those of LTP induced by tetanic stimulation of corticostriatal fibres (t-LTP), which is thought to represent a cellular substrate of learning and memory. Activation of N-methyl-D-aspartate (NMDA) receptors was required for the induction of both forms of synaptic plasticity. The intraneuronal injection of the calcium chelator BAPTA [bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate] and inhibitors of the mitogen-activated protein kinase pathway blocked both forms of synaptic plasticity. However, while t-LTP showed input specificity, i-LTP occurred also at synaptic pathways inactive during the ischaemic period. In addition, scopolamine, a muscarinic receptor antagonist, prevented the induction of t-LTP but not of i-LTP, indicating that endogenous acetylcholine is required for physiological but not for pathological synaptic potentiation. Finally, we found that striatal cholinergic interneurones, which are resistant to in vivo ischaemia, do not express i-LTP while they express t-LTP. We suggest that i-LTP represents a pathological form of synaptic plasticity that may account for the cell type-specific vulnerability observed in striatal spiny neurones following ischaemia and energy deprivation.

  6. Potential multiple steady-states in the long-term carbon cycle

    CERN Document Server

    Tennenbaum, Stephen; Schwartzman, David

    2013-01-01

    Modelers of the long term carbon cycle in Earth history have previously assumed there is only one stable climatic steady state. Here we investigate the possibility of multiple steady states. We find them in Abiotic World, lacking any biotic influence, resulting from possible variations in planetary albedo in different temperature, atmospheric carbon dioxide level regimes, with the same weathering forcing balancing a volcanic source to the atmosphere, ocean pool. In Plant World modeling relevant to the Phanerozoic, we include the additional effects of biotic enhancement of weathering on land, organic carbon burial, oxidation of reduced organic carbon in terrestrial sediments and the variation of biotic productivity with temperature, finding a second stable steady state appearing between twenty and fifty degrees C. The very warm early Triassic climate may be the prime candidate for an upper temperature steady state. Given our results, the anthropogenic driven rise of atmospheric carbon dioxide could potentially...

  7. Increased learning and brain long-term potentiation in aged mice lacking DNA polymerase μ.

    Directory of Open Access Journals (Sweden)

    Daniel Lucas

    Full Text Available A definitive consequence of the aging process is the progressive deterioration of higher cognitive functions. Defects in DNA repair mechanisms mostly result in accelerated aging and reduced brain function. DNA polymerase µ is a novel accessory partner for the non-homologous end-joining DNA repair pathway for double-strand breaks, and its deficiency causes reduced DNA repair. Using associative learning and long-term potentiation experiments, we demonstrate that Polµ(-/- mice, however, maintain the ability to learn at ages when wild-type mice do not. Expression and biochemical analyses suggest that brain aging is delayed in Polµ(-/- mice, being associated with a reduced error-prone DNA oxidative repair activity and a more efficient mitochondrial function. This is the first example in which the genetic ablation of a DNA-repair function results in a substantially better maintenance of learning abilities, together with fewer signs of brain aging, in old mice.

  8. Impaired long-term potentiation-like cortical plasticity in presymptomatic genetic frontotemporal dementia.

    Science.gov (United States)

    Benussi, Alberto; Cosseddu, Maura; Filareto, Ilaria; Dell'Era, Valentina; Archetti, Silvana; Sofia Cotelli, Maria; Micheli, Anna; Padovani, Alessandro; Borroni, Barbara

    2016-09-01

    Neurophysiological biomarkers were assessed using a transcranial magnetic stimulation multiparadigm approach in 13 presymptomatic (n = 13 Granulin) and 14 symptomatic (n = 11 Granulin, n = 3 C9orf72) subjects with a pathogenic mutation for frontotemporal dementia (FTD). Intracortical facilitation and long-term potentiation-like plasticity were impaired in presymptomatic carriers, compared to healthy controls, more than 15 years before expected symptom onset. In symptomatic carriers, a decrease in short-interval intracortical inhibition, compared to presymptomatic carriers, was found. In conclusion, these biomarkers could provide the footprints of specific physiopathological processes in the development of this disease and possibly support the diagnosis of autosomal-dominant FTD. Ann Neurol 2016;80:472-476.

  9. Receptor protein tyrosine phosphatase alpha is essential for hippocampal neuronal migration and long-term potentiation

    DEFF Research Database (Denmark)

    Petrone, Angiola; Battaglia, Fortunato; Wang, Cheng

    2003-01-01

    Despite clear indications of their importance in lower organisms, the contributions of protein tyrosine phosphatases (PTPs) to development or function of the mammalian nervous system have been poorly explored. In vitro studies have indicated that receptor protein tyrosine phosphatase alpha (RPTPa....... However, these synapses are unable to undergo long-term potentiation. Mice lacking RPTPalpha also underperform in the radial-arm water-maze test. These studies identify RPTPalpha as a key mediator of neuronal migration and synaptic plasticity....... neuronal migration. The migratory abnormality likely results from a radial glial dysfunction rather than from a neuron-autonomous defect. In spite of this aberrant development, basic synaptic transmission from the Schaffer collateral pathway to CA1 pyramidal neurons remains intact in Ptpra(-/-) mice...

  10. Colorado Plateau Rapid Ecoregion Assessment Change Agents - Development - Current, Near-Term, and Long-Term Potential High Landscape Development

    Data.gov (United States)

    Bureau of Land Management, Department of the Interior — This map shows areas of high current, near-term, and long-term potential landscape development, based on factors such as urban areas, agriculture, roads, and energy...

  11. Theta pulse stimulation: a natural stimulus pattern can trigger long-term depression but fails to reverse long-term potentiation in morphine withdrawn hippocampus area CA1.

    Science.gov (United States)

    Hosseinmardi, Narges; Fathollahi, Yaghoub; Naghdi, Nasser; Javan, Mohammad

    2009-11-03

    The effects of chronic morphine exposure on synaptic plasticity in the CA1 region of the hippocampal slice preparation using extracellular recordings of the population spike (PS) evoked in response to Schaffer collateral stimulation were studied. High frequency stimulation (HFS; 1X100 Hz) and theta pulse stimulation (TPS; 5 Hz trains for 3 min) were used as patterned activities. The results showed that in rats chronically treated with morphine (dependent group), TPS induced long-term depression (LTD) of PS in CA1 in the absence of in vitro morphine. This TPS-induced PS LTD was blocked in the presence of either AP5 (NMDAR antagonist) or CPX (A1 adenosine receptor antagonist) alone, but was not blocked when AP5 and CPX were co-applied. This TPS-induced PS LTD was also blocked in the presence of either 8-PT (a selective A1 adenosine receptor antagonist) or MRS1220 (a specific A3 receptor antagonist). Additionally, when TPS was applied prior to HFS, PS long-term potentiation (LTP) was blocked. However, when TPS was applied after HFS, there was no reversal of PS LTP in slices from dependent rats in contrast to controls which displayed reversal of LTP. Both the PS LTD and the absence of PS LTP reversal were blocked by in vitro application of morphine. It is concluded that morphine withdrawal was associated with greater depression of CA1 PS elicited by natural stimulus induced activity pattern. This effect was associated with changes in NMDA and adenosine receptors due to chronic morphine administration. Such an in vitro preparation could provide a novel paradigm to investigate withdrawal effects on synaptic plasticity.

  12. Loganin enhances long-term potentiation and recovers scopolamine-induced learning and memory impairments.

    Science.gov (United States)

    Hwang, Eun-Sang; Kim, Hyun-Bum; Lee, Seok; Kim, Min-Ji; Lee, Sung-Ok; Han, Seung-Moo; Maeng, Sungho; Park, Ji-Ho

    2017-03-15

    Although the incidence rate of dementia is rapidly growing in the aged population, therapeutic and preventive reagents are still suboptimal. Various model systems are used for the development of such reagents in which scopolamine is one of the favorable pharmacological tools widely applied. Loganin is a major iridoid glycoside obtained from Corni fructus (Cornusofficinalis et Zucc) and demonstrated to have anti-inflammatory, anti-tumor and osteoporosis prevention effects. It has also been found to attenuate Aβ-induced inflammatory reactions and ameliorate memory deficits induced by scopolamine. However, there has been limited information available on how loganin affects learning and memory both electrophysiologically and behaviorally. To assess its effect on learning and memory, we investigated the influence of acute loganin administration on long-term potentiation (LTP) using organotypic cultured hippocampal tissues. In addition, we measured the effects of loganin on the behavior performance related to avoidance memory, short-term spatial navigation memory and long-term spatial learning and memory in the passive avoidance, Y-maze, and Morris water maze learning paradigms, respectively. Loganin dose-dependently increased the total activity of fEPSP after high frequency stimulation and attenuated scopolamine-induced blockade of fEPSP in the hippocampal CA1 area. In accordance with these findings, loganin behaviorally attenuated scopolamine-induced shortening of step-through latency in the passive avoidance test, reduced the percent alternation in the Y-maze, and increased memory retention in the Morris water maze test. These results indicate that loganin can effectively block cholinergic muscarinic receptor blockade -induced deterioration of LTP and memory related behavioral performance. Based on these findings, loganin may aid in the prevention and treatment of Alzheimer's disease and learning and memory-deficit disorders in the future.

  13. Long-term variability of the thunderstorm and hail potential in Europe

    Science.gov (United States)

    Mohr, Susanna; Kunz, Michael; Speidel, Johannes; Piper, David

    2016-04-01

    Severe thunderstorms and associated hazardous weather events such as hail frequently cause considerable damage to buildings, crops, and automobiles, resulting in large monetary costs in many parts of Europe and the world. To relate single extreme hail events to the historic context and to estimate their return periods and possible trends related to climate change, long-term statistics of hail events are required. Due to the local-scale nature of hail and a lack of suitable observation systems, however, hailstorms are not captured reliably and comprehensively for a long period of time. In view of this fact, different proxies (indirect climate data) obtained from sounding stations and regional climate models can be used to infer the probability and intensity of thunderstorms or hailstorms. In contrast to direct observational data, such proxies are available homogeneously over a long time period. The aim of the study is to investigate the potential for severe thunderstorms and their changes over past decades. Statistical analyses of sounding data show that the convective potential over the past 20 - 30 years has significantly increased over large parts of Central Europe, making severe thunderstorms more likely. A similar picture results from analyses of weather types that are most likely associated with damaging hailstorms. These weather patterns have increased, even if only slightly but nevertheless statistically significantly, in the time period from 1971 to 2000. To improve the diagnostics of hail events in regional climate models, a logistic hail model has been developed by means of a multivariate analysis method. The model is based on a combination of appropriate hail-relevant meteorological parameters. The output of the model is a new index that estimates the potential of the atmosphere for hailstorm development, referred to as potential hail index (PHI). Applied to a high-resolved reanalysis run for Europe driven by NCEP/NCAR1, long-term changes of the PHI for

  14. Long-term stability, biocompatibility and oral delivery potential of risperidone-loaded solid lipid nanoparticles.

    Science.gov (United States)

    Silva, A C; Kumar, A; Wild, W; Ferreira, D; Santos, D; Forbes, B

    2012-10-15

    A solid lipid nanoparticles (SLN) formulation to improve the oral delivery of risperidone (RISP), a poorly water-soluble drug, was designed and tested. Initially, lipid-RISP solubility was screened to select the best lipid for SLN preparation. Compritol(®)-based formulations were chosen and their long-term stability was assessed over two years of storage (at 25 °C and 4 °C) by means of particle size, polydispersity index (PI), zeta potential (ZP) and encapsulation efficiency (EE) measurements. SLN shape was observed by transmission electron microscopy (TEM) at the beginning and end of the study. The oxidative potential (OP) of the SLN was measured and their biocompatibility with Caco-2 cells was evaluated using the (4,5-dimethylthiazol-2-yl)2,5-dyphenyl-tetrazolium bromide (MTT) assay. In vitro drug release and transport studies were performed to predict the in vivo release profile and to evaluate the drug delivery potential of the SLN formulations, respectively. The RISP-loaded SLN systems were stable and had high EE and similar shape to the placebo formulations before and after storage. Classical Fickian diffusion was identified as the release mechanism for RISP from the SLN formulation. Biocompatibility and dose-dependent RISP transport across Caco-2 cells were observed for the prepared SLN formulations. The viability of SLN as formulations for oral delivery of poorly water-soluble drugs such as RISP was illustrated.

  15. Long-term potentiation in hilar circuitry modulates gating by the dentate gyrus.

    Science.gov (United States)

    Wright, Brandon J; Jackson, Meyer B

    2014-07-16

    The dentate gyrus serves as a gateway to the hippocampus, filtering and processing sensory inputs as an animal explores its environment. The hilus occupies a strategic position within the dentate gyrus from which it can play a pivotal role in these functions. Inputs from dentate granule cells converge on the hilus, and excitatory hilar mossy cells redistribute these signals back to granule cells to transform a pattern of cortical input into a new pattern of output to the hippocampal CA3 region. Using voltage-sensitive dye to image electrical activity in rat hippocampal slices, we explored how long-term potentiation (LTP) of different excitatory synapses modifies the flow of information. Theta burst stimulation of the perforant path potentiated responses throughout the molecular layer, but left responses in the CA3 region unchanged. By contrast, theta burst stimulation of the granule cell layer potentiated responses throughout the molecular layer, as well as in the CA3 region. Theta burst stimulation of the granule cell layer potentiated CA3 responses not only to granule cell layer stimulation but also to perforant path stimulation. Potentiation of responses in the CA3 region reflected NMDA receptor-dependent LTP of upstream synapses between granule cells and mossy cells, with no detectable contribution from NMDA receptor-independent LTP of local CA3 mossy fiber synapses. Potentiation of transmission to the CA3 region required LTP in both granule cell→mossy cell and mossy cell→granule cell synapses. This bidirectional plasticity enables hilar circuitry to regulate the flow of information through the dentate gyrus and on to the hippocampus. Copyright © 2014 the authors 0270-6474/14/349743-11$15.00/0.

  16. Influence of Physical Activity on Human Sensory Long-Term Potentiation.

    Science.gov (United States)

    Smallwood, Nicola; Spriggs, Meg J; Thompson, Christopher S; Wu, Carolyn C; Hamm, Jeff P; Moreau, David; Kirk, Ian J

    2015-11-01

    A growing body of literature has explored the influence of physical activity on brain structure and function. While the mechanisms of this relationship remain largely speculative, recent research suggests that one of the effects of physical exercise is an increase in synaptic long-term potentiation (LTP). This has not yet been explored directly in humans due to the difficulty of measuring LTP non-invasively. However, we have previously established that LTP-like changes in visual-evoked potentials (VEPs) can be measured in humans. Here, we investigated whether physical fitness status affects the degree of visual sensory LTP. Using a self-report measure of physical activity, participants were split into two groups: a high-activity group, and a low-activity group. LTP was measured and compared between the two groups using the previously established electroencephalography-LTP paradigm, which assesses the degree to which the N1b component of the VEP elicited by a sine grating is potentiated (enhanced) following a rapid "tetanic" presentation of that grating. Both groups demonstrated increased negativity in the amplitude of the N1b component of the VEP immediately after presentation of the visual "tetanus," indicating potentiation. However, after a 30-min rest period, the N1b for the high-activity group remained potentiated while the N1b for the low-activity group returned to baseline. This study presents the first evidence for the impact of self-reported levels of physical activity on LTP in humans, and sheds light on potential neurological mechanisms underlying the relationship between physical fitness and cognition.

  17. Possible involvement of plasmin in long-term potentiation of rat hippocampal slices.

    Science.gov (United States)

    Mizutani, A; Saito, H; Matsuki, N

    1996-11-11

    Effects of proteases and protease inhibitors on generation of long-term potentiation (LTP) were investigated in the CA1 and dentate regions of rat hippocampus. Plasmin, a serine protease, and its precursor plasminogen significantly enhanced short-term potentiation (STP) induced by a weak tetanic stimulation, without affecting basal responses. The STP-enhancing effect of plasmin disappeared by concomitant perfusion of alpha 2-antiplasmin, an endogenous plasmin inhibitor. Other proteases, such as thrombin, trypsin and cathepsin B, did not affect STP. On the other hand, alpha 2-antiplasmin and leupeptin significantly attenuated LTP induced by a strong tetanus though plasminogen or plasmin itself did not influence LTP. Furthermore, plasminogen and plasmin did not affect NMDA receptor-mediated synaptic responses in the absence of extracellular Mg2+. These results suggest that endogenous plasmin is involved in the mechanism of LTP in CA1 and dentate regions of rat hippocampus and that the STP-enhancing effect of plasmin is independent of NMDA receptors.

  18. Circadian rhythm modulates long-term potentiation induced at CA1 in rat hippocampal slices.

    Science.gov (United States)

    Nakatsuka, Hiroki; Natsume, Kiyohisa

    2014-03-01

    Circadian rhythm affects neuronal plasticity. Consistent with this, some forms of synaptic long-term potentiation (LTP) are modulated by the light/dark cycle (LD cycle). For example, this type of modulation is observed in hippocampal slices. In rodents, which are nocturnal, LTP is usually facilitated in the dark phase, but the rat hippocampal CA1 is an exception. The reason why LTP in the dark phase is suppressed in CA1 remains unknown. Previously, LTP was induced with high-frequency stimulation. In this study, we found that in the dark phase, theta-burst stimulation-induced LTP is indeed facilitated in CA1, similar to other regions in the rodent brain. Population excitatory postsynaptic potentials (pEPSP)-LTP and population spikes (PS)-LTP were recorded at CA1. The magnitude of PS-LTP in dark-phase slices was significantly larger than in light-phase slices, while that of pEPSP-LTP was unchanged. Using antidromic-orthodromic stimulation, we found that recurrent inhibition is suppressed in the dark phase. Local gabazine-application to stratum pyramidale in light-phase slices mimicked this disinhibition and facilitated LTP in dark-phase slices. These results suggest that the disinhibition of a GABAA recurrent inhibitory network can be induced in the dark phase, thereby facilitating LTP.

  19. Neonatal exposure to novelty enhances long-term potentiation in CA1 of the rat hippocampus.

    Science.gov (United States)

    Tang, Akaysha C; Zou, Bende

    2002-01-01

    Exposing rats to an enriched environment over an extended period of time has been shown to enhance hippocampal long-term potentiation (LTP). Whether such prolonged exposure to environmental manipulation is necessary for LTP enhancement and whether the environmentally induced enhancement can persist long after the cessation of the environmental manipulation remain unknown. Using a novelty exposure procedure modified from the method of neonatal handling, we exposed neonatal rats to a non-home environment for 3 min/day during the first 3 weeks of life. We examined the LTP of both population spikes and excitatory postsynaptic potentials (EPSPs), in vitro, in the CA1 of the hippocampus during adulthood (7-8 and 13-14 months of age). We found that both the LTP of population spikes and the LTP of EPSPs were enhanced among animals who experienced neonatal novelty exposure. These results demonstrate that effective environmental enhancement of LTP can be achieved by as brief and as transient a manipulation as a 3-min/day exposure over the first 3 weeks of life. The resulting enhancement can outlast the environmental manipulation by at least 1 year.

  20. 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.

  1. Overexpression of Protein Kinase Mζ in the Hippocampus Enhances Long-Term Potentiation and Long-Term Contextual But Not Cued Fear Memory in Rats.

    Science.gov (United States)

    Schuette, Sven R M; Fernández-Fernández, Diego; Lamla, Thorsten; Rosenbrock, Holger; Hobson, Scott

    2016-04-13

    The persistently active protein kinase Mζ (PKMζ) has been found to be involved in the formation and maintenance of long-term memory. Most of the studies investigating PKMζ, however, have used either putatively unselective inhibitors or conventional knock-out animal models in which compensatory mechanisms may occur. Here, we overexpressed an active form of PKMζ in rat hippocampus, a structure highly involved in memory formation, and embedded in several neural networks. We investigated PKMζ's influence on synaptic plasticity using electrophysiological recordings of basal transmission, paired pulse facilitation, and LTP and combined this with behavioral cognitive experiments addressing formation and retention of both contextual memory during aversive conditioning and spatial memory during spontaneous exploration. We demonstrate that hippocampal slices overexpressing PKMζ show enhanced basal transmission, suggesting a potential role of PKMζ in postsynaptic AMPAR trafficking. Moreover, the PKMζ-overexpressing slices augmented LTP and this effect was not abolished by protein-synthesis blockers, indicating that PKMζ induces enhanced LTP formation in a protein-synthesis-independent manner. In addition, we found selectively enhanced long-term memory for contextual but not cued fear memory, underlining the theory of the hippocampus' involvement in the contextual aspect of aversive reinforced tasks. Memory for spatial orientation during spontaneous exploration remained unaltered, suggesting that PKMζ may not affect the neural circuits underlying spontaneous tasks that are different from aversive tasks. In this study, using an overexpression strategy as opposed to an inhibitor-based approach, we demonstrate an important modulatory role of PKMζ in synaptic plasticity and selective memory processing. Most of the literature investigating protein kinase Mζ (PKMζ) used inhibitors with selectivity that has been called into question or conventional knock-out animal

  2. Inducible molecular switches for the study of long-term potentiation.

    Science.gov (United States)

    Hédou, Gaël; Mansuy, Isabelle M

    2003-04-29

    This article reviews technical and conceptual advances in unravelling the molecular bases of long-term potentiation (LTP), learning and memory using genetic approaches. We focus on studies aimed at testing a model suggesting that protein kinases and protein phosphatases balance each other to control synaptic strength and plasticity. We describe how gene 'knock-out' technology was initially exploited to disrupt the Ca(2+)/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) gene and how refined knock-in techniques later allowed an analysis of the role of distinct phosphorylation sites in CaMKII. Further to gene recombination, regulated gene expression using the tetracycline-controlled transactivator and reverse tetracycline-controlled transactivator systems, a powerful new means for modulating the activity of specific molecules, has been applied to CaMKIIalpha and the opposing protein phosphatase calcineurin. Together with electro-physiological and behavioural evaluation of the engineered mutant animals, these genetic methodologies have helped gain insight into the molecular mechanisms of plasticity and memory. Further technical developments are, however, awaited for an even higher level of finesse.

  3. Long-term potentiation decay and memory loss are mediated by AMPAR endocytosis.

    Science.gov (United States)

    Dong, Zhifang; Han, Huili; Li, Hongjie; Bai, Yanrui; Wang, Wei; Tu, Man; Peng, Yan; Zhou, Limin; He, Wenting; Wu, Xiaobin; Tan, Tao; Liu, Mingjing; Wu, Xiaoyan; Zhou, Weihui; Jin, Wuyang; Zhang, Shu; Sacktor, Todd Charlton; Li, Tingyu; Song, Weihong; Wang, Yu Tian

    2015-01-01

    Long-term potentiation (LTP) of synaptic strength between hippocampal neurons is associated with learning and memory, and LTP dysfunction is thought to underlie memory loss. LTP can be temporally and mechanistically classified into decaying (early-phase) LTP and nondecaying (late-phase) LTP. While the nondecaying nature of LTP is thought to depend on protein synthesis and contribute to memory maintenance, little is known about the mechanisms and roles of decaying LTP. Here, we demonstrated that inhibiting endocytosis of postsynaptic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) prevents LTP decay, thereby converting it into nondecaying LTP. Conversely, restoration of AMPAR endocytosis by inhibiting protein kinase Mζ (PKMζ) converted nondecaying LTP into decaying LTP. Similarly, inhibition of AMPAR endocytosis prolonged memory retention in normal animals and reduced memory loss in a murine model of Alzheimer's disease. These results strongly suggest that an active process that involves AMPAR endocytosis mediates the decay of LTP and that inhibition of this process can prolong the longevity of LTP as well as memory under both physiological and pathological conditions.

  4. Pharmacological activation of CB1 receptor modulates long term potentiation by interfering with protein synthesis.

    Science.gov (United States)

    Navakkode, Sheeja; Korte, Martin

    2014-04-01

    Cognitive impairment is one of the most important side effects associated with cannabis drug abuse, as well as the serious issue concerning the therapeutic use of cannabinoids. Cognitive impairments and neuropsychiatric symptoms are caused by early synaptic dysfunctions, such as loss of synaptic connections in different brain structures including the hippocampus, a region that is believed to play an important role in certain forms of learning and memory. We report here that metaplastic priming of synapses with a cannabinoid type 1 receptor (CB1 receptor) agonist, WIN55,212-2 (WIN55), significantly impaired long-term potentiation in the apical dendrites of CA1 pyramidal neurons. Interestingly, the CB1 receptor exerts its effect by altering the balance of protein synthesis machinery towards higher protein production. Therefore the activation of CB1 receptor, prior to strong tetanization, increased the propensity to produce new proteins. In addition, WIN55 priming resulted in the expression of late-LTP in a synaptic input that would have normally expressed early-LTP, thus confirming that WIN55 priming of LTP induces new synthesis of plasticity-related proteins. Furthermore, in addition to the effects on protein translation, WIN55 also induced synaptic deficits due to the ability of CB1 receptors to inhibit the release of acetylcholine, mediated by both muscarinic and nicotinic acetylcholine receptors. Taken together this supports the notion that the modulation of cholinergic activity by CB1 receptor activation is one mechanism that regulates the synthesis of plasticity-related proteins.

  5. Exposure of mouse to high gravitation forces induces long-term potentiation in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Ishii M

    2004-06-01

    Full Text Available The central nervous system is highly plastic and has been shown to undergo both transient and chronic adaptive changes in response to environmental influences. The purpose of this study was to investigate the effect of hypergravic field on long-term potentiation (LTP in the mouse hippocampus. Exposure of mice to 4G fields for 48 h had no effect on input-output coupling during extracellular stimulation of Schaffer collaterals and paired pulse facilitation, suggesting that the hypergravic exposure had no detrimental effect on basal neurotransmission in the hippocampus. However, the exposure to 4G fields for 48 h significantly induced LTP compared with the control mouse hippocampus. In contrast, no significant changes of late-phase LTP (L-LTP were found in the hippocampi of mice exposed to the hypergravic field. Exposure of mice to 4G fields for 48 h enhanced AMPA receptor phosphorylation but not cyclic AMP-responsive element binding protein (CREB phosphorylation. These results suggest that exposure to hyperdynamic fields influences the synaptic plasticity in the hippocampus.

  6. Short-term plasticity and long-term potentiation mimicked in single inorganic synapses.

    Science.gov (United States)

    Ohno, Takeo; Hasegawa, Tsuyoshi; Tsuruoka, Tohru; Terabe, Kazuya; Gimzewski, James K; Aono, Masakazu

    2011-06-26

    Memory is believed to occur in the human brain as a result of two types of synaptic plasticity: short-term plasticity (STP) and long-term potentiation (LTP; refs 1-4). In neuromorphic engineering, emulation of known neural behaviour has proven to be difficult to implement in software because of the highly complex interconnected nature of thought processes. Here we report the discovery of a Ag(2)S inorganic synapse, which emulates the synaptic functions of both STP and LTP characteristics through the use of input pulse repetition time. The structure known as an atomic switch, operating at critical voltages, stores information as STP with a spontaneous decay of conductance level in response to intermittent input stimuli, whereas frequent stimulation results in a transition to LTP. The Ag(2)S inorganic synapse has interesting characteristics with analogies to an individual biological synapse, and achieves dynamic memorization in a single device without the need of external preprogramming. A psychological model related to the process of memorizing and forgetting is also demonstrated using the inorganic synapses. Our Ag(2)S element indicates a breakthrough in mimicking synaptic behaviour essential for the further creation of artificial neural systems that emulate characteristics of human memory.

  7. Long-term potentiation in the neonatal rat barrel cortex in vivo.

    Science.gov (United States)

    An, Shuming; Yang, Jenq-Wei; Sun, Haiyan; Kilb, Werner; Luhmann, Heiko J

    2012-07-11

    Long-term potentiation (LTP) is important for the activity-dependent formation of early cortical circuits. In the neonatal rodent barrel cortex, LTP has been studied only in vitro. We combined voltage-sensitive dye imaging with extracellular multielectrode recordings to study whisker stimulation-induced LTP in the whisker-to-barrel cortex pathway of the neonatal rat barrel cortex in vivo. Single whisker stimulation at 2 Hz for 10 min induced an age-dependent expression of LTP in postnatal day (P) 0 to P14 rats, with the strongest expression of LTP at P3-P5. The magnitude of LTP was largest in the activated barrel-related column, smaller in the surrounding septal region, and no LTP could be observed in the neighboring barrel. Current source density analyses revealed an LTP-associated increase of synaptic current sinks in layer IV/lower layer II/III at P3-P5 and in the cortical plate/upper layer V at P0-P1. Our study demonstrates for the first time an age-dependent and spatially confined LTP in the barrel cortex of the newborn rat in vivo.

  8. Short-term plasticity and long-term potentiation mimicked in single inorganic synapses

    Science.gov (United States)

    Ohno, Takeo; Hasegawa, Tsuyoshi; Tsuruoka, Tohru; Terabe, Kazuya; Gimzewski, James K.; Aono, Masakazu

    2011-08-01

    Memory is believed to occur in the human brain as a result of two types of synaptic plasticity: short-term plasticity (STP) and long-term potentiation (LTP; refs , , , ). In neuromorphic engineering, emulation of known neural behaviour has proven to be difficult to implement in software because of the highly complex interconnected nature of thought processes. Here we report the discovery of a Ag2S inorganic synapse, which emulates the synaptic functions of both STP and LTP characteristics through the use of input pulse repetition time. The structure known as an atomic switch, operating at critical voltages, stores information as STP with a spontaneous decay of conductance level in response to intermittent input stimuli, whereas frequent stimulation results in a transition to LTP. The Ag2S inorganic synapse has interesting characteristics with analogies to an individual biological synapse, and achieves dynamic memorization in a single device without the need of external preprogramming. A psychological model related to the process of memorizing and forgetting is also demonstrated using the inorganic synapses. Our Ag2S element indicates a breakthrough in mimicking synaptic behaviour essential for the further creation of artificial neural systems that emulate characteristics of human memory.

  9. Impairment of long-term potentiation in the hippocampus of alcohol-treated OLETF rats.

    Science.gov (United States)

    Min, Jung-Ah; Lee, Hye-Ryeon; Kim, Jae-Ick; Ju, Anes; Kim, Dai-Jin; Kaang, Bong-Kiun

    2011-08-01

    Type 2 diabetes and chronic heavy alcohol consumption each have been known to be associated with the impairment of hippocampus-dependent cognitive functions. Although both conditions often coexist clinically and there is accumulated evidence of a relationship between the two, the combined effect on hippocampal long-term potentiation (LTP) has not yet been investigated. We compared the effect of type 2 diabetes itself with that of type 2 diabetes with chronic heavy alcohol consumption on the hippocampal LTP using Otsuka Long-Evans Tokushima Fatty (OLETF) rat model, which resembles the characteristics of human type 2 diabetes. Ten of 16-week-old male OLETF rats were randomized into two treatment groups according to weight: the OLETF-Alcohol (O-A, n=5) and the OLETF-Control (O-C, n=5). The rats in the O-A group were fed Lieber-DeCarli Regular EtOH over a 10-week period and the amount of alcohol consumption was 8.42±2.52g/kg/day. To ensure the effect of poor glycemic control on LTP, intraperitoneal glucose tolerance test was performed after a 10-week treatment. The hippocampal LTP was measured by extracellular field excitatory post-synaptic potentials at Shaffer collateral (SC) synapses in the CA1 region. Although the O-A group showed significantly lower fasting and postprandial glucose (Palcohol consumption could potentiate the impairment of hippocampal LTP in individuals with impaired glucose tolerance or early type 2 diabetes, even though it did not aggravate, but did improve glycemic control. Clinical attention to chronic heavy drinking will be required in preventing cognitive impairment in individuals with type 2 diabetes.

  10. Long-term potentiation promotes proliferation/survival and neuronal differentiation of neural stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Taesup Cho

    Full Text Available Neural stem cell (NSC replacement therapy is considered a promising cell replacement therapy for various neurodegenerative diseases. However, the low rate of NSC survival and neurogenesis currently limits its clinical potential. Here, we examined if hippocampal long-term potentiation (LTP, one of the most well characterized forms of synaptic plasticity, promotes neurogenesis by facilitating proliferation/survival and neuronal differentiation of NSCs. We found that the induction of hippocampal LTP significantly facilitates proliferation/survival and neuronal differentiation of both endogenous neural progenitor cells (NPCs and exogenously transplanted NSCs in the hippocampus in rats. These effects were eliminated by preventing LTP induction by pharmacological blockade of the N-methyl-D-aspartate glutamate receptor (NMDAR via systemic application of the receptor antagonist, 3-[(R-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP. Moreover, using a NPC-neuron co-culture system, we were able to demonstrate that the LTP-promoted NPC neurogenesis is at least in part mediated by a LTP-increased neuronal release of brain-derived neurotrophic factor (BDNF and its consequent activation of tropomysosin receptor kinase B (TrkB receptors on NSCs. Our results indicate that LTP promotes the neurogenesis of both endogenous and exogenously transplanted NSCs in the brain. The study suggests that pre-conditioning of the host brain receiving area with a LTP-inducing deep brain stimulation protocol prior to NSC transplantation may increase the likelihood of success of using NSC transplantation as an effective cell therapy for various neurodegenerative diseases.

  11. Enhanced hippocampal long-term potentiation and fear memory in Btbd9 mutant mice.

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    Mark P DeAndrade

    Full Text Available Polymorphisms in BTBD9 have recently been associated with higher risk of restless legs syndrome (RLS, a neurological disorder characterized by uncomfortable sensations in the legs at rest that are relieved by movement. The BTBD9 protein contains a BTB/POZ domain and a BACK domain, but its function is unknown. To elucidate its function and potential role in the pathophysiology of RLS, we generated a line of mutant Btbd9 mice derived from a commercial gene-trap embryonic stem cell clone. Btbd9 is the mouse homolog of the human BTBD9. Proteins that contain a BTB/POZ domain have been reported to be associated with synaptic transmission and plasticity. We found that Btbd9 is naturally expressed in the hippocampus of our mutant mice, a region critical for learning and memory. As electrophysiological characteristics of CA3-CA1 synapses of the hippocampus are well characterized, we performed electrophysiological recordings in this region. The mutant mice showed normal input-output relationship, a significant impairment in pre-synaptic activity, and an enhanced long-term potentiation. We further performed an analysis of fear memory and found the mutant mice had an enhanced cued and contextual fear memory. To elucidate a possible molecular basis for these enhancements, we analyzed proteins that have been associated with synaptic plasticity. We found an elevated level of dynamin 1, an enzyme associated with endocytosis, in the mutant mice. These results suggest the first identified function of Btbd9 as being involved in regulating synaptic plasticity and memory. Recent studies have suggested that enhanced synaptic plasticity, analogous to what we have observed, in other regions of the brain could enhance sensory perception similar to what is seen in RLS patients. Further analyses of the mutant mice will help shine light on the function of BTBD9 and its role in RLS.

  12. Effects of high power microwave pulses on synaptic transmission and long term potentiation in hippocampus.

    Science.gov (United States)

    Pakhomov, Andrei G; Doyle, Joanne; Stuck, Bruce E; Murphy, Michael R

    2003-04-01

    Effects of short, extremely high power microwave pulses (EHPP) on neuronal network function were explored by electrophysiological techniques in the isolated rat hippocampal slice model. Population spikes (PS) in the CA1 area were evoked by repeated stimulation (1 per 30 s) of the Schaffer collateral pathway. A brief tetanus (2 s at 50 Hz) was used to induce long term potentiation (LTP) of synaptic transmission. In three different series of experiments with a total of 160 brain slices, the EHPP irradiation was performed before, during, or after the tetanus. The EHPP carrier frequency was 9.3 GHz, the pulse width and repetition rate were from 0.5 to 2 micros and from 0.5 to 10 Hz, respectively, and the peak specific absorption rate (SAR) in brain slices reached up to 500 MW/kg. Microwave heating of the preparation ranged from 0.5 degrees C (at 0.3 kW/kg time average SAR) to 6 degrees C (at 3.6 kW/kg). The experiments established that the only effect caused by EHPP exposure within the studied range of parameters was a transient and fully reversible decrease in the PS amplitude. Recovery took no more than a few minutes after the cessation of exposure and return to the initial temperature. This effect's features were characteristic of an ordinary thermal response: it was proportional to the temperature rise but not to any specific parameter of EHPP, and it could also be induced by a continuous wave (CW) irradiation or conventional heating. Irradiation did not affect the ability of neurons to develop LTP in response to tetanus or to retain the potentiated state that was induced before irradiation. No lasting or delayed effects of EHPP were observed. The results are consistent with the thermal mechanism of EHPP action and thus far provided no indication of EHPP-specific effects on neuronal function.

  13. Multi-configuration electromagnetic induction measurements at long term agricultural test sites in Germany with different fertilizer and irrigation managements

    Science.gov (United States)

    Kaufmann, Manuela Sarah; von Hebel, Christian; Brogi, Cosimo; Baumecker, Michael; Döring, Thomas; Amelung, Wulf; Vereecken, Harry; van der Kruk, Jan

    2017-04-01

    Electromagnetic induction (EMI) data are often being used to investigate large scale soil properties including clay content, soil water content, and salinity changes for a wide range of applications. For agricultural sites, different management practices such as organic/mineral fertilization, tillage, and/or irrigation are important when interpreting the measured apparent electrical conductivity (ECa). Here, we present EMI data recorded at two long term field experiment (LTFE) agricultural test sites in Thyrow near Berlin (Germany), where different long term fertilizer and irrigation management practices were applied. We used two fixed-boom multi-coil EMI instruments that simultaneously measure over nine different depths of investigation (DOI), recording information ranging between the very shallow (0-0.25 m) ploughing zone including the organic matter and the surface soil (A-Horizon) down to the relatively deep (0-2.7 m) subsoil (B-Horizon) or even substratum (C-Horizon). At both test sites, the prevailing sandy to silty sand in the A- and B-Horizon is underlain by a glacial till C-Horizon resulting in generally low ECa values between 0.5 and 5 mS/m. At one test site, a "static nutrient deficiency experiment" is performed since 1937, where organic fertilizer (farm yard manure) and mineral fertilizers (nitrogen-phosphate-potassium (NPK) and liming) are applied at specific grids. Comparing the fertilizer application grid to the measured EMI data, the lowest ECa values coincide to unfertilized grids whereas the ECa values increase with liming, farm yard manure, and NPK. The visually observed correlation between ECa and the liming treatment was possibly due to the increased pH of the soil, because the fertilizer application increases ion contents that increase the soil electrical conductivity. At the second test site, a "Static Irrigation and Fertilizer Experiment" is conducted, where next to the fertilizer treatment (farm yard manure and nitrogen) part of the field

  14. Activity-induced long-term potentiation of excitatory synapses in developing zebrafish retina in vivo.

    Science.gov (United States)

    Wei, Hong-ping; Yao, Yuan-yuan; Zhang, Rong-wei; Zhao, Xiao-feng; Du, Jiu-lin

    2012-08-09

    Neural activity-induced long-term potentiation (LTP) of synaptic transmission is believed to be one of the cellular mechanisms underlying experience-dependent developmental refinement of neural circuits. Although it is well established that visual experience and neural activity are critical for the refinement of retinal circuits, whether and how LTP occurs in the retina remain unknown. Using in vivo perforated whole-cell recording and two-photon calcium imaging, we find that both repeated electrical and visual stimulations can induce LTP at excitatory synapses formed by bipolar cells on retinal ganglion cells in larval but not juvenile zebrafish. LTP induction requires the activation of postsynaptic N-methyl-D-aspartate receptors, and its expression involves arachidonic acid-dependent presynaptic changes in calcium dynamics and neurotransmitter release. Physiologically, both electrical and visual stimulation-induced LTP can enhance visual responses of retinal ganglion cells. Thus, LTP exists in developing retinae with a presynaptic locus and may serve for visual experience-dependent refinement of retinal circuits.

  15. Cholecystokinin-octapeptide restored morphine-induced hippocampal long-term potentiation impairment in rats.

    Science.gov (United States)

    Wen, Di; Zang, Guoqing; Sun, DongLei; Yu, Feng; Mei, Dong; Ma, Chunling; Cong, Bin

    2014-01-24

    Cholecystokinin-octapeptide (CCK-8), which is a typical brain-gut peptide, exerts a wide range of biological activities on the central nervous system. We have previously reported that CCK-8 significantly alleviated morphine-induced amnesia and reversed spine density decreases in the CA1 region of the hippocampus in morphine-treated animals. Here, we investigated the effects of CCK-8 on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of rat dentate gyrus (DG) in acute saline or morphine-treated rats. Population spikes (PS), which were evoked by stimulation of the LPP, were recorded in the DG region. Acute morphine (30mg/kg, s.c.) treatment significantly attenuated hippocampal LTP and CCK-8 (1μg, i.c.v.) restored the amplitude of PS that was attenuated by morphine injection. Furthermore, microinjection of CCK-8 (0.1 and 1μg, i.c.v.) also significantly augmented hippocampal LTP in saline-treated (1ml/kg, s.c.) rats. Pre-treatment of the CCK2 receptor antagonist L-365,260 (10μg, i.c.v) reversed the effects of CCK-8, but the CCK1 receptor antagonist L-364,718 (10μg, i.c.v) did not. The present results demonstrate that CCK-8 attenuates the effect of morphine on hippocampal LTP through CCK2 receptors and suggest an ameliorative function of CCK-8 on morphine-induced memory impairment.

  16. Opposing Actions of Chronic[Deta][superscript 9] Tetrahydrocannabinol and Cannabinoid Antagonists on Hippocampal Long-Term Potentiation

    Science.gov (United States)

    Hoffman, Alexander F.; Oz, Murat; Yang, Ruiqin; Lichtman, Aron H.; Lupica, Carl R.

    2007-01-01

    Memory deficits produced by marijuana arise partly via interaction of the psychoactive component, [Deta][superscript 9]-tetrahydrocannabinol ([Deta][superscript 9]-THC), with cannabinoid receptors in the hippocampus. Although cannabinoids acutely reduce glutamate release and block hippocampal long-term potentiation (LTP), a potential substrate for…

  17. Effects of exposure to an extremely low frequency electromagnetic field on hippocampal long-term potentiation in rat.

    Science.gov (United States)

    Komaki, Alireza; Khalili, Afshin; Salehi, Iraj; Shahidi, Siamak; Sarihi, Abdolrahman

    2014-05-20

    Modern lifestyle exposes nearly all humans to electromagnetic fields, particularly to extremely low frequency electromagnetic fields (ELF-EMFs). Prolonged exposure to ELF-EMFs induces persistent changes in neuronal activity. However, the modulation of synaptic efficiency by ELF-EMFs in vivo is still unclear. In the present study, we investigated whether ELF-EMFs can change induction of long-term potentiation (LTP) and paired-pulse ratio (PPR) in the rat hippocampal area. Twenty-nine adult male Wistar rats were divided into 3 groups (ELF-EMF exposed, sham and control groups). The ELF-EMF group was exposed to a magnetic field for 90 consecutive days (2h/day). ELF-EMFs were produced by a circular coil (50Hz, 100 micro Tesla). The sham-exposed controls were placed in an identical chamber with no electromagnetic field. After this period, rats were deeply anesthetized with urethane (2.0mg/kg) and then a bipolar stimulating and recording electrode was implanted into the perforant pathway (PP) and dentate gyrus (DG), respectively. LTP in hippocampal area was induced by high-frequency stimulation (HFS). Prolonged exposure to ELF-EMFs increased LTP induction. There was a significant difference in the slope of EPSP and amplitude of PS between the ELF-EMF group and other groups. In conclusion, our data suggest that exposure to ELF-EMFs produces a marked change in the synaptic plasticity generated in synapses of the PP-DG. No significant difference in PPR of ELF-EMF group before and after HFS suggests a postsynaptic expression site of LTP.

  18. Potential Effect of Conservation Tillage on Sustainable Land Use: A Review of Global Long-Term Studies

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-Bin; CAI Dian-Xiong; W. B. HOOGMOED; O. OENEMA; U. D. PERDOK

    2006-01-01

    Although understood differently in different parts of the world, conservation tillage usually includes leaving crop residues on the soil surface to reduce tillage. Through a global review of long-term conservation tillage research, this paper discusses the long-term effect of conservation tillage on sustainable land use, nutrient availability and crop yield response. Research has shown several potential benefits associated with conservation tillage, such as potential carbon sequestration, nutrient availability, and yield response. This research would provide a better perspective of the role of soil conservation tillage and hold promise in promoting application of practical technologies for dryland farming systems in China.

  19. Hormonal and Monoamine Signaling during Reinforcement of Hippocampal Long-Term Potentiation and Memory Retrieval

    Science.gov (United States)

    Korz, Volker; Frey, Julietta U.

    2007-01-01

    Recently it was shown that holeboard training can reinforce, i.e., transform early-LTP into late-LTP in the dentate gyrus during the initial formation of a long-term spatial reference memory in rats. The consolidation of LTP as well as of the reference memory was dependent on protein synthesis. We have now investigated the transmitter systems…

  20. The long term effects of {sup 137}Cs {gamma}-rays and tritiated water on induction on teratogenesis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Shoji, Shuneki [Hiroshima Univ., Research Institute for Radiation Biology and Medicine, Hiroshima (Japan)

    2003-07-01

    The purpose of the present study is to evaluate the teratogenesis caused by {sup 137}Cs {gamma}-rays radiation and tritiated water (tritium {beta}-rays, HTO) in rats under long-term exposures. Many congenital anomalies are caused by environmental factors, and it is likely that this assessment of teratogenesis will be very important in the future. Pregnant Donryu strain rats were irradiated with {sup 137}Cs {gamma}-rays on days 9-18 of gestation. The animals were sacrificed on day 18 of gestation and the contents of each uterine horn were examined. The numbers of surviving, dead and resorbed fetuses were recorded. The surviving fetuses were examined for external and visceral malformations. Also given here is a measure of the relative biological effectiveness (RBE) of tritiated water (HTO) compared to that for {sup 137}Cs {gamma}-rays regarding the induction of developmental anomalies such as neurocristopathy in pregnant Donryu rats. Radiation exposures were approximately 0, 1, 2, 3, 4, 5 and 6 Gy for both tritiated water and {sup 137}Cs {gamma}-rays. Teratogenesis was dose dependent for both radiation groups. Our studies show that {sup 137}Cs {gamma}-rays and HTO irradiation induce similar malformations of the cardiovascular, respiratory and skeletal systems in rat fetuses. However, a number of fetuses exhibiting growth retardation, general edema, persistent atrioventricular canal, eye defects, microcephaly and craniofacial defects following maternal exposure to HTO. These include hypoplasia of the pulmonary trunk (tetralogy of Fallot), DORV, ventricular septal defect, right aortic arch, coarctation of the aorta, aberrant right subclavian artery, hypoplasia of the thymus, craniofacial anomalies, hypoplasia or incomplete lungs and trachea, as well as limb and tail malformations in HTO syndrome. These results are similar to those found in human DiGeorge syndrome, which are considered pharyngeal arch syndromes related to a cephalic neutrocristopathy. A best estimation

  1. Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex.

    Science.gov (United States)

    Sale, Martin V; Nydam, Abbey S; Mattingley, Jason B

    2017-03-01

    Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repeatedly and predictably pairs a peripheral electrical stimulus with transcranial magnetic stimulation (TMS) to the contralateral motor region. Many studies have reported small or inconsistent effects of PAS. Given that uncertain stimuli can promote learning, the predictable nature of the stimulation in conventional PAS paradigms might serve to attenuate plasticity induction. Here, we introduced stimulus uncertainty into the PAS paradigm to investigate if it can boost plasticity induction. Across two experimental sessions, participants (n = 28) received a modified PAS paradigm consisting of a random combination of 90 paired stimuli and 90 unpaired (TMS-only) stimuli. Prior to each of these stimuli, participants also received an auditory cue which either reliably predicted whether the upcoming stimulus was paired or unpaired (no uncertainty condition) or did not predict the upcoming stimulus (maximum uncertainty condition). Motor evoked potentials (MEPs) evoked from abductor pollicis brevis (APB) muscle quantified cortical excitability before and after PAS. MEP amplitude increased significantly 15 min following PAS in the maximum uncertainty condition. There was no reliable change in MEP amplitude in the no uncertainty condition, nor between post-PAS MEP amplitudes across the two conditions. These results suggest that stimulus uncertainty may provide a novel means to enhance plasticity induction with the PAS paradigm in human motor cortex. To provide further support to the notion that stimulus uncertainty and prediction error promote plasticity, future studies should further explore the time course of these changes, and investigate what aspects of stimulus uncertainty are critical in boosting plasticity.

  2. Worldwide impact of aerosol's time scale on the predicted long-term concentrating solar power potential.

    Science.gov (United States)

    Ruiz-Arias, Jose A; Gueymard, Christian A; Santos-Alamillos, Francisco J; Pozo-Vázquez, David

    2016-08-10

    Concentrating solar technologies, which are fuelled by the direct normal component of solar irradiance (DNI), are among the most promising solar technologies. Currently, the state-of the-art methods for DNI evaluation use datasets of aerosol optical depth (AOD) with only coarse (typically monthly) temporal resolution. Using daily AOD data from both site-specific observations at ground stations as well as gridded model estimates, a methodology is developed to evaluate how the calculated long-term DNI resource is affected by using AOD data averaged over periods from 1 to 30 days. It is demonstrated here that the use of monthly representations of AOD leads to systematic underestimations of the predicted long-term DNI up to 10% in some areas with high solar resource, which may result in detrimental consequences for the bankability of concentrating solar power projects. Recommendations for the use of either daily or monthly AOD data are provided on a geographical basis.

  3. 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

  4. Corticosterone Time-Dependently Modulates [beta]-Adrenergic Effects on Long-Term Potentiation in the Hippocampal Dentate Gyrus

    Science.gov (United States)

    Pu, Zhenwei; Krugers, Harm J.; Joels, Marian

    2007-01-01

    Previous experiments in the hippocampal CA1 area have shown that corticosterone can facilitate long-term potentiation (LTP) in a rapid non-genomic fashion, while the same hormone suppresses LTP that is induced several hours after hormone application. Here, we elaborated on this finding by examining whether corticosterone exerts opposite effects on…

  5. Corticosterone time-dependently modulates {beta}-adrenergic effects on long-term potentiation in the hippocampal dentate gyrus.

    NARCIS (Netherlands)

    Pu, Z.; Krugers, H.; Joëls, M.

    2007-01-01

    Previous experiments in the hippocampal CA1 area have shown that corticosterone can facilitate long-term potentiation (LTP) in a rapid non-genomic fashion, while the same hormone suppresses LTP that is induced several hours after hormone application. Here, we elaborated on this finding by examining

  6. The APP-Interacting Protein FE65 is Required for Hippocampus-Dependent Learning and Long-Term Potentiation

    Science.gov (United States)

    Wang, Yan; Zhang, Ming; Moon, Changjong; Hu, Qubai; Wang, Baiping; Martin, George; Sun, Zhongsheng; Wang, Hongbing

    2009-01-01

    FE65 is expressed predominantly in the brain and interacts with the C-terminal domain of [beta]-amyloid precursor protein (APP). We examined hippocampus-dependent memory and in vivo long-term potentiation (LTP) at the CA1 synapses with isoform-specific FE65 knockout (p97FE65[superscript -/-]) mice. When examined using the Morris water maze,…

  7. A systematic review of potential long-term effects of sport-related concussion.

    Science.gov (United States)

    Manley, Geoff; Gardner, Andrew J; Schneider, Kathryn J; Guskiewicz, Kevin M; Bailes, Julian; Cantu, Robert C; Castellani, Rudolph J; Turner, Michael; Jordan, Barry D; Randolph, Christopher; Dvořák, Jiří; Hayden, K Alix; Tator, Charles H; McCrory, Paul; Iverson, Grant L

    2017-06-01

    Systematic review of possible long-term effects of sports-related concussion in retired athletes. Ten electronic databases. Original research; incidence, risk factors or causation related to long-term mental health or neurological problems; individuals who have suffered a concussion; retired athletes as the subjects and possible long-term sequelae defined as >10 years after the injury. Study population, exposure/outcome measures, clinical data, neurological examination findings, cognitive assessment, neuroimaging findings and neuropathology results. Risk of bias and level of evidence were evaluated by two authors. Following review of 3819 studies, 47 met inclusion criteria. Some former athletes have depression and cognitive deficits later in life, and there is an association between these deficits and multiple prior concussions. Former athletes are not at increased risk for death by suicide (two studies). Former high school American football players do not appear to be at increased risk for later life neurodegenerative diseases (two studies). Some retired professional American football players may be at increased risk for diminishment in cognitive functioning or mild cognitive impairment (several studies), and neurodegenerative diseases (one study). Neuroimaging studies show modest evidence of macrostructural, microstructural, functional and neurochemical changes in some athletes. Multiple concussions appear to be a risk factor for cognitive impairment and mental health problems in some individuals. More research is needed to better understand the prevalence of chronic traumatic encephalopathy and other neurological conditions and diseases, and the extent to which they are related to concussions and/or repetitive neurotrauma sustained in sports. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Effects of repeated prenatal glucocorticoid exposure on long-term potentiation in the juvenile guinea-pig hippocampus.

    Science.gov (United States)

    Setiawan, Elaine; Jackson, Michael F; MacDonald, John F; Matthews, Stephen G

    2007-06-15

    Synthetic glucocorticoids (sGCs) are routinely used to treat women at risk of preterm labour to promote fetal lung maturation. There is now strong evidence that exposure to excess glucocorticoid during periods of rapid brain development has permanent consequences for endocrine function and behaviour in the offspring. Prenatal exposure to sGC alters the expression of N-methyl-D-aspartate receptor (NMDA-R) subunits in the fetal and neonatal hippocampus. Given the integral role of the NMDA-R in synaptic plasticity, we hypothesized that prenatal sGC exposure will have effects on hippocampal long-term potentiation (LTP) after birth. Further, this may occur in either the presence or absence of elevated cortisol concentrations, in vitro. Pregnant guinea-pigs were injected with betamethasone (Beta, 1 mg kg(-1)) or vehicle on gestational days (gd) 40, 41, 50, 51, 60 and 61 (term approximately 70 days), a regimen comparable to that given to pregnant women. On postnatal day 21, LTP was examined at Schaffer collateral synapses in the CA1 region of hippocampal slices prepared from juvenile animals exposed to betamethasone or vehicle, in utero. Subsequently, the acute glucocorticoid receptor (GR)- and mineralocorticoid receptor (MR)-dependent effects of cortisol (0.1-10 microM; bath applied 30 min before LTP induction) were examined. There was no effect of prenatal sGC treatment on LTP under basal conditions. The application of 10 microM cortisol depressed excitatory synaptic transmission in all treatment groups regardless of sex. Similarly, LTP was depressed by 10 microM cortisol in all groups, with the exception of Beta-exposed females, in which LTP was unaltered. Hippocampal MR and GR protein levels were increased in Beta-exposed females, but not in any other prenatal treatment group. This study reveals sex-specific effects of prenatal exposure to sGC on LTP in the presence of elevated cortisol, a situation that would occur in vivo during stress.

  9. Long-term potentiation of inhibitory synaptic transmission onto cerebellar Purkinje neurons contributes to adaptation of vestibulo-ocular reflex.

    Science.gov (United States)

    Tanaka, Shinsuke; Kawaguchi, Shin-Ya; Shioi, Go; Hirano, Tomoo

    2013-10-23

    Synaptic plasticity in the cerebellum is thought to contribute to motor learning. In particular, long-term depression (LTD) at parallel fiber (PF) to Purkinje neuron (PN) excitatory synapses has attracted much attention of neuroscientists as a primary cellular mechanism for motor learning. In contrast, roles of plasticity at cerebellar inhibitory synapses in vivo remain unknown. Here, we have investigated the roles of long-lasting enhancement of transmission at GABAergic synapses on a PN that is known as rebound potentiation (RP). Previous studies demonstrated that binding of GABAA receptor with GABAA receptor-associated protein (GABARAP) is required for RP, and that a peptide that blocks this binding suppresses RP induction. To address the functional roles of RP, we generated transgenic mice that express this peptide fused to a fluorescent protein selectively in PNs using the PN-specific L7 promoter. These mice failed to show RP, although they showed no changes in the basal amplitude or frequency of miniature IPSCs. The transgenic mice also showed no abnormality in gross cerebellar morphology, LTD, or other excitatory synaptic properties, or intrinsic excitability of PNs. Next, we attempted to evaluate their motor control and learning ability by examining reflex eye movements. The basal dynamic properties of the vestibulo-ocular reflex and optokinetic response, and adaptation of the latter, were normal in the transgenic mice. In contrast, the transgenic mice showed defects in the adaptation of vestibulo-ocular reflex, a model paradigm of cerebellum-dependent motor learning. These results together suggest that RP contributes to a certain type of motor learning.

  10. DIFFERENTIAL FOS-PROTEIN INDUCTION IN RAT FOREBRAIN REGIONS AFTER ACUTE AND LONG-TERM HALOPERIDOL AND CLOZAPINE TREATMENT

    NARCIS (Netherlands)

    SEBENS, JB; KOCH, T; TERHORST, GJ; KORF, J

    1995-01-01

    Both acute and long-term effects of haloperidol and clozapine on Fos-like immunoreactive nuclei in several rat forebrain areas were quantified. Rats were treated with saline (1 ml/kg.day, control), haloperidol (1 mg/kg.day) and clozapine (20 mg/kg.day) i.p. for 21 days. Two hours before perfusion fi

  11. Deliberating and communicating the potential of fusion power based on long-term foresight knowledge

    Energy Technology Data Exchange (ETDEWEB)

    Laes, Erik [SCK-CEN - Belgian Nuclear Research Centre, Boeretang 200, 2400 Mol (Belgium)], E-mail: erik.laes@sckcen.be; Bombaerts, Gunter [SCK-CEN - Belgian Nuclear Research Centre, Boeretang 200, 2400 Mol (Belgium); UGent (Ghent University) (Belgium)

    2007-10-15

    The main aim of this contribution is to provide guidance (in terms of quality criteria) for setting up foresight exercises as a platform for discussion and communication of the benefits and drawbacks of fusion with a broad range of stakeholders. At the same time, we explore conditions that might enhance the resonance of such foresight exercises in the policy sphere. In order to address this dual aim, we first introduce a philosophical framework called 'constructivism'. Next, we give a constructivist reading of scientific foresight as a combined scientific-political practice and point out some of the main points of interest regarding the relationship between foresight knowledge and policy. We illustrate these points of interest with practical case-study examples. Finally, we draw upon our theoretical and case-study research to propose some points of particular interest for the fusion community wishing to develop long-term energy scenarios.

  12. Potentials for energy savings and long term energy demands for Croatian households sector

    DEFF Research Database (Denmark)

    Pukšec, Tomislav; Mathiesen, Brian Vad; Duic, Neven

    2011-01-01

    demand in the future, based on careful and rational energy planning. Different financial, legal and technological mechanisms can lead to significant savings in the households sector which also leads to lesser greenhouse gas emissions and lower Croatian dependence on foreign fossil fuels....... relevant. In order to plan future energy systems it is important to know future possibilities and needs regarding energy demand for different sectors. Through this paper long term energy demand projections for Croatian households sector will be shown with a special emphasis on different mechanisms, both...... financial, legal but also technological that will influence future energy demand scenarios. It is important to see how these mechanisms influence, positive or negative, on future energy demand and which mechanism would be most influential. Energy demand predictions in this paper are based upon bottom...

  13. Potentials for energy savings and long term energy demands for Croatian households sector

    DEFF Research Database (Denmark)

    Pukšec, Tomislav; Mathiesen, Brian Vad; Duic, Neven

    2013-01-01

    demand in the future, based on careful and rational energy planning. Different financial, legal and technological mechanisms can lead to significant savings in the households sector which also leads to lesser greenhouse gas emissions and lower Croatian dependence on foreign fossil fuels....... relevant. In order to plan future energy systems it is important to know future possibilities and needs regarding energy demand for different sectors. Through this paper long term energy demand projections for Croatian households sector will be shown with a special emphasis on different mechanisms, both...... financial, legal but also technological that will influence future energy demand scenarios. It is important to see how these mechanisms influence, positive or negative, on future energy demand and which mechanism would be most influential. Energy demand predictions in this paper are based upon bottom...

  14. Inhibition of G9a/GLP Complex Promotes Long-Term Potentiation and Synaptic Tagging/Capture in Hippocampal CA1 Pyramidal Neurons.

    Science.gov (United States)

    Sharma, Mahima; Razali, Nuralyah Bte; Sajikumar, Sreedharan

    2016-06-01

    Epigenetic regulations play an important role in regulating the learning and memory processes. G9a/G9a-like protein (GLP) lysine dimethyltransferase complex controls a prominent histone H3 lysine9 dimethylation (H3K9me2) that results in transcriptional silencing of the chromatin. Here, we report that the inhibition of G9a/GLP complex by either of the substrate competitive inhibitors UNC 0638 or BIX 01294 reinforces protein synthesis-independent long-term potentiation (early-LTP) to protein synthesis-dependent long-term potentiation (late-LTP). The reinforcement effect was observed if the inhibitors were present during the induction of early-LTP and in addition when G9a/GLP complex inhibition was carried out by priming of synapses within an interval of 30 min before or after the induction of early-LTP. Surprisingly, the reinforced LTP by G9a/GLP complex inhibition was able to associate with a weak plasticity event from nearby independent synaptic populations, resulting in synaptic tagging/capture (STC). We have identified brain-derived neurotrophic factor (BDNF) as a critical plasticity protein that maintains G9a/GLP complex inhibition-mediated LTP facilitation and its STC. Our study reveals an epigenetic mechanism for promoting plasticity and associativity by G9a/GLP complex inhibition, and it may engender a promising epigenetic target for enhancing memory in neural networks.

  15. Net sulfur mineralization potential in Swedish arable soils in relation to long-term treatment history and soil properties

    DEFF Research Database (Denmark)

    Boye, Kristin; Nilsson, S Ingvar; Eriksen, Jørgen

    2009-01-01

    The long-term treatment effect (since 1957-1966) of farmyard manure (FYM) application compared with crop residue incorporation was investigated in five soils (sandy loam to silty clay) with regards to the net sulfur (S) mineralization potential. An open incubation technique was used to determine...... accumulated net S mineralization (SAccMin) and a number of soil physical and chemical properties were determined. Treatments and soil differences in SAccMin, as well as correlations with soil variables, were tested with single and multivariate analyses. Long-term FYM application resulted in a significantly (p...... = 0.012) higher net S mineralization potential, although total amounts of C, N, and S were not significantly (p mineralization differed significantly (p 

  16. Rethinking teaching nursing homes: potential for improving long-term care.

    Science.gov (United States)

    Mezey, Mathy D; Mitty, Ethel L; Burger, Sarah Green

    2008-02-01

    To meet the special needs of and provide quality health care to nursing home residents, the health care workforce must be knowledgeable about the aging process. Health professionals are minimally prepared in their academic programs to care for older adults, and few programs have required rotations in geriatrics. Teaching nursing homes (TNHs) have shown promise as sites for the preparation of a health workforce to care for older adults in nursing homes as well as improvement of quality outcomes. This article reports on the process and recommendations of a TNH summit of experts in geriatric education and practice as to the feasibility of developing a sustainable and replicable TNH model that would prepare a professional workforce knowledgeable about and prepared to work in long-term care. The TNH summit identified characteristics of partnerships between academia, nursing home(s), and other stakeholders that would constitute a successful TNH collaboration. Goals of a TNH partnership between service and academia include interdisciplinary education and practice, research and dissemination of evidence-based practices, and benchmarks of a nursing home professional learning environment.

  17. Hypoxia-induced neonatal seizures diminish silent synapses and long-term potentiation in hippocampal CA1 neurons.

    Science.gov (United States)

    Zhou, Chengwen; Lippman, Jocelyn J Bell; Sun, Hongyu; Jensen, Frances E

    2011-12-14

    Neonatal seizures can lead to epilepsy and long-term cognitive deficits into adulthood. Using a rodent model of the most common form of human neonatal seizures, hypoxia-induced seizures (HS), we aimed to determine whether these seizures modify long-term potentiation (LTP) and silent NMDAR-only synapses in hippocampal CA1. At 48-72 h after HS, electrophysiology and immunofluorescent confocal microscopy revealed a significant decrease in the incidence of silent synapses, and an increase in AMPARs at the synapses. Coincident with this decrease in silent synapses, there was an attenuation of LTP elicited by either tetanic stimulation of Schaffer collaterals or a pairing protocol, and persistent attenuation of LTP in slices removed in later adulthood after P10 HS. Furthermore, postseizure treatment in vivo with the AMPAR antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX) protected against the HS-induced depletion of silent synapses and preserved LTP. Thus, this study demonstrates a novel mechanism by which early life seizures could impair synaptic plasticity, suggesting a potential target for therapeutic strategies to prevent long-term cognitive deficits.

  18. Involvement of microglial P2X7 receptors and downstream signaling pathways in long-term potentiation of spinal nociceptive responses.

    Science.gov (United States)

    Chu, Yu-Xia; Zhang, Yan; Zhang, Yu-Qiu; Zhao, Zhi-Qi

    2010-10-01

    Tetanic stimulation of the sciatic nerve (TSS) produces long-term potentiation (LTP) of C-fiber-evoked field potentials in the spinal cord. This potentiation is considered to be a substrate for long-lasting sensitization in the spinal pain pathway. Because microglia have previously been shown to regulate the induction of spinal LTP, we hypothesize that P2X7 receptors (P2X7R), which are predominantly expressed in microglia and participate in the communication between microglia and neurons, may play a role in this induction. This study investigated the potential roles of P2X7Rs in spinal LTP and persistent pain induced by TSS in rats. OxATP or BBG, a P2X7R antagonist, prevented the induction of spinal LTP both in vivo and in spinal cord slices in vitro and alleviated mechanical allodynia. Down-regulation of P2X7Rs with P2X7-siRNA blocked the induction of spinal LTP and inhibited mechanical allodynia. Double immunofluorescence showed colocalization of P2X7Rs with the microglial marker OX-42, but not with the astrocytic marker GFAP or the neuronal marker NeuN. Intrathecal injection of BBG suppressed the up-regulation of microglial P2X7Rs and increased expression of Fos in the spinal superficial dorsal horn. Further, pre-administration of BBG inhibited increased expression of the microglial marker Iba-1, phosphorylated p38 (p-p38), interleukin 1β (IL-1β) and GluR1 following TSS. Pre-administration of the IL-1 receptor antagonist (IL-1ra) blocked both the induction of spinal LTP and the up-regulation of GluR1. These results suggest that microglial P2X7Rs and its downstream signaling pathways play a pivotal role in the induction of spinal LTP and persistent pain induced by TSS.

  19. Potential role of plasma myeloperoxidase level in predicting long-term outcome of acute myocardial infarction.

    Science.gov (United States)

    Kaya, Mehmet Gungor; Yalcin, Ridvan; Okyay, Kaan; Poyraz, Fatih; Bayraktar, Nilufer; Pasaoglu, Hatice; Boyaci, Bulent; Cengel, Atiye

    2012-01-01

    We investigated the prognostic importance of plasma myeloperoxidase levels in patients with ST-elevation myocardial infarction (STEMI) at long-term follow-up, and we analyzed the correlations between plasma myeloperoxidase levels and other biochemical values. We evaluated 73 consecutive patients (56 men; mean age, 56 ± 11 yr) diagnosed with acute STEMI and 46 age- and sex-matched healthy control participants. Patients were divided into 2 groups according to the median myeloperoxidase level (Group 1: plasma myeloperoxidase ≤ 68 ng/mL; and Group 2: plasma myeloperoxidase > 68 ng/mL). Patients were monitored for the occurrence of major adverse cardiovascular events (MACE), which were defined as cardiac death; reinfarction; new hospital admission for angina; heart failure; and revascularization procedures. The mean follow-up period was 25 ± 16 months. Plasma myeloperoxidase levels were higher in STEMI patients than in control participants (82 ± 34 vs 20 ± 12 ng/mL; P = 0.001). Composite MACE occurred in 12 patients with high myeloperoxidase levels (33%) and in 4 patients with low myeloperoxidase levels (11%) (P = 0.02). The incidences of nonfatal recurrent myocardial infarction and verified cardiac death were higher in the high-myeloperoxidase group. In multivariate analysis, high plasma myeloperoxidase levels were independent predictors of MACE (odds ratio = 3.843; <95% confidence interval, 1.625-6.563; P = 0.003). High plasma myeloperoxidase levels identify patients with a worse prognosis after acute STEMI at 2-year follow-up. Evaluation of plasma myeloperoxidase levels might be useful in determining patients at high risk of death and MACE who can benefit from further aggressive treatment and closer follow-up.

  20. Study on Long-term Potentiation in Developing Rat Visual Cortex during the Critical Period of Plasticity

    Institute of Scientific and Technical Information of China (English)

    Pengfen Gao; Zhengqin Yin; Yingbing Liu; Shijun Wang; Huimin Fan

    2005-01-01

    Purpose: To study the property of LTP in layers Ⅱ~Ⅳof the rats visual cortex at different postnatal days induced by pairing low-frequency stimulation at layer Ⅳ with post synaptic depolarization in order to explore the synaptic and cellular mechanism of experience-dependent plasticity in the visual cortex.Methods: Postsynaptic currents (PSCs) of layers Ⅱ~Ⅳ in visual cortex slices of Wistar rats aged P0-29 d were recorded by patch-clamp whole cell recording method. Long-term potentiation (LTP) was induced by low-frequency stimulation (LFS) at 1Hz for 60~90 s.Each pulse of the LFS paired with depolarization of post-synaptic neurons to -20 mV.100μM APV, a kind of competitive N-methyl-d-aspartate (NMDA) receptor antagonist, was both applied to some slices to test the property of LTP.Results: 1. The LTP incidence was very low before P10d (5/34), and increased rapidly to the top at P15-24 d (17/28), then decreased sharply to 1/5 at P25-29 d, coinciding well with the critical period of plasticity of rat visual cortex. The LTP incidence of P15-29d (after eye opening, 18/33) was significantly higher than that of P0-14 d (before eye opening, 12/43, P < 0.05). 2. Compared with non-APV applied group (30/76), LTP incidence of APV applied group (4/33) was significantly decreased (P < 0.01 ). There were 4 Ⅳ-Ⅳ horizontal synapses. APV application could not block the LTP induction.Conclusions: 1. LTP was a reflection of naturally occurring, experience-dependent plasticity in rat visual cortex. The patterned visual stimuli received after eye opening might be an activation factor of the synaptic plasticity. 2. LTP of visual cortex induced by LFS in layer Ⅳ paired with postsynaptic depolarization was NMDA receptor dependent during the critical period of visual plasticity. However, there were LTP existed in Ⅳ-Ⅳ horizontal synapses which could not be blocked by 100μM APV.

  1. LTP的研究进展(Ⅰ)%Recent advances in the study of long-term potentiation(Part I)

    Institute of Scientific and Technical Information of China (English)

    崔光成; 叶桂兰

    2002-01-01

    LTP(长时程动作电位增强,或称长时程增强)是目前神经科学热点课题.各方面研究支持LTP与学习及记忆过程相关.基于其发生机制,LTP可分为NMDA受体依赖性和Mossy fiber LTP两类.前一类由突触后NMDA受体激活,导致钙离子内流,钙浓度升高而引发,后一类则是蛋白激酶A活动引起突触前膜内钙离子浓度升高.结果神经递质释放增强,最终引起LTP.本文概述了脑片技术对LTP研究的贡献,LTP发生与维持的相关因素,以及最新LTP研究的有趣发现.下期继续LTP话题,我们将介绍最近与LTP相关的BDNF(脑组织神经生长因子)及基因遗传学研究.%Long-term potentiation of synaptic activity is the most popular and widely researched model of synaptic plastic changes because it is believed underling learning and memory. Calcium influx mediated by NMDA receptor activation is responsible for the induction of NMDA receptor dependent LTP, whereas protein kinase A mediated calcium concentration increase in presynaptic site induced NMDA receptor independent LTP or mossy fiber LTP. Here we also summarized the current concept on brain slice as a preparation of LTP study, recent research of protein and protein kinase activity involved in LTP expression, and some other interesting findings contributed to LTP. In part two on the next issue, we will focus on BDNF and LTP, several activity-dependent genes which related to LTP and learning and memory, and introduce some interesting LTP related work.

  2. Activation of presynaptic and postsynaptic ryanodine-sensitive calcium stores is required for the induction of long-term depression at GABAergic synapses in the neonatal rat hippocampus.

    Science.gov (United States)

    Caillard, O; Ben-Ari, Y; Gaïarsa, J L

    2000-09-01

    The role of internal calcium stores in the induction of long-term depression at GABAergic synapses was investigated in the neonatal rat hippocampus. Whole-cell recordings of CA3 pyramidal neurons were performed on hippocampal slices from neonatal (2-4 d old) rats. In control conditions, tetanic stimulation (TS) evoked an NMDA-dependent long-term depression of GABA(A) receptor-mediated postsynaptic responses (LTD(GABA-A)). LTD(GABA-A) was prevented when the cells were loaded with ruthenium red, a blocker of Ca2+-induced Ca2+ release (CICR) stores, whereas loading the cells with heparin, a blocker of IP3-induced Ca2+ release stores, had no effect. The effects of ryanodine, another compound that interferes with CICR stores, were also investigated. Intracellular injection of ryanodine prevented the induction of LTD(GABA-A) only when the TS was preceded by depolarizing pulses that increase intracellular Ca2+ concentration. When applied in the bath, ryanodine prevented the induction of LTD(GABA-A). Altogether, these results suggest that ryanodine acts as a Ca2+-dependent blocker of CICR stores and that the induction of LTD(GABA-A) required the activation of both presynaptic and postsynaptic CICR stores.

  3. Reducing soil phosphorus fertility brings potential long-term environmental gains: A UK analysis

    Science.gov (United States)

    Withers, Paul J. A.; Hodgkinson, Robin A.; Rollett, Alison; Dyer, Chris; Dils, Rachael; Collins, Adrian L.; Bilsborrow, Paul E.; Bailey, Geoff; Sylvester-Bradley, Roger

    2017-05-01

    Soil phosphorus (P) fertility arising from historic P inputs is a major driver of P mobilisation in agricultural runoff and increases the risk of aquatic eutrophication. To determine the environmental benefit of lowering soil P fertility, a meta-analysis of the relationship between soil test P (measured as Olsen-P) and P concentrations in agricultural drainflow and surface runoff in mostly UK soils was undertaken in relation to current eutrophication control targets (30-35 µg P L-1). At agronomic-optimum Olsen P (16-25 mg kg-1), concentrations of soluble reactive P (SRP), total dissolved P (TDP), total P (TP) and sediment-P (SS-P) in runoff were predicted by linear regression analysis to vary between 24 and 183 µg L-1, 38 and 315 µg L-1, 0.2 and 9.6 mg L-1, and 0.31 and 3.2 g kg-1, respectively. Concentrations of SRP and TDP in runoff were much more sensitive to changes in Olsen-P than were TP and SS-P concentrations, which confirms that separate strategies are required for mitigating the mobilisation of dissolved and particulate P forms. As the main driver of eutrophication, SRP concentrations in runoff were reduced on average by 60 µg L-1 (71%) by lowering soil Olsen-P from optimum (25 mg kg-1) to 10 mg kg-1. At Olsen-P concentrations below 12 mg kg-1, dissolved hydrolysable P (largely organic) became the dominant form of soluble P transported. We concluded that maintaining agronomic-optimum Olsen-P could still pose a eutrophication risk, and that a greater research focus on reducing critical soil test P through innovative agro-engineering of soils, crops and fertilisers would give long-term benefits in reducing the endemic eutrophication risk arising from legacy soil P. Soil P testing should become compulsory in priority catchments suffering, or sensitive to, eutrophication to ensure soil P reserves are fully accounted for as part of good fertiliser and manure management.

  4. Long-Term Fatigue Life Expenditure of Turbine Shafts Owing to Noncharacteristic Harmonics Produced by Slip Energy Recovery Induction Motor Drives

    Science.gov (United States)

    Tsai, Jong-Ian

    In this paper, the long-term effect of noncharacteristic harmonics resulting from a slip energy recovery induction motor drive (SERIMD) on the fatigue life expenditure of turbine-generator shafts is analyzed. A feed-water pump (FP) in power plants is one of the most essential pieces of auxiliary equipment and consumes considerably large quantities of energy. An SERIMD has many advantages and is an adequate candidate for the purpose of variable speed control. However, it gives rise to sustainable variable frequency subharmonics which induce electromechanical subsynchronous oscillations in turbine shafts through proposed deductions. Accordingly, the author has determined that the long-term effect of these subharmonics is a cause of fatigue damage on turbine shafts even under normal operating conditions through fatigue life estimation.

  5. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis : long-term follow-up

    NARCIS (Netherlands)

    Harper, Lorraine; Morgan, Matthew D.; Walsh, Michael; Hoglund, Peter; Westman, Kerstin; Flossmann, Oliver; Tesar, Vladimir; Vanhille, Phillipe; de Groot, Kirsten; Luqmani, Raashid; Felipe Flores-Suarez, Luis; Watts, Richard; Pusey, Charles; Bruchfeld, Annette; Rasmussen, Niels; Blockmans, Daniel; Savage, Caroline O.; Jayne, David

    2012-01-01

    Introduction The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were

  6. Ischemic long-term-potentiation (iLTP: perspectives to set the threshold of neural plasticity toward therapy

    Directory of Open Access Journals (Sweden)

    Maximilian Lenz

    2015-01-01

    Full Text Available The precise role of neural plasticity under pathological conditions remains not well understood. It appears to be well accepted, however, that changes in the ability of neurons to express plasticity accompany neurological diseases. Here, we discuss recent experimental evidence, which suggests that synaptic plasticity induced by a pathological stimulus, i.e., ischemic long-term-potentiation (iLTP of excitatory synapses, could play an important role for post-stroke recovery by influencing the post-lesional reorganization of surviving neuronal networks.

  7. A long-term "memory" of HIF induction in response to chronic mild decreased oxygen after oxygen normalization

    Directory of Open Access Journals (Sweden)

    Green Dixy E

    2007-01-01

    Full Text Available Abstract Background Endothelial dysfunction (ED is functionally characterized by decreased vasorelaxation, increased thrombosis, increased inflammation, and altered angiogenic potential, has been intimately associated with the progression and severity of cardiovascular disease. Patients with compromised cardiac function oftentimes have a state of chronic mild decreased oxygen at the level of the vasculature and organs, which has been shown to exacerbate ED. Hypoxia inducible factor (HIF is a transcription factor complex shown to be the master regulator of the cellular response to decreased oxygen levels and many HIF target genes have been shown to be associated with ED. Methods Human endothelial and aortic smooth muscle cells were exposed either to A normoxia (21% O2 for three weeks, or to B mild decreased oxygen (15% O2 for three weeks to mimic blood oxygen levels in patients with heart failure, or to C mild decreased oxygen for two weeks followed by one week of normoxia ("memory" treatment. Levels of HIF signaling genes (HIF-1α, HIF-2α, VEGF, BNIP3, GLUT-1, PAI-1 and iNOS were measured both at the protein and mRNA levels. Results It was found that chronic exposure to mild decreased oxygen resulted in significantly increased HIF signaling. There was also a "memory" of HIF-1α and HIF target gene induction when oxygen levels were normalized for one week, and this "memory" could be interrupted by adding a small molecule HIF inhibitor to the last week of normalized oxygen. Finally, levels of ubiquitylated HIF-1α were reduced in response to chronic mild decreased oxygen and were not full restored after oxygen normalization. Conclusion These data suggest that HIF signaling may be contributing to the pathogenesis of endothelial dysfunction and that normalization of oxygen levels may not be enough to reduce vascular stress.

  8. Prenatal stress enhances excitatory synaptic transmission and impairs long-term potentiation in the frontal cortex of adult offspring rats.

    Directory of Open Access Journals (Sweden)

    Joanna Sowa

    Full Text Available The effects of prenatal stress procedure were investigated in 3 months old male rats. Prenatally stressed rats showed depressive-like behavior in the forced swim test, including increased immobility, decreased mobility and decreased climbing. In ex vivo frontal cortex slices originating from prenatally stressed animals, the amplitude of extracellular field potentials (FPs recorded in cortical layer II/III was larger, and the mean amplitude ratio of pharmacologically-isolated NMDA to the AMPA/kainate component of the field potential--smaller than in control preparations. Prenatal stress also resulted in a reduced magnitude of long-term potentiation (LTP. These effects were accompanied by an increase in the mean frequency, but not the mean amplitude, of spontaneous excitatory postsynaptic currents (sEPSCs in layer II/III pyramidal neurons. These data demonstrate that stress during pregnancy may lead not only to behavioral disturbances, but also impairs the glutamatergic transmission and long-term synaptic plasticity in the frontal cortex of the adult offspring.

  9. Electrical high-frequency stimulation of the human thoracolumbar fascia evokes long-term potentiation-like pain amplification.

    Science.gov (United States)

    Schilder, Andreas; Magerl, Walter; Hoheisel, Ulrich; Klein, Thomas; Treede, Rolf-Detlef

    2016-10-01

    Nociceptive long-term potentiation, a use dependent increase in synaptic efficacy in the dorsal horn of the spinal cord is thought to contribute to the development of persistent pain states. So far, no study has analyzed the effects of high-frequency stimulation (HFS) of afferents from deep tissues (muscle and fascia) on pain perception in the back in humans. In 16 healthy volunteers, the multifidus muscle and the overlying thoracolumbar fascia were stimulated with electrical high-frequency pulses (5 × 100 pulses at 100 Hz) through bipolar concentric needle electrodes placed at lumbar level (L3/L4). Electrical pain thresholds were lower (P fascia compared with muscle stimulation (P fascia, from 8 to 12 numerical rating scale for muscle; both P Fascia HFS increased fascia pain ratings 2.17 times compared with the unconditioned control site (P fascia by 20% (P 60 minutes post-HFS, potentiation by fascia HFS was similar to that of skin HFS. These findings show that the spinal input from the fascia can induce long-term changes in pain sensitivity for at least 60 minutes making it a candidate potentially contributing to nonspecific low back pain.

  10. Potential for assessing long-term dynamics in soil nitrogen availability from variations in delta15N of tree rings.

    Science.gov (United States)

    Hart, S C; Classen, A T

    2003-03-01

    Numerous researchers have used the isotopic signatures of C, H, and O in tree rings to provide a long-term record of changes in the physiological status, climate, or water-source use of trees. The frequently limiting element N is also found in tree rings, and variation in its isotopic signature may provide insight into long-term changes in soil N availability of a site. However, research has suggested that N is readily translocated among tree ring of different years; such infidelity between the isotopic compositions of the N taken up from the soil and the N contained in the ring of that growth year would obscure the long-term N isotopic record. We used a 15-year 15N-tracer study to assess the degree of N translocation among tree rings in ponderosa pine (Pinus ponderosa) trees growing in a young, mixed-conifer plantation. We also measured delta13C and delta15N values in unlabeled trees to assess the degree of their covariance in wood tissue, and to explore the potential for a biological linkage between them. We found that the maximum delta15N values in rings from the labeled trees occurred in the ring formed one-year after the 15N was applied to the roots. The delta15N value of rings from labeled trees declined exponentially and bidirectionally from this maximum peak, toward younger and older rings. The unlabeled trees showed considerable interannual variation in the delta15N values of their rings (up to 3 and 5 per thousand), but these values correlated poorly between trees over time and differed by as much as 6 per thousand. Removal of extractives from the wood reduced their delta15N value, but the change was fairly small and consistent among unlabeled trees. The delta13C and delta15N values of tree rings were correlated over time in only one of the unlabeled trees. Across all trees, both delta13C values of tree rings and annual stem wood production were well correlated with annual precipitation, suggesting that soil water balance is an important environmental

  11. Neo-synthesis of estrogenic or androgenic neurosteroids determine whether long-term potentiation or depression is induced in hippocampus of male rat

    Directory of Open Access Journals (Sweden)

    Michela eDi Mauro

    2015-10-01

    Full Text Available Estrogenic and androgenic steroids synthesized in the brain may rapidly modulate synaptic plasticity interacting with specific membrane receptors. We explored by electrophysiological recordings in hippocampal slices of male rat the influence of 17b-estradiol (E2 and 5a-dihydrotestosterone (DHT neo-synthesis on the synaptic changes induced in the CA1 region. Induction of long-term depression (LTD and depotentiation (DP by low frequency stimulation (LFS, 15 min-1 Hz and of long-term potentiation (LTP by high (HFS, 1 s-100 Hz, medium (MFS, 1 s-50 Hz, or weak (WFS, 1 s-25 Hz frequency stimulation was assayed under inhibitors of enzymes converting testosterone (T into DHT (5a-reductase and T into E2 (P450-aromatase. We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved. Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2. For intermediate stimulation protocols DHT, but not E2 synthesis, was involved in the production of a small LTP induced by WFS, while the E2 synthesis was required for the MFS-dependent LTP. Under the combined block of DHT and E2 synthesis all stimulation frequencies induced partial LTP. Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects.

  12. SAMP8 mice have altered hippocampal gene expression in long term potentiation, phosphatidylinositol signaling, and endocytosis pathways.

    Science.gov (United States)

    Armbrecht, Harvey J; Siddiqui, Akbar M; Green, Michael; Farr, Susan A; Kumar, Vijaya B; Banks, William A; Patrick, Ping; Shah, Gul N; Morley, John E

    2014-01-01

    The senescence-accelerated mouse (SAMP8) strain exhibits decreased learning and memory and increased amyloid beta (Aβ) peptide accumulation at 12 months. To detect differences in gene expression in SAMP8 mice, we used a control mouse that was a 50% cross between SAMP8 and CD-1 mice and which showed no memory deficits (50% SAMs). We then compared gene expression in the hippocampus of 4- and 12-month-old SAMP8 and control mice using Affymetrix gene arrays. At 12 months, but not at 4 months, pathway analysis revealed significant differences in the long term potentiation (6 genes), phosphatidylinositol signaling (6 genes), and endocytosis (10 genes) pathways. The changes in long term potentiation included mitogen-activated protein kinase (MAPK) signaling (N-ras, cAMP responsive element binding protein [CREB], protein phosphatase inhibitor 1) and Ca-dependent signaling (inositol triphosphate [ITP] receptors 1 and 2 and phospholipase C). Changes in phosphatidylinositol signaling genes suggested altered signaling through phosphatidylinositol-3-kinase, and Western blotting revealed phosphorylation changes in serine/threonine protein kinase AKT and 70S6K. Changes in the endocytosis pathway involved genes related to clathrin-mediated endocytosis (dynamin and clathrin). Endocytosis is required for receptor recycling, is involved in Aβ metabolism, and is regulated by phosphatidylinositol signaling. In summary, these studies demonstrate altered gene expression in 3 SAMP8 hippocampal pathways associated with memory formation and consolidation. These pathways might provide new therapeutic targets in addition to targeting Aβ metabolism itself.

  13. Chronic treatment with ginsenoside Rg1 promotes memory and hippocampal long-term potentiation in middle-aged mice.

    Science.gov (United States)

    Zhu, G; Wang, Y; Li, J; Wang, J

    2015-04-30

    Ginseng serves as a potential candidate for the treatment of aging-related memory decline or memory loss. However, the related mechanism is not fully understood. In this study, we applied an intraperitoneal injection of ginsenoside Rg1, an active compound from ginseng in middle-aged mice and detected memory improvement and the underlying mechanisms. Our results showed that a period of 30-day administration of ginsenoside Rg1 enhanced long-term memory in the middle-aged animals. Consistent with the memory improvement, ginsenoside Rg1 administration facilitated weak theta-burst stimulation (TBS)-induced long-term potentiation (LTP) in acute hippocampal slices from middle-aged animals. Ginsenoside Rg1 administration increased the dendritic apical spine numbers and area in the CA1 region. In addition, ginsenoside Rg1 administration up-regulated the expression of hippocampal p-AKT, brain-derived neurotrophic factor (BDNF), proBDNF and glutamate receptor 1 (GluR1), but not p-ERK. Interestingly, the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor (bpV) mimicked the ginsenoside Rg1 effects, including increasing p-AKT expression, promoting hippocampal basal synaptic transmission, LTP and memory. Taken together, our data suggest that ginsenoside Rg1 treatment improves memory in middle-aged mice possibly through regulating the PI3K/AKT pathway, altering apical spines and facilitating hippocampal LTP. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Mixtures of Uncaria and Tabebuia extracts are potentially chemopreventive in CBA/Ca mice: a long-term experiment.

    Science.gov (United States)

    Budán, Ferenc; Szabó, István; Varjas, Tímea; Nowrasteh, Ghodratollah; Dávid, Tamás; Gergely, Péter; Varga, Zsuzsa; Molnár, Kornélia; Kádár, Balázs; Orsós, Zsuzsa; Kiss, István; Ember, István

    2011-04-01

    A long-term experimental animal model was developed by our research group for the evaluation of potential chemopreventive effects. The inhibitory effects of agents on carcinogen (7,12-dimethylbenz[a]anthracene (DMBA) induced molecular epidemiological biomarkers, in this case the expression of key onco/suppressor genes were investigated. The expression pattern of c-myc, Ha-ras, Bcl-2, K-ras protooncogene and p53 tumour suppressor gene were studied to elucidate early carcinogenic and potential chemopreventive effects. The consumption of so-called Claw of Dragon tea (CoD™ tea) containing the bark of Uncaria guianensis, Cat's Claw (Uncaria sp. U. tomentosa) and Palmer trumpet-tree (Tabebuia sp. T. avellanedae) was able to decrease the DMBA-induced onco/suppressor gene overexpression in a short-term animal experiment. In a following study CBA/Ca mice were treated with 20 mg/kg bw DMBA intraperitoneally (i.p.) and the expression patterns of onco/suppressor genes were examined at several time intervals. According to the examined gene expression patterns in this long-term experiment the chemopreventive effect of CoD™ tea consumption could be confirmed.

  15. Upregulation of CD11A on Hematopoietic Stem Cells Denotes the Loss of Long-Term Reconstitution Potential

    Directory of Open Access Journals (Sweden)

    John W. Fathman

    2014-11-01

    Full Text Available Small numbers of hematopoietic stem cells (HSCs generate large numbers of mature effector cells through the successive amplification of transiently proliferating progenitor cells. HSCs and their downstream progenitors have been extensively characterized based on their cell-surface phenotype and functional activities during transplantation assays. These cells dynamically lose and acquire specific sets of surface markers during differentiation, leading to the identification of markers that allow for more refined separation of HSCs from early hematopoietic progenitors. Here, we describe a marker, CD11A, which allows for the enhanced purification of mouse HSCs. We show through in vivo transplantations that upregulation of CD11A on HSCs denotes the loss of their long-term reconstitution potential. Surprisingly, nearly half of phenotypic HSCs (defined as Lin−KIT+SCA-1+CD150+CD34− are CD11A+ and lack long-term self-renewal potential. We propose that CD11A+Lin−KIT+SCA-1+CD150+CD34− cells are multipotent progenitors and CD11A−Lin−KIT+SCA-1+CD150+CD34− cells are true HSCs.

  16. Endogenous 17ß-estradiol is required for activity-dependent long-term potentiation in the striatum: interaction with the dopaminergic system

    Directory of Open Access Journals (Sweden)

    Alessandro eTozzi

    2015-05-01

    Full Text Available 17β-estradiol (E2, a neurosteroid synthesized by P450-aromatase (ARO, modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs and dopamine (DA receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP in both medium spiny neurons (MSNs and cholinergic interneurons (ChIs. Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson's disease.

  17. Possible Long Term Effects of Chemical Warfare Using Visual Evoked Potentials

    Directory of Open Access Journals (Sweden)

    Abbas Riazi

    2014-09-01

    Full Text Available Some studies have already addressed the effects of occupational organic solvent exposure on the visually evoked potentials (VEPs. Visual system is an important target for Sulphur Mustard (SM toxicity. A number of Iranian victims of Sulphur Mustard (SM agent were apprehensive about the delay effect of SM on their vision and a possible delay effect of SM on their visual cortex. This investigation was performed on 34 individuals with a history of chemical exposure and a control group of 15 normal people. The Toennies electro-diagnosis device was used and its signals were saved as the latencies. The mean of N75, N140 and P100 of victims of chemical warfare (VCWs and control group indicated no significant results (P>0.05. The VCWs did not show any visual symptoms and there was no clear deficit in their VEPs.

  18. Analyzing long-term correlated stochastic processes by means of recurrence networks: Potentials and pitfalls

    CERN Document Server

    Zou, Yong; Kurths, Jürgen

    2014-01-01

    Long-range correlated processes are ubiquitous, ranging from climate variables to financial time series. One paradigmatic example for such processes is fractional Brownian motion (fBm). In this work, we highlight the potentials and conceptual as well as practical limitations when applying the recently proposed recurrence network (RN) approach to fBm and related stochastic processes. In particular, we demonstrate that the results of a previous application of RN analysis to fBm (Liu \\textit{et al.,} Phys. Rev. E \\textbf{89}, 032814 (2014)) are mainly due to an inappropriate treatment disregarding the intrinsic non-stationarity of such processes. Complementarily, we analyze some RN properties of the closely related stationary fractional Gaussian noise (fGn) processes and find that the resulting network properties are well-defined and behave as one would expect from basic conceptual considerations. Our results demonstrate that RN analysis can indeed provide meaningful results for stationary stochastic processes, ...

  19. Effects of tetrahydrohyperforin in mouse hippocampal slices: neuroprotection, long-term potentiation and TRPC channels.

    Science.gov (United States)

    Montecinos-Oliva, C; Schuller, A; Parodi, J; Melo, F; Inestrosa, N C

    2014-01-01

    Tetrahydrohyperforin (IDN5706) is a semi-synthetic compound derived from hyperforin (IDN5522) and is the main active principle of St. John's Wort. IDN5706 has shown numerous beneficial effects when administered to wild-type and double transgenic (APPswe/PSEN1ΔE9) mice that model Alzheimer's disease. However, its mechanism of action is currently unknown. Toward this end, we analysed field excitatory postsynaptic potentials (fEPSPs) in mouse hippocampal slices incubated with IDN5706 and in the presence of the TRPC3/6/7 activator 1-oleoyl-2-acetyl-sn-glycerol (OAG), the TRPC channel blocker SKF96365, and neurotoxic amyloid β-protein (Aβ) oligomers. To study spatial memory, Morris water maze (MWM) behavioural tests were conducted on wild-type mice treated with IDN5706 and SKF96365. In silico studies were conducted to predict a potential pharmacophore. IDN5706 and OAG had a similar stimulating effect on fEPSPs, which was inhibited by SKF96365. IDN5706 protected from reduced fEPSPs induced by Aβ oligomers. IDN5706 improved spatial memory in wild-type mice, an effect that was counteracted by co-administration of SKF96365. Our in silico studies suggest strong pharmacophore similarity of IDN5706 and other reported TRPC6 activators (IDN5522, OAG and Hyp9). We propose that the effect of IDN5706 is mediated through activation of the TRPC3/6/7 channel subfamily. The unveiling of the drug's mechanism of action is a necessary step toward the clinical use of IDN5706 in Alzheimer's disease.

  20. Evidence that heterosynaptic depolarization underlies associativity of long-term potentiation in rat hippocampus.

    Science.gov (United States)

    Clark, K A; Collingridge, G L

    1996-01-15

    1. Whole-cell patch-clamp recording has been used to study the effect of heterosynaptic depolarization on pure N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission in the CA1 region of rat hippocampal slices. 2. In neurones voltage clamped at -60 mV, paired-pulse stimulation of one set of Schaffer collateral-commissural fibres resulted in homosynaptic paired-pulse facilitation of the NMDA receptor-mediated excitatory postsynaptic current (EPSCN). In contrast, stimulation of one set of fibres prior to stimulation of a second set of fibres (i.e. heterosynaptic paired-pulse stimulation) did not result in any heterosynaptic interactions. 3. However, under current-clamp conditions, heterosynaptic paired-pulse stimulation resulted in heterosynaptic 'paired-pulse facilitation' of the NMDA receptor-mediated excitatory postsynaptic potential (EPSPN). 4. In neurones held at -50 or -40 mV, perfusion of nominally Mg(2+)-free medium converted the response to heterosynaptic paired-pulse stimulation from 'heterosynaptic facilitation' to 'heterosynaptic depression' of EPSPN. 5. When neurones were held at potentials of between -30 and +40 mV then heterosynaptic paired-pulse stimulation, in normal Mg(2+)-containing medium, resulted in 'paired-pulse depression' of EPSPN. Under voltage-clamp conditions (tested at +40 mV) no heterosynaptic interactions were seen. 6. The time course of 'heterosynaptic facilitation' at -60 mV and of 'heterosynaptic depression' at +40 mV of EPSPN was similar to the time course of EPSCN. 7. We conclude, firstly, that the voltage clamp is able to prevent any voltage breakthrough associated with the synaptic activation of NMDA receptors from influencing neighbouring synapses. Secondly, when the neurone is not voltage clamped these same synapses are strongly influenced by the spreading depolarization generated by the synaptic activation of their neighbours. The time course and direction of this influence are compatible with the hypothesis that

  1. Forebrain NR2B overexpression facilitating the prefrontal cortex long-term potentiation and enhancing working memory function in mice.

    Science.gov (United States)

    Cui, Yihui; Jin, Jing; Zhang, Xuliang; Xu, Hao; Yang, Liguo; Du, Dan; Zeng, Qingwen; Tsien, Joe Z; Yu, Huiting; Cao, Xiaohua

    2011-01-01

    Prefrontal cortex plays an important role in working memory, attention regulation and behavioral inhibition. Its functions are associated with NMDA receptors. However, there is little information regarding the roles of NMDA receptor NR2B subunit in prefrontal cortical synaptic plasticity and prefrontal cortex-related working memory. Whether the up-regulation of NR2B subunit influences prefrontal cortical synaptic plasticity and working memory is not yet clear. In the present study, we measured prefrontal cortical synaptic plasticity and working memory function in NR2B overexpressing transgenic mice. In vitro electrophysiological data showed that overexpression of NR2B specifically in the forebrain region resulted in enhancement of prefrontal cortical long-term potentiation (LTP) but did not alter long-term depression (LTD). The enhanced LTP was completely abolished by a NR2B subunit selective antagonist, Ro25-6981, indicating that overexpression of NR2B subunit is responsible for enhanced LTP. In addition, NR2B transgenic mice exhibited better performance in a set of working memory paradigms including delay no-match-to-place T-maze, working memory version of water maze and odor span task. Our study provides evidence that NR2B subunit of NMDA receptor in prefrontal cortex is critical for prefrontal cortex LTP and prefrontal cortex-related working memory.

  2. Nicotine blocks stress-induced impairment of spatial memory and long-term potentiation of the hippocampal CA1 region.

    Science.gov (United States)

    Aleisa, Abdulaziz M; Alzoubi, Karem H; Gerges, Nashaat Z; Alkadhi, Karim A

    2006-08-01

    The effect of chronic nicotine treatment on chronic psychosocial stress-induced impairment of short-term memory and long-term potentiation (LTP) was determined. An "intruder" stress model was used to induce psychosocial stress for 4-6 wk, during which rats were injected with saline or nicotine (1 mg/kg s.c.) twice a day. The radial arm water maze memory task was used to test hippocampus-dependent spatial memory. Chronic psychosocial stress impaired short-term memory without affecting the learning phase or long-term memory. Concurrent chronic nicotine treatment prevented stress-induced short-term memory impairment. In normal rats chronic nicotine treatment had no effect on learning and memory. Extracellular recordings from the CA1 region of anaesthetized rats showed severe reduction of LTP magnitude in stressed rats, which was normalized in nicotine-treated stressed rats. Nicotine had no effect on LTP in control animals. These results showed that chronic nicotine treatment improved hippocampus-dependent spatial memory and LTP only when impaired by stress.

  3. Potential long-term consequences of fad diets on health, cancer, and longevity: lessons learned from model organism studies.

    Science.gov (United States)

    Ruden, Douglas M; Rasouli, Parsa; Lu, Xiangyi

    2007-06-01

    While much of the third world starves, many in the first world are undergoing an obesity epidemic, and the related epidemics of type II diabetes, heart disease, and other diseases associated with obesity. The amount of economic wealth being directly related to a decline in health by obesity is ironic because rich countries contribute billions of dollars to improve the health of their citizens. Nevertheless, nutritional experiments in model organisms such as yeast, C. elegans, Drosophila, and mice confirm that "caloric restriction" (CR), which is defined generally as a 30-40% decrease in caloric intake, a famine-like condition for humans seen only in the poorest of countries, promotes good health and increases longevity in model organisms. Because caloric restriction, and dieting in general, requires a great deal of will power to deal with the feelings of deprivation, many fad diets, such as the Atkins, South Beach, and Protein Power, have been developed which allow people to lose weight purportedly without the severe feelings of deprivation. However, the long-term effects of such fad diets are not known and few experiments have been performed in the laboratory to investigate possible side affects and adverse consequences. In this paper, we review studies with fad-like dietary conditions in humans and model organisms, and we propose a "Dietary Ames Test" to rapidly screen fad diets, dietary supplements, and drugs for potential long-term health consequences in model organisms.

  4. Caffeine prevents sleep loss-induced deficits in long-term potentiation and related signaling molecules in the dentate gyrus.

    Science.gov (United States)

    Alhaider, Ibrahim A; Aleisa, Abdulaziz M; Tran, Trinh T; Alkadhi, Karim A

    2010-04-01

    We have previously reported that caffeine prevented sleep deprivation-induced impairment of long-term potentiation (LTP) of area CA1 as well as hippocampus-dependent learning and memory performance in the radial arm water maze. In this report we examined the impact of long-term (4-week) caffeine consumption (0.3 g/L in drinking water) on synaptic plasticity (Alhaider et al., 2010) deficit in the dentate gyrus (DG) area of acutely sleep-deprived rats. The sleep deprivation and caffeine/sleep deprivation groups were sleep-deprived for 24 h by using the columns-in-water technique. We tested the effect of caffeine and/or sleep deprivation on LTP and measured the basal levels as well as stimulated levels of LTP-related molecules in the DG. The results showed that chronic caffeine administration prevented the impairment of early-phase LTP (E-LTP) in the DG of sleep-deprived rats. Additionally, chronic caffeine treatment prevented the sleep deprivation-associated decreases in the basal levels of the phosphorylated calcium/calmodulin-dependent protein kinase II (P-CaMKII) and brain derived neurotrophic factor (BDNF) as well as in the stimulated levels of P-CaMKII in the DG area. The results suggest that chronic use of caffeine prevented anomalous changes in the basal levels of P-CaMKII and BDNF associated with sleep deprivation and as a result contributes to the revival of LTP in the DG region.

  5. Forebrain NR2B overexpression facilitating the prefrontal cortex long-term potentiation and enhancing working memory function in mice.

    Directory of Open Access Journals (Sweden)

    Yihui Cui

    Full Text Available Prefrontal cortex plays an important role in working memory, attention regulation and behavioral inhibition. Its functions are associated with NMDA receptors. However, there is little information regarding the roles of NMDA receptor NR2B subunit in prefrontal cortical synaptic plasticity and prefrontal cortex-related working memory. Whether the up-regulation of NR2B subunit influences prefrontal cortical synaptic plasticity and working memory is not yet clear. In the present study, we measured prefrontal cortical synaptic plasticity and working memory function in NR2B overexpressing transgenic mice. In vitro electrophysiological data showed that overexpression of NR2B specifically in the forebrain region resulted in enhancement of prefrontal cortical long-term potentiation (LTP but did not alter long-term depression (LTD. The enhanced LTP was completely abolished by a NR2B subunit selective antagonist, Ro25-6981, indicating that overexpression of NR2B subunit is responsible for enhanced LTP. In addition, NR2B transgenic mice exhibited better performance in a set of working memory paradigms including delay no-match-to-place T-maze, working memory version of water maze and odor span task. Our study provides evidence that NR2B subunit of NMDA receptor in prefrontal cortex is critical for prefrontal cortex LTP and prefrontal cortex-related working memory.

  6. Arrested geomorphic trajectories and the long-term hidden potential for change.

    Science.gov (United States)

    James, L Allan

    2017-11-01

    Geomorphic systems often experience morphological changes that define a trajectory over decadal time periods. These trends can be halted by natural inhibitors such as vegetation, knickpoints, bed armor, or bank cohesion, or by anthropogenic inhibitors such as revetment, levees, or dams. Details about where and how channels and floodplains are stabilized are often poorly understood, which poses a risk that modern projects could unwittingly remove critical stabilizing elements (inhibitors) and unleash an episode of rapid change. The potential for destabilization is particularly keen for rivers that were severely altered by human activities but were stabilized by an inhibitor before readjustment was complete. This study uses aerial photographs to examine two cases of arrested geomorphic trajectories in the lower Yuba and Feather Rivers of northern California after 150 years of severe human disturbance. Channel adjustments were inhibited in distinctly different ways. First, channelization of the Feather River across a high-amplitude meander bend ∼4 km below the Yuba-Feather River confluence resulted in a knickpoint at Shanghai Shoals that retreated upstream at an average rate of 3.67 m/yr from 1963 to 2013 with two episodes of rapid retreat. Shanghai Shoals was breached in 2013. Second, numerous wing dams on the Yuba River constructed in the early nineteenth century limit floodplain widening and prevent return to an anastomosing channel planform. Their stabilizing role is important to preventing mobilization of mining sediment with high concentrations of mercury. These rivers exemplify how arrested geomorphic trajectories may impact sustainable river management, and how recognition of fluvial evolution is essential to sustainable river management. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Sol-gels with fiber-optic chemical sensor potential: Effects of preparation, aging, and long-term storage

    Science.gov (United States)

    Badini, G. E.; Grattan, K. T. V.; Tseung, A. C. C.

    1995-08-01

    The features of sol-gels, incorporating pH-sensitive dyes, designed as potential substrates for fiber-optic chemical sensors, have been investigated in terms of a variety of characteristics resulting from the preparation methods used and following the storage of samples for a period of several years. These materials, organically doped sol-gels, have been used as the heart of a number of prototype chemical sensing instruments, and a key issue in their effective use in instrumentation is their long-term durability and stability. In this work, it has been shown that such aged gel substrates can withstand immersion in water, drying, and reimmersion without fragmenting. Such impregnated gels were shown to still exhibit strong fluorescence, although some changes to the gel structure, determined from microhardness measurements, were observed and reported, reflecting their potential for use in chemically sensitive fiber optic-based instruments.

  8. Effects of electroacupuncture versus nimodipine on long-term potentiation and synaptophysin expression in a rat model of vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Dengming Wei; Xuemin Jia; Xiangxu Yin; Wenwen Jiang

    2011-01-01

    The present study stimulated Baihui (DU 20) and Dazhui (DU 14) acupoints in a rat model of vascular dementia with electroacupuncture to investigate changes in long-term potentiation and synaptophysin expression in the hippocampus. The results revealed that synaptophysin expression in brain tissues was increased after electroacupuncture. After high-frequency stimulation, the population spike latencywas shortened and the excitatory postsynaptic potential slope and population spike amplitude were increased. In addition, cognitive function was enhanced, similar to the effects of intragastric perfusion of nimodipine. The results indicated that electroacupuncture at Baihui and Dazhui acupoints can improve learning and memory functions of a rat model of vascular dementia by promoting synaptophysinexpression, enhancing hippocampal synaptic plasticity and accelerating synaptic transmission.

  9. Decellularized allogeneic heart valves demonstrate self-regeneration potential after a long-term preclinical evaluation.

    Science.gov (United States)

    Iop, Laura; Bonetti, Antonella; Naso, Filippo; Rizzo, Stefania; Cagnin, Stefano; Bianco, Roberto; Dal Lin, Carlo; Martini, Paolo; Poser, Helen; Franci, Paolo; Lanfranchi, Gerolamo; Busetto, Roberto; Spina, Michel; Basso, Cristina; Marchini, Maurizio; Gandaglia, Alessandro; Ortolani, Fulvia; Gerosa, Gino

    2014-01-01

    Tissue-engineered heart valves are proposed as novel viable replacements granting longer durability and growth potential. However, they require extensive in vitro cell-conditioning in bioreactor before implantation. Here, the propensity of non-preconditioned decellularized heart valves to spontaneous in body self-regeneration was investigated in a large animal model. Decellularized porcine aortic valves were evaluated for right ventricular outflow tract (RVOT) reconstruction in Vietnamese Pigs (n = 11) with 6 (n = 5) and 15 (n = 6) follow-up months. Repositioned native valves (n = 2 for each time) were considered as control. Tissue and cell components from explanted valves were investigated by histology, immunohistochemistry, electron microscopy, and gene expression. Most substitutes constantly demonstrated in vivo adequate hemodynamic performances and ex vivo progressive repopulation during the 15 implantation months without signs of calcifications, fibrosis and/or thrombosis, as revealed by histological, immunohistochemical, ultrastructural, metabolic and transcriptomic profiles. Colonizing cells displayed native-like phenotypes and actively synthesized novel extracellular matrix elements, as collagen and elastin fibers. New mature blood vessels, i.e. capillaries and vasa vasorum, were identified in repopulated valves especially in the medial and adventitial tunicae of regenerated arterial walls. Such findings correlated to the up-regulated vascular gene transcription. Neoinnervation hallmarks were appreciated at histological and ultrastructural levels. Macrophage populations with reparative M2 phenotype were highly represented in repopulated valves. Indeed, no aspects of adverse/immune reaction were revealed in immunohistochemical and transcriptomic patterns. Among differentiated elements, several cells were identified expressing typical stem cell markers of embryonic, hematopoietic, neural and mesenchymal lineages in significantly higher number

  10. Decellularized allogeneic heart valves demonstrate self-regeneration potential after a long-term preclinical evaluation.

    Directory of Open Access Journals (Sweden)

    Laura Iop

    Full Text Available Tissue-engineered heart valves are proposed as novel viable replacements granting longer durability and growth potential. However, they require extensive in vitro cell-conditioning in bioreactor before implantation. Here, the propensity of non-preconditioned decellularized heart valves to spontaneous in body self-regeneration was investigated in a large animal model. Decellularized porcine aortic valves were evaluated for right ventricular outflow tract (RVOT reconstruction in Vietnamese Pigs (n = 11 with 6 (n = 5 and 15 (n = 6 follow-up months. Repositioned native valves (n = 2 for each time were considered as control. Tissue and cell components from explanted valves were investigated by histology, immunohistochemistry, electron microscopy, and gene expression. Most substitutes constantly demonstrated in vivo adequate hemodynamic performances and ex vivo progressive repopulation during the 15 implantation months without signs of calcifications, fibrosis and/or thrombosis, as revealed by histological, immunohistochemical, ultrastructural, metabolic and transcriptomic profiles. Colonizing cells displayed native-like phenotypes and actively synthesized novel extracellular matrix elements, as collagen and elastin fibers. New mature blood vessels, i.e. capillaries and vasa vasorum, were identified in repopulated valves especially in the medial and adventitial tunicae of regenerated arterial walls. Such findings correlated to the up-regulated vascular gene transcription. Neoinnervation hallmarks were appreciated at histological and ultrastructural levels. Macrophage populations with reparative M2 phenotype were highly represented in repopulated valves. Indeed, no aspects of adverse/immune reaction were revealed in immunohistochemical and transcriptomic patterns. Among differentiated elements, several cells were identified expressing typical stem cell markers of embryonic, hematopoietic, neural and mesenchymal lineages in significantly

  11. Long-Term Warming Alters Carbohydrate Degradation Potential in Temperate Forest Soils.

    Science.gov (United States)

    Pold, Grace; Billings, Andrew F; Blanchard, Jeff L; Burkhardt, Daniel B; Frey, Serita D; Melillo, Jerry M; Schnabel, Julia; van Diepen, Linda T A; DeAngelis, Kristen M

    2016-11-15

    As Earth's climate warms, soil carbon pools and the microbial communities that process them may change, altering the way in which carbon is recycled in soil. In this study, we used a combination of metagenomics and bacterial cultivation to evaluate the hypothesis that experimentally raising soil temperatures by 5°C for 5, 8, or 20 years increased the potential for temperate forest soil microbial communities to degrade carbohydrates. Warming decreased the proportion of carbohydrate-degrading genes in the organic horizon derived from eukaryotes and increased the fraction of genes in the mineral soil associated with Actinobacteria in all studies. Genes associated with carbohydrate degradation increased in the organic horizon after 5 years of warming but had decreased in the organic horizon after warming the soil continuously for 20 years. However, a greater proportion of the 295 bacteria from 6 phyla (10 classes, 14 orders, and 34 families) isolated from heated plots in the 20-year experiment were able to depolymerize cellulose and xylan than bacterial isolates from control soils. Together, these findings indicate that the enrichment of bacteria capable of degrading carbohydrates could be important for accelerated carbon cycling in a warmer world. The massive carbon stocks currently held in soils have been built up over millennia, and while numerous lines of evidence indicate that climate change will accelerate the processing of this carbon, it is unclear whether the genetic repertoire of the microbes responsible for this elevated activity will also change. In this study, we showed that bacteria isolated from plots subject to 20 years of 5°C of warming were more likely to depolymerize the plant polymers xylan and cellulose, but that carbohydrate degradation capacity is not uniformly enriched by warming treatment in the metagenomes of soil microbial communities. This study illustrates the utility of combining culture-dependent and culture-independent surveys of

  12. Long-term potentiation in bone – a role for glutamate in strain-induced cellular memory?

    Directory of Open Access Journals (Sweden)

    Genever Paul G

    2003-07-01

    Full Text Available Abstract Background The adaptive response of bone cells to mechanical strain is a primary determinant of skeletal architecture and bone mass. In vivo mechanical loading induces new bone formation and increases bone mineral density whereas disuse, immobilisation and weightlessness induce bone loss. The potency of mechanical strain is such that a single brief period of loading at physiological strain magnitude is able to induce a long-lasting osteogenic response that lasts for days. Although the process of mechanotransduction in bone is incompletely understood, observations that responses to mechanical strain outlast the duration of stimulation necessitate the existence of a form of cellular memory through which transient strain episodes are recorded, interpreted and remembered by bone cells. Recent evidence supports the existence of a complex multicellular glutamate-signalling network in bone that shares functional similarities to glutamatergic neurotransmission in the central nervous system. In neurones, these signalling molecules coordinate synaptic communication required to support learning and memory formation, through a complex process of long-term potentiation. Presentation of the hypothesis We hypothesise that osteoblasts use a cellular mechanism similar or identical to neuronal long-term potentiation in the central nervous system to mediate long-lasting changes in osteogenesis following brief periods of mechanical strain. Testing the hypothesis N-methyl-D-aspartate (NMDA receptor antagonism should inhibit the saturating response of mechanical strain and reduce the enhanced osteogenicity of segregated loading to that of an equivalent period of uninterrupted loading. Changes in α-amino-3-hydroxy-5-methyl-isoxazole propionate (AMPA receptor expression, localisation and electrophysiological responses should be induced by mechanical strain and inhibited by modulators of neuronal long-term potentiation. Implications of the hypothesis If true

  13. Synaptic long-term potentiation and depression in the rat medial vestibular nuclei depend on neural activation of estrogenic and androgenic signals.

    Directory of Open Access Journals (Sweden)

    Mariangela Scarduzio

    Full Text Available Estrogenic and androgenic steroids can be synthesised in the brain and rapidly modulate synaptic transmission and plasticity through direct interaction with membrane receptors for estrogens (ERs and androgens (ARs. We used whole cell patch clamp recordings in brainstem slices of male rats to explore the influence of ER and AR activation and local synthesis of 17β-estradiol (E2 and 5α-dihydrotestosterone (DHT on the long-term synaptic changes induced in the neurons of the medial vestibular nucleus (MVN. Long-term depression (LTD and long-term potentiation (LTP caused by different patterns of high frequency stimulation (HFS of the primary vestibular afferents were assayed under the blockade of ARs and ERs or in the presence of inhibitors for enzymes synthesizing DHT (5α-reductase and E2 (P450-aromatase from testosterone (T. We found that LTD is mediated by interaction of locally produced androgens with ARs and LTP by interaction of locally synthesized E2 with ERs. In fact, the AR block with flutamide prevented LTD while did not affect LTP, and the blockade of ERs with ICI 182,780 abolished LTP without influencing LTD. Moreover, the block of P450-aromatase with letrozole not only prevented the LTP induction, but inverted LTP into LTD. This LTD is likely due to the local activation of androgens, since it was abolished under blockade of ARs. Conversely, LTD was still induced in the presence of finasteride the inhibitor of 5α-reductase demonstrating that T is able to activate ARs and induce LTD even when DHT is not synthesized. This study demonstrates a key and opposite role of sex neurosteroids in the long-term synaptic changes of the MVN with a specific role of T-DHT for LTD and of E2 for LTP. Moreover, it suggests that different stimulation patterns can lead to LTD or LTP by specifically activating the enzymes involved in the synthesis of androgenic or estrogenic neurosteroids.

  14. Long-term neurocognitive outcome and auditory event-related potentials after complex febrile seizures in children.

    Science.gov (United States)

    Tsai, Min-Lan; Hung, Kun-Long; Tsan, Ying-Ying; Tung, William Tao-Hsin

    2015-06-01

    Whether prolonged or complex febrile seizures (FS) produce long-term injury to the hippocampus is a critical question concerning the neurocognitive outcome of these seizures. Long-term event-related evoked potential (ERP) recording from the scalp is a noninvasive technique reflecting the sensory and cognitive processes associated with attention tasks. This study aimed to investigate the long-term outcome of neurocognitive and attention functions and evaluated auditory event-related potentials in children who have experienced complex FS in comparison with other types of FS. One hundred and forty-seven children aged more than 6 years who had experienced complex FS, simple single FS, simple recurrent FS, or afebrile seizures (AFS) after FS and age-matched healthy controls were enrolled. Patients were evaluated with Wechsler Intelligence Scale for Children (WISC; Chinese WISC-IV) scores, behavior test scores (Chinese version of Conners' continuous performance test, CPT II V.5), and behavior rating scales. Auditory ERPs were recorded in each patient. Patients who had experienced complex FS exhibited significantly lower full-scale intelligence quotient (FSIQ), perceptual reasoning index, and working memory index scores than did the control group but did not show significant differences in CPT scores, behavior rating scales, or ERP latencies and amplitude compared with the other groups with FS. We found a significant decrease in the FSIQ and four indices of the WISC-IV, higher behavior rating scales, a trend of increased CPT II scores, and significantly delayed P300 latency and reduced P300 amplitude in the patients with AFS after FS. We conclude that there is an effect on cognitive function in children who have experienced complex FS and patients who developed AFS after FS. The results indicated that the WISC-IV is more sensitive in detecting cognitive abnormality than ERP. Cognition impairment, including perceptual reasoning and working memory defects, was identified in

  15. Exploration of conditioned pain modulation effect on long-term potentiation-like pain amplification in humans

    DEFF Research Database (Denmark)

    Xia, Weiwei; Mørch, Carsten Dahl; Matre, D.;

    2017-01-01

    BACKGROUND: This study aimed to explore conditioned pain modulation (CPM) effect on long-term potentiation (LTP)-like pain amplification induced by cutaneous 10-Hz conditioning electrical stimulation (CES). METHODS: Conditioned pain modulation was induced by cold pressor conditioning stimulus (CPCS...... session. Moreover, CPCS resulted in lower pain intensity ratings during CES process but without affecting the SF-MPQ scores between two sessions. The SBF and ST increased after CES and then gradually declined but without differences between CPCS and control sessions. CPM did not affect HPT and pain......). SIGNIFICANCE: Conditioned pain modulation (CPM) may play a role in inhibiting the pain amplificatory process at the central nervous system and prompting central desensitization. CPM has a special inhibition effect for the development of perception amplification to non-painful mechanical stimuli....

  16. Potential long-term effects of previous schistosome infection may reduce the atherogenic index of plasma in Chinese men.

    Science.gov (United States)

    Shen, Shi-Wei; Lu, Yun; Li, Feng; Shen, Zhen-Hai; Xu, Ming; Yao, Wei-Feng; Feng, Yin-Bo; Yun, Jing-Ting; Wang, Ya-Ping; Ling, Wang; Qi, Hua-Jin; Tong, Da-Xin

    2015-04-01

    The major purpose of this study was to assess the association between the potential long-term effects of previous schistosome infection and atherogenic dyslipidemia. Among 1597 men aged ⩾45 years who received health examinations and lived in previous schistosomiasis-endemic regions of China, 465 patients with previous schistosome infection were selected as study subjects, and 1132 subjects formed the control group. The risk factors for cardiovascular disease were measured and compared between the previous schistosome infection and control groups. The Atherogenic Index of Plasma, triglycerides, waist circumference and body mass index were significantly lower in the previous schistosome infection group than in the control group (all P values immune response against schistosome infections. The development of a schistosomiasis vaccine may effectively prevent the development and progression of atherosclerosis.

  17. Different contributions of platelet-activating factor and nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

    Science.gov (United States)

    Pettorossi, V E; Grassi, S

    2001-01-01

    In rat brainstem slices, we investigated the differential role of nitric oxide (NO) and platelet-activating factor (PAF) in long-term potentiation (LTP) induced in the ventral portion of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferents. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and the PAF receptor antagonist ginkgolide B (BN-52021) were administered before and after induction of potentiation. The effect of carboxy-PTIO was to completely prevent LTP. By contrast, BN-52021 only reduced the amplitude of HFS potentiation, which could develop fully at the drug washout or decline to zero, becoming a short-term phenomenon, in the case of long-lasting PAF receptor block. Both drugs, when given after HFS, had no effect on the already established potentiation, but whilst BN-52021 showed an influence within 5 min of the LTP induction, carboxy-PTIO did not affect the response once HFS was delivered. Moreover, we showed that the NO donor, sodium nitroprusside, and methylcarbamyl PAF (mc-PAF) induced LTP which was associated with an increase in glutamate release as shown by reduction in the paired-pulse facilitation ratio. The mc-PAF LTP was prevented by the NO scavenger, while NO LTP was only reduced by BN-52021. We suggest that NO and PAF are implicated as retrograde messengers in two different phases of vestibular LTP: NO in the induction phase; and PAF in the full expression phase.

  18. Amyloid-β Peptide Is Needed for cGMP-Induced Long-Term Potentiation and Memory.

    Science.gov (United States)

    Palmeri, Agostino; Ricciarelli, Roberta; Gulisano, Walter; Rivera, Daniela; Rebosio, Claudia; Calcagno, Elisa; Tropea, Maria Rosaria; Conti, Silvia; Das, Utpal; Roy, Subhojit; Pronzato, Maria Adelaide; Arancio, Ottavio; Fedele, Ernesto; Puzzo, Daniela

    2017-07-19

    High levels of amyloid-β peptide (Aβ) have been related to Alzheimer's disease pathogenesis. However, in the healthy brain, low physiologically relevant concentrations of Aβ are necessary for long-term potentiation (LTP) and memory. Because cGMP plays a key role in these processes, here we investigated whether the cyclic nucleotide cGMP influences Aβ levels and function during LTP and memory. We demonstrate that the increase of cGMP levels by the phosphodiesterase-5 inhibitors sildenafil and vardenafil induces a parallel release of Aβ due to a change in the approximation of amyloid precursor protein (APP) and the β-site APP cleaving enzyme 1. Moreover, electrophysiological and behavioral studies performed on animals of both sexes showed that blocking Aβ function, by using anti-murine Aβ antibodies or APP knock-out mice, prevents the cGMP-dependent enhancement of LTP and memory. Our data suggest that cGMP positively regulates Aβ levels in the healthy brain which, in turn, boosts synaptic plasticity and memory.SIGNIFICANCE STATEMENT Amyloid-β (Aβ) is a key pathogenetic factor in Alzheimer's disease. However, low concentrations of endogenous Aβ, mimicking levels of the peptide in the healthy brain, enhance hippocampal long-term potentiation (LTP) and memory. Because the second messenger cGMP exerts a central role in LTP mechanisms, here we studied whether cGMP affects Aβ levels and function during LTP. We show that cGMP enhances Aβ production by increasing the APP/BACE-1 convergence in endolysosomal compartments. Moreover, the cGMP-induced enhancement of LTP and memory was disrupted by blockade of Aβ, suggesting that the physiological effect of the cyclic nucleotide on LTP and memory is dependent upon Aβ. Copyright © 2017 the authors 0270-6474/17/376926-12$15.00/0.

  19. Long-term no-till and stover retention each decrease the global warming potential of irrigated continuous corn.

    Science.gov (United States)

    Jin, Virginia L; Schmer, Marty R; Stewart, Catherine E; Sindelar, Aaron J; Varvel, Gary E; Wienhold, Brian J

    2017-07-01

    Over the last 50 years, the most increase in cultivated land area globally has been due to a doubling of irrigated land. Long-term agronomic management impacts on soil organic carbon (SOC) stocks, soil greenhouse gas (GHG) emissions, and global warming potential (GWP) in irrigated systems, however, remain relatively unknown. Here, residue and tillage management effects were quantified by measuring soil nitrous oxide (N2 O) and methane (CH4 ) fluxes and SOC changes (ΔSOC) at a long-term, irrigated continuous corn (Zea mays L.) system in eastern Nebraska, United States. Management treatments began in 2002, and measured treatments included no or high stover removal (0 or 6.8 Mg DM ha(-1)  yr(-1) , respectively) under no-till (NT) or conventional disk tillage (CT) with full irrigation (n = 4). Soil N2 O and CH4 fluxes were measured for five crop-years (2011-2015), and ΔSOC was determined on an equivalent mass basis to ~30 cm soil depth. Both area- and yield-scaled soil N2 O emissions were greater with stover retention compared to removal and for CT compared to NT, with no interaction between stover and tillage practices. Methane comprised <1% of total emissions, with NT being CH4 neutral and CT a CH4 source. Surface SOC decreased with stover removal and with CT after 14 years of management. When ΔSOC, soil GHG emissions, and agronomic energy usage were used to calculate system GWP, all management systems were net GHG sources. Conservation practices (NT, stover retention) each decreased system GWP compared to conventional practices (CT, stover removal), but pairing conservation practices conferred no additional mitigation benefit. Although cropping system, management equipment/timing/history, soil type, location, weather, and the depth to which ΔSOC is measured affect the GWP outcomes of irrigated systems at large, this long-term irrigated study provides valuable empirical evidence of how management decisions can impact soil GHG emissions and surface SOC

  20. Spatial, contextual and working memory are not affected by the absence of mossy fiber long-term potentiation and depression

    NARCIS (Netherlands)

    Hensbroek, R.A.; Kamal, A.; Baars, A.M.; Verhage, M.; Spruijt, B.M.

    2003-01-01

    The mossy fibers of the hippocampus display NMDA-receptor independent long-term plasticity. A number of studies addressed the role of mossy fiber long-term plasticity in memory, but have provided contrasting results. Here, we have exploited a genetic model, the rab3A null-mutant, which is

  1. Spatial, contextual and working memory are not affected by the absence of mossy fiber long-term potentiation and depression

    NARCIS (Netherlands)

    Hensbroek, R.A.; Kamal, A.; Baars, A.M.; Verhage, M.; Spruijt, B.M.

    2003-01-01

    The mossy fibers of the hippocampus display NMDA-receptor independent long-term plasticity. A number of studies addressed the role of mossy fiber long-term plasticity in memory, but have provided contrasting results. Here, we have exploited a genetic model, the rab3A null-mutant, which is characteri

  2. Potential effect of conservation tillage on sustainable land use : a review of global long-term studies

    NARCIS (Netherlands)

    Wang Xiaobin,; Cai, D.; Hoogmoed, W.B.; Oenema, O.; Perdok, U.D.

    2006-01-01

    Although understood differently in different parts of the world, conservation tillage usually includes leaving crop residues on the soil surface to reduce tillage. Through a global review of long-term conservation tillage research, this paper discusses the long-term effect of conservation tillage on

  3. Metabolic Profile as a Potential Modifier of Long-Term Radiation Effects on Peripheral Lymphocyte Subsets in Atomic Bomb Survivors.

    Science.gov (United States)

    Yoshida, Kengo; Nakashima, Eiji; Kyoizumi, Seishi; Hakoda, Masayuki; Hayashi, Tomonori; Hida, Ayumi; Ohishi, Waka; Kusunoki, Yoichiro

    2016-09-01

    Immune system impairments reflected by the composition and function of circulating lymphocytes are still observed in atomic bomb survivors, and metabolic abnormalities including altered blood triglyceride and cholesterol levels have also been detected in such survivors. Based on closely related features of immune and metabolic profiles of individuals, we investigated the hypothesis that long-term effects of radiation exposure on lymphocyte subsets might be modified by metabolic profiles in 3,113 atomic bomb survivors who participated in health examinations at the Radiation Effect Research Foundation, Hiroshima and Nagasaki, in 2000-2002. The lymphocyte subsets analyzed involved T-, B- and NK-cell subsets, and their percentages in the lymphocyte fraction were assessed using flow cytometry. Health examinations included metabolic indicators, body mass index, serum levels of total cholesterol, high-density lipoprotein cholesterol, C-reactive protein and hemoglobin A1c, as well as diabetes and fatty liver diagnoses. Standard regression analyses indicated that several metabolic indicators of obesity/related disease, particularly high-density lipoprotein cholesterol levels, were positively associated with type-1 helper T- and B-cell percentages but were inversely associated with naïve CD4 T and NK cells. A regression analysis adjusted for high-density lipoprotein cholesterol revealed a radiation dose relationship with increasing NK-cell percentage. Additionally, an interaction effect was suggested between radiation dose and C-reactive protein on B-cell percentage with a negative coefficient of the interaction term. Collectively, these findings suggest that radiation exposure and subsequent metabolic profile changes, potentially in relationship to obesity-related inflammation, lead to such long-term alterations in lymphocyte subset composition. Because this study is based on cross-sectional and exploratory analyses, the implications regarding radiation exposure, metabolic

  4. Acid rock drainage passive remediation: Potential use of alkaline clay, optimal mixing ratio and long-term impacts.

    Science.gov (United States)

    Plaza, Fernando; Wen, Yipei; Perone, Hanna; Xu, Yi; Liang, Xu

    2017-01-15

    Acid rock drainage (ARD) is one of the most adverse environmental problems of the mining industry. Surface and ground water affected by this pollution are characterized by their acidity and the high content of sulfates and metals/metalloids. In this study, alkaline clay (AC), an industrial waste with a high alkalinity, which is utilized in the alumina refining process, was used as the remediation material to inhibit pyrite oxidation in waste coal piles. Through a series of laboratory experiments (static and kinetic), complemented with field measurements and geochemical modeling, three important issues associated with this passive and sustainable ARD remediation method were investigated: 1) the potential use of alkaline clay as an ARD remediation material, 2) the adequate alkaline clay/coal refuse mixing ratio (AC/CR) to ensure pH values close to neutral conditions, and, 3) the implications for long-term performance, in terms of the trends of the main parameters involved in this process such as pH, concentrations of sulfate, iron and other dissolved contaminants. Both field measurements and the samples used for the experiments came from a local waste coal site. Through the analysis of the field measurements and the outcome of the laboratory experiments, AC proved to be an effective remediation material for ARD. Compared to those found in mine tailings, the concentrations of contaminants such as iron, manganese or sulfate were significantly reduced with this remediation approach. Moreover, results suggest a reliable long-term stability of the remediation (i.e. neutral pH conditions are maintained), thus enhancing the generation of iron precipitates that could produce pyrite grain coating. These processes also made the amended layer less porous, thus increased water retention and hindered oxygen diffusion.

  5. Drivers, trends, and potential impacts of long-term coastal reclamation in China from 1985 to 2010

    Science.gov (United States)

    Tian, Bo; Wu, Wenting; Yang, Zhaoqing; Zhou, Yunxuan

    2016-03-01

    The reclamation of coastal land for agricultural, industrial, and urban land use-a common worldwide practice-has occurred extensively in the coastal region of China. In recent decades, all coastal provinces and metropolises in China have experienced severe coastal reclamation related to land scarcity caused by rapid economic growth and urbanization. However, the value of coastal wetlands and ecosystems has not been well understood and appreciated until recent development of advantageous methods of restoring reclaimed land to coastal wetlands in many developed countries. The overall objective of this study is to provide detailed spatial and temporal distributions of coastal reclamation; analyze drivers such as coastal economy, population growth, and urbanization; and understand the relationships among the drivers and land reclamation. We used long-term Landsat image time series from 1985 to 2010 in 5-year intervals, in combination with remotely sensed image interpretation and spatial analysis, to map the reclamation status and changes across the coastal region of China. The Landsat images time-series analysis was also conducted to evaluate the effects of the economy, population, and urbanization drivers on coastal reclamation. The analysis results indicated that 754,697 ha of coastal wetlands have been reclaimed across all coastal provinces and metropolises from 1985 to 2010, and the trend increased sharply after 2005. High-intensity coastal reclamation was mainly driven by the booming economy, especially after 2000, associated with urbanization and industrial development in China's coastal region; this was closely correlated with the gross domestic product (GDP) per capita. The continuous large-scale coastal reclamation of its coastal region now means China is facing a great challenge, including the enormous loss of vegetated coastal wetlands, negative environmental effects, and potential disaster risks related to coastal flooding under future change climate

  6. Potential of thorium-based fuel cycle for PWR core to reduce plutonium and long-term toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Hyung Kook; Kim, Taek Kyum; Kim, Young Jin [Korea Atomic Energy Research Institute, Taejon (Korea)

    1999-01-01

    The cross section libraries and calculation methods of the participants were inter-compared through the first stage benchmark calculation. The multiplication factor of unit cell benchmark are in good agreement, but there is significant discrepancies of 2.3 to 3.5 %k at BOC and at EOC between the calculated infinite multiplication factors of each participants for the assembly benchmark. Our results with HELIOS show a reasonable agreement with the others except the MTC value at EOC. To verify the potential of the thorium-based fuel to consume the plutonium and to reduce the radioactivity from the spent fuel, the conceptual core with ThO{sub 2}-PuO{sub 2} or MOX fuel were constructed. The composition and quantity of plutonium isotopes and the radioactivity level of spent fuel for conceptual cores were analyzed, and the neutronic characteristics of conceptual cores were also calculated. The nuclear characteristics for ThO{sub 2}-PuO{sub 2} thorium fueled core was similar to MOX fueled core, mainly due to the same seed fuel material, plutonium. For the capability of plutonium consumption, ThO{sub 2}-PuO{sub 2} thorium fuel can consume plutonium 2.1-2.4 times MOX fuel. The fraction of fissile plutonium in the spent ThO{sub 2}-PuO{sub 2} thorium fuel is more favorable in view of plutonium consumption and non-proliferation than MOX fuel. The radioactivity of spent ThO{sub 2}-PuO{sub 2} thorium and MOX fuel batches were calculated. Since plutonium isotopes are dominant for the long-term radioactivity, ThO{sub 2}-PuO{sub 2} thorium has almost the same level of radioactivity as in MOX fuel for a long-term perspective. (author). 22 figs., 11 tabs.

  7. Repeated long-term potentiation induces mossy fibre sprouting and changes the sensibility of hippocampal granule cells to subconvulsive doses of pentylenetetrazol.

    Science.gov (United States)

    Hassan, H; Pohle, W; Rüthrich, H; Brödemann, R; Krug, M

    2000-04-01

    Electrical and chemical kindling induces sprouting of the mossy fibre system and potentiation of evoked field potentials in the dentate gyrus. It has been postulated that such changes may also be induced by repeated induction of long-term potentiation (LTP) with tetanic stimulation of the perforant pathway. LTP was induced in rats chronically implanted with stimulation electrodes in the ipsilateral and contralateral angular bundles and with a recording electrode in the ipsilateral dorsal dentate gyrus. The animals were stimulated 10 times on 10 consecutive days but with different tetanization strengths. Sprouting of the mossy fibres terminating in the CA3 region was significantly induced only in the group of 'strongly' tetanized animals, but not in that of 'weakly' tetanized animals, or in low-frequency stimulated animals. Additionally, a novel form of potentiation which was previously found in pentylenetetrazol (PTZ)-kindled animals was also observed in the group of 'strongly' and 'weakly' tetanized rats. Differences in duration of this potentiation were found between the two groups of animals tetanized with different strengths. The results further demonstrate that morphological and functional changes in the hippocampus, similar to those seen after kindling, can also occur in an activation paradigm leading to long-lasting synaptic plasticity but not accompanied by seizure activity.

  8. Myosin II ATPase activity mediates the long-term potentiation-induced exodus of stable F-actin bound by drebrin A from dendritic spines.

    Directory of Open Access Journals (Sweden)

    Toshiyuki Mizui

    Full Text Available The neuronal actin-binding protein drebrin A forms a stable structure with F-actin in dendritic spines. NMDA receptor activation causes an exodus of F-actin bound by drebrin A (DA-actin from dendritic spines, suggesting a pivotal role for DA-actin exodus in synaptic plasticity. We quantitatively assessed the extent of DA-actin localization to spines using the spine-dendrite ratio of drebrin A in cultured hippocampal neurons, and found that (1 chemical long-term potentiation (LTP stimulation induces rapid DA-actin exodus and subsequent DA-actin re-entry in dendritic spines, (2 Ca(2+ influx through NMDA receptors regulates the exodus and the basal accumulation of DA-actin, and (3 the DA-actin exodus is blocked by myosin II ATPase inhibitor, but is not blocked by myosin light chain kinase (MLCK or Rho-associated kinase (ROCK inhibitors. These results indicate that myosin II mediates the interaction between NMDA receptor activation and DA-actin exodus in LTP induction. Furthermore, myosin II seems to be activated by a rapid actin-linked mechanism rather than slow MLC phosphorylation. Thus the myosin-II mediated DA-actin exodus might be an initial event in LTP induction, triggering actin polymerization and spine enlargement.

  9. Myosin II ATPase activity mediates the long-term potentiation-induced exodus of stable F-actin bound by drebrin A from dendritic spines.

    Science.gov (United States)

    Mizui, Toshiyuki; Sekino, Yuko; Yamazaki, Hiroyuki; Ishizuka, Yuta; Takahashi, Hideto; Kojima, Nobuhiko; Kojima, Masami; Shirao, Tomoaki

    2014-01-01

    The neuronal actin-binding protein drebrin A forms a stable structure with F-actin in dendritic spines. NMDA receptor activation causes an exodus of F-actin bound by drebrin A (DA-actin) from dendritic spines, suggesting a pivotal role for DA-actin exodus in synaptic plasticity. We quantitatively assessed the extent of DA-actin localization to spines using the spine-dendrite ratio of drebrin A in cultured hippocampal neurons, and found that (1) chemical long-term potentiation (LTP) stimulation induces rapid DA-actin exodus and subsequent DA-actin re-entry in dendritic spines, (2) Ca(2+) influx through NMDA receptors regulates the exodus and the basal accumulation of DA-actin, and (3) the DA-actin exodus is blocked by myosin II ATPase inhibitor, but is not blocked by myosin light chain kinase (MLCK) or Rho-associated kinase (ROCK) inhibitors. These results indicate that myosin II mediates the interaction between NMDA receptor activation and DA-actin exodus in LTP induction. Furthermore, myosin II seems to be activated by a rapid actin-linked mechanism rather than slow MLC phosphorylation. Thus the myosin-II mediated DA-actin exodus might be an initial event in LTP induction, triggering actin polymerization and spine enlargement.

  10. The proliferative potential of human cardiac stem cells was unaffected after a long-term cryopreservation of tissue blocks

    Science.gov (United States)

    Iguchi, Nobuo; Cho, Yasunori; Inoue, Masaki; Murakami, Tsutomu; Tabata, Minoru; Takanashi, Shuichiro; Tomoike, Hitonobu

    2017-01-01

    Background Human c-kit-positive cardiac stem cells (CSCs) have been used to treat patients suffering from ischemic cardiomyopathy. This study aimed to investigate whether a long-term storage of cardiac tissues would influence the growth potential of the subsequently isolated CSCs. Methods A total of 34 fresh samples were obtained from various cardiac regions [right atrium (RA), left atrium (LA), and/or left ventricle (LV)] of 21 patients. From 12 of these patients, 18 samples kept frozen for ~2 years were employed to prepare and characterize the CSCs. After confirming the specificity of the cell sorting by c-kit immunolabeling, the growth rate (number of doublings per day), BrdU positivity, and colony forming unit (CFU) were measured in each CSC population; the values were compared among distinct cardiac regions as well as between fresh and frozen tissues from which CSCs were derived. Results Among independent measurements indicating growth potential, the growth rate and BrdU positivity remarkably correlated in freshly prepared CSCs. The cells obtained from every examined region displayed a high proliferative capacity with the growth rate of 0.48±0.19 and the BrdU positivity of 15.0%±7.6%. The right atrial CSCs tended to show a greater growth than those in the other two areas. Similarly, the CSCs were isolated from tissue blocks, cryopreserved for ~2 years, and compared with CSCs derived from the fresh specimens of the same patients. Importantly, we were able to obtain and culture CSCs from every frozen material, and their proliferative potential, represented by the growth rate of 0.47±0.22 and the BrdU positivity of 13.7%±7.9%, was not inferior to that of the freshly prepared cells. Conclusions The long-term cryopreservation of cardiac tissues did not affect the growth potential of the derivative CSCs. Our findings should expand the therapeutic applications of these cells over a longer time span. PMID:28251120

  11. Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation

    Directory of Open Access Journals (Sweden)

    Roberto Narcisi

    2015-03-01

    Full Text Available Mesenchymal stem cells (MSCs are a potential source of chondrogenic cells for the treatment of cartilage disorders, but loss of chondrogenic potential during in vitro expansion and the propensity of cartilage to undergo hypertrophic maturation impede their therapeutic application. Here we report that the signaling protein WNT3A, in combination with FGF2, supports long-term expansion of human bone marrow-derived MSCs. The cells retained their chondrogenic potential and other phenotypic and functional properties of multipotent MSCs, which were gradually lost in the absence of WNT3A. Moreover, we discovered that endogenous WNT signals are the main drivers of the hypertrophic maturation that follows chondrogenic differentiation. Inhibition of WNT signals during differentiation prevented calcification and maintained cartilage properties following implantation in a mouse model. By maintaining potency during expansion and preventing hypertrophic maturation following differentiation, the modulation of WNT signaling removes two major obstacles that impede the clinical application of MSCs in cartilage repair.

  12. X11beta rescues memory and long-term potentiation deficits in Alzheimer's disease APPswe Tg2576 mice.

    LENUS (Irish Health Repository)

    Mitchell, Jacqueline C

    2009-12-01

    Increased production and deposition of amyloid beta-protein (Abeta) are believed to be key pathogenic events in Alzheimer\\'s disease. As such, routes for lowering cerebral Abeta levels represent potential therapeutic targets for Alzheimer\\'s disease. X11beta is a neuronal adaptor protein that binds to the intracellular domain of the amyloid precursor protein (APP). Overexpression of X11beta inhibits Abeta production in a number of experimental systems. However, whether these changes to APP processing and Abeta production induced by X11beta overexpression also induce beneficial effects to memory and synaptic plasticity are not known. We report here that X11beta-mediated reduction in cerebral Abeta is associated with normalization of both cognition and in vivo long-term potentiation in aged APPswe Tg2576 transgenic mice that model the amyloid pathology of Alzheimer\\'s disease. Overexpression of X11beta itself has no detectable adverse effects upon mouse behaviour. These findings support the notion that modulation of X11beta function represents a therapeutic target for Abeta-mediated neuronal dysfunction in Alzheimer\\'s disease.

  13. Effects of a human milk oligosaccharide, 2'-fucosyllactose, on hippocampal long-term potentiation and learning capabilities in rodents.

    Science.gov (United States)

    Vázquez, Enrique; Barranco, Alejandro; Ramírez, Maria; Gruart, Agnes; Delgado-García, José M; Martínez-Lara, Esther; Blanco, Santos; Martín, María Jesús; Castanys, Esther; Buck, Rachael; Prieto, Pedro; Rueda, Ricardo

    2015-05-01

    Human milk oligosaccharides (HMOs) are unique with regard to their diversity, quantity and complexity, particularly in comparison to bovine milk oligosaccharides. HMOs are associated with functional development during early life, mainly related to immunity and intestinal health. Whether HMOs elicit a positive effect on cognitive capabilities of lactating infants remains an open question. This study evaluated the role of the most abundant HMO, 2'-fucosyllactose (2'-FL), in synaptic plasticity and learning capabilities in rodents. Mice and rats were prepared for the chronic recording of field excitatory postsynaptic potentials evoked at the hippocampal CA3-CA1 synapse. Following chronic oral administration of 2'-FL, both species showed improvements in input/output curves and in long-term potentiation (LTP) evoked experimentally in alert behaving animals. This effect on LTP was related to better performance of animals in various types of learning behavioral tests. Mice were tested for spatial learning, working memory and operant conditioning using the IntelliCage system, while rats were submitted to a fixed-ratio schedule in the Skinner box. In both cases, 2'-FL-treated animals performed significantly better than controls. In addition, chronic administration of 2'-FL increased the expression of different molecules involved in the storage of newly acquired memories, such as the postsynaptic density protein 95, phosphorylated calcium/calmodulin-dependent kinase II and brain-derived neurotrophic factor in cortical and subcortical structures. Taken together, the data show that dietary 2'-FL affects cognitive domains and improves learning and memory in rodents.

  14. Thymoglobulin versus basiliximab induction therapy for simultaneous kidney-pancreas transplantation: impact on rejection, graft function, and long-term outcome.

    Science.gov (United States)

    Bazerbachi, Fateh; Selzner, Markus; Boehnert, Markus U; Marquez, Max A; Norgate, Andrea; McGilvray, Ian D; Schiff, Jeffrey; Cattral, Mark S

    2011-11-15

    Thymoglobulin (ATG) and basiliximab induction therapies are used by the majority of centers for pancreas transplantation today. Although both strategies have different mechanisms, there is a paucity of studies comparing them. We compared the efficacy and side effects of both methods in simultaneous pancreas-kidney (SPK) transplantation. We analyzed 128 SPKs at our institution between January 2001 and August 2008. Forty-nine patients received basiliximab (40 mg), whereas 79 patients had ATG (5 mg/kg). Graft function, complications, rejection, and survival rates were analyzed. ATG versus basiliximab therapy was associated with decreased 3-month (6% vs. 21%; P=0.01) and 1-year (14% vs. 27%; P=0.049) rejection rate. Steroid-resistant rejections were decreased with ATG (3%) vs. basiliximab (14%) (P=0.01). In a univariate regression analysis, basiliximab induction was a risk factor for rejection (HR, 7.1; CI, 3.8-13). No differences were observed regarding complications and graft function up to 5 years. ATG versus basiliximab therapy resulted in identical 1-year (90% vs. 93%), 3-year (87% vs. 89%), and 5-year (78% vs. 83%) pancreas survival (P=0.7). No difference was observed in kidney survival after 1 year (99% vs. 98%), 3 years (97% vs. 98%), and 5 years (95% vs. 95%) (P=0.4). ATG versus basiliximab induction therapy results in decreased acute cellular rejection in the first year after SPK with similar side effects. Long-term graft function and survival are not affected by induction regimen.

  15. D-cycloserine prevents relational memory deficits and suppression of long-term potentiation induced by scopolamine in the hippocampus.

    Science.gov (United States)

    Portero-Tresserra, Marta; Del Olmo, Nuria; Martí-Nicolovius, Margarita; Guillazo-Blanch, Gemma; Vale-Martínez, Anna

    2014-11-01

    Previous research has demonstrated that systemic D-cycloserine (DCS), a partial agonist of the N-methyl-D-aspartate receptor (NMDAR), enhances memory processes in different learning paradigms and attenuates mnemonic deficits produced by diverse pharmacological manipulations. In the present study two experiments were conducted in rats to investigate whether DCS administered in the hippocampus may rescue relational memory deficits and improve deficient synaptic plasticity, both induced by an intracerebral injection of the muscarinic receptor antagonist scopolamine (SCOP). In experiment 1, we assessed whether DCS would prevent SCOP-induced amnesia in an olfactory learning paradigm requiring the integrity of the cholinergic system, the social transmission of food preference (STFP). The results showed that DCS (10 μg/site) injected into the ventral hippocampus (vHPC) before STFP acquisition compensated the 24-h retention deficit elicited by post-training intra-vHPC SCOP (40 μg/site), although it did not affect memory expression in non-SCOP treated rats. In experiment 2, we evaluated whether the perfusion of DCS in hippocampal slices may potentiate synaptic plasticity in CA1 synapses and thus recover SCOP-induced deficits in long-term potentiation (LTP). We found that DCS (50 µM and 100 µM) was able to rescue SCOP (100 µM)-induced LTP maintenance impairment, in agreement with the behavioral findings. Additionally, DCS alone (50 µM and 100 µM) enhanced field excitatory postsynaptic potentials prior to high frequency stimulation, although it did not significantly potentiate LTP. Our results suggest that positive modulation of the NMDAR, by activation of the glycine-binding site, may compensate relational memory impairments due to hippocampal muscarinic neurotransmission dysfunction possibly through enhancements in LTP maintenance.

  16. The taurine transporter substrate guanidinoethyl sulfonate mimics the action of taurine on long-term synaptic potentiation.

    Science.gov (United States)

    Suárez, Luz M; Muñoz, María-Dolores; González, José C; Bustamante, Julián; Del Río, Rafael Martín; Solís, José M

    2016-11-01

    Taurine is especially abundant in rodent brain where it appears to be involved in osmoregulation and synaptic plasticity mechanisms. The demonstration of a physiological role for taurine has been hampered by the difficulty in modifying taurine levels in most tissues, including the brain. We used an experimental strategy to reduce taurine levels, involving treatment with guanidinoethyl sulfonate (GES), a structural analogue of taurine that, among other properties, acts as a competitive inhibitor of taurine transport. GES delivered in the drinking water of rats for 1 month effectively reduced taurine levels in brain structures (hippocampus, cerebellum and cortex) and outside the brain (heart, muscle, kidney, liver and plasma) by between 50 and 80 %, depending on the tissue. This partial taurine depletion did not affect either basal synaptic transmission or the late phase of long-term potentiation (late-LTP) in hippocampal slices. In vivo microdialysis studies in the hippocampus revealed that GES treatment reduced extracellular taurine levels and the magnitude of taurine released in response to the application of either N-methyl-D-aspartate (NMDA) or a hypoosmotic solution, without affecting release mechanisms. Finally, we demonstrated in hippocampal slices that a brief GES application can mimic taurine action on the conversion of a decremental LTP into a perdurable late-LTP, concluding that GES might replace taurine function in some mechanisms such as those implicated in synaptic plasticity.

  17. Enhanced deficits in long-term potentiation in the adult dentate gyrus with 2nd trimester ethanol consumption.

    Directory of Open Access Journals (Sweden)

    Jennifer L Helfer

    Full Text Available Ethanol exposure during pregnancy can cause structural and functional changes in the brain that can impair cognitive capacity. The hippocampal formation, an area of the brain strongly linked with learning and memory, is particularly vulnerable to the teratogenic effects of ethanol. In the present experiments we sought to determine if the functional effects of developmental ethanol exposure could be linked to ethanol exposure during any single trimester-equivalent. Ethanol exposure during the 1(st or 3(rd trimester-equivalent produced only minor changes in synaptic plasticity in adult offspring. In contrast, ethanol exposure during the 2(nd trimester equivalent resulted in a pronounced decrease in long-term potentiation, indicating that the timing of exposure influences the severity of the deficit. Together, the results from these experiments demonstrate long-lasting alterations in synaptic plasticity as the result of developmental ethanol exposure and dependent on the timing of exposure. Furthermore, these results allude to neural circuit malfunction within the hippocampal formation, perhaps relating to the learning and memory deficits observed in individuals with fetal alcohol spectrum disorders.

  18. Long-term monitoring of airborne nickel (Ni) pollution in association with some potential source processes in the urban environment.

    Science.gov (United States)

    Kim, Ki-Hyun; Shon, Zang-Ho; Mauulida, Puteri T; Song, Sang-Keun

    2014-09-01

    The environmental behavior and pollution status of nickel (Ni) were investigated in seven major cities in Korea over a 13-year time span (1998-2010). The mean concentrations of Ni measured during the whole study period fell within the range of 3.71 (Gwangju: GJ) to 12.6ngm(-3) (Incheon: IC). Although Ni values showed a good comparability in a relatively large spatial scale, its values in most cities (6 out of 7) were subject to moderate reductions over the study period. To assess the effect of major sources on the long-term distribution of Ni, the relationship between their concentrations and the potent source processes like non-road transportation sources (e.g., ship and aircraft emissions) were examined from some cities with port and airport facilities. The potential impact of long-range transport of Asian dust particles in controlling Ni levels was also evaluated. The overall results suggest that the Ni levels were subject to gradual reductions over the study period irrespective of changes in such localized non-road source activities. The pollution of Ni at all the study sites was maintained well below the international threshold (Directive 2004/107/EC) value of 20ngm(-3).

  19. Gender-dependent ATPA-induced changes in long-term potentiation in the rat lateral amygdala.

    Science.gov (United States)

    Schubert, Manja; Drephal, Christian; Albrecht, Doris

    2008-04-01

    There is increasing evidence that kainate receptors contribute to both postsynaptic and presynaptic signaling not only in the hippocampus but also in the amygdala. The present study demonstrates that low concentrations of the specific kainate GLU(K5) receptor agonist, ATPA, depressed baseline activity in the lateral nucleus of the rat amygdala (LA), induced by stimulation of external capsule fibers or by intranuclear stimulation in horizontal brain slices. ATPA reduced high-frequency-induced long-term potentiation (LTP) in males while it enhanced LTP in females during certain phases of the estrus cycle. In untreated slices from females, LA-LTP differed depending on the phase of the estrus cycle. In addition, we show for the first time that the p38 mitogen-activated protein (MAP) kinase inhibitor, SKF 86002, reduced LA-LTP. In males, the effects of ATPA and SKF 86002 were not additive. To the contrary, in females, the exposure to ATPA in control plus SKF 86002 increases LTP relative to control plus SKF 86002 alone. Thus, we demonstrate that the effectiveness of GLU(K5) stimulation on plasticity changes in the amygdala is gender-dependent and that the MAP kinase pathway might be involved in males.

  20. Matrix metalloproteinases regulate the formation of dendritic spine head protrusions during chemically induced long-term potentiation.

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    Zsuzsanna Szepesi

    Full Text Available Dendritic spines are are small membranous protrusions that extend from neuronal dendrites and harbor the majority of excitatory synapses. Increasing evidence has shown that matrix metalloproteinases (MMPs, a family of extracellularly acting and Zn(2+-dependent endopeptidases, are able to rapidly modulate dendritic spine morphology. Spine head protrusions (SHPs are filopodia-like processes that extend from the dendritic spine head, representing a form of postsynaptic structural remodeling in response to altered neuronal activity. Herein, we show that chemically induced long-term potentiation (cLTP in dissociated hippocampal cultures upregulates MMP-9 activity that controls the formation of SHPs. Blocking of MMPs activity or microtubule dynamics abolishes the emergence of SHPs. In addition, autoactive recombinant MMP-9, promotes the formation of SHPs in organotypic hippocampal slices. Furthermore, spines with SHPs gained postsynaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA receptors upon cLTP and the synaptic delivery of AMPA receptors was controlled by MMPs. The present results strongly imply that MMP-9 is functionally involved in the formation of SHPs and the control of postsynaptic receptor distribution upon cLTP.

  1. In-situ strain analysis of potential habitat composites exposed to a simulated long-term lunar radiation exposure

    Science.gov (United States)

    Rojdev, Kristina; O'Rourke, Mary Jane E.; Hill, Charles; Nutt, Steven; Atwell, William

    2013-03-01

    NASA is studying the effects of long-term space radiation on potential multifunctional composite materials for habitats to better determine their characteristics in harsh space environments. Two epoxy-matrix composite materials were selected for the study and were mounted in a test stand that simulated the biaxial stresses of a pressure vessel wall. The samples in the test stand were exposed to radiation at fast (0.1478 krad/s) and slow (0.0139 krad/s) dose rates, and the strain and temperature were recorded during the exposure. During a fast dose rate exposure, negative strain was recorded, decreasing with time, an indication of matrix shrinkage. Given previous radiation studies of polymers, this is expected to be a result of radiation-induced crosslinking in the epoxy matrix. However, with a slow dose rate, the materials exhibited a positive strain that increased with time, corresponding to stretching of the materials. This result is consistent with scission or degradation of the matrix occurring, possibly due to oxidative degradation.

  2. DCP-LA neutralizes mutant amyloid beta peptide-induced impairment of long-term potentiation and spatial learning.

    Science.gov (United States)

    Nagata, Tetsu; Tomiyama, Takami; Tominaga, Takemi; Mori, Hiroshi; Yaguchi, Takahiro; Nishizaki, Tomoyuki

    2010-01-01

    Long-term potentiation (LTP) was monitored from the CA1 region of the intact rat hippocampus by delivering high frequency stimulation (HFS) to the Schaffer collateral commissural pathway. Intraventricular injection with mutant amyloid beta(1-42) peptide lacking glutamate-22 (Abeta(1-42)E22Delta), favoring oligomerization, 10 min prior to HFS, inhibited expression of LTP, with the potency more than wild-type amyloid beta(1-42) peptide. Intraperitoneal injection with the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) 70 min prior to HFS neutralized mutant Abeta(1-42)E22Delta peptide-induced LTP inhibition. In the water maze test, continuous intraventricular injection with mutant Abeta(1-42)E22Delta peptide for 14 days prolonged the acquisition latency as compared with that for control, with the potency similar to wild-type Abeta(1-42) peptide, and intraperitoneal injection with DCP-LA shortened the prolonged latency to control levels. The results of the present study indicate that DCP-LA neutralizes mutant Abeta(1-42)E22Delta peptide-induced impairment of LTP and spatial learning.

  3. Hippocampal NR2B-containing NMDA receptors enhance long-term potentiation in rats with chronic visceral pain.

    Science.gov (United States)

    Chen, Yu; Chen, Ai-qin; Luo, Xiao-qing; Guo, Li-xia; Tang, Ying; Bao, Cheng-jia; Lin, Ling; Lin, Chun

    2014-06-27

    Pain and learning memory have striking similarities in synaptic plasticity. Activation of the N-methyl-D-aspartic acid receptors 2B subunits (NR2B-NMDAs) is responsible for the hippocampal LTP in memory formation. In our previous studies, we found the significant enhancement of CA1 hippocampal long-term potentiation (LTP) induced by high-frequency stimulation (HFS) in rats with chronic visceral pain. However, it is unclear whether the NR2B-NMDAs are required for the LTP in chronic visceral pain. In this study, a rat model with irritable bowel syndrome (IBS) was established by colorectal distention (CRD). The sensitivity of visceral pain and HFS-induced LTP at SC-CA1 synapses were significantly enhanced in IBS-like rats (pvisceral hypersensitivity. In conclusion, hippocampal NR2B-NMDAs are responsible for the facilitation of CA1 LTP via tyrosine phosphorylation, which leads to visceral hypersensitivity. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Dopamine Inhibits High-Frequency Stimulation-Induced Long-Term Potentiation of Intrinsic Excitability in CA1 Hippocampal Pyramidal Neurons

    Directory of Open Access Journals (Sweden)

    Chun-ling Wei

    2012-09-01

    Full Text Available The efficiency of neural circuits is modified by changes not only in synaptic strength, but also in intrinsic excitability of neurons. In CA1 hippocampal pyramidal neurons, bidirectional changes in the intrinsic excitability are often presented after induction of synaptic long-term potentiation or depression. This plasticity of intrinsic excitability has been identified as a cellular correlate of learning. Besides, behavioral learning often involves action of reinforcement or rewarding mediated by dopamine (DA. Here, we examined how DA influences the intrinsic plasticity of CA1 hippocampal pyramidal neurons when high-frequency stimulation (HFS was applied to Schaffer collaterals. The results showed that DA inhibits the decrease in rheobase and increase in mean firing rate of pyramidal neurons induced by HFS, and that this inhibition was abolished by the D1-like receptor antagonist SCH23390 but not by the D2-like receptor antagonist sulpiride. The results suggest that DA inhibits the potentiation of excitability induced by presynaptic HFS, and that this inhibition depends on the activation of D1-like receptors.

  5. A juvenile form of postsynaptic hippocampal long-term potentiation in mice deficient for the AMPA receptor subunit GluR-A.

    Science.gov (United States)

    Jensen, Vidar; Kaiser, Katharina M M; Borchardt, Thilo; Adelmann, Giselind; Rozov, Andrei; Burnashev, Nail; Brix, Christian; Frotscher, Michael; Andersen, Per; Hvalby, Øivind; Sakmann, Bert; Seeburg, Peter H; Sprengel, Rolf

    2003-12-15

    In adult mice, long-term potentiation (LTP) of synaptic transmission at CA3-to-CA1 synapses induced by tetanic stimulation requires L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors containing GluR-A subunits. Here, we report a GluR-A-independent form of LTP, which is comparable in size to LTP in wild-type mice at postnatal day 14 (P14) but diminishes between P14 and P42 in brain slices of GluR-A-deficient mice. The GluR-A-independent form of LTP is sensitive to D(-)-2-amino-5-phosphonopentanoic acid (D-AP5), but lacks short-term potentiation (STP) and can also be observed in the pairing induction protocol. As judged by unaltered paired-pulse facilitation, this LTP form is postsynaptically expressed despite depleted extrasynaptic AMPA receptor pools with reduced levels of GluR-B, which accumulates in somata and synapses of CA1 pyramidal neurons in GluR-A-deficient mice. Our results show that in the developing hippocampus synaptic plasticity can be expressed by AMPA receptors lacking the GluR-A subunit.

  6. Humans with Type-2 Diabetes Show Abnormal Long-Term Potentiation-Like Cortical Plasticity Associated with Verbal Learning Deficits

    Science.gov (United States)

    Fried, Peter J.; Schilberg, Lukas; Brem, Anna-Katharine; Saxena, Sadhvi; Wong, Bonnie; Cypess, Aaron M.; Horton, Edward S.; Pascual-Leone, Alvaro

    2016-01-01

    Background Type-2 diabetes mellitus (T2DM) accelerates cognitive aging and increases risk of Alzheimer’s disease. Rodent models of T2DM show altered synaptic plasticity associated with reduced learning and memory. Humans with T2DM also show cognitive deficits, including reduced learning and memory, but the relationship of these impairments to the efficacy of neuroplastic mechanisms has never been assessed. Objective Our primary objective was to compare mechanisms of cortical plasticity in humans with and without T2DM. Our secondary objective was to relate plasticity measures to standard measures of cognition. Methods A prospective cross-sectional cohort study was conducted on 21 adults with T2DM and 15 demographically-similar non-diabetic controls. Long-term potentiation-like plasticity was assessed in primary motor cortex by comparing the amplitude of motor evoked potentials (MEPs) from single-pulse transcranial magnetic stimulation before and after intermittent theta-burst stimulation (iTBS). Plasticity measures were compared between groups and related to neuropsychological scores. Results In T2DM, iTBS-induced modulation of MEPs was significantly less than controls, even after controlling for potential confounds. Furthermore, in T2DM, modulation of MEPs 10-min post-iTBS was significantly correlated with Rey Auditory Verbal Learning Task (RAVLT) performance. Conclusion Humans with T2DM show abnormal cortico-motor plasticity that is correlated with reduced verbal learning. Since iTBS after-effects and the RAVLT are both NMDA receptor-dependent measures, their relationship in T2DM may reflect brain-wide alterations in the efficacy of NMDA receptors. These findings offer novel mechanistic insights into the brain consequences of T2DM and provide a reliable means to monitor brain health and evaluate the efficacy of clinical interventions. PMID:27636847

  7. Wnt-5a prevents Aβ-induced deficits in long-term potentiation and spatial memory in rats.

    Science.gov (United States)

    Zhang, Gui-Li; Zhang, Jun; Li, Shao-Feng; Lei, Liu; Xie, Hong-Yan; Deng, Fang; Feng, Jia-Chun; Qi, Jin-Shun

    2015-10-01

    Although the neurotoxicity of amyloid β (Aβ) protein in Alzheimer's disease (AD) has been reported widely, the exact molecular mechanism underlying the Aβ-induced synaptic dysfunction and memory impairment remains largely unclear. Growing evidence indicates that wingless-type (Wnt) signaling plays an important role in neuronal development, synapse formation and synaptic plasticity. In the present study, we investigated the neuroprotective action of Wnt-5a against the synaptic damage and memory deficit induced by Aβ25-35 by using in vivo electrophysiological recording and Morris water maze (MWM) test. We found that intracerebroventricular (i.c.v.) injection of Aβ25-35 alone did not affect the baseline field excitatory postsynaptic potentials (fEPSPs) and the paired-pulse facilitation (PPF) in the hippocampal CA1 region of rats, but significantly suppressed high frequency stimulation (HFS) induced long-term potentiation (LTP); pretreatment with Wnt-5a prevented the Aβ25-35-induced suppression of hippocampal LTP in a dose-dependent manner; soluble Frizzled-related protein (sFRP), a specific Wnt antagonist, effectively attenuated the protective effects of Wnt-5a. In MWM test, Aβ25-35 alone significantly disrupted spatial learning and memory ability of rats, while pretreatment with Wnt-5a effectively prevented the impairments induced by Aβ25-35. These results in the present study demonstrated for the first time the neuroprotective effects of Wnt-5a against Aβ-induced in vivo synaptic plasticity impairment and memory disorder, suggesting that Wnt signaling pathway is one of the important targets of Aβ neurotoxicity and Wnt-5a might be used as one of the putative candidates for the therapeutic intervention of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Harmful potential toxic elements in greenhouse soils under long-term cultivation in Almería (Spain)

    Science.gov (United States)

    Joaquin Ramos-Miras, Jose; Rodríguez Martín, Jose Antonio; Boluda, Rafael; Bech, Jaume; Gil, Carlos

    2014-05-01

    Heavy metals (HM) are considered highly significant environmental contaminants and are the object of many scientific research works into the soil environment. Activities like agriculture or industry can increase the concentration of these contaminants in soils and waters, which can affect the food chain. Intensification of certain agricultural practices, constant and excessive use of fertilizers and phytosanitary products, and using machinery, increase the HM content in agricultural soils. Many studies have dealt with HM accumulation over time. Despite these works, the influence of long periods of time on these contents, the dynamics and evolution of these elements in agricultural soils, especially soils used for intensive farming purposes under greenhouse conditions, remain unknown to a certain extent. The western Almería region (Spain) is a very important area from both the socio-economic and agricultural viewpoints. A common practice in greenhouse agriculture is the addition of agrochemicals to soils and crops to improve nutrient supply or crop protection and disease control. Such intense agricultural activity has a strong impact, which may have negative repercussions on both these greenhouse soils and the environment. A research has been carried out to determine the total and available levels of six harmful potentially toxic elements (Cd, Cu, Pb, Ni, Zn and Co), and to assess long-term variations in the greenhouse soils of western Almeria. The results indicate that managing soils in the greenhouse preparation stage determines major changes in total and available HM contents. Furthermore, Cd, Cu and Pb enrichment in soil was observed depending on the element and years of growth.

  9. Preventive effect of theanine intake on stress-induced impairments of hippocamapal long-term potentiation and recognition memory.

    Science.gov (United States)

    Tamano, Haruna; Fukura, Kotaro; Suzuki, Miki; Sakamoto, Kazuhiro; Yokogoshi, Hidehiko; Takeda, Atsushi

    2013-06-01

    Theanine, γ-glutamylethylamide, is one of the major amino acid components in green tea. On the basis of the preventive effect of theanine intake after birth on mild stress-induced attenuation of hippocamapal CA1 long-term potentiation (LTP), the present study evaluated the effect of theanine intake after weaning on stress-induced impairments of LTP and recognition memory. Young rats were fed water containing 0.3% theanine for 3 weeks after weaning and subjected to water immersion stress for 30min, which was more severe than tail suspension stress for 30s used previously. Serum corticosterone levels were lower in theanine-administered rats than in the control rats even after exposure to stress. CA1 LTP induced by a 100-Hz tetanus for 1s was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an N-methyl-d-aspartate (NMDA) receptor antagonist, in hippocampal slices from the control rats and was attenuated by water immersion stress. In contrast, CA1 LTP was not significantly inhibited in the presence of APV in hippocampal slices from theanine-administered rats and was not attenuated by the stress. Furthermore, object recognition memory was impaired in the control rats, but not in theanine-administered rats. The present study indicates the preventive effect of theanine intake after weaning on stress-induced impairments of hippocampal LTP and recognition memory. It is likely that the modification of corticosterone secretion after theanine intake is involved in the preventive effect. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. ErbB4 in parvalbumin-positive interneurons is critical for neuregulin 1 regulation of long-term potentiation.

    Science.gov (United States)

    Chen, Yong-Jun; Zhang, Meng; Yin, Dong-Min; Wen, Lei; Ting, Annie; Wang, Pu; Lu, Yi-Sheng; Zhu, Xin-Hong; Li, Shu-Ji; Wu, Cui-Ying; Wang, Xue-Ming; Lai, Cary; Xiong, Wen-Cheng; Mei, Lin; Gao, Tian-Ming

    2010-12-14

    Neuregulin 1 (NRG1) is a trophic factor that acts by stimulating ErbB receptor tyrosine kinases and has been implicated in neural development and synaptic plasticity. In this study, we investigated mechanisms of its suppression of long-term potentiation (LTP) in the hippocampus. We found that NRG1 did not alter glutamatergic transmission at SC-CA1 synapses but increased the GABA(A) receptor-mediated synaptic currents in CA1 pyramidal cells via a presynaptic mechanism. Inhibition of GABA(A) receptors blocked the suppressing effect of NRG1 on LTP and prevented ecto-ErbB4 from enhancing LTP, implicating a role of GABAergic transmission. To test this hypothesis further, we generated parvalbumin (PV)-Cre;ErbB4(-/-) mice in which ErbB4, an NRG1 receptor in the brain, is ablated specifically in PV-positive interneurons. NRG1 was no longer able to increase inhibitory postsynaptic currents and to suppress LTP in PV-Cre;ErbB4(-/-) hippocampus. Accordingly, contextual fear conditioning, a hippocampus-dependent test, was impaired in PV-Cre;ErbB4(-/-) mice. In contrast, ablation of ErbB4 in pyramidal neurons had no effect on NRG1 regulation of hippocampal LTP or contextual fear conditioning. These results demonstrate a critical role of ErbB4 in PV-positive interneurons but not in pyramidal neurons in synaptic plasticity and support a working model that NRG1 suppresses LTP by enhancing GABA release. Considering that NRG1 and ErbB4 are susceptibility genes of schizophrenia, these observations contribute to a better understanding of how abnormal NRG1/ErbB4 signaling may be involved in the pathogenesis of schizophrenia.

  11. Exposure to Kynurenic Acid during Adolescence Increases Sign-tracking and Impairs Long-term Potentiation in Adulthood

    Directory of Open Access Journals (Sweden)

    Nicole eDeAngeli

    2015-01-01

    Full Text Available Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently there are few treatments for persons with a dual-diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA, a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and α7 nicotinic acetylcholine receptors, both of which are critically involved in neurodevelopment, plasticity, and behavior. In Experiment 1, rats were treated throughout adolescence with l-kynurenine (L-KYN, the precursor of KYNA. As adults, the rats were tested drug-free in an autoshaping procedure in which a lever was paired with food. Rats treated with L-KYN during adolescence exhibited increased sign-tracking behavior (lever pressing when they were tested as adults. Sign-tracking is thought to reflect the lever acquiring incentive salience (motivational value as a result of its pairing with reward. Thus, KYNA exposure may increase the incentive salience of cues associated with reward, perhaps contributing to an increase in sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2, we tested the effects of exposure to KYNA during adolescence on hippocampal long-term potentiation (LTP. Rats treated with L-KYN exhibited no LTP after a burst of high frequency stimulation that was sufficient to produce robust LTP in vehicle-treated rats. This finding represents the first demonstrated consequence of elevated KYNA concentration during development and provides insight into the basis for cognitive and behavioral deficits that result from exposure to KYNA during

  12. Daily acclimation handling does not affect hippocampal long-term potentiation or cause chronic sleep deprivation in mice.

    Science.gov (United States)

    Vecsey, Christopher G; Wimmer, Mathieu E J; Havekes, Robbert; Park, Alan J; Perron, Isaac J; Meerlo, Peter; Abel, Ted

    2013-04-01

    Gentle handling is commonly used to perform brief sleep deprivation in rodents. It was recently reported that daily acclimation handling, which is often used before behavioral assays, causes alterations in sleep, stress, and levels of N-methyl-D-aspartate receptor subunits prior to the actual period of sleep deprivation. It was therefore suggested that acclimation handling could mediate some of the observed effects of subsequent sleep deprivation. Here, we examine whether acclimation handling, performed as in our sleep deprivation studies, alters sleep/wake behavior, stress, or forms of hippocampal synaptic plasticity that are impaired by sleep deprivation. Adult C57BL/6J mice were either handled daily for 6 days or were left undisturbed in their home cages. On the day after the 6(th) day of handling, long-term potentiation (LTP) was induced in hippocampal slices with spaced four-train stimulation, which we previously demonstrated to be impaired by brief sleep deprivation. Basal synaptic properties were also assessed. In three other sets of animals, activity monitoring, polysomnography, and stress hormone measurements were performed during the 6 days of handling. Daily gentle handling alone does not alter LTP, rest/activity patterns, or sleep/wake architecture. Handling initially induces a minimal stress response, but by the 6(th) day, stress hormone levels are unaltered by handling. It is possible to handle mice daily to accustom them to the researcher without causing alterations in sleep, stress, or synaptic plasticity in the hippocampus. Therefore, effects of acclimation handling cannot explain the impairments in signaling mechanisms, synaptic plasticity, and memory that result from brief sleep deprivation.

  13. Health-related quality of life in long-term esophageal cancer survivors after potentially curative treatment

    NARCIS (Netherlands)

    Courrech Staal, E.F.W.; van Sandick, J.W.; van Tinteren, H.; Cats, A.; Aaronson, N.K.

    2010-01-01

    Objective Clinical outcomes have been investigated extensively in studies of esophageal cancer treatment. Less is known about long-term health-related quality of life outcomes. The aim of this study was to assess a range of health-related quality of life outcomes in patients with esophageal cancer t

  14. Congenital Heart Disease With and Without Cyanotic Potential and the Long-term Risk of Diabetes Mellitus

    DEFF Research Database (Denmark)

    Madsen, Nicolas L; Marino, Bradley S; Woo, Jessica G

    2016-01-01

    BACKGROUND: Long-term survival for persons born with congenital heart disease (CHD) is improved, but limited knowledge exists of this growing population's acquired cardiovascular risk profile. This study's purpose was to assess CHD survivors' risk for type 2 diabetes mellitus (T2DM) with attention...

  15. Long-Term Effects of Child Corporal Punishment on Depressive Symptoms in Young Adults: Potential Moderators and Mediators

    Science.gov (United States)

    Turner, Heather A.; Muller, Paul A.

    2004-01-01

    Based on a sample of 649 students from 3 New England colleges, this study examined the long-term effects of childhood corporal punishment on symptoms of depression and considered factors that may moderate or mediate the association. Similar to national studies, approximately 40% of the sample reported experiencing some level of corporal punishment…

  16. An associativity requirement for locus coeruleus-induced long-term potentiation in the dentate gyrus of the urethane-anesthetized rat.

    Science.gov (United States)

    Reid, Andrew T; Harley, Carolyn W

    2010-01-01

    Norepinephrine has been hypothesized to provide a learning and memory signal. Norepinephrine long-term potentiation of perforant path input to the dentate gyrus of the hippocampus provides a model for norepinephrine initiated memory processes. However, in vitro, the pairing of perforant path stimulation and norepinephrine is not required for the occurrence of norepinephrine-dependent long-term potentiation. Since bath application of norepinephrine induces long-term changes in 2nd messenger signalling and differs in a number of ways from physiological norepinephrine release, the present study is an in vivo test of the associative requirement for the pairing of perforant path input with norepinephrine to induce long-term potentiation. Phasic activation of the locus coeruleus is provided by glutamate infusion into the locus coeruleus to initiate transient norepinephrine release in the hippocampus of urethane-anesthetized Sprague-Dawley rats. Perforant path stimulation (0.067 Hz) was given throughout the experiment in the paired condition. In the unpaired condition perforant path stimulation was interrupted 10 min prior to locus coeruleus activation and resumed 10 min after locus coeruleus activation. Locus coeruleus-induced long-term potentiation of both EPSP slope and population spike only occurred in the pairing condition. This result argues that, in vivo, temporal proximity of locus coeruleus-associated norepinephrine release and perforant path stimulation are required to induce long-term plasticity. The associativity requirement for locus coeruleus activation and perforant path stimulation in vivo is consistent with the hypothesis that norepinephrine can initiate circuit changes supporting learning and memory.

  17. Long-term potentiation and memory processes in the psychological works of Sigmund Freud and in the formation of neuropsychiatric symptoms.

    Science.gov (United States)

    Centonze, D; Siracusano, A; Calabresi, P; Bernardi, G

    2005-01-01

    Far from disproving the model of mind functioning proposed by psychoanalysis, the recent advances in neuropsychiatrical research confirmed the crucial ideas of Sigmund Freud. The hypothesis that the origin of mental illnesses lies in the impossibility for a subject to erase the long-term effects of a remote adverse event is in tune with the view that several psychiatric disturbances reflect the activation of aberrant unconscious memory processes. Freud's insights did not stop here, but went on to describe in an extremely precise manner the neural mechanisms of memory formation almost a century before the description of long-term synaptic potentiation.

  18. Potential of the solid-Earth response for limiting long-term West Antarctic Ice Sheet retreat

    Science.gov (United States)

    Konrad, Hannes; Sasgen, Ingo; Pollard, David; Klemann, Volker

    2016-04-01

    for asthenosphere viscosities of 3x10^20 Pa s or higher. References Gomez, N., Pollard, D., Mitrovica, J. X., Huybers, P., & Clark, P. U. (2012). Evolution of a coupled marine ice sheet-sea level model. J. Geophys. Res. 117(F1). Konrad, H., Sasgen, I., Pollard, D. & Klemann, V. (2015). Potential of the solid-Earth response for limiting long-term West Antarctic Ice Sheet retreat in a warming climate. Earth Planet. Sci. Lett. 432, 2015.

  19. Evaluating long-term annual sediment yield estimating potential of GIS interfaced MUSLE model on two micro-watersheds.

    Science.gov (United States)

    Arekhi, Saleh

    2008-01-15

    Use of an event scale MUSLE model for obtaining accurate long-term annual sediment yield estimates from micro-watersheds was evaluated. Such estimates are extremely important for designing appropriate soil/water conserving measures. For easy extraction and inputting of model input parameters, the proposed model was interfaced to an Arc-View/Spatial Analyst geographic information system. Application of this GIS interfaced MUSLE model on two gauged (pine and oak forest) hilly micro-watersheds viz., Salla Rautella (0.47 km2) and Naula (0.42 km2), in Almora district of Uttaranchal, India showed that it could estimate annual sediment yields with absolute mean relative errors ranging between 12-14%. Even long-term average sediment yields for Salla Rautella (observed: 9.58 tons and estimated: 10.92 tons) and Naula: (Observed: 23.89 tons and estimated: 26.61 tons) micro-watersheds could be quite realistically simulated by the proposed model.

  20. Worldwide impact of aerosol’s time scale on the predicted long-term concentrating solar power potential

    Science.gov (United States)

    Ruiz-Arias, Jose A.; Gueymard, Christian A.; Santos-Alamillos, Francisco J.; Pozo-Vázquez, David

    2016-01-01

    Concentrating solar technologies, which are fuelled by the direct normal component of solar irradiance (DNI), are among the most promising solar technologies. Currently, the state-of the-art methods for DNI evaluation use datasets of aerosol optical depth (AOD) with only coarse (typically monthly) temporal resolution. Using daily AOD data from both site-specific observations at ground stations as well as gridded model estimates, a methodology is developed to evaluate how the calculated long-term DNI resource is affected by using AOD data averaged over periods from 1 to 30 days. It is demonstrated here that the use of monthly representations of AOD leads to systematic underestimations of the predicted long-term DNI up to 10% in some areas with high solar resource, which may result in detrimental consequences for the bankability of concentrating solar power projects. Recommendations for the use of either daily or monthly AOD data are provided on a geographical basis. PMID:27507711

  1. INDUCTION OF CHRONIC KIDNEY FAILURE IN A LONG-TERM PERITONEAL EXPOSURE MODEL IN THE RAT: EFFECTS ON FUNCTIONAL AND STRUCTURAL PERITONEAL ALTERATIONS

    NARCIS (Netherlands)

    F. Vrtovsnik; A. Coester; D. Lopes-Barreto; D.R. de Waart; A. van der Wal; D.G. Struijk; R. Krediet; M. Zweers

    2010-01-01

    Background: A long-term peritoneal exposure model has been developed in Wistar rats. Chronic daily exposure to 3.86% glucose based, lactate buffered, conventional dialysis solutions is possible for up to 20 weeks and induces morphological abnormalities similar to those in long-term peritoneal dialys

  2. An associativity requirement for locus coeruleus-induced long-term potentiation in the dentate gyrus of the urethane-anesthetized rat.

    NARCIS (Netherlands)

    Reid, A.T.; Harley, C.W.

    2010-01-01

    Norepinephrine has been hypothesized to provide a learning and memory signal. Norepinephrine long-term potentiation of perforant path input to the dentate gyrus of the hippocampus provides a model for norepinephrine initiated memory processes. However, in vitro, the pairing of perforant path stimula

  3. Assessing Potential Implications of Climate Change for Long-Term Water Resources Planning in the Colorado River Basin, Texas

    Science.gov (United States)

    Munevar, A.; Butler, S.; Anderson, R.; Rippole, J.

    2008-12-01

    exploring climate change projections and methods to assess potential impacts over the project's expected life. Following an initial qualitative risk assessment, quantitative climate scenarios were developed based on multiple coupled atmosphere-ocean general circulation model (AOGCM) simulations under a range of global emission scenarios. Projected temperature and precipitation changes were evaluated from 112 downscaled AOGCM projections. A Four scenarios were selected for detailed hydrologic evaluations using the Variable Infiltration Capacity (VIC) macroscale model. A quantile mapping procedure was applied to map future climatological period change statistics onto the long-term natural climate variability in the observed record. Simulated changes in runoff, river flow, evaporation, and evapotranspiration are used to generate adjustments to historical hydrology for assessment of potential changes to surface water availability, river water quality, riverine habitat, and Bay health. Projected temperature, precipitation, and atmospheric CO2 concentrations are used to estimate changes in agricultural demand. Sea level rise scenarios that include trends in Gulf Coast shelf subsidence are combined with changes in inflows to evaluate increased coastal erosion, upland migration of the estuary, and changes to the salinity regime. Results of the scenario-based analyses are being considered in the development of adaptive management strategies for future operations of the system and the proposed project.

  4. Identifying flood deposits in lake sediments: Changing frequencies and potential links to long-term climate change

    Energy Technology Data Exchange (ETDEWEB)

    Stoeren, Eivind Wilhelm Nagel

    2011-05-15

    ,000 years, including floods that have also been recorded by instrumental and historical data. The minimum number of individual floods recorded for this period is c. 100. On centennial timescales significant change in flood frequency is observed that arguably can be attributed to large-scale climatic changes such as the varying amount of winter precipitation and number of summer rainstorms. The flood frequency was low during the early Holocene (9770-7700 cal. years BP), and was even lower for the period that followed, lasting until 5500 cal. years BP. For the next 2500 years, a modest increase in flood activity followed. This trend was truncated at 2500 cal. years BP by a sudden shift towards increased flooding frequency. With the exception of a short interval around 1000 cal. years BP, when the number of floods was again low, this tendency of increased flood activity prevailed until the present day; including Stor-Ofsen, a large flood that occurred in AD 1789, and also three other historically documented river floods. In Parer III we compared the record from Jotunheimen to a second continuous, high resolution palaeo flood record from Butjoenna (62' N 10' E) and found that both the frequency and distribution of flood events over southern Norway has changed significantly during the Holocene. The present regional-discharge regime is dominated by spring-summer snow melt, and results indicate that the changing flood frequency cannot be explained by local conditions associated with the respective catchment of the two lakes, but rather by long-term variations of solid winter precipitation and related snow melt. Applying available instrumental winter precipitation data and associated sea-level pressure re-analysis data as a modern analogue, we document that atmospheric-circulation anomalies, significantly different from the North Atlantic Oscillation (NAO), have some potential in explaining the variability of the two different palaeo flood records. Centennial

  5. Electric stimulation at sciatic nerve evokes long-term potentiation of cornu dorsale medullae spinalis field potential in rats at various developmental phases

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Long-term potentiation of cornu dorsale medullae spinalis field potential in adult rats has already been reported; however, there is lack of correlated researches on naenonate, infant and adult rats which have different responses to pain conduction information.OBJECTIVE: To observe the various effects of electric stimulation at sciatic nerve on long-term potentiation of evoked field potential at superficial layer of cornu dorsale medullae spinalis of rats at various developmental phases and analyze manifestations of pain conduction information at superficial layers ( Ⅰ - Ⅱ)of cornu dorsale medullae spinalis in immature rats.DESIGN: Grouping controlled study.SETTING: Department of Physiology, Medical College of Wuhan University.MATERIALS: The experiment was carried out in the Laboratory of Physiology (provincial laboratory),Medical College of Wuhan University from March 2006 to May 2007. A total of 27 healthy male Sprague-Dawley (SD) rats, 17- 90 days old, SPF grade, weighing 41 -200 g, were provided by Experimental Animal Center, Medical College of Wuhan University.METHODS: Based on their birthdays, rats were divided into naenonate group (17 - 20 days old, weighing 41-52 g, n =10), infant group (35 - 50 days old, weighing 87 - 125 g, n =10) and adult group (60 - 90 days old, weighing 180 -200 g, n =7). Left sciatic nerve was separated and stimulated with single square wave (15 V, 0.5 ms). Meanwhile, evoked field potential was recorded at superficial layers of lateral T13 - L1 cornu dorsale medullae spinalis and then stimulated with high-frequent and high-intensive tetanizing current (30 -40 V, 0.5 ms, 100 Hz, 1 s per bundle, 10 s in bundle interval) four times. After the operation, onset of long-term potentiation was observed; meanwhile, amplitude changes and latency of field potential were analyzed.MAIN OUTCOME MEASURES: Amplitude and latency changes of field potential at superficial layers of cornu dorsale medullae spinalis of rats in the three

  6. The regulatory T cells induction by epicutaneous immunotherapy is sustained and mediates long-term protection from eosinophilic disorders in peanut-sensitized mice.

    Science.gov (United States)

    Dioszeghy, V; Mondoulet, L; Dhelft, V; Ligouis, M; Puteaux, E; Dupont, C; Benhamou, P-H

    2014-06-01

    Allergen-specific immunotherapy favours immune deviation from a Th2 to a Th1 response and increases the number of regulatory T cells (Tregs). Epicutaneous immunotherapy (EPIT) of sensitized mice decreases the clinical and the allergen-specific Th2 responses and increases local and peripheral Foxp3(+) Tregs. To investigate the role of Tregs in EPIT and characterize their phenotype and maintenance following EPIT. Tregs were investigated using in vivo depletion or adoptive transfer into BALB/c mice. Tregs were depleted using anti-CD25 antibody injection during EPIT, and allergen-specific responses were compared with Sham, EPIT alone and naïve mice. To demonstrate that Tregs can mediate protection by their own, and to study their maintenance following the end of EPIT, CD25(+) CD4(+) Tregs isolated from mice just after or 8 weeks after EPIT were transferred into peanut-sensitized mice. Foxp3-IRES-mRFP mice were transferred with EPIT-induced Tregs to analyse the induction of host Tregs. The anti-CD25 antibody injection to EPIT mice abrogated the induction of Tregs in spleen and the expression of Foxp3 in oesophagus. This resulted in levels of peanut-induced eosinophilic infiltration in oesophagus similar to Sham and significantly higher than EPIT. Whereas the transfer of Tregs from Sham-treated mice demonstrated no effect, the transfer of Tregs isolated just after EPIT prevented peanut-induced eosinophil infiltration and eotaxin expression and induced Foxp3 in oesophagus. The transfer of Tregs isolated 8 weeks after EPIT suppressed allergen-specific responses as efficiently as did Tregs isolated just after EPIT and increased spleen Foxp3(+) CD25(+) CD4(+) cells similarly. The use of reporter mice demonstrated an increase in host Tregs. These results confirm the Tregs-mediated mechanism of EPIT and demonstrate the persistence of efficient Tregs during a long period of time after treatment cessation. This suggests that EPIT induces long-term tolerance in peanut

  7. Potentials, Limitations and Applications of long-term and mobile ad-hoc Wireless Sensor Networks for Environmental Monitoring

    Science.gov (United States)

    Bumberger, Jan; Mollenhauer, Hannes; Lapteva, Yulia; Hutschenreuther, Tino; Toepfer, Hannes; Dietrich, Peter

    2014-05-01

    To characterize environmental systems it is necessary to identify and describe processes with suitable methods. Environmental systems are often characterized by their high heterogeneity, so individual measurements for their complete representation are often not sufficient. The application of wireless sensor networks in terrestrial and aquatic ecosystems offer significant benefits as a better consideration of the local test conditions becomes possible. This can be essential for the monitoring of heterogeneous environmental systems. Significant advantages in the application of mobile ad-hoc wireless sensor networks are their self-organizing behavior, resulting in a major reduction in installation and operation costs and time. In addition, a point measurement with a sensor is significantly improved by measuring at several points. It is also possible to perform analog and digital signal processing and computation on the basis of the measured data close to the sensor. Hence, a significant reduction of the data to be transmitted can be achieved which leads to a better energy management of sensor nodes. Furthermore, their localization via satellite, the miniaturization of the nodes and long-term energy self-sufficiency are current topics under investigation. The possibilities and limitations of the applicability of wireless sensor networks for long-term and mobile environmental monitoring are presented. A concepts and realization example are given in the field of micrometeorology and soil parameters for the interaction of biotic and abiotic processes .This long term monitoring is part of the Global Change Experimental Facility (GCEF), a large field-based experimental platform to assess the effects of climate change on ecosystem functions and processes under different land-use scenarios. Furthermore a mobile ad-hoc sensor network is presented for the monitoring of water induced mass wasting processes.

  8. Acquisition of contextual discrimination involves the appearance of a RAS-GRF1/p38 mitogen-activated protein (MAP) kinase-mediated signaling pathway that promotes long term potentiation (LTP).

    Science.gov (United States)

    Jin, Shan-Xue; Arai, Junko; Tian, Xuejun; Kumar-Singh, Rajendra; Feig, Larry A

    2013-07-26

    RAS-GRF1 is a guanine nucleotide exchange factor with the ability to activate RAS and RAC GTPases in response to elevated calcium levels. We previously showed that beginning at 1 month of age, RAS-GRF1 mediates NMDA-type glutamate receptor (NMDAR)-induction of long term depression in the CA1 region of the hippocampus of mice. Here we show that beginning at 2 months of age, when mice first acquire the ability to discriminate between closely related contexts, RAS-GRF1 begins to contribute to the induction of long term potentiation (LTP) in the CA1 hippocampus by mediating the action of calcium-permeable, AMPA-type glutamate receptors (CP-AMPARs). Surprisingly, LTP induction by CP-AMPARs through RAS-GRF1 occurs via activation of p38 MAP kinase rather than ERK MAP kinase, which has more frequently been linked to LTP. Moreover, contextual discrimination is blocked by knockdown of Ras-Grf1 expression specifically in the CA1 hippocampus, infusion of a p38 MAP kinase inhibitor into the CA1 hippocampus, or the injection of an inhibitor of CP-AMPARs. These findings implicate the CA1 hippocampus in the developmentally dependent capacity to distinguish closely related contexts through the appearance of a novel LTP-supporting signaling pathway.

  9. Predictive Potential of Preoperative Nutritional Status in Long-Term Outcome Projections for Patients with Gastric Cancer.

    Science.gov (United States)

    Sakurai, Katsunobu; Ohira, Masaichi; Tamura, Tatsuro; Toyokawa, Takahiro; Amano, Ryosuke; Kubo, Naoshi; Tanaka, Hiroaki; Muguruma, Kazuya; Yashiro, Masakazu; Maeda, Kiyoshi; Hirakawa, Kosei

    2016-02-01

    Preoperative nutritional status not only correlates with the incidence of postoperative complications but also may be indicative of long-term outcomes for patients with cancer. The impact of preoperative nutritional status on outcomes for patients undergoing gastrectomy for gastric cancer (GC) was investigated. The study reviewed 594 patients treated for GC by gastrectomy at the authors' hospital between January, 2004 and December, 2010. Onodera's prognostic nutritional index (PNI) was invoked, using an optimal cut point to group patients as having high (PNI > 45; n = 449) or low (PNI ≤ 45; n = 145) nutritional status. Clinicopathologic features, perioperative results, and long-term outcomes, including cause of death, were compared. Multivariate analysis of 5-year overall survival (OS) and disease-specific survival (DSS) indicated that low PNI was independently associated with unfavorable outcomes for patients with GC. In subgroup analysis, the 5-year OS and DSS rates for patients with GC at stages 1 and 2 were significantly worse in the low PNI group than in the high PNI group. Although wound and extrasurgical field infections also tended to be more frequent in the low PNI group, postoperative intraabdominal infections did not differ significantly by group. Preoperative PNI may have merit as a gauge of prognosis for patients with GC at stages 1 and 2, but PNI and postoperative morbidity showed no correlation in this setting.

  10. Maternal separation impairs long term-potentiation in CA1-CA3 synapses and hippocampal-dependent memory in old rats.

    Science.gov (United States)

    Sousa, Vasco C; Vital, Joana; Costenla, Ana Rita; Batalha, Vânia L; Sebastião, Ana M; Ribeiro, Joaquim A; Lopes, Luísa V

    2014-07-01

    Exposure to chronic stress during the neonatal period is known to induce permanent long-term changes in the central nervous system and hipothalamic-pituitary-adrenal axis reactivity that are associated with increased levels of depression, anxiety, and cognitive impairments. In rodents, a validated model of early life stress is the maternal separation (MS) paradigm, which has been shown to have long-term consequences for the pups that span to adulthood. We hypothesized that the early life stress-associated effects could be exacerbated with aging, because it is often accompanied by cognitive decline. Using a MS model in which rat pups were separated from their mothers for 3 hours daily, during postnatal days 2-14, we evaluated the long-term functional consequences to aged animals (70-week-old), by measuring synaptic plasticity and cognitive performance. The baseline behavioral deficits of aged control rats were further exacerbated in MS animals, indicating that early-life stress induces sustained changes in anxiety-like behavior and hippocampal-dependent memory that are maintained much later in life. We then investigated whether these differences are linked to impaired function of hippocampal neurons by recording hippocampal long-term potentiation from Schaffer collaterals/CA1 synapses. The magnitude of the hippocampal long-term potentiation induced by high-frequency stimulation was significantly lower in aged MS animals than in age-matched controls. These results substantiate the hypothesis that the neuronal and endocrine alterations induced by early-life stress are long lasting, and are able to exacerbate the mild age-associated deficits. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. The effect of extensive reading and paired-associate learning on long-term vocabulary retention: an event-related potential study.

    Science.gov (United States)

    Chun, Eunjin; Choi, Sungmook; Kim, Junsoo

    2012-07-19

    We investigated the relative efficacy of extensive reading (ER) and paired-associate learning (PAL) in the ability of second language (L2) learners to retain new vocabulary words. To that end, we combined behavioral measures (i.e., vocabulary tests) and an event-related potential (ERP) investigation with a focus on the N400 ERP component to track short- and long-term vocabulary retention as a consequence of the two different approaches. Behavioral results indicated that both ER and PAL led to substantial short-term retention of the target words. In contrast, on a long-term basis, ER was more effective than PAL to a considerable degree as indicated by a large-size effect (d=1.35). Evidence from the N400 effects (d=1.70) observed in the parietal electrode group (P3, Pz, P4) provided further support for the superior effects of ER over PAL on long-term vocabulary retention. The converging evidence challenges the assumptions of some L2 researchers and makes a significant contribution to the literature of vocabulary acquisition, because it provides the first ERP evidence that ER is more conducive to long-term vocabulary retention than PAL.

  12. Effect of chloramine-T on long-term potentiation at synapses between perforant path and dentate gyrus in hippocampus of rats in vivo.

    Science.gov (United States)

    Yang, Jun; Hu, Zhuang-Li; Jiang, Bo; Ni, Lan; Jin, You; Chen, Jian-Guo; Wang, Fang

    2011-03-01

    Reactive oxygen species (ROS), including superoxide, are generally considered as neurotoxic molecules whose effects can be alleviated by antioxidant enzymes. However, ROS also are known to be necessary components of the signal transduction cascades underlying normal synaptic plasticity. The oxidant chloramine-T (Ch-T), a specific oxidant to sulphur-containing residues, can oxidize methionine (Met) residues in proteins to alter protein function. To investigate the effect of Ch-T on the induction of hippocampal long-term potentiation (LTP) in dentate gyrus (DG), in vivo electrophysiological recording was employed. It was found that intracerebroventricular (ICV) injection of 0.1 μM Ch-T in 5 μL enhanced hippocampal LTP of rats slightly, whereas, 20 mM Ch-T in 5 μL greatly attenuated LTP. These effects can be reversed by pretreatment with 0.1 mM dithiothretol (DTT), a special thiol reductant. In addition, 0.1 μM Ch-T elevated LTP-induced increase in phosphorylation of Ca²+/calmodulin (CaM)-dependent protein kinase (CaMKII) and neurogranin (Ng), whereas 2 μM and 20 mM Ch-T reduced LTP-induced increase in phosphorylation status of the two key proteins, especially for 20 mM Ch-T. Pretreatment with DTT significantly prevented these effects. Taken together, these findings demonstrated that Ch-T has concentration-dependent effects on the induction of hippocampal LTP in vivo. In brief, low concentration of Ch-T facilitated hippocampal LTP by enhancing LTP-induced increase in p-CaMKII and p-Ng compared to controls, whereas high concentration of Ch-T obviously attenuated LTP accompanied by a decrease in the phosphorylated proteins, and both of these effects can be prevented by DTT. These results indicate that Ch-T modulates hippocampal LTP through regulating phosphorylation status of CaMKII and Ng. Published by Elsevier B.V.

  13. Evaluation of fracture risk and potential drug holidays for postmenopausal women on long-term bisphosphonate therapy

    Directory of Open Access Journals (Sweden)

    Kostoff MD

    2014-04-01

    Full Text Available Matthew D Kostoff, Joseph J Saseen, Laura M BorgeltDepartments of Clinical Pharmacy and Family Medicine, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences and School of Medicine, Aurora, CO, USAStudy objective: To describe characteristics of postmenopausal women on long-term bisphosphonate therapy who fall into one of four fracture risk categories (low, mild, moderate, high, and to determine the prevalence of women eligible for a drug holiday.Design: Retrospective electronic health record review.Setting: Eight primary care clinics within a university-based health care system.Patients: A total of 201 postmenopausal women of ages 55–89 years, with osteopenia or osteoporosis, prescribed bisphosphonate therapy for >4 years, between October 10, 2002 and September 9, 2012.Main results: The patients' mean age was 71.4 (±8.2 years; their mean body mass index was 25.3 (±5.6 kg/m2; and 73.1% were white. Seventy-four out of 201 patients (36.8% were low-risk; 10/201 (5.0% were mild-risk; 72/201 (35.8% were moderate-risk; and 45/201 (22.4% were high-risk. Eighty-one women (40.3% were eligible for a drug holiday or discontinuation. The estimated drug cost avoided per eligible patient was $574.80. Calcium and/or vitamin D supplementation was documented in 52.7% of women.Conclusion: More than one-third of postmenopausal women taking long-term bisphosphonate therapy had low fracture risk, and over 40% of our patients were eligble for a drug holiday or discontinuation. These data emphasize the need to accurately assess risk and benefit in patients treated with bisphosphonate therapy.Keywords: postmenopausal osteoporosis, bisphosphonates, drug holiday, fracture

  14. Autonomous isolation, long-term culture and differentiation potential of adult salivary gland-derived stem/progenitor cells.

    Science.gov (United States)

    Baek, Hyunjung; Noh, Yoo Hun; Lee, Joo Hee; Yeon, Soo-In; Jeong, Jaemin; Kwon, Heechung

    2014-09-01

    Salivary gland stem/progenitor cells belong to the endodermal lineage and may serve as good candidates to replace their dysfunctional counterparts. The objective of this study was to isolate large numbers of salivary gland tissue-derived stem cells (SGSCs) from adult rats in order to develop a clinically applicable method that does not involve sorting or stem cell induction by duct ligation. We analysed SGSCs isolated from normal rat salivary glands to determine whether they retained the major characteristics of stem cells, self-renewal and multipotency, especially with respect to the various endodermal cell types. SGSCs expressed high levels of integrin α6β1 and c-kit, which are surface markers of SGSCs. In particular, the integrin α6β1(+) /c-kit(+) salivary gland cells maintained the morphology, proliferation activity and multipotency of stem cells for up to 92 passages in 12 months. Furthermore, we analysed the capacity of SGSCs to differentiate into endoderm lineage cell types, such as acinar-like and insulin-secreting cells. When cultured on growth factor reduced matrigel, the morphology of progenitor cells changed to acinar-like structures and these cells expressed the acinar cell-specific marker, α-amylase, and tight junction markers. Moreover, reverse transcription-polymerase chain reaction (RT-PCR) data showed increased expression of pancreatic cell markers, including insulin, Pdx1, pan polypeptide and neurogenin-3, when these cells formed pancreatic clusters in the presence of activin A, exendin-4 and retinoic acid. These data demonstrate that adult salivary stem/progenitor cells may serve as a potential source for cell therapy in salivary gland hypofunction and diabetes.

  15. Brevican-deficient mice display impaired hippocampal CA1 long-term potentiation but show no obvious deficits in learning and memory

    DEFF Research Database (Denmark)

    Brakebusch, Cord; Seidenbecher, Constanze I; Asztely, Fredrik

    2002-01-01

    to be less prominent in mutant than in wild-type mice. Brevican-deficient mice showed significant deficits in the maintenance of hippocampal long-term potentiation (LTP). However, no obvious impairment of excitatory and inhibitory synaptic transmission was found, suggesting a complex cause for the LTP defect....... Detailed behavioral analysis revealed no statistically significant deficits in learning and memory. These data indicate that brevican is not crucial for brain development but has restricted structural and functional roles....

  16. Long-term collections

    CERN Multimedia

    Collectes à long terme

    2007-01-01

    The Committee of the Long Term Collections (CLT) asks for your attention for the following message from a young Peruvian scientist, following the earthquake which devastated part of her country a month ago.

  17. Burn injury during long-term oxygen therapy in Denmark and Sweden: the potential role of smoking

    Directory of Open Access Journals (Sweden)

    Tanash HA

    2017-01-01

    Full Text Available Hanan A Tanash,1 Thomas Ringbaek,2 Fredrik Huss,3,4 Magnus Ekström1 1Department of Respiratory Medicine, Skåne University Hospital, Lund University, Lund, Sweden; 2Respiratory Department, Hvidovre Hospital, Copenhagen, Denmark; 3Department of Surgical Sciences, Plastic Surgery, 4Department of Plastic and Maxillofacial Surgery, Burn Center, Uppsala University Hospital, Uppsala, Sweden Background: Long-term oxygen therapy (LTOT increases life expectancy in patients with COPD and severe hypoxemia. Smoking is the main cause of burn injury during LTOT. Policy regarding smoking while on LTOT varies between countries. In this study, we compare the incidence of burn injury that required contact with a health care specialist, between Sweden (a country with a strict policy regarding smoking while on LTOT and Denmark (a country with less strict smoking policy. Methods: This was a population-based, cohort study of patients initiating LTOT due to any cause in Sweden and Denmark. Data on diagnoses, external causes, and procedures were obtained from the Swedish and Danish National Patient Registers for inpatient and outpatient care. Patients were followed from January 1, 2000, until the first of the following: LTOT withdrawal, death, or study end (December 31, 2009. The primary end point was burn injury during LTOT. Results: A total of 23,741 patients received LTOT in Denmark and 7,754 patients in Sweden. Most patients started LTOT due to COPD, both in Sweden (74% and in Denmark (62%. The rate of burn injury while on LTOT was higher in Denmark than in Sweden; 170 (95% confidence interval [CI], 126–225 vs 85 (95% CI, 44–148 per 100,000 person-years; rate ratio 2.0 (95% CI, 1.0–4.1. The risk remained higher after adjustment for gender, age, and diagnosis in multivariate Cox regression, hazard ratio 1.8 (95% CI, 1.0-3.5. Thirty-day mortality after burn injury was 8% in both countries. Conclusion: Compared to Sweden, the rate of burn injury was twice

  18. [The mathematical modelling of Ca2(+)-dependent postsynaptic processes in the hippocampus (the induction of long-term potentiation and long-term depression)].

    Science.gov (United States)

    Murzina, G B; Sil'kis, I G

    1996-01-01

    The computational model was put forward of calcium-dependent posttetanic processes in the dendritic spine of CA3 hippocampal pyramidal neuron which received excitatory and inhibitory afferents. The system of differential equations enables description and evaluation of changes in protein kinase and protein phosphatase activity induced by changes in postsynaptic Ca2+ ion concentration (Cap2+). It was shown that the synaptic efficacy is determined by the ratio between active protein kinases and active protein phosphatase I. According to the proposed model, increase/decrease in Cap2+ concentration relative to the Cap2+ rise, produced by prior stimulation, results in the increase/decrease in the number of phosphorylated ionotropic receptors and in LTP/LTD synaptic efficacy. It follows form the model calculations that the same mechanisms underlie the LTP, LTD, and depotentiation. Some results of experimental study of the hippocampal and neocortical synaptic plasticity are explained and systematized.

  19. Drivers, trends, and potential impacts of long-term coastal reclamation in China from 1985 to 2010

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Bo; Wu, Wenting; Yang, Zhaoqing; Zhou, Yunxuan

    2016-03-01

    Driven by rapid economic development, population growth, and urbanization, China has experienced severe coastal land reclamation over the last decades, which resulted in significant loss of coastal wetland and wildlife habitat, and degradation of marine ecosystems. This study used advanced remote-sensing techniques to analyze the spatial and temporal distributions of coastal reclamation in China and investigated the relationships between coastal land reclamation and coastal economy, population growth, and urbanization. Analysis of long-term Landsat images time series from 1985 to 2010 in 5-year intervals, in combination with remotely sensed image techniques, indicated a sharp increasing trend of land reclamation after 2005, which accounted for over 35% of China’s total reclamation during the 25-year period since 1985. High-intensity coastal reclamation in China was mainly driven by the booming economy associated with urbanization and industrial development in the coastal region. Analysis indicated that coastal land reclamation is closely correlated with the GDP per capita in China. Study results of Landsat images showed that 754,697 ha of coastal wetlands have been reclaimed across all coastal provinces and metropolises from 1985 to 2010, at an annual rate of 5.9%. Coastal areas within the three major economic zones (Bohai Bay, Yangtze River Delta, and Pearl River Delta) were found to generally have higher reclamation rates. For example, the built-up area in Shanghai, which is located in the Yangtze River Delta, increased more than five times from 1985 to 2010. Approximately 35% of the reclamation occurred in Bohai Bay, in which the CRI between 2005 and 2010 was three times higher than the average CRI over the 25-year period.

  20. Burn injury during long-term oxygen therapy in Denmark and Sweden: the potential role of smoking

    Science.gov (United States)

    Tanash, Hanan A; Ringbaek, Thomas; Huss, Fredrik; Ekström, Magnus

    2017-01-01

    Background Long-term oxygen therapy (LTOT) increases life expectancy in patients with COPD and severe hypoxemia. Smoking is the main cause of burn injury during LTOT. Policy regarding smoking while on LTOT varies between countries. In this study, we compare the incidence of burn injury that required contact with a health care specialist, between Sweden (a country with a strict policy regarding smoking while on LTOT) and Denmark (a country with less strict smoking policy). Methods This was a population-based, cohort study of patients initiating LTOT due to any cause in Sweden and Denmark. Data on diagnoses, external causes, and procedures were obtained from the Swedish and Danish National Patient Registers for inpatient and outpatient care. Patients were followed from January 1, 2000, until the first of the following: LTOT withdrawal, death, or study end (December 31, 2009). The primary end point was burn injury during LTOT. Results A total of 23,741 patients received LTOT in Denmark and 7,754 patients in Sweden. Most patients started LTOT due to COPD, both in Sweden (74%) and in Denmark (62%). The rate of burn injury while on LTOT was higher in Denmark than in Sweden; 170 (95% confidence interval [CI], 126–225) vs 85 (95% CI, 44–148) per 100,000 person-years; rate ratio 2.0 (95% CI, 1.0–4.1). The risk remained higher after adjustment for gender, age, and diagnosis in multivariate Cox regression, hazard ratio 1.8 (95% CI, 1.0−3.5). Thirty-day mortality after burn injury was 8% in both countries. Conclusion Compared to Sweden, the rate of burn injury was twice as high in Denmark where smoking is not a contraindication for prescribing LTOT. PMID:28123292

  1. Long-term durability of nevirapine-based ART in a cohort of 82 patients after induction with protease inhibitor treatment

    Directory of Open Access Journals (Sweden)

    J Rump

    2012-11-01

    . Conclusions: Long-term durability of nevirapine containing ART regimens following an induction phase with PIs is very high. No risk of treatment failure by resistance mutations was seen in a follow up of more than 48 months. Liver toxicity was not seen when ART was changed to nevirapine neither in female nor in male patients. The study was supported by Boehringer Ingelheim Pharma GmbH.

  2. Encapsulated living choroid plexus cells: potential long-term treatments for central nervous system disease and trauma

    Science.gov (United States)

    Skinner, S. J. M.; Geaney, M. S.; Lin, H.; Muzina, M.; Anal, A. K.; Elliott, R. B.; Tan, P. L. J.

    2009-12-01

    . Previously reported evidence demonstrated that CP cells support the survival and differentiation of neuronal cells in vitro and effectively treat acute brain injury and disease in rodents and non-human primates in vivo. The accumulated preclinical data together with the long-term survival of implanted encapsulated cells in vivo provide a sound base for the investigation of these treatments for chronic inherited and established neurodegenerative conditions.

  3. The effects of prolonged administration of norepinephrine reuptake inhibitors on long-term potentiation in dentate gyrus, and on tests of spatial and object recognition memory in rats.

    Science.gov (United States)

    Walling, Susan G; Milway, J Stephen; Ingram, Matthew; Lau, Catherine; Morrison, Gillian; Martin, Gerard M

    2016-02-01

    Phasic norepinephrine (NE) release events are involved in arousal, novelty detection and in plasticity processes underlying learning and memory in mammalian systems. Although the effects of phasic NE release events on plasticity and memory are prevalently documented, it is less understood what effects chronic NE reuptake inhibition and sustained increases in noradrenergic tone, might have on plasticity and cognitive processes in rodent models of learning and memory. This study investigates the effects of chronic NE reuptake inhibition on hippocampal plasticity and memory in rats. Rats were administered NE reuptake inhibitors (NRIs) desipramine (DMI; 0, 3, or 7.5mg/kg/day) or nortriptyline (NTP; 0, 10 or 20mg/kg/day) in drinking water. Long-term potentiation (LTP; 200 Hz) of the perforant path-dentate gyrus evoked potential was examined in urethane anesthetized rats after 30-32 days of DMI treatment. Short- (4-h) and long-term (24-h) spatial memory was tested in separate rats administered 0 or 7.5mg/kg/day DMI (25-30 days) using a two-trial spatial memory test. Additionally, the effects of chronically administered DMI and NTP were tested in rats using a two-trial, Object Recognition Test (ORT) at 2- and 24-h after 45 and 60 days of drug administration. Rats administered 3 or 7.5mg/kg/day DMI had attenuated LTP of the EPSP slope but not the population spike at the perforant path-dentate gyrus synapse. Short- and long-term memory for objects is differentially disrupted in rats after prolonged administration of DMI and NTP. Rats that were administered 7.5mg/kg/day DMI showed decreased memory for a two-trial spatial task when tested at 4-h. In the novel ORT, rats receiving 0 or 7.5mg/kg/day DMI showed a preference for the arm containing a Novel object when tested at both 2- and 24-h demonstrating both short- and long-term memory retention of the Familiar object. Rats that received either dose of NTP or 3mg/kg/day DMI showed impaired memory at 2-h, however this

  4. Long-Term Collections

    CERN Multimedia

    Comité des collectes à long terme

    2011-01-01

    It is the time of the year when our fireman colleagues go around the laboratory for their traditional calendars sale. A part of the money of the sales will be donated in favour of the long-term collections. We hope that you will welcome them warmly.

  5. In vivo sodium salicylate causes tolerance to acute morphine exposure and alters the ability of high frequency stimulation to induce long-term potentiation in hippocampus area CA1.

    Science.gov (United States)

    Hosseinmardi, Narges; Azimi, Lila; Fathollahi, Yaghoub; Javan, Mohammad; Naghdi, Naser

    2011-11-30

    Effects of morphine on synaptic transmission and plasticity in the hippocampus area CA1 following in vivo sodium salicylate and the potential molecular mechanism were investigated. Population spikes (PS) were recorded from stratum pylamidale of area CA1 following stimulation of Schaffer collaterals in slices taken from control and sodium salicylate injected rats. To induce long term potentiation (LTP), a 100Hz tetanic stimulation was used. Acute in vitro morphine increased baseline PS amplitude in control slices but not in slices taken from sodium salicylate treated rats. In vivo chronic salicylate did slightly decrease and/or destabilize LTP of CA1 synaptic transmission. We also found that mRNA of NR2A subunit of NMDA receptor was reduced in the hippocampus of sodium salicylate treated rats as compared to control ones. Following LTP induction, the mRNA of NR2A and PP1 (protein phosphatase 1) in slices taken from salicylate-treated rats were more than those of control ones. After long-term exposure to in vitro morphine, high frequency stimulation (HFS) decreased NR2A mRNA level significantly in sodium salicylate treated slices. It is concluded that in vivo sodium salicylate causes tolerance to excitatory effect of morphine and changes the ability of HFS to induce PS LTP in the hippocampus area CA1 in vitro. These changes in synaptic response may be due to alterations in NR2A and PP1 expression.

  6. Effect of Prenatal Protein Malnutrition on Long-Term Potentiation and BDNF Protein Expression in the Rat Entorhinal Cortex after Neocortical and Hippocampal Tetanization

    OpenAIRE

    Alejandro Hernández; Héctor Burgos; Mauricio Mondaca; Rafael Barra; Héctor Núñez; Hernán Pérez; Rubén Soto-Moyano; Walter Sierralta; Victor Fernández; Ricardo Olivares; Luis Valladares

    2008-01-01

    Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP) of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC) in the adult progeny. Unlike normal eutrophic controls, 55–60-day-old prenatally malnourished rats were unabl...

  7. Low-fat, high-carbohydrate parenteral nutrition (PN) may potentially reverse liver disease in long-term PN-dependent infants

    DEFF Research Database (Denmark)

    Jakobsen, Marianne Skytte; Jørgensen, Marianne Hørby; Husby, Steffen

    2015-01-01

    , which prevents and reverses PNAC in adults, could do the same in infants. This regimen could potentially avoid the problem of diminished energy input after removing nutritional lipids. METHODS: Infants developing PNAC over a 2-year period were started on a low-fat PN regimen with calories primarily from......INTRODUCTION: Parenteral nutrition-associated cholestasis (PNAC) is a complication of long-term parenteral nutrition (PN). Removal of lipids may reverse PNAC but compromises the energy to ensure infant growth. The purpose of this study was to test whether a low-fat, high-carbohydrate PN regimen...

  8. Active Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII Regulates NMDA Receptor Mediated Postischemic Long-Term Potentiation (i-LTP by Promoting the Interaction between CaMKII and NMDA Receptors in Ischemia

    Directory of Open Access Journals (Sweden)

    Ning Wang

    2014-01-01

    Full Text Available Active calcium/calmodulin-dependent protein kinase II (CaMKII has been reported to take a critical role in the induction of long-term potentiation (LTP. Changes in CaMKII activity were detected in various ischemia models. It is tempting to know whether and how CaMKII takes a role in NMDA receptor (NMDAR-mediated postischemic long-term potentiation (NMDA i-LTP. Here, we monitored changes in NMDAR-mediated field excitatory postsynaptic potentials (NMDA fEPSPs at different time points following ischemia onset in vitro oxygen and glucose deprivation (OGD ischemia model. We found that 10 min OGD treatment induced significant i-LTP in NMDA fEPSPs, whereas shorter (3 min or longer (25 min OGD treatment failed to induce prominent NMDA i-LTP. CaMKII activity or CaMKII autophosphorylation displays a similar bifurcated trend at different time points following onset of ischemia both in vitro OGD or in vivo photothrombotic lesion (PT models, suggesting a correlation of increased CaMKII activity or CaMKII autophosphorylation with NMDA i-LTP. Disturbing the association between CaMKII and GluN2B subunit of NMDARs with short cell-permeable peptides Tat-GluN2B reversed NMDA i-LTP induced by OGD treatment. The results provide support to a notion that increased interaction between NMDAR and CaMKII following ischemia-induced increased CaMKII activity and autophosphorylation is essential for induction of NMDA i-LTP.

  9. Long-Term Acid-Generating and Metal Leaching Potential of a Sub-Arctic Oil Shale

    Directory of Open Access Journals (Sweden)

    Kathryn A. Mumford

    2014-04-01

    Full Text Available Shales are increasingly being exploited for oil and unconventional gas. Exploitation of sub-arctic oil shales requires the creation of gravel pads to elevate workings above the heaving effects of ground ice. These gravel pads can potentially generate acidic leachate, which can enhance the mobility of metals from the shale. To examine this potential, pyrite-bearing shale originating from sub-Arctic gravel pad sites were subjected to leaching tests for 600 days at initial pH values ranging from 2 to 5, to simulate potential real world conditions. At set times over the 600 day experiment, pH, oxidation reduction potential (ORP, dissolved oxygen and temperature were recorded and small liquid samples withdrawn and analysed for elemental concentrations using total reflection X-ray fluorescence spectrometry (TRXRF. Six of eight shale samples were found to be acid generating, with pH declining and ORP becoming increasingly positive after 100 days. Two of the eight shale samples produced increasingly alkaline leachate conditions with relatively low ORP after 100 days, indicating an inbuilt buffering capacity. By 600 days the buffering capacity of all samples had been consumed and all leachate samples were acidic. TRXRF analyses demonstrated significant potential for the leaching of S, Fe, Ni, Cu, Zn and Mn with greatest concentrations found in reaction vessels with most acidic pH and highest ORP.

  10. Virtual Models of Long-Term Care

    Science.gov (United States)

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

    Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

  11. Long-term effects of cropping system on N2O emission potential

    DEFF Research Database (Denmark)

    Petersen, Søren O.; Ambus, Per; Elsgaard, Lars;

    2013-01-01

    systems, it showed higher N2O evolution at all three matric potentials. Estimates of relative gas diffusivity (DP/D0) in soil from the four cropping systems indicated that C input affected soil aeration. Soil from the two cropping systems with highest C input showed N2O evolution at DP/D0 in excess of 0...

  12. Induction of long-term oscillations in the γ frequency band by nAChR activation in rat hippocampal CA3 area.

    Science.gov (United States)

    Zhang, X; Ge, X Y; Wang, J G; Wang, Y L; Wang, Y; Yu, Y; Li, P P; Lu, C B

    2015-08-20

    The hippocampal neuronal network oscillation at γ frequency band (γ oscillation) is generated by the precise interaction between interneurons and principle cells. γ oscillation is associated with attention, learning and memory and is impaired in the diseased conditions such as Alzheimer's disease (AD) and schizophrenia. Nicotinic acetylcholine receptor (nAChR) plays an important role in the regulation of hippocampal neurotransmission and network activity. It is not known whether nicotine modulates plasticity of network activity at γ oscillations in the hippocampus. In this study we investigated the effects of nicotine on the long-term changes of KA-induced γ oscillations. We found that hippocampal γ oscillations can be enhanced by a low concentration of nicotine (1μM), such an enhancement lasts for hours after washing out of nicotine, suggesting a form of synaptic plasticity, named as long-term oscillation at γ frequency band (LTOγ). Nicotine-induced LTOγ was mimicked by the selective α4β2 but not by α7 nAChR agonist and was involved in N-methyl-d-aspartate (NMDA) receptor activation as well as depended on excitatory and inhibitory neurotransmission. Our results indicate that nAChR activation induced plasticity in γ oscillation, which may be beneficial for the improvement of cognitive deficiency in AD and schizophrenia.

  13. Long-term Trend of Cold Air Mass Amount below a Designated Potential Temperature in Northern and Southern Hemisphere Winters with 7 Different Reanalysis Datasets

    Science.gov (United States)

    Kanno, Y.; Abdillah, M. R.; Iwasaki, T.

    2015-12-01

    This study addresses that the hemispheric total cold air mass amount defined below a threshold potential temperature of 280 K is a good indicator of the long-term trend of climate change in the polar region. We demonstrate quantitative analyses of warming trend in the Northern Hemisphere (NH) and Southern Hemisphere (SH) winters, using 7 different reanalysis datasets (JRA-55, JRA-55C, JRA-55AMIP, ERA-interim, CFSR, JRA-25, NCEP-NCAR). Hemispheric total cold air mass amount in the NH winter exhibit a statistically significant decreasing trend in all reanalysis datasets at a rate about -1.37 to -0.77% per decade over the period 1959-2012 and at a rate about -1.57 to -0.82% per decade over 1980-2012. There is no statistically significant trend in the equatorward cold air mass flux across latitude of 45N, which is an indicator for hemispheric-scale cold air outbreak, over the period 1980-2012 except for NCEP-NCAR reanalysis dataset which shows substantial decreasing trend of about -3.28% per decade. The spatial distribution of the long-term trend of cold air mass amount in the NH winter is almost consistent among reanalysis datasets except for JRA-55AMIP over the period 1980-2012. Cold air mass amount increases over Central Siberia, Kamchatka peninsula, and Bering Sea, while it decreases over Norwegian Sea, Barents Sea, Kara Sea, Greenland, Canada, Northern part of United States, and East Asia. In the SH winter, on the other hand, there is a large discrepancy in hemispheric total cold air mass amount and equatorward cold air mass flux across latitude of 50S over the period 1980-2010 among reanalysis datasets. This result indicate that there is a large uncertainty in the long-term trend of cold air mass amount in the SH winter.

  14. FXR1P Limits Long-Term Memory, Long-Lasting Synaptic Potentiation, and De Novo GluA2 Translation

    Directory of Open Access Journals (Sweden)

    Denise Cook

    2014-11-01

    Full Text Available Translational control of mRNAs allows for rapid and selective changes in synaptic protein expression that are required for long-lasting plasticity and memory formation in the brain. Fragile X Related Protein 1 (FXR1P is an RNA-binding protein that controls mRNA translation in nonneuronal cells and colocalizes with translational machinery in neurons. However, its neuronal mRNA targets and role in the brain are unknown. Here, we demonstrate that removal of FXR1P from the forebrain of postnatal mice selectively enhances long-term storage of spatial memories, hippocampal late-phase long-term potentiation (L-LTP, and de novo GluA2 synthesis. Furthermore, FXR1P binds specifically to the 5′ UTR of GluA2 mRNA to repress translation and limit the amount of GluA2 that is incorporated at potentiated synapses. This study uncovers a mechanism for regulating long-lasting synaptic plasticity and spatial memory formation and reveals an unexpected divergent role of FXR1P among Fragile X proteins in brain plasticity.

  15. Leptin attenuates the detrimental effects of β-amyloid on spatial memory and hippocampal later-phase long term potentiation in rats.

    Science.gov (United States)

    Tong, Jia-Qing; Zhang, Jun; Hao, Ming; Yang, Ju; Han, Yu-Fei; Liu, Xiao-Jie; Shi, Hui; Wu, Mei-Na; Liu, Qing-Song; Qi, Jin-Shun

    2015-07-01

    β-Amyloid (Aβ) is the main component of amyloid plaques developed in the brain of patients with Alzheimer's disease (AD). The increasing burden of Aβ in the cortex and hippocampus is closely correlated with memory loss and cognition deficits in AD. Recently, leptin, a 16kD peptide derived mainly from white adipocyte tissue, has been appreciated for its neuroprotective function, although less is known about the effects of leptin on spatial memory and synaptic plasticity. The present study investigated the neuroprotective effects of leptin against Aβ-induced deficits in spatial memory and in vivo hippocampal late-phase long-term potentiation (L-LTP) in rats. Y maze spontaneous alternation was used to assess short term working memory, and the Morris water maze task was used to assess long term reference memory. Hippocampal field potential recordings were performed to observe changes in L-LTP. We found that chronically intracerebroventricular injection of leptin (1μg) effectively alleviated Aβ1-42 (20μg)-induced spatial memory impairments of Y maze spontaneous alternation and Morris water maze. In addition, chronic administration of leptin also reversed Aβ1-42-induced suppression of in vivo hippocampal L-LTP in rats. Together, these results suggest that chronic leptin treatments reversed Aβ-induced deficits in learning and memory and the maintenance of L-LTP. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Acutely applied MDMA enhances long-term potentiation in rat hippocampus involving D1/D5 and 5-HT2 receptors through a polysynaptic mechanism.

    Science.gov (United States)

    Rozas, C; Loyola, S; Ugarte, G; Zeise, M L; Reyes-Parada, M; Pancetti, F; Rojas, P; Morales, B

    2012-08-01

    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a drug of abuse that induces learning and memory deficit. However, there are no experimental data that correlate the behavioral evidence with models of synaptic plasticity such as long-term potentiation (LTP) or long-term depression (LTD). Using field potential recordings in rat hippocampal slices of young rats, we found that acute application of MDMA enhances LTP in CA3-CA1 synapses without affecting LTD. Using specific antagonists and paired-pulse facilitation protocols we observed that the MDMA-dependent increase of LTP involves presynaptic 5-HT₂ serotonin receptors and postsynaptic D1/D5 dopamine receptors. In addition, the inhibition of PKA suppresses the MDMA-dependent increase in LTP, suggesting that dopamine receptor agonism activates cAMP-dependent intracellular pathways. We propose that MDMA exerts its LTP-altering effect involving a polysynaptic interaction between serotonergic and dopaminergic systems in hippocampal synapses. Our results are compatible with the view that the alterations in hippocampal LTP could be responsible for MDMA-dependent cognitive deficits observed in humans and animals.

  17. Long-Term Fructose Intake Increases Adipogenic Potential: Evidence of Direct Effects of Fructose on Adipocyte Precursor Cells

    Directory of Open Access Journals (Sweden)

    María Guillermina Zubiría

    2016-04-01

    Full Text Available We have previously addressed that fructose rich diet (FRD intake for three weeks increases the adipogenic potential of stromal vascular fraction cells from the retroperitoneal adipose tissue (RPAT. We have now evaluated the effect of prolonged FRD intake (eight weeks on metabolic parameters, number of adipocyte precursor cells (APCs and in vitro adipogenic potential from control (CTR and FRD adult male rats. Additionally, we have examined the direct fructose effects on the adipogenic capacity of normal APCs. FRD fed rats had increased plasma levels of insulin, triglyceride and leptin, and RPAT mass and adipocyte size. FACS studies showed higher APCs number and adipogenic potential in FRD RPAT pads; data is supported by high mRNA levels of competency markers: PPARγ2 and Zfp423. Complementary in vitro experiments indicate that fructose-exposed normal APCs displayed an overall increased adipogenic capacity. We conclude that the RPAT mass expansion observed in eight week-FRD fed rats depends on combined accelerated adipogenesis and adipocyte hypertrophy, partially due to a direct effect of fructose on APCs.

  18. Long Term Sugarcane Crop Residue Retention Offers Limited Potential to Reduce Nitrogen Fertilizer Rates in Australian Wet Tropical Environments.

    Science.gov (United States)

    Meier, Elizabeth A; Thorburn, Peter J

    2016-01-01

    The warming of world climate systems is driving interest in the mitigation of greenhouse gas (GHG) emissions. In the agricultural sector, practices that mitigate GHG emissions include those that (1) reduce emissions [e.g., those that reduce nitrous oxide (N2O) emissions by avoiding excess nitrogen (N) fertilizer application], and (2) increase soil organic carbon (SOC) stocks (e.g., by retaining instead of burning crop residues). Sugarcane is a globally important crop that can have substantial inputs of N fertilizer and which produces large amounts of crop residues ('trash'). Management of N fertilizer and trash affects soil carbon and nitrogen cycling, and hence GHG emissions. Trash has historically been burned at harvest, but increasingly is being retained on the soil surface as a 'trash blanket' in many countries. The potential for trash retention to alter N fertilizer requirements and sequester SOC was investigated in this study. The APSIM model was calibrated with data from field and laboratory studies of trash decomposition in the wet tropics of northern Australia. APSIM was then validated against four independent data sets, before simulating location × soil × fertilizer × trash management scenarios. Soil carbon increased in trash blanketed soils relative to SOC in soils with burnt trash. However, further increases in SOC for the study region may be limited because the SOC in trash blanketed soils could be approaching equilibrium; future GHG mitigation efforts in this region should therefore focus on N fertilizer management. Simulated N fertilizer rates were able to be reduced from conventional rates regardless of trash management, because of low yield potential in the wet tropics. For crops subjected to continuous trash blanketing, there was substantial immobilization of N in decomposing trash so conventional N fertilizer rates were required for up to 24 years after trash blanketing commenced. After this period, there was potential to reduce N fertilizer

  19. Premature loss of primary anterior teeth due to trauma--potential short- and long-term sequelae.

    Science.gov (United States)

    Holan, Gideon; Needleman, Howard L

    2014-04-01

    Traumatic dental injuries (TDIs) can result in the premature loss of primary anterior teeth due to an immediate avulsion, extraction later after the injury because of poor prognosis or late complications, or early exfoliation. There are a number of potential considerations or sequelae as a result of this premature loss that have been cited in the dental literature, which include esthetics, quality of life, eating, speech development, arch integrity (space loss), development and eruption of the permanent successors, and development of oral habits. This article provides a comprehensive review of the dental literature on the possible consequences of premature loss of maxillary primary incisors following TDI.

  20. Japan's long-term energy outlook to 2050: Estimation for the potential of massive CO2 mitigation

    Energy Technology Data Exchange (ETDEWEB)

    Komiyama, Ryoichi

    2010-09-15

    This paper analyzes Japan's energy outlook and CO2 emissions to 2050. Scenario analysis reveals that Japan's CO2 emissions in 2050 could be potentially reduced by 58% from the emissions in 2005. For achieving this massive mitigation, it is required to reduce primary energy supply per GDP by 60% in 2050 from the 2005 level and to expand the share of non-fossil fuel in total supply to 50% by 2050. Concerning power generation mix, nuclear will account for 60%, renewable for 30% in 2050. For massive CO2 abatement, Japan should tackle technological and economic challenges for large-scale deployment of advanced technologies.

  1. Long-Term Waste Package Degradation Studies at the Yucca Mountain Potential High-Level Nuclear Waste Repository

    Energy Technology Data Exchange (ETDEWEB)

    Mon, K. G.; Bullard, B. E.; Longsine, D. E.; Mehta, S.; Lee, J. H.; Monib, A. M.

    2002-02-26

    The Site Recommendation (SR) process for the potential repository for spent nuclear fuel (SNF) and high-level nuclear waste (HLW) at Yucca Mountain, Nevada is underway. Fulfillment of the requirements for substantially complete containment of the radioactive waste emplaced in the potential repository and subsequent slow release of radionuclides from the Engineered Barrier System (EBS) into the geosphere will rely on a robust waste container design, among other EBS components. Part of the SR process involves sensitivity studies aimed at elucidating which model parameters contribute most to the drip shield and waste package degradation characteristics. The model parameters identified included (a) general corrosion rate model parameters (temperature-dependence and uncertainty treatment), and (b) stress corrosion cracking (SCC) model parameters (uncertainty treatment of stress and stress intensity factor profiles in the Alloy 22 waste package outer barrier closure weld regions, the SCC initiation stress threshold, and the fraction of manufacturing flaws oriented favorably for through-wall penetration by SCC). These model parameters were reevaluated and new distributions were generated. Also, early waste package failures due to improper heat treatment were added to the waste package degradation model. The results of these investigations indicate that the waste package failure profiles are governed by the manufacturing flaw orientation model parameters and models used.

  2. Long-term use of biosolids as organic fertilizers in agricultural soils: potentially toxic elements occurrence and mobility.

    Science.gov (United States)

    Marguí, E; Iglesias, M; Camps, F; Sala, L; Hidalgo, M

    2016-03-01

    The presence of potentially toxic elements (PTEs) may hinder a more widespread application of biosolids in agriculture. At present, the European Directive 86/278/CEE limit the total concentrations of seven metals (Cu, Cr, Ni, Pb, Zn, Cd and Hg) in agricultural soils and in sewage sludges used as fertilizers but it has not taken into consideration the potential impacts of other emerging micropollutants that may be present in the biosolids as well as their mobility. The aim of this study was to evaluate the accumulation and mobility of 13 elements (including regulated metals and other inorganic species) in agricultural soils repeatedly amended with biosolids for 15 years. Firstly, three digestions programs using different acid mixtures were tested to evaluate the most accurate and efficient method for analysis of soil and sludge. Results demonstrated that sewage sludge application increased concentrations of Pb and Hg in soil, but values did not exceed the quality standard established by legislation. In addition, other elements (As, Co, Sb, Ag, Se and Mn) that at present are not regulated by the Spanish and European directives were identified in the sewage sludge, and significant differences were found between Ag content in soils amended with biosolids in comparison with control soils. This fact can be related to the increasing use of silver nanoparticles in consumer products due to their antibacterial properties. Results from the leaching tests show up that, in general, the mobility degree for both regulated and non-regulated elements in soils amended with biosolids was quite low (<10 %).

  3. A greener Greenland? Climatic potential and long-term constraints on future expansions of trees and shrubs.

    Science.gov (United States)

    Normand, Signe; Randin, Christophe; Ohlemüller, Ralf; Bay, Christian; Høye, Toke T; Kjær, Erik D; Körner, Christian; Lischke, Heike; Maiorano, Luigi; Paulsen, Jens; Pearman, Peter B; Psomas, Achilleas; Treier, Urs A; Zimmermann, Niklaus E; Svenning, Jens-Christian

    2013-08-19

    Warming-induced expansion of trees and shrubs into tundra vegetation will strongly impact Arctic ecosystems. Today, a small subset of the boreal woody flora found during certain Plio-Pleistocene warm periods inhabits Greenland. Whether the twenty-first century warming will induce a re-colonization of a rich woody flora depends on the roles of climate and migration limitations in shaping species ranges. Using potential treeline and climatic niche modelling, we project shifts in areas climatically suitable for tree growth and 56 Greenlandic, North American and European tree and shrub species from the Last Glacial Maximum through the present and into the future. In combination with observed tree plantings, our modelling highlights that a majority of the non-native species find climatically suitable conditions in certain parts of Greenland today, even in areas harbouring no native trees. Analyses of analogous climates indicate that these conditions are widespread outside Greenland, thus increasing the likelihood of woody invasions. Nonetheless, we find a substantial migration lag for Greenland's current and future woody flora. In conclusion, the projected climatic scope for future expansions is strongly limited by dispersal, soil development and other disequilibrium dynamics, with plantings and unintentional seed dispersal by humans having potentially large impacts on spread rates.

  4. [Biographical work in inpatient long-term care for people with dementia: potential of the DEMIAN nursing concept].

    Science.gov (United States)

    Berendonk, C; Stanek, S; Schönit, M; Kaspar, R; Bär, M; Kruse, A

    2011-02-01

    In nursing care for people with dementia, biographical work is a popular concept. In the literature and practice, many different viewpoints of the way biographical work can/should be promoted exist. In the DEMIAN concept, a nursing concept to promote emotional well-being for people with dementia, it is also of major significance. This article gives an overview of the importance of biographical work in caring for people with dementia. In particular, the role and arrangement of biographical work in the DEMIAN concept are described. Within the anamnesis of the DEMIAN concept, meaningful themes are identified in conversations with different participants (person with dementia, reference persons, and care workers) and through observations. From these findings, specific interventions, aimed at supporting emotional well-being of people with dementia, are derived and integrated into everyday nursing care to promote emotional well-being. The potential of the DEMIAN nursing concept are discussed and further possibilities are highlighted.

  5. Preliminary Assessment of Potential Habitat Composites' Durability when Exposed to a Long-Term Radiation Environment and Micrometeoroid Impacts

    Science.gov (United States)

    Rojdev, Kristina; Graves, Russell; Golden, John; Atwell, William; O'Rouke, Mary Jane; Hill, Charles; Alred, John

    2011-01-01

    NASA's exploration goals include extending human presence beyond low earth orbit (LEO). As a result, habitation for crew is a critical requirement for meeting this goal. However, habitats are very large structures that contain a multitude of subsystems to sustain human life over long-durations in space, and one of the key challenges has been keeping weight to a minimum in order to reduce costs. Thus, light-weight and multifunctional structural materials are of great interest for habitation. NASA has started studying polymeric composite materials as potential lightweight and multifunctional structural materials for use in long-duration spaceflight. However, little is known about the survivability of these materials when exposed to the space environment outside of LEO for long durations. Thus, a study has been undertaken to investigate the durability of composite materials when exposed to long-duration radiation. Furthermore, as an addition to the primary study, a secondary preliminary investigation has been started on the micrometeoroid and orbital debris (MMOD) susceptibility of these materials after radiation exposure. The combined effects of radiation and MMOD impacts are the focus of this paper.

  6. Long-term implications of sustained wind power growth in the United States: Potential benefits and secondary impacts

    Energy Technology Data Exchange (ETDEWEB)

    Wiser, Ryan; Bolinger, Mark; Heath, Garvin; Keyser, David; Lantz, Eric; Macknick, Jordan; Mai, Trieu; Millstein, Dev

    2016-10-01

    We model scenarios of the U.S. electric sector in which wind generation reaches 10% of end-use electricity demand in 2020, 20% in 2030, and 35% in 2050. As shown in a companion paper, achieving these penetration levels would have significant implications for the wind industry and the broader electric sector. Compared to a baseline that assumes no new wind deployment, under the primary scenario modeled, achieving these penetrations imposes an incremental cost to electricity consumers of less than 1% through 2030. These cost implications, however, should be balanced against the variety of environmental and social implications of such a scenario. Relative to a baseline that assumes no new wind deployment, our analysis shows that the high-penetration wind scenario yields potential greenhouse-gas benefits of $85-$1,230 billion in present-value terms, with a central estimate of $400 billion. Air-pollution-related health benefits are estimated at $52-$272 billion, while annual electric-sector water withdrawals and consumption are lower by 15% and 23% in 2050, respectively. We also find that a high-wind-energy future would have implications for the diversity and risk of energy supply, local economic development, and land use and related local impacts on communities and ecosystems; however, these additional impacts may not greatly affect aggregate social welfare owing to their nature, in part, as resource transfers.

  7. Paired-Associative Stimulation-Induced Long-term Potentiation-Like Motor Cortex Plasticity in Healthy Adolescents

    Directory of Open Access Journals (Sweden)

    Jonathan C. Lee

    2017-05-01

    Full Text Available ObjectiveThe objective of this study was to evaluate the feasibility of using paired-associative stimulation (PAS to study excitatory and inhibitory plasticity in adolescents while examining variables that may moderate plasticity (such as sex and environment.MethodsWe recruited 34 healthy adolescents (aged 13–19, 13 males, 21 females. To evaluate excitatory plasticity, we compared mean motor-evoked potentials (MEPs elicited by single-pulse transcranial magnetic stimulation (TMS before and after PAS at 0, 15, and 30 min. To evaluate inhibitory plasticity, we evaluated the cortical silent period (CSP elicited by single-pulse TMS in the contracted hand before and after PAS at 0, 15, and 30 min.ResultsAll participants completed PAS procedures. No adverse events occurred. PAS was well tolerated. PAS-induced significant increases in the ratio of post-PAS MEP to pre-PAS MEP amplitudes (p < 0.01 at all post-PAS intervals. Neither socioeconomic status nor sex was associated with post-PAS MEP changes. PAS induced significant CSP lengthening in males but not females.ConclusionPAS is a feasible, safe, and well-tolerated index of adolescent motor cortical plasticity. Gender may influence PAS-induced changes in cortical inhibition. PAS is safe and well tolerated by healthy adolescents and may be a novel tool with which to study adolescent neuroplasticity.

  8. Long-term persistence of sedimentary copper contamination in Lake Orta: potential environmental risks 20 years after liming

    Directory of Open Access Journals (Sweden)

    Davide A.L. Vignati

    2016-04-01

    Full Text Available Lake Orta, northern Italy, has suffered from severe copper pollution and human-induced acidification between the 1920s and the 1990s because of discharges from a rayon factory and electroplating industries located in its water basin. Following liming operations in the late 1990s, the chemical quality of the water column has been restored and signs of, still ongoing, biological recovery observed. Examination of two sediment cores collected close to the main historical Cu discharge and in the central part of the Lake shows that Cu concentrations in the uppermost layers of bottom sediments remain 10 to 40-fold higher than background levels. Past studies demonstrated the toxic potential of Lake Orta sediments to a variety of organisms at Cu concentrations comparable to present ones. Comparison with published results suggests that current level of Cu contamination may still pose a risk to sediment-ingesting organisms and slow down further ecological recovery of Lake Orta. Particular attention should be given to understand the effects of dietary ingestion of Cu from sediments which, unlike in previous ecotoxicological studies, may now represent the main route of Cu exposure for sediment-ingesting benthic organisms.

  9. Long-Term Task- and Dopamine-Dependent Dynamics of Subthalamic Local Field Potentials in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Sara J. Hanrahan

    2016-11-01

    Full Text Available Subthalamic nucleus (STN local field potentials (LFP are neural signals that have been shown to reveal motor and language behavior, as well as pathological parkinsonian states. We use a research-grade implantable neurostimulator (INS with data collection capabilities to record STN-LFP outside the operating room to determine the reliability of the signals over time and assess their dynamics with respect to behavior and dopaminergic medication. Seven subjects were implanted with the recording augmented deep brain stimulation (DBS system, and bilateral STN-LFP recordings were collected in the clinic over twelve months. Subjects were cued to perform voluntary motor and language behaviors in on and off medication states. The STN-LFP recorded with the INS demonstrated behavior-modulated desynchronization of beta frequency (13–30 Hz and synchronization of low gamma frequency (35–70 Hz oscillations. Dopaminergic medication did not diminish the relative beta frequency oscillatory desynchronization with movement. However, movement-related gamma frequency oscillatory synchronization was only observed in the medication on state. We observed significant inter-subject variability, but observed consistent STN-LFP activity across recording systems and over a one-year period for each subject. These findings demonstrate that an INS system can provide robust STN-LFP recordings in ambulatory patients, allowing for these signals to be recorded in settings that better represent natural environments in which patients are in a variety of medication states.

  10. Long-term potentiation of evoked presynaptic response at CA3-CA1 synapses by transient oxygen-glucose deprivation in rat brain slices.

    Science.gov (United States)

    Ai, Jinglu; Baker, Andrew

    2006-02-01

    Physiological activity-dependent long-term changes in synaptic transmission, as long-term potentiation (LTP) are thought to be the substrate of learning and memory. However, a form of postsynaptic pathological LTP at the CA3-CA1 synapses has been demonstrated following few minutes of anoxia and aglycemia in vitro. The ischemia LTP shared many molecular mechanisms with the physiological LTP, and was believed to be involved in the delayed neuronal death following ischemia. However, the role of the presynaptic component in this regard is not known. Here we show that a short period of oxygen-glucose deprivation can induce a form of LTP (lasting for hours) of the presynaptic response at the CA3-CA1 synapses. This form of LTP is independent of postsynaptic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors, but Ca(2+) dependent. This presynaptic LTP may represent a presynaptic hyperexcitability of the afferent fibers following ischemia, and responsible for the excitotoxicity to the CA1 neurons (ischemia-induced increases of glutamate release that kills neurons) and the postsynaptic pathological ischemic LTP.

  11. Long-term operation of biological activated carbon pre-treatment for microfiltration of secondary effluent: Correlation between the organic foulants and fouling potential.

    Science.gov (United States)

    Pramanik, Biplob Kumar; Roddick, Felicity A; Fan, Linhua

    2016-03-01

    The impact of long-term (>2 years) biological activated carbon (BAC) treatment for mitigating organic fouling in the microfiltration of biologically treated secondary effluent was investigated. Correlation between the organic constituents and hydraulic filtration resistance was investigated to identify the major components responsible for fouling. Over two years operation, the removal efficiency for dissolved organic carbon (DOC) by the BAC treatment was fairly consistent (30 ± 3%), although the reduction in UVA254 gradually decreased from 56 to 34%. BAC treatment effectively decreased the organic foulants in the effluent and so contributed to the mitigation of membrane fouling as shown by reduction in the unified membrane fouling index (UMFI). BAC consistently removed biopolymers whereas the removal of humic substances decreased from 52 to 25% after two years of BAC operation, and thus led to a gradual decrease in UMFI reduction efficiency from 78 to 43%. This was due to gradual reduction in adsorption capacity of the activated carbon as confirmed by analysis of its pore size distribution. Hence humics also played an important role in membrane fouling. However, there was a good correlation between protein and carbohydrate contents with hydraulically reversible and irreversible filtration resistance, compared with UVA254, turbidity and DOC. Although the mitigation of membrane fouling decreased over time, this study demonstrated that the long-term use of BAC pre-treatment of biologically treated secondary effluent prior to microfiltration has potential to reduce the need for frequent chemical cleaning and so increase membrane life span.

  12. Spatial performance in a complex maze is associated with persistent long-term potentiation enhancement in mouse hippocampal slices at early training stages.

    Science.gov (United States)

    Lange-Asschenfeldt, C; Lohmann, P; Riepe, M W

    2007-06-29

    Long-term potentiation (LTP) and long-term depression (LTD) are principal reflections of synaptic plasticity that have been implicated in learning and memory. We have previously shown that spatial learning in a newly validated complex maze is accompanied by depression of hippocampal CA1 synaptic activity in hippocampal slices of trained mice ("behavioral LTD"). In the present study, we investigated whether behavioral LTD is accompanied by alterations of subsequent LTP induced by high-frequency stimulation (HFS). Moreover, we were interested in the time course of such alterations in relation to training stage. Animals underwent 1, 2, and 8 days of spatial training in the complex maze, respectively. Hippocampal slices were taken 24 h after the last training session. We found a simultaneous decrease of basal synaptic response and increase of HFS induced LTP magnitude compared with slices of untrained animals. Synaptic plasticity was not influenced by repeated running wheel exercise in an additional control group without spatial learning. The mentioned alterations occurred already after day 2 of maze exploration parallel to the most pronounced improvement of behavioral performance but did not change thereafter until day 8 despite further learning progress. They were also found when animals were trained for 2 days and kept at rest for a subsequent 6 days. In conclusion, spatial learning may be reflected by distinct and persistent measurable alterations of synaptic plasticity in hippocampal CA1 neurons at early training stages.

  13. 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.

  14. Potential for long-term transfer of dissolved organic carbon from riparian zones to streams in boreal catchments.

    Science.gov (United States)

    Ledesma, José L J; Grabs, Thomas; Bishop, Kevin H; Schiff, Sherry L; Köhler, Stephan J

    2015-08-01

    Boreal regions store most of the global terrestrial carbon, which can be transferred as dissolved organic carbon (DOC) to inland waters with implications for both aquatic ecology and carbon budgets. Headwater riparian zones (RZ) are important sources of DOC, and often just a narrow 'dominant source layer' (DSL) within the riparian profile is responsible for most of the DOC export. Two important questions arise: how long boreal RZ could sustain lateral DOC fluxes as the sole source of exported carbon and how its hydromorphological variability influences this role. We estimate theoretical turnover times by comparing carbon pools and lateral exports in the DSL of 13 riparian profiles distributed over a 69 km(2) catchment in northern Sweden. The thickness of the DSL was 36 ± 18 (average ± SD) cm. Thus, only about one-third of the 1-m-deep riparian profile contributed 90% of the lateral DOC flux. The 13 RZ exported 8.7 ± 6.5 g C m(-2) year(-1) , covering the whole range of boreal stream DOC exports. The variation could be explained by local hydromorphological characteristics including RZ width (R(2) = 0.90). The estimated theoretical turnover times were hundreds to a few thousands of years, that is there is a potential long-lasting supply of DOC. Estimates of net ecosystem production in the RZ suggest that lateral fluxes, including both organic and inorganic C, could be maintained without drawing down the riparian pools. This was supported by measurements of stream DO(14) C that indicated modern carbon as the predominant fraction exported, including streams disturbed by ditching. The transfer of DOC into boreal inland waters from new and old carbon sources has a major influence on surface water quality and global carbon balances. This study highlights the importance of local variations in RZ hydromorphology and DSL extent for future DOC fluxes under a changing climate. © 2015 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.

  15. Long-term changes in spinal cord evoked potentials after compression spinal cord injury in the rat.

    Science.gov (United States)

    Vanický, Ivo; Ondrejcák, Tomás; Ondrejcáková, Miriam; Sulla, Igor; Gálik, Ján

    2006-01-01

    1. After traumatic spinal cord injury (SCI), histological and neurological consequences are developing for several days and even weeks. However, little is known about the dynamics of changes in spinal axonal conductivity. The aim of this study was to record and compare repeated spinal cord evoked potentials (SCEP) after SCI in the rat during a 4 weeks' interval. These recordings were used: (i) for studying the dynamics of functional changes in spinal axons after SCI, and (ii) to define the value of SCEP as an independent outcome parameter in SCI studies. 2. We have used two pairs of chronically implanted epidural electrodes for stimulation/recording. The electrodes were placed below and above the site of injury, respectively. Animals with implanted electrodes underwent spinal cord compression injury induced by epidural balloon inflation at Th8-Th9 level. There were five experimental groups of animals, including one control group (sham-operated, no injury), and four injury groups (different degrees of SCI). 3. After SCI, SCEP waveform was either significantly reduced or completely lost. Partial recovery of SCEPs was observed in all groups. The onset and extent of recovery clearly correlated with the severity of injury. There was good correlation between quantitated SCEP variables and the volumes of the compressing balloon. However, sensitivity of electropohysiological parameters was inferior compared to neurological and morphometric outcomes. 4. Our study shows for the first time, that the dynamics of axonal recovery depends on the degree of injury. After mild injury, recovery of signal is rapid. However, after severe injury, axonal conductivity can re-appear after as long as 2 weeks postinjury. In conclusion, SCEPs can be used as an independent parameter of outcome after SCI, but in general, the sensitivity of electrophysiological data were worse than standard morphological and neurological evaluations.

  16. An exploration of the effectiveness of artificial mini-magnetospheres as a potential Solar Storm shelter for long term human space missions

    CERN Document Server

    Bamford, Ruth; Bradford, John; Todd, Tom N; Stafford-Allen, Robin; Alves, E Paulo; Silva, Luis; Collingwood, Cheryl; Crawford, Ian A; Bingham, Robert

    2014-01-01

    In this paper we explore the effectiveness of an artificial mini-magnetosphere as a potential radiation shelter for long term human space missions. Our study includes the differences that the plasma environment makes to the efficiency of the shielding from the high energy charged particle component of solar and cosmic rays, which radically alters the power requirements. The incoming electrostatic charges are shielded by fields supported by the self captured environmental plasma of the solar wind, potentially augmented with additional density. The artificial magnetic field generated on board acts as the means of confinement and control. Evidence for similar behaviour of electromagnetic fields and ionised particles in interplanetary space can be gained by the example of the enhanced shielding effectiveness of naturally occurring "mini-magnetospheres" on the moon. The shielding effect of surface magnetic fields of the order of ~100s nanoTesla is sufficient to provide effective shielding from solar proton bombard...

  17. Impact of potentially lethal ventricular arrhythmias on long-term outcome in patients with chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    LIU Ye-hong; SHEN Wei-feng; SU Jing-ying; WANG Lin-jie; LI Jin-ping; ZHOU Qing-fen; GAN Qian; CHAI Xi-chen; DAI Li-ying; ZHANG Feng-ru

    2012-01-01

    Background Potentially lethal ventricular arrhythmias (PLVAs) occur frequently in survivors after acute myocardial infarction and are increasingly recognized in other forms of structural heart diseases.This study investigated the prevalence and prognostic significance of PLVAs in patients with chronic heart failure (CHF).Methods Data concerning demographics,etiology of heart failure,NYHA functional class,biochemical variables,electrocardiographic and echocardiographic findings,and medical treatments were collected by reviewing hospital medical records from 1080 patients with NYHA Ⅱ-Ⅳ and a left ventricular (LV) ejection fraction ≤45%.PLVAs were defined as multi-focal ventricular ectopy (>30 beats/h on Holter monitoring),bursts of ventricular premature beats,and nonsustained ventricular tachycardia.All-cause mortality,sudden death,and rehospitalization due to worsening heart failure,or cardiac transplantation during 5-year follow-up after discharge were recorded.Results The occurrence rate of PLVAs in CHF was 30.2%,and increased with age; 23.4% in patients <45 years old,27.8% in those between 45-65 years old,and 33.5% in patients >65 years old (P=0.033).Patients with PLVAs had larger LV size and lower ejection fraction (both P <0.01) and higher all-cause mortality (P=0.014) during 5-year follow-up than those without PLVAs.Age (OR 1.041,95% Cl 1.004-1.079,P=0.03) and LV end-diastolic dimension (OR 1.068,95% Cl 1.013-1.126,P=0.015) independently predicted the occurrence of PLVAs.And PLVA was an independent factor for all-cause mortality (RR 1.702,95% Cl 1.017-2.848,P=0.031) and sudden death (RR 1.937,95% CI 1.068-3.516,P=0.030) in patients with CHF.Conclusion PLVAs are common and exert a negative impact on Iona-term clinical outcome in patients with CHF.

  18. Long-Term Collections

    CERN Multimedia

    Staff Association

    2016-01-01

    45 years helping in developing countries! CERN personnel have been helping the least fortunate people on the planet since 1971. How? With the Long-Term Collections! Dear Colleagues, The Staff Association’s Long-Term Collections (LTC) Committee is delighted to share this important milestone in the life of our Laboratory with you. Indeed, whilst the name of CERN is known worldwide for scientific discoveries, it also shines in the many humanitarian projects which have been supported by the LTC since 1971. Several schools and clinics, far and wide, carry its logo... Over the past 45 years, 74 projects have been supported (9 of which are still ongoing). This all came from a group of colleagues who wanted to share a little of what life offered them here at CERN, in this haven of mutual understanding, peace and security, with those who were less fortunate elsewhere. Thus, the LTC were born... Since then, we have worked as a team to maintain the dream of these visionaries, with the help of regular donat...

  19. Long-Term Collection

    CERN Document Server

    Staff Association

    2016-01-01

    Dear Colleagues, As previously announced in Echo (No. 254), your delegates took action to draw attention to the projects of the Long-Term Collections (LTC), the humanitarian body of the CERN Staff Association. On Tuesday, 11 October, at noon, small Z-Cards were widely distributed at the entrances of CERN restaurants and we thank you all for your interest. We hope to have achieved an important part of our goal, which was to inform you, convince you and find new supporters among you. We will find out in the next few days! An exhibition of the LTC was also set up in the Main Building for the entire week. The Staff Association wants to celebrate the occasion of the Long-Term Collection’s 45th anniversary at CERN because, ever since 1971, CERN personnel have showed great support in helping the least fortunate people on the planet in a variety of ways according to their needs. On a regular basis, joint fundraising appeals are made with the Directorate to help the victims of natural disasters around th...

  20. Collectes à long terme

    CERN Document Server

    Collectes à long terme

    2014-01-01

    En cette fin d’année 2014 qui approche à grands pas, le Comité des Collectes à Long Terme remercie chaleureusement ses fidèles donatrices et donateurs réguliers pour leurs contributions à nos actions en faveur des plus démunis de notre planète. C’est très important, pour notre Comité, de pouvoir compter sur l’appui assidu que vous nous apportez. Depuis plus de 40 ans maintenant, le modèle des CLT est basé principalement sur des actions à long terme (soit une aide pendant 4-5 ans par projet, mais plus parfois selon les circonstances), et sa planification demande une grande régularité de ses soutiens financiers. Grand MERCI à vous ! D’autres dons nous parviennent au cours de l’année, et ils sont aussi les bienvenus. En particulier, nous tenons à remercier...

  1. Pairing-specific long-term depression of Purkinje cell excitatory postsynaptic potentials results from a classical conditioning procedure in the rabbit cerebellar slice.

    Science.gov (United States)

    Schreurs, B G; Oh, M M; Alkon, D L

    1996-03-01

    1. Using a rabbit cerebellar slice preparation, we stimulated a classical conditioning procedure by stimulating parallel fiber inputs to Purkinje cells with the use of a brief, high-frequency train of eight constant-current pulses 80 ms before climbing fiber inputs to the same Purkinje cell were stimulated with the use of a brief, lower frequency train of three constant-current pulses. In all experiments, we assessed the effects of stimulation by measuring the peak amplitude of Purkinje cell excitatory postsynaptic potentials (EPSPs) to single parallel fiber test pulses. 2. Intradendritically recorded Purkinje cell EPSPs underwent a long-term (> 20 min) reduction in peak amplitude (30%) after paired stimulation of the parallel and climbing fibers but not after unpaired or parallel fiber alone stimulation. We call this phenomenon pairing-specific long-term depression (PSD). 3. Facilitation of the peak amplitude of a second EPSP elicited by a parallel fiber train occurred both before and after paired stimulation suggesting that the locus of depression was not presynaptic. Depression of the peak amplitude of a depolarizing response to focal application of glutamate following pairings of parallel and climbing fiber stimulation added support to a suggested postsynaptic locus of the PSD effect. 4. The application of aniracetam potentiated EPSP peak amplitude by 40%, but these values returned to baseline as a result of pairings. With the removal of aniracetam from the bath 20 min after pairings, normal levels of pairing-specific EPSP depression were observed, indicating that the effect did not result from direct desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) receptors. 5. Incubation of slices in the protein kinase inhibitor H-7 potentiated EPSP peak amplitudes slightly (9%), but peak amplitudes returned to baseline levels after pairings. The net reduction in EPSP peak amplitude of classical conditioning.

  2. Improvement in Memory and Brain Long-term Potentiation Deficits Due to Permanent Hypoperfusion/Ischemia by Grape Seed Extract in Rats

    Directory of Open Access Journals (Sweden)

    Alireza Sarkaki

    2013-09-01

    Full Text Available   Objective(s: Cerebral hypoperfusion/ischemia (CHI is a neurological disease where impaired hippocampus electrical activity and cognition caused by a serial pathophysiological events. This study aimed to evaluate the effects of chronic oral administration of grape seed extract (GSE on passive avoidance memory and long-term potentiation (LTP after permanent bilateral common carotid arteries occlusion (2CCAO in male adult rats.   Materials and Methods: Thirty-two adult male Wistar rats were randomly divided into: 1 Sham+Veh, 2 Isch+Veh, 3 Sham+GSE, 4 Isch+GSE. In order to make 2CCAO as an animal model of CHI, carotid arteries were ligatured and then cut bilaterally. To evaluation of passive avoidance memory, step-down latency (STL was measured and LTP was recorded from hippocampal dentate gyrus (DG after high frequency stimulation (HFS in all rats. Results: We found that memory was significantly impaired in rats after CHI (P

  3. Effect of Prenatal Protein Malnutrition on Long-Term Potentiation and BDNF Protein Expression in the Rat Entorhinal Cortex after Neocortical and Hippocampal Tetanization

    Directory of Open Access Journals (Sweden)

    Alejandro Hernández

    2008-01-01

    Full Text Available Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC in the adult progeny. Unlike normal eutrophic controls, 55–60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

  4. Effect of prenatal protein malnutrition on long-term potentiation and BDNF protein expression in the rat entorhinal cortex after neocortical and hippocampal tetanization.

    Science.gov (United States)

    Hernández, Alejandro; Burgos, Héctor; Mondaca, Mauricio; Barra, Rafael; Núñez, Héctor; Pérez, Hernán; Soto-Moyano, Rubén; Sierralta, Walter; Fernández, Victor; Olivares, Ricardo; Valladares, Luis

    2008-01-01

    Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP) of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC) in the adult progeny. Unlike normal eutrophic controls, 55-60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF) in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

  5. Acute stress causes rapid synaptic insertion of Ca2+ -permeable AMPA receptors to facilitate long-term potentiation in the hippocampus.

    Science.gov (United States)

    Whitehead, Garry; Jo, Jihoon; Hogg, Ellen L; Piers, Thomas; Kim, Dong-Hyun; Seaton, Gillian; Seok, Heon; Bru-Mercier, Gilles; Son, Gi Hoon; Regan, Philip; Hildebrandt, Lars; Waite, Eleanor; Kim, Byeong-Chae; Kerrigan, Talitha L; Kim, Kyungjin; Whitcomb, Daniel J; Collingridge, Graham L; Lightman, Stafford L; Cho, Kwangwook

    2013-12-01

    The neuroendocrine response to episodes of acute stress is crucial for survival whereas the prolonged response to chronic stress can be detrimental. Learning and memory are particularly susceptible to stress with cognitive deficits being well characterized consequences of chronic stress. Although there is good evidence that acute stress can enhance cognitive performance, the mechanism(s) for this are unclear. We find that hippocampal slices, either prepared from rats following 30 min restraint stress or directly exposed to glucocorticoids, exhibit an N-methyl-d-aspartic acid receptor-independent form of long-term potentiation. We demonstrate that the mechanism involves an NMDA receptor and PKA-dependent insertion of Ca2+ -permeable AMPA receptors into synapses. These then trigger the additional NMDA receptor-independent form of LTP during high frequency stimulation.

  6. Testicular hormones do not regulate sexually dimorphic Pavlovian fear conditioning or perforant-path long-term potentiation in adult male rats.

    Science.gov (United States)

    Anagnostaras, S G; Maren, S; DeCola, J P; Lane, N I; Gale, G D; Schlinger, B A; Fanselow, M S

    1998-04-01

    We recently reported that Pavlovian fear conditioning and hippocampal perforant-path long-term potentiation (LTP) are sexually dimorphic in rats. Males show greater contextual fear conditioning, which depends on the hippocampus, as well as greater hippocampal LTP. In order to examine the role of circulating gonadal hormones in adult male rats, animals were castrated in two experiments, and Pavlovian fear conditioning and in vivo perforant-path LTP were examined. It was found that sexually-dimorphic LTP and fear conditioning are not regulated by the activational effects of testicular hormones in adult male rats. That is, in every respect, castrated male rats were similar to intact male rats in Pavlovian fear conditioning and hippocampal LTP. It is likely that sexual dimorphism in this system is established earlier in development by the organizational effects of gonadal hormones.

  7. New experimental data reveal possible relation of chaotic behavior of the long-term geoelectric potential difference to seismic activity in Western Greece

    Energy Technology Data Exchange (ETDEWEB)

    Ifantis, Apostolos [Control Systems and Signals Laboratory, Department of Electrical Engineering, Technological Educational Institute of Patras, Patras 26334 (Greece) and Seismological Laboratory, Department of Geology, University of Patras, Patras 26500 (Greece)]. E-mail: ifantisa@teipat.gr; Giannakopoulos, Konstantine [Electronics Laboratory, Department of Physics, University of Patras, Patras 26500 (Greece)]. E-mail: kgian1@physics.upatras.gr

    2007-11-15

    In this paper, observations of the long-term geoelectric potential difference are presented based on data collected during a six-year (1998-2003) investigating period. Moreover, this paper constitutes a continuation of a previously published work with five-year (1993-1997) experimental data. For data logging purposes, an automatic system for collection of geoelectric measurements operates at the Seismological Laboratory of the University of Patras. The analysis of these data using Lyapunov exponents and Takens estimator confirm their quite chaotic behavior. The Lyapunov exponents have also been calculated for short periods of fifteen days, ten days before and five days after the earthquakes occurred during this six-year period. By thorough examination of the resulting Lyapunov spectrums, it seems that these are subject to possible changes prior to an earthquake.

  8. Effects of Joint Attention on Long-Term Memory in 9-Month-Old Infants: An Event-Related Potentials Study

    Science.gov (United States)

    Kopp, Franziska; Lindenberger, Ulman

    2011-01-01

    Joint attention develops during the first year of life but little is known about its effects on long-term memory. We investigated whether joint attention modulates long-term memory in 9-month-old infants. Infants were familiarized with visually presented objects in either of two conditions that differed in the degree of joint attention (high…

  9. The Screening of Genes Sensitive to Long-Term, Low-Level Microwave Exposure and Bioinformatic Analysis of Potential Correlations to Learning and Memory

    Institute of Scientific and Technical Information of China (English)

    ZHAO Ya Li; LI Ying Xian; MA Hong Bo; LI Dong; LI Hai Liang; JIANG Rui; KAN Guang Han; YANG Zhen Zhong; HUANG Zeng Xin

    2015-01-01

    Objective To gain a better understanding of gene expression changes in the brain following microwave exposure in mice. This study hopes to reveal mechanisms contributing to microwave-induced learning and memory dysfunction. Methods Mice were exposed to whole body 2100 MHz microwaves with specific absorption rates (SARs) of 0.45 W/kg, 1.8 W/kg, and 3.6 W/kg for 1 hour daily for 8 weeks. Differentially expressing genes in the brains were screened using high-density oligonucleotide arrays, with genes showing more significant differences further confirmed by RT-PCR. Results The gene chip results demonstrated that 41 genes (0.45 W/kg group), 29 genes (1.8 W/kg group), and 219 genes (3.6 W/kg group) were differentially expressed. GO analysis revealed that these differentially expressed genes were primarily involved in metabolic processes, cellular metabolic processes, regulation of biological processes, macromolecular metabolic processes, biosynthetic processes, cellular protein metabolic processes, transport, developmental processes, cellular component organization, etc. KEGG pathway analysis showed that these genes are mainly involved in pathways related to ribosome, Alzheimer's disease, Parkinson's disease, long-term potentiation, Huntington's disease, and Neurotrophin signaling. Construction of a protein interaction network identified several important regulatory genes including synbindin (sbdn), Crystallin (CryaB), PPP1CA, Ywhaq, Psap, Psmb1, Pcbp2, etc., which play important roles in the processes of learning and memory. Conclusion Long-term, low-level microwave exposure may inhibit learning and memory by affecting protein and energy metabolic processes and signaling pathways relating to neurological functions or diseases.

  10. Evaluation of a deposit in the vicinity of the PBU L-106 Site, North Slope, Alaska, for a potential long-term test of gas production from hydrates

    Energy Technology Data Exchange (ETDEWEB)

    Moridis, G.J.; Reagan, M.T.; Boyle, K.L.; Zhang, K.

    2010-05-01

    As part of the effort to investigate the technical feasibility of gas production from hydrate deposits, a long-term field test (lasting 18-24 months) is under consideration in a project led by the U.S. Department of Energy. We evaluate a candidate deposit involving the C-Unit in the vicinity of the PBU-L106 site in North Slope, Alaska. This deposit is stratigraphically bounded by impermeable shale top and bottom boundaries (Class 3), and is characterized by high intrinsic permeabilities, high porosity, high hydrate saturation, and a hydrostatic pressure distribution. The C-unit deposit is composed of two hydrate-bearing strata separated by a 30-ft-thick shale interlayer, and its temperatrure across its boundaries ranges between 5 and 6.5 C. We investigate by means of numerical simulation involving very fine grids the production potential of these two deposits using both vertical and horizontal wells. We also explore the sensitivity of production to key parameters such as the hydrate saturation, the formation permeability, and the permeability of the bounding shale layers. Finally, we compare the production performance of the C-Unit at the PBU-L106 site to that of the D-Unit accumulation at the Mount Elbert site, a thinner, single-layer Class 3 deposit on the North Slope of Alaska that is shallower, less-pressurized and colder (2.3-2.6 C). The results indicate that production from horizontal wells may be orders of magnitude larger than that from vertical ones. Additionally, production increases with the formation permeability, and with a decreasing permeability of the boundaries. The effect of the hydrate saturation on production is complex and depends on the time frame of production. Because of higher production, the PBU-L106 deposit appears to have an advantage as a candidate for the long-term test.

  11. LONG TERM COLLECTIONS

    CERN Multimedia

    STAFF ASSOCIATION

    2010-01-01

    ACKNOWLEDGMENTS The Long-Term Collections (CLT) committee would like to warmly thank its faithful donors who, year after year, support our actions all over the world. Without you, all this would not be possible. We would like to thank, in particular, the CERN Firemen’s Association who donated 5000 CHF in the spring thanks to the sale of their traditional calendar, and the generosity of the CERN community. A huge thank you to the firemen for their devotion to our cause. And thank you to all those who have opened their door, their heart, and their purses! Similarly, we warmly thank the CERN Yoga Club once again for its wonderful donation of 2000 CHF we recently received. We would also like to tell you that all our projects are running well. Just to remind you, we are currently supporting the activities of the «Réflexe-Partage» Association in Mali; the training centre of «Education et Développement» in Abomey, Benin; and the orphanage and ...

  12. Invasive fungal diseases during first induction chemotherapy affect complete remission achievement and long-term survival of patients with acute myeloid leukemia.

    Science.gov (United States)

    Girmenia, Corrado; Micozzi, Alessandra; Piciocchi, Alfonso; Gentile, Giuseppe; Di Caprio, Luigi; Nasso, Daniela; Minotti, Clara; Capria, Saveria; Cartoni, Claudio; Alimena, Giuliana; Meloni, Giovanna; Amadori, Sergio; Foà, Robin; Venditti, Adriano

    2014-04-01

    We retrospectively evaluated, in a logistic-regression-model, the role of proven/probable invasive fungal diseases (PP-IFD), occurring during first induction chemotherapy, on the achievement of complete remission (CR) and overall survival (OS) in 198 acute myeloid leukemia (AML) patients. A PP-IFD was documented in 34 (17.2%) patients. Younger age, good performance status at AML diagnosis and no development of a PP-IFD (OR 4.09, 95% CI 1.71-9.81, p<0.0001) were independent factors associated to CR achievement. Younger age, good performance status, favorable genetic risk and no development of PP-IFD (HR 1.86, 95% CI 1.20-2.88, p=0.005) were independent factors associated to OS at 3 years. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Short and long term bystander effect induction by fathead minnows (Pimephales promelas, Rafinesque, 1820) injected with environmentally relevant whole body doses of 226Ra.

    Science.gov (United States)

    Smith, Richard W; Seymour, Colin B; Mothersill, Carmel E

    2013-12-01

    Bystander effect induction by fathead minnows injected with environmentally relevant doses of (226)Ra was investigated. Twenty four h and 6 months after injection with a single dose of 21, 210 or 2100 μBq, fin tissue samples emitted a pro-apoptotic signal, which reduced the clonogenic survival of an apoptosis sensitive reporter cell line. Twenty four h and 10 weeks after injection explants from non-injected bystander fish, swum with the injected fish, also emitted a pro-apoptotic signal. However 6 months after injection the bystander fish to 21 and 210 μBq injected fish emitted an anti-apoptotic signal. This demonstrates that extremely low dose irradiation can have effects outside of the irradiated fish. This has implications for population and ecosystem responses to contamination. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Long-term tolerability of capnography and respiratory inductance plethysmography for respiratory monitoring in pediatric patients treated with patient-controlled analgesia

    Science.gov (United States)

    Miller, Karen M.; Kim, Andrew Y.; Yaster, Myron; Kudchadkar, Sapna R.; White, Elizabeth; Fackler, James; Monitto, Constance L.

    2016-01-01

    Background The Anesthesia Patient Safety Foundation has advocated the use of continuous electronic monitoring of oxygenation and ventilation to preemptively identify opioid-induced respiratory depression. In adults, capnography is the gold standard in respiratory monitoring. An alternative technique used in sleep laboratories is respiratory inductance plethysmography (RIP). However, it is not known if either monitor is well tolerated by pediatric patients for prolonged periods of time. Aim The goal of this study was to determine whether capnography or RIP is better tolerated in non-intubated, spontaneously breathing pediatric patients being treated with intravenous patient-controlled analgesia (IVPCA). Methods Nasal cannula capnography with oral sampling and thoracic and abdominal inductance plethysmography bands were placed along with routine monitors on pediatric patients being treated for acute pain with IVPCA. Study monitors were left in place for as long as they were tolerated by the patient, for a maximum of 24 consecutive hours. If the patient did not wear a particular study monitor for any reason, but tolerated the remaining monitor, participation in the study continued. If the patient would not wear either monitor, participation was terminated. Results Twenty-six patients (18 female, 8 male, average age 10.1 ± 5.5 years) consented to participate, but only 14 patients attempted to wear one or both devices. Among those who wore either device, median time to device removal was 8.33 hours (range 0.3–23.6 hours) for capnography and 23.5 hours (range 0.7–24 hours) for RIP bands. Conclusion Children did not tolerate wearing capnography cannulae for prolonged periods of time, limiting the usefulness of this device as a continuous monitor of ventilation in children. RIP bands were better tolerated; however, they require further assessment of their utility. Until more effective, child-friendly monitors are developed and their utility validated, guidelines

  15. The role of BRAF V600E mutation as a potential marker for prognostic stratification of papillary thyroid carcinoma: a long-term follow-up study.

    Science.gov (United States)

    Daliri, Mahdi; Abbaszadegan, Mohammad Reza; Bahar, Mostafa Mehrabi; Arabi, Azadeh; Yadollahi, Mona; Ghafari, Azar; Taghehchian, Negin; Zakavi, Seyed Rasoul

    2014-01-01

    Abstract Papillary carcinoma is the most prevalent malignancy of thyroid gland, and its incidence has been recently increased. The BRAF(V600E) mutation is the most frequent genetic alteration in papillary thyroid carcinoma (PTC). The role of BRAF(V600E) mutation as a potential prognostic factor has been controversially reported in different studies, with short-term follow-up. In this study, we evaluated the role of BRAF(V600E) mutation as a potential marker for prognostic stratification of patients with PTC in long-term follow-up. We studied 69 PTC patients with a mean follow-up period of 63.9 months (median: 60 m). The BRAF(V600E) mutation was analyzed by PCR-single-strand conformational polymorphism and sequencing. The correlation between the presence or absence of the BRAF(V600E) mutation, clinicopathological features and prognosis of PTC patients were studied. The BRAF(V600E) mutation was found in 28 of 69 (40.6%) PTC patients, and it was significantly more frequent in older patients (p papillary thyroid cancer in northeast of Iran. The BRAF(V600E) mutation was associated with older age and advanced tumor stage but was not correlated with incomplete response during follow-up.

  16. Caffeine treatment prevents rapid eye movement sleep deprivation-induced impairment of late-phase long-term potentiation in the dentate gyrus.

    Science.gov (United States)

    Alhaider, Ibrahim A; Alkadhi, Karim A

    2015-11-01

    The CA1 and dentate gyrus (DG) are physically and functionally closely related areas of the hippocampus, but they differ in various respects, including their reactions to different insults. The purpose of this study was to determine the protective effects of chronic caffeine treatment on late-phase long-term potentiation (L-LTP) and its signalling cascade in the DG area of the hippocampus of rapid eye movement sleep-deprived rats. Rats were chronically treated with caffeine (300 mg/L drinking water) for 4 weeks, after which they were sleep-deprived for 24 h. L-LTP was induced in in anaesthetized rats, and extracellular field potentials from the DG area were recorded in vivo. The levels of L-LTP-related signalling proteins were assessed by western blot analysis. Sleep deprivation markedly reduced L-LTP magnitude, and basal levels of total cAMP response element-binding protein (CREB), phosphorylated CREB (P-CREB), and calcium/calmodulin kinase IV (CaMKIV). Chronic caffeine treatment prevented the reductions in the basal levels of P-CREB, total CREB and CaMKIV in sleep-deprived rats. Furthermore, caffeine prevented post-L-LTP sleep deprivation-induced downregulation of P-CREB and brain-derived neurotrophic factor in the DG. The current findings show that caffeine treatment prevents acute sleep deprivation-induced deficits in brain function.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Fernández-Ruiz, Antonio; Makarov, Valeri A; Herreras, Oscar

    2012-01-01

    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 it difficult to estimate 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 (STA) 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. They 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.

  19. Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trial†.

    Science.gov (United States)

    Fernandez-Martos, C; Garcia-Albeniz, X; Pericay, C; Maurel, J; Aparicio, J; Montagut, C; Safont, M J; Salud, A; Vera, R; Massuti, B; Escudero, P; Alonso, V; Bosch, C; Martin, M; Minsky, B D

    2015-08-01

    The primary results of our phase II randomized trial suggested that compared with conventional preoperative chemoradiation (CRT), the addition of chemotherapy (CT) before CRT and surgery allows most patients receive their planned treatment with a better toxicity profile without compromising the pathological complete response and complete resection rates. We now report the 5-year outcomes. Patients with distal or middle third, T3-T4 and/or N+ rectal adenocarcinoma selected by magnetic resonance imaging, were randomly assigned to arm A-preoperative CRT followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-four cycles of CAPOX followed by CRT and surgery. The following 5-year actuarial outcomes were assessed: the cumulative incidence of local relapse (LR) and distant metastases (DM), disease-free (DFS) and overall survival (OS). A total of 108 eligible patients were randomly assigned to arm A (n = 52) or arm B (n = 56). With a median follow-up of 69.5 months, 5-year DFS was 64% in arm A and 62% in arm B (P = 0.85) and 5-year OS was 78% in arm A and 75% in arm B (P = 0.64). The 5-year cumulative incidence of LR was 2% and 5% (P = 0.61) and 5-year cumulative incidence of DM was 21% and 23%; (P = 0.79) in arms A and B, respectively. Both treatment approaches yield similar outcomes. Given the lower acute toxicity and improved compliance with induction CT compared with adjuvant CT, integrating effective systemic therapy before CRT and surgery is a promising strategy and should be examined in phase III trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Dose-dependent effect of donepezil administration on long-term enhancement of visually evoked potentials and cholinergic receptor overexpression in rat visual cortex.

    Science.gov (United States)

    Chamoun, Mira; Groleau, Marianne; Bhat, Menakshi; Vaucher, Elvire

    2016-09-01

    Stimulation of the cholinergic system tightly coupled with periods of visual stimulation boosts the processing of specific visual stimuli via muscarinic and nicotinic receptors in terms of intensity, priority and long-term effect. However, it is not known whether more diffuse pharmacological stimulation with donepezil, a cholinesterase inhibitor, is an efficient tool for enhancing visual processing and perception. The goal of the present study was to potentiate cholinergic transmission with donepezil treatment (0.5 and 1mg/kg) during a 2-week visual training to examine the effect on visually evoked potentials and to profile the expression of cholinergic receptor subtypes. The visual training was performed daily, 10min a day, for 2weeks. One week after the last training session, visual evoked potentials were recorded, or the mRNA expression level of muscarinic (M1-5) and nicotinic (α/β) receptors subunits was determined by quantitative RT-PCR. The visual stimulation coupled with any of the two doses of donepezil produced significant amplitude enhancement of cortical evoked potentials compared to pre-training values. The enhancement induced by the 1mg/kg dose of donepezil was spread to neighboring spatial frequencies, suggesting a better sensitivity near the visual detection threshold. The M3, M4, M5 and α7 receptors mRNA were upregulated in the visual cortex for the higher dose of donepezil but not the lower one, and the receptors expression was stable in the somatosensory (non-visual control) cortex. Therefore, higher levels of acetylcholine within the cortex sustain the increased intensity of the cortical response and trigger the upregulation of cholinergic receptors.

  1. Critical involvement of postsynaptic protein kinase activation in long-term potentiation at hippocampal mossy fiber synapses on CA3 interneurons.

    Science.gov (United States)

    Galván, Emilio J; Cosgrove, Kathleen E; Mauna, Jocelyn C; Card, J Patrick; Thiels, Edda; Meriney, Stephen D; Barrionuevo, Germán

    2010-02-24

    Hippocampal mossy fiber (MF) synapses on area CA3 lacunosum-moleculare (L-M) interneurons are capable of undergoing a Hebbian form of NMDA receptor (NMDAR)-independent long-term potentiation (LTP) induced by the same type of high-frequency stimulation (HFS) that induces LTP at MF synapses on pyramidal cells. LTP of MF input to L-M interneurons occurs only at synapses containing mostly calcium-impermeable (CI)-AMPA receptors (AMPARs). Here, we demonstrate that HFS-induced LTP at these MF-interneuron synapses requires postsynaptic activation of protein kinase A (PKA) and protein kinase C (PKC). Brief extracellular stimulation of PKA with forskolin (FSK) alone or in combination with 1-Methyl-3-isobutylxanthine (IBMX) induced a long-lasting synaptic enhancement at MF synapses predominantly containing CI-AMPARs. However, the FSK/IBMX-induced potentiation in cells loaded with the specific PKA inhibitor peptide PKI(6-22) failed to be maintained. Consistent with these data, delivery of HFS to MFs synapsing onto L-M interneurons loaded with PKI(6-22) induced posttetanic potentiation (PTP) but not LTP. Hippocampal sections stained for the catalytic subunit of PKA revealed abundant immunoreactivity in interneurons located in strata radiatum and L-M of area CA3. We also found that extracellular activation of PKC with phorbol 12,13-diacetate induced a pharmacological potentiation of the isolated CI-AMPAR component of the MF EPSP. However, HFS delivered to MF synapses on cells loaded with the PKC inhibitor chelerythrine exhibited PTP followed by a significant depression. Together, our data indicate that MF LTP in L-M interneurons at synapses containing primarily CI-AMPARs requires some of the same signaling cascades as does LTP of glutamatergic input to CA3 or CA1 pyramidal cells.

  2. Modulation of Long-Term Potentiation of Cortico-Amygdala Synaptic Responses and Auditory Fear Memory by Dietary Polyunsaturated Fatty Acid

    Science.gov (United States)

    Yamada, Daisuke; Wada, Keiji; Sekiguchi, Masayuki

    2016-01-01

    Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA) in the brain is involved in mental illnesses such as anxiety disorders. However, the underlying mechanism is unknown. We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory. In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala (BLA). However, it is not known whether long-term synaptic plasticity in the amygdala is influenced by the dietary ratio of ω3 to ω6 PUFA. In the present study, we examined long-term potentiation (LTP) of optogenetically-evoked excitatory synaptic responses in synapses between the terminal of the projection from the auditory cortex (ACx) and the pyramidal cells in the lateral nucleus of the amygdala. We found that LTP in this pathway was attenuated in mice fed with a high ω3 to ω6 PUFA ratio diet (0.97), compared with mice fed with a low ω3 to ω6 PUFA ratio diet (0.14). Furthermore, mice in the former condition showed reduced fear responses in an auditory fear conditioning test, compared with mice in the latter condition. In both electrophysiological and behavioral experiments, the effect of a diet with a high ω3 to ω6 PUFA diet ratio was completely blocked by treatment with a CB1 receptor antagonist. Furthermore, a significant reduction was observed in cholesterol content, but not in the level of an endogenous CB1 receptor agonist, 2-arachidonoylglycerol (2-AG), in brain samples containing the amygdala. These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor–dependent manner. PMID:27601985

  3. Methodological Aspects of the Potential Use of Dendrochronological Techniques When Analyzing the Long-Term Impact of Tourism on Protected Areas

    Science.gov (United States)

    Ciapała, Szymon; Adamski, Paweł

    2015-01-01

    Intensification of pedestrian tourism causes damage to trees near tourist tracks, and likewise changes the soil structure. As a result, one may expect that annual amount of trees growing near tracks is significantly lower than deeper in the forest. However, during the study of the long-term impact of tourism on the environment (determined from tree increment dynamics), some methodological problems may occur. It is particularly important in protected areas where law and administrative regulations related to nature conservation force research to be conducted using small samples. In this paper we have analyzed the data collected in the Polish part of the Tatra National Park in the two study plots divided into two zones each: the area directly under the influence of the tourist's trampling and the control group. The aim of such analyses was to present the potential effects of the factors which may affect the results of dendrochronological analysis: (i) small size of samples that affects their representativeness, (ii) spatial differences in the rates of the process, as a result of spatial variability of environmental factors and (iii) temporal differences in the rates of the process. This study confirms that the factors mentioned above could significantly influence the results and should be taken into consideration during the analysis. PMID:26325062

  4. Long-term effects of application of sewage sludge to soil on composition of herbage with respect to potentially toxic elements

    Energy Technology Data Exchange (ETDEWEB)

    Purves, D.

    1986-03-01

    Repeated applications of metal-contaminated sewage sludge can have a drastic effect on soil levels of trace elements and lead to serious toxicity effects in plants. In some cases, land can be rendered sterile. It has been demonstrated that contamination of soils with respect to cadmium, copper, lead, mercury, nickel and zinc is largely irreversible, although there does appear to be a long-term tendency for these metals to become progressively less available to plants over a long period of time. Most national guidelines designed to regulate the disposal of sewage sludge on agricultural land are based on the assumption that relatively rapid fixation of contaminant metals does take place in the soil after sludge application. There is a dearth of information relating to the rates at which potentially toxic-elements commonly present in sewage sludge become immobilized in soils, although it is clear that contaminant boron can be leached down the profile in the short term. Evidence is presented that contamination of top soil can persist for a period of six years after a single application of sludge (150 tons dry matter/ha). Over this period, there was little change in a available levels of boron, cadmium, copper, lead and zinc in the top soil and the degree of enhancement of these elements in perennial ryegrass grown in the sludge-treated area remained more or less unchanged. 15 references, 4 tables.

  5. Global aerosol retrieval by synergistic use of ESA ENVISAT instruments and potential for long-term aerosol records from Sentinel-3

    Science.gov (United States)

    North, P. R.; Bevan, S. L.; Brockmann, C.; Fischer, J.; Gomez-Chova, L.; Grey, W.; Heckel, A.; Moreno, J. F.; Munoz Mari, J.; Preusker, R.; Regner, P.

    2009-12-01

    We present research on for improved global aerosol retrieval by synergistic use of optical sensors on the European Space Agency ENVISAT satellite, MERIS and AATSR. Previously aerosol retrievals have been developed in isolation for these instruments, using spectral and mult-angular approaches respectively. These sensors will be succeeded with improved specification on the Sentinel-3 mission (2012-2030) with the aim to offer data suitable for long-term climate records. The research aims to use combined multi-angular and spectral approaches to constrain the inverse problem. The MERIS and AATSR instruments onboard ENVISAT provide similar resolution and swath but complementary information, encompassing different spectral domains and viewing geometries. Substantial success has been obtained previously by a number of researchers in using the instruments independently; for example MERIS aerosol retrieval using spectral methods over known targets, and AATSR approaches using the dual-view capability. The research explores the gain by using information from both instruments simultaneously to constrain atmospheric profile, characterise cloud, and provide improved atmospheric correction to surface reflectance. Results suggest improved estimation of aerosol properties compared to single-instrument retrievals, when compared with AERONET. A sensitivity study is performed to evaluate potential of Sentinel-3 for aerosol retreval, to be launched in 2012, which will give continuity with enhanced instrument specifications for the successor instruments OLCI and SLSTR.

  6. Methodological Aspects of the Potential Use of Dendrochronological Techniques When Analyzing the Long-Term Impact of Tourism on Protected Areas.

    Science.gov (United States)

    Ciapała, Szymon; Adamski, Paweł

    2015-01-01

    Intensification of pedestrian tourism causes damage to trees near tourist tracks, and likewise changes the soil structure. As a result, one may expect that annual amount of trees growing near tracks is significantly lower than deeper in the forest. However, during the study of the long-term impact of tourism on the environment (determined from tree increment dynamics), some methodological problems may occur. It is particularly important in protected areas where law and administrative regulations related to nature conservation force research to be conducted using small samples. In this paper we have analyzed the data collected in the Polish part of the Tatra National Park in the two study plots divided into two zones each: the area directly under the influence of the tourist's trampling and the control group. The aim of such analyses was to present the potential effects of the factors which may affect the results of dendrochronological analysis: (i) small size of samples that affects their representativeness, (ii) spatial differences in the rates of the process, as a result of spatial variability of environmental factors and (iii) temporal differences in the rates of the process. This study confirms that the factors mentioned above could significantly influence the results and should be taken into consideration during the analysis.

  7. Temporal Variation in Honey Production by the Stingless Bee Melipona subnitida (Hymenoptera: Apidae): Long-Term Management Reveals its Potential as a Commercial Species in Northeastern Brazil.

    Science.gov (United States)

    Koffler, Sheina; Menezes, Cristiano; Menezes, Paulo Roberto; Kleinert, Astrid de Matos Peixoto; Imperatriz-Fonseca, Vera Lucia; Pope, Nathaniel; Jaffé, Rodolfo

    2015-06-01

    Even though stingless beekeeping has a great potential as a sustainable development tool, the activity remains essentially informal, technical knowledge is scarce, and management practices lack the sophistication and standardization found in apiculture. Here, we contributed to the further development of stingless beekeeping by investigating the long-term impact of management and climate on honey production and colony survival in the stingless bee Melipona subnitida Ducke (1910). We analyzed a 10-yr record of 155 M. subnitida colonies kept by a commercial honey producer of northeastern Brazil. This constitutes the longest and most accurate record available for a stingless bee. We modeled honey production in relation to time (years), age, management practices (colony division and food supplementation), and climatic factors (temperature and precipitation), and used a model selection approach to identify which factors best explained honey production. We also modeled colony mortality in relation to climatic factors. Although the amount of honey produced by each colony decreased over time, we found that the probability of producing honey increased over the years. Colony divisions decreased honey production, but did not affect honey presence, while supplementary feeding positively affected honey production. In warmer years, the probability of producing honey decreased and the amount of honey produced was lower. In years with lower precipitation, fewer colonies produced honey. In contrast, colony mortality was not affected by climatic factors, and some colonies lived up to nine years, enduring extreme climatic conditions. Our findings provide useful guidelines to improve management and honey production in stingless bees.

  8. Alzheimer amyloid beta-peptide A-beta25-35 blocks adenylate cyclase-mediated forms of hippocampal long-term potentiation.

    Science.gov (United States)

    Bisel, Blaine E; Henkins, Kristen M; Parfitt, Karen D

    2007-02-01

    Progressive memory loss and deposition of amyloid beta (Abeta) peptides throughout cortical regions are hallmarks of Alzheimer's disease (AD). Several studies in mice and rats have shown that overexpression of amyloid precursor protein (APP) or pretreatment with Abeta peptide fragments results in the inhibition of hippocampal long-term potentiation (LTP) as well as impairments in learning and memory of hippocampal-dependent tasks. For these studies we have investigated the effects of the Abeta(25-35) peptide fragment on LTP induced by adenylate cyclase stimulation followed immediately by application of Mg(++)-free aCSF ("chemLTP"). Treatment of young adult slices with the Abeta(25-35) peptide had no significant effect on basal synaptic transmission in area CA1, but treatment with the peptide for 20 min before inducing chemLTP with isoproterenol (ISO; 1 microM) or forskolin (FSK;10 microM) + Mg(++)-free aCSF resulted in complete blockade of LTP. In contrast, normal ISO-chemLTP was observed after treatment with the control peptide Abeta(35-25). The ability of the Abeta(25-35) peptide fragment to block this and other forms of synaptic plasticity may help elucidate the mechanisms underlying hippocampal deficits observed in animal models of AD and/or AD individuals.

  9. Adolescent mice show anxiety- and aggressive-like behavior and the reduction of long-term potentiation in mossy fiber-CA3 synapses after neonatal maternal separation.

    Science.gov (United States)

    Shin, S Y; Han, S H; Woo, R-S; Jang, S H; Min, S S

    2016-03-01

    Exposure to maternal separation (MS) during early life is an identified risk factor for emotional disorders such as anxiety and depression later in life. This study investigated the effects of neonatal MS on the behavior and long-term potentiation (LTP) as well as basic synaptic transmission at hippocampal CA3-CA1 and mossy fiber (MF)-CA3 synapses in adolescent mice for 19days. When mice were adolescents, we measured depression, learning, memory, anxious and aggressive behavior using the forced swimming test (FST), Y-maze, Morris water maze (MWM), elevated plus maze (EPM), three consecutive days of the open field test, the social interaction test, the tube-dominance test and the resident-intruder test. The results showed that there was no difference in FST, Y-maze, and MWM performance. However, MS mice showed more anxiety-like behavior in the EPM test and aggressive-like behavior in the tube-dominance and resident-intruder tests. In addition, the magnitude of LTP and release probability in the MF-CA3 synapses was reduced in the MS group but not in the CA3-CA1 synapse. Our results indicate that early life stress due to MS may induce anxiety- and aggressive-like behavior during adolescence, and these effects are associated with synaptic plasticity at the hippocampal MF-CA3 synapses.

  10. Expression of p53 Target Genes in the Early Phase of Long-Term Potentiation in the Rat Hippocampal CA1 Area

    Directory of Open Access Journals (Sweden)

    Vladimir O. Pustylnyak

    2015-01-01

    Full Text Available Gene expression plays an important role in the mechanisms of long-term potentiation (LTP, which is a widely accepted experimental model of synaptic plasticity. We have studied the expression of at least 50 genes that are transcriptionally regulated by p53, as well as other genes that are related to p53-dependent processes, in the early phase of LTP. Within 30 min after Schaffer collaterals (SC tetanization, increases in the mRNA and protein levels of Bax, which are upregulated by p53, and a decrease in the mRNA and protein levels of Bcl2, which are downregulated by p53, were observed. The inhibition of Mdm2 by nutlin-3 increased the basal p53 protein level and rescued its tetanization-induced depletion, which suggested the involvement of Mdm2 in the control over p53 during LTP. Furthermore, nutlin-3 caused an increase in the basal expression of Bax and a decrease in the basal expression of Bcl2, whereas tetanization-induced changes in their expression were occluded. These results support the hypothesis that p53 may be involved in transcriptional regulation during the early phase of LTP. We hope that the presented data may aid in the understanding of the contribution of p53 and related genes in the processes that are associated with synaptic plasticity.

  11. The group I metabotropic glutamate receptor mGluR5 is required for fear memory formation and long-term potentiation in the lateral amygdala.

    Science.gov (United States)

    Rodrigues, Sarina M; Bauer, Elizabeth P; Farb, Claudia R; Schafe, Glenn E; LeDoux, Joseph E

    2002-06-15

    The group I metabotropic glutamate receptor subtype mGluR5 has been shown to play a key role in the modulation of synaptic plasticity. The present experiments examined the function of mGluR5 in the circuitry underlying Pavlovian fear conditioning using neuroanatomical, electrophysiological, and behavioral techniques. First, we show using immunocytochemical and tract-tracing methods that mGluR5 is localized to dendritic shafts and spines in the lateral nucleus of the amygdala (LA) and is postsynaptic to auditory thalamic inputs. In electrophysiological experiments, we show that long-term potentiation at thalamic input synapses to the LA is impaired by bath application of a specific mGluR5 antagonist, 2-methyl-6-(phenyle-thynyl)-pyridine (MPEP), in vitro. Finally, we show that intra-amygdala administration of MPEP dose-dependently impairs the acquisition, but not expression or consolidation, of auditory and contextual fear conditioning. Collectively, the results of this study indicate that mGluR5 in the LA plays a crucial role in fear conditioning and in plasticity at synapses involved in fear conditioning.

  12. β-adrenergic modulation of in vivo long-term potentiation in area CA1 and its role in spatial learning in rats

    Institute of Scientific and Technical Information of China (English)

    JI; Jinzhao; (季今朝); ZHANG; Xuehan; (张雪寒); LI; Baoming; (李葆明)

    2003-01-01

    Activation of β-adrenoceptors in area CA1 of the hippocampus facilitates in vitro long-term potentiation (LTP) in this region. However, it is unclear if in vivo LTP in area CA1 and hippocampus-dependent learning are subjected to β-adrenergic regulation. To address this question, we investigated the effects of the β-adrenergic agonist L-isoproterenol or antagonist DL-propranolol on in vivo LTP of area CA1 and the spatial learning in Morris water maze. In the presence of L-isoproterenol (through local infusion into area CA1), the theta-pulse stimulation with the parameter of 10 Hz, 150 pulses/train, 1 train, a frequency weakly modifying synaptic strength, induced a robust LTP, and this effect was blocked when DL-propranolol was co-administered. By contrast, the theta-pulse stimulation with the parameter of 5 Hz, 150 pulses/train, 3 trains, a frequency strongly modifying synaptic strength, induced a significantly smaller LTP when DL-propranolol was administered into area CA1. Accordingly, DL-propranolol impaired the spatial learning in the water maze when infused into area CA1 20 min pretraining. Compared with control rats, the DL-propranolol-treated rats showed significantly slower learning in the water maze and subsequently exhibited poor memory retention at 24-h test. These results suggest that β-adrenoceptors in area CA1 are involved in regulating in vivo synaptic plasticity of this area and are important for spatial learning.

  13. Effects of Chronic Administration of Melatonin on Spatial Learning Ability and Long-term Potentiation in Lead-exposed and Control Rats

    Institute of Scientific and Technical Information of China (English)

    XIU-JING CAO; MING WANG; WEI-HENG CHEN; DA-MIAO ZHU; JIA-QI SHE; DI-YUN RUAN

    2009-01-01

    Objective To explore the changes in spatial learning performance and long-term potentiation (LTP) which is recognized as a component of the cellular basis of learning and memory in normal and lead-exposed rats after administration of melatonin (MT) for two months. Methods Experiment was performed in adult male Wistar rats (12 controls, 12 exposed to melatonin treatment, 10 exposed to lead and 10 exposed to lead and melatonin treatment). The lead-exposed rats received 0.2% lead acetate solution from their birth day while the control rats drank tap water. Melatonin (3 mg/kg) or vehicle was administered to the control and lead-exposed rats from the time of their weaning by gastric garage each day for 60 days, depending on their groups. At the age of 81-90 days, all the animals were subjected to Morris water maze test and then used for extracellular recording of LTP in the dentate gyrus (DG) area of the hippocampus in vivo. Results Low dose of melatonin given from weaning for two months impaired LTP in the DG area of hippocampus and induced learning and memory deficit in the control rats. When melatonin was administered over a prolonged period to the lead-exposed rats, it exacerbated LTP impairment, learning and memory deficit induced by lead. Conclusion Melatonin is not suitable for normal and lead-exposed children.

  14. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui [Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang (China); Teng, Weiping, E-mail: twpendocrine@yahoo.com.cn [Liaoning Provincial Key Laboratory of Endocrine Diseases, the First Hospital of China Medical University, Shenyang (China); Chen, Jie, E-mail: chenjie@mail.cmu.edu.cn [Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang (China)

    2013-09-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  15. IN VIVO EVALUATION OF SKIN IRRITATION POTENTIAL, MELASMA AND SEBUM CONTENT FOLLOWING LONG TERM APPLICATION OF SKIN CARE CREAM IN HEALTHY ADULTS, USING NON-INVASIVE BIOMETROLOGICAL TECHNIQUES.

    Science.gov (United States)

    Arshad, Atif I; Khan, Shoaib H M; Akhtar, Naveed; Mahmood, Asif; Sarfraz, Rai Muhammad

    2016-01-01

    The present investigation was conducted to evaluate non-invasively, various functional skin parameters i.e., irritation potential, melasma and sebum contents following long term application of topical cream (w/o) loaded with 2% methanolic extract of Ananas comosus L. versus placebo control (base) in healthy adults. Healthy human volunteers (n = 11, aged 20-30 years) were recruited for investigation and written informed consent was taken from each volunteer. In this single blinded study every volunteer applied formulation on one side of face and placebo on the other side of face twice daily for a period of 12 weeks (three months). Different skin parameters i.e., skin irritancy, melasma, and sebum contents were measured on both sides of face at baseline and after two weeks interval, using photometric device Mexameter and Sebumeter in a draught free room with modulated conditions of temperature (22-25°C) and humidity (55-60%). It was evident from the results that no primary skin irritancy was observed with patch test. Besides, statistical interpretation indicates that treatment with formulation is superior to placebo because it significantly (p ≤ 0.05) reduced the skin irritancy, melasma and sebum secretions throughout the study and reaching maximum -20.76 ± 0.89, -54.2 ± 0.37 and -40.71 ± 0.75%, respectively, at the end of study period. Antioxidant activity of extract was 92% compared to standard antioxidant. Conclusively, active cream loaded with fruit extract was well tolerated by all the volunteers and suitable to treat contact dermatitis, greasy skin, acne and seborrheic dermatitis and augmenting beauty and attraction by depigmentation of human skin. So, in the future, there is need to clinically evaluate these formulations in patients with compromised skin functions i.e., contact dermatitis, melasma, and acne vulgaris in order to explore the actual potential of this fruit.

  16. Hydrocarbon degradation potential and plant growth-promoting activity of culturable endophytic bacteria of Lotus corniculatus and Oenothera biennis from a long-term polluted site.

    Science.gov (United States)

    Pawlik, Małgorzata; Cania, Barbara; Thijs, Sofie; Vangronsveld, Jaco; Piotrowska-Seget, Zofia

    2017-07-06

    Many endophytic bacteria exert beneficial effects on their host, but still little is known about the bacteria associated with plants growing in areas heavily polluted by hydrocarbons. The aim of the study was characterization of culturable hydrocarbon-degrading endophytic bacteria associated with Lotus corniculatus L. and Oenothera biennis L. collected in long-term petroleum hydrocarbon-polluted site using culture-dependent and molecular approaches. A total of 26 hydrocarbon-degrading endophytes from these plants were isolated. Phylogenetic analyses classified the isolates into the phyla Proteobacteria and Actinobacteria. The majority of strains belonged to the genera Rhizobium, Pseudomonas, Stenotrophomonas, and Rhodococcus. More than 90% of the isolates could grow on medium with diesel oil, approximately 20% could use n-hexadecane as a sole carbon and energy source. PCR analysis revealed that 40% of the isolates possessed the P450 gene encoding for cytochrome P450-type alkane hydroxylase (CYP153). In in vitro tests, all endophytic strains demonstrated a wide range of plant growth-promoting traits such as production of indole-3-acetic acid, hydrogen cyanide, siderophores, and phosphate solubilization. More than 40% of the bacteria carried the gene encoding for the 1-aminocyclopropane-1-carboxylic acid deaminase (acdS). Our study shows that the diversity of endophytic bacterial communities in tested plants was different. The results revealed also that the investigated plants were colonized by endophytic bacteria possessing plant growth-promoting features and a clear potential to degrade hydrocarbons. The properties of isolated endophytes indicate that they have the high potential to improve phytoremediation of petroleum hydrocarbon-polluted soils.

  17. A cost of long-term memory in Drosophila

    OpenAIRE

    Mery, Frederic; Kawecki, Tadeusz J.

    2005-01-01

    Two distinct forms of consolidated associative memory are known in Drosophila: long-term memory and so-called anesthesia-resistant memory. Long-term memory is more stable, but unlike anesthesia-resistant memory, its formation requires protein synthesis. We show that flies induced to form long-term memory become more susceptible to extreme stress (such as desiccation). In contrast, induction of anesthesia-resistant memory had no detectable effect on desiccation resistance. This finding may hel...

  18. Test-Retest Reliability of 10 Hz Conditioning Electrical Stimulation Inducing Long-Term Potentiation (LTP)-Like Pain Amplification in Humans

    Science.gov (United States)

    Xia, Weiwei; Mørch, Carsten Dahl; Andersen, Ole Kæseler

    2016-01-01

    Background 10 Hz conditioning electrical stimulation (CES) has been shown to induce long-term potentiation (LTP)-like pain amplification similar to traditional 100 Hz CES in healthy humans. The aim of this study was to assess the test-retest reliability and to estimate sample sizes required for future crossover and parallel study designs. Methods The 10 Hz paradigm (500 rectangular pulses lasting 50 s) was repeated on two separate days with one week interval in twenty volunteers. Perceptual intensities to single electrical stimulation (SES) at the conditioned skin site and to mechanical stimuli (pinprick and light stroking) in immediate vicinity to the conditioned skin site were recorded. Superficial blood flow (SBF) was assessed as indicator of neurogenic inflammation. All outcome measures were assessed with 10 min interval three times before and six times after the CES. The coefficient of variation and intra-class correlation coefficient were calculated within session and between sessions. Sample sizes were estimated for future crossover (Ncr) and parallel (Np) drug testing studies expected to detect a 30% decrease for the individual outcome measure following 10 Hz CES. Results Perceptual intensity ratings to light stroking (Ncr = 2, Np = 33) and pinprick stimulation (491 mN) (Ncr = 6, Np = 54) increased after CES and showed better reliability in crossover than parallel design. The SBF increased after CES, and then declined until reaching a plateau 20 minutes postCES. SBF showed acceptable reliability both in crossover and parallel designs (Ncr = 3, Np = 13). Pain ratings to SES were reliable, but with large estimated sample sizes (Ncr = 634, Np = 11310) due to the minor pain amplification. Conclusions The reliability of 10 Hz CES was acceptable in inducing LTP-like effects in the assessments of superficial blood flow, heterotopic mechanical hyperalgesia, and dysesthesia in terms of sample sizes for future crossover study designs. PMID:27529175

  19. Investigating the potential for long-term permeable reactive barrier (PRB) monitoring from the electrical signatures associated with the reduction in reactive iron performance

    Energy Technology Data Exchange (ETDEWEB)

    Slater, Lee D.; Korte, N.; Baker, J.

    2005-12-14

    The objective of this work was to conduct laboratory and field experiments to determine the sensitivity of low frequency electrical measurements (resistivity and induced polarization) to the processes of corrosion and precipitation that are believed to limit permeable reactive barrier (PRB) performance. The research was divided into four sets of experiments that were each written up and submitted to a peer-reviewed journal: [1] A laboratory experiment to define the controls of aqueous chemistry (electrolyte activity; pH; valence) and total zero valent iron (Fe0) available surface area on the electrical properties of Fe0 columns. [2] A laboratory experiment to determine the impact of corrosion and precipitation on the electrical response of synthetic Fe0 columns as a result of geochemical reactions with NaSO4 and NaCO3 electrolytes. [3] Laboratory experiments on a sequence of cores retrieved from the Kansas City PRB to determine the magnitude of electrical and geochemical changes within a field active PRB after eight years of operation [4] Field-scale cross borehole resistivity and induced polarization monitoring of the Kansas City PRB to evaluate the potential of electrical imaging as a technology for non-invasive, long-term monitoring of indicators of reduced PRB performance This report first summarizes the findings of the four major experiments conducted under this research. The reader is referred to the four papers in Appendices 1-4 for a full description of each experiment, including motivation and significance, technical details, findings and implications. The deliverables of the project, including the publications, conference papers and new collaborative arrangements that have resulted are then described. Appendices 5-6 contain two technical reports written by co-PI Korte describing (1) supporting geochemical measurements, and (2) the coring procedure, conducted at the Kansas City PRB as part of this project.

  20. Loss of α1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING.

    Science.gov (United States)

    Gu, Wei; Fukuda, Tomohiko; Isaji, Tomoya; Hang, Qinglei; Lee, Ho-hsun; Sakai, Seiichiro; Morise, Jyoji; Mitoma, Junya; Higashi, Hideyoshi; Taniguchi, Naoyuki; Yawo, Hiromu; Oka, Shogo; Gu, Jianguo

    2015-07-10

    Core fucosylation is catalyzed by α1,6-fucosyltransferase (FUT8), which transfers a fucose residue to the innermost GlcNAc residue via α1,6-linkage on N-glycans in mammals. We previously reported that Fut8-knock-out (Fut8(-/-)) mice showed a schizophrenia-like phenotype and a decrease in working memory. To understand the underlying molecular mechanism, we analyzed early form long term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. The scale of E-LTP induced by high frequency stimulation was significantly decreased in Fut8(-/-) mice. Tetraethylammonium-induced LTP showed no significant differences, suggesting that the decline in E-LTP was caused by postsynaptic events. Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. The activation of AMPARs was further confirmed by Fura-2 calcium imaging using primary cultured neurons. Taken together, loss of core fucosylation on AMPARs enhanced their heteromerization, which increase sensitivity for postsynaptic depolarization and persistently activate N-methyl-d-aspartate receptors as well as Ca(2+) influx and CaMKII and then impair LTP. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Genetic knockout of the α7 nicotinic acetylcholine receptor gene alters hippocampal long-term potentiation in a background strain-dependent manner.

    Science.gov (United States)

    Freund, Ronald K; Graw, Sharon; Choo, Kevin S; Stevens, Karen E; Leonard, Sherry; Dell'Acqua, Mark L

    2016-08-01

    Reduced α7 nicotinic acetylcholine receptor (nAChR) function is linked to impaired hippocampal-dependent sensory processing and learning and memory in schizophrenia. While knockout of the Chrna7 gene encoding the α7nAChR on a C57/Bl6 background results in changes in cognitive measures, prior studies found little impact on hippocampal synaptic plasticity in these mice. However, schizophrenia is a multi-genic disorder where complex interactions between specific genetic mutations and overall genetic background may play a prominent role in determining phenotypic penetrance. Thus, we compared the consequences of knocking out the α7nAChR on synaptic plasticity in C57/Bl6 and C3H mice, which differ in their basal α7nAChR expression levels. Homozygous α7 deletion in C3H mice, which normally express higher α7nAChR levels, resulted in impaired long-term potentiation (LTP) at hippocampal CA1 synapses, while C3H α7 heterozygous mice maintained robust LTP. In contrast, homozygous α7 deletion in C57 mice, which normally express lower α7nAChR levels, did not alter LTP, as had been previously reported for this strain. Thus, the threshold of Chrna7 expression required for LTP may be different in the two strains. Measurements of auditory gating, a hippocampal-dependent behavioral paradigm used to identify schizophrenia-associated sensory processing deficits, was abnormal in C3H α7 knockout mice confirming that auditory gating also requires α7nAChR expression. Our studies highlight the importance of genetic background on the regulation of synaptic plasticity and could be relevant for understanding genetic and cognitive heterogeneity in human studies of α7nAChR dysfunction in mental disorders.

  2. Inhibition of the Motor Protein Eg5/Kinesin-5 in Amyloid β-Mediated Impairment of Hippocampal Long-Term Potentiation and Dendritic Spine Loss.

    Science.gov (United States)

    Freund, Ronald K; Gibson, Emily S; Potter, Huntington; Dell'Acqua, Mark L

    2016-05-01

    Alzheimer's disease (AD) is characterized by neurofibrillary tangles, amyloid plaques, and neurodegeneration. However, this pathology is preceded by increased soluble amyloid beta (Aβ) 1-42 oligomers that interfere with the glutamatergic synaptic plasticity required for learning and memory, includingN-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP). In particular, soluble Aβ(1-42) acutely inhibits LTP and chronically causes synapse loss. Many mechanisms have been proposed for Aβ-induced synaptic dysfunction, but we recently found that Aβ(1-42) inhibits the microtubule motor protein Eg5/kinesin-5. Here we compared the impacts of Aβ(1-42) and monastrol, a small-molecule Eg5 inhibitor, on LTP in hippocampal slices and synapse loss in neuronal cultures. Acute (20-minute) treatment with monastrol, like Aβ, completely inhibited LTP at doses >100 nM. In addition, 1 nM Aβ(1-42) or 50 nM monastrol inhibited LTP #x223c;50%, and when applied together caused complete LTP inhibition. At concentrations that impaired LTP, neither Aβ(1-42) nor monastrol inhibited NMDAR synaptic responses until #x223c;60 minutes, when only #x223c;25% inhibition was seen for monastrol, indicating that NMDAR inhibition was not responsible for LTP inhibition by either agent when applied for only 20 minutes. Finally, 48 hours of treatment with either 0.5-1.0μM Aβ(1-42) or 1-5μM monastrol reduced the dendritic spine/synapse density in hippocampal cultures up to a maximum of #x223c;40%, and when applied together at maximal concentrations, no additional spine loss resulted. Thus, monastrol can mimic and in some cases occlude the impact of Aβon LTP and synapse loss, suggesting that Aβinduces acute and chronic synaptic dysfunction in part through inhibiting Eg5.

  3. Long-term urethral catheterisation.

    Science.gov (United States)

    Turner, Bruce; Dickens, Nicola

    This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

  4. Effects of long-term in vitro culturing of transgenic bovine donor fibroblasts on cell viability and in vitro developmental potential after nuclear transfer.

    Science.gov (United States)

    Bressan, F F; Miranda, M S; Bajgelman, M C; Perecin, F; Mesquita, L G; Fantinato-Neto, P; Merighe, G F K; Strauss, B E; Meirelles, F V

    2013-04-01

    with early or late-passage cells when fusion (63.1% and 49%), cleavage (67.7% and 69.9%), eight-cell embryo (36.4% and 44.4%) and blastocyst (21.6% and 20.8%) rates were compared. In conclusion, culture behavior was different between control and eGFP cells. However, when different in vitro culturing periods were compared, long-term cultured transgenic fetal fibroblasts remained competent for blastocyst production when used as nuclei donors in the nuclear transfer technique, a feature needed for the genetic manipulation of cell culture experiments aiming for transgenic animal production.

  5. LTP研究进展(Ⅲ)——LTP和神经趋向因子%Recent advances in the study of long-term potentiation( part Ⅲ) -LTP and Neurotrophin

    Institute of Scientific and Technical Information of China (English)

    李勇; 叶桂兰

    2002-01-01

    长时程增强(LTP)是学习和记忆过程的分子水平现象.参与LTP机制的因素很多,最近研究发现神经趋向因子,特别是其中的脑衍生的神经趋向因子(BDNF)对LTP起着重要的调节作用,而且对短时程及长时程突触可塑性均有影响.已经明确的神经趋向因子的功能包括调节神经分化,神经元轴突和树突的生长和修复,以及突触形成.本文综述了BDNF与LTP相关性的实验性根据.总结了BDNF通过突触前以及突触后机制影响LTP的引发和后期维持.BDNF的直接作用机制是作用于突触前后膜上的受体,导致突触前递质小泡增多从而增加递质释放.在突触后引起突触后膜去极化,从而打开电压依赖性钙通道、钙离子浓度增高,最终导致AMPA受体数目增多,功能强化,产生LTP.%Long-term potentiation (LTP) is believed underlined learning and memory. Recent research has attracted to brain-derived neurotrophic factor (BDNF) that may affect synaptic plasticity in both short- and long-term actions at the synapse. In vitro, neurotrophin regulate neuronal differentiation, axonal and dendritic growth and repair, synaptic formation, and synaptic plasticity. Here we summarized the experimental evidence linking BDNF to LTP. BDNF plays a role in LTP induction and late phase maintenance. The actions of BDNF are mediated by the TrkB receptor tyrosine kinase. BDNF potentiate LTP by modulating the number of docked vesicles and the level of vesicle protein on pre-synapse to increase neurotransmitter release, and by inducing postsynaptic depolarization to open voltage dependent Ca2+ channels. We also introduced the effects of LTP on the secretion of the neurotrophin. The experimental evidence strongly supports a role for BDNF in synaptic plasticity and should prompt further exploration of their functions at the synapse.

  6. Brazilian network for the surveillance of maternal potentially life threatening morbidity and maternal near-miss and a multidimensional evaluation of their long term consequences

    Directory of Open Access Journals (Sweden)

    Surita Fernanda G

    2009-09-01

    Full Text Available Abstract Background It has been suggested that the study of women who survive life-threatening complications related to pregnancy (maternal near-miss cases may represent a practical alternative to surveillance of maternal morbidity/mortality since the number of cases is higher and the woman herself is able to provide information on the difficulties she faced and the long-term repercussions of the event. These repercussions, which may include sexual dysfunction, postpartum depression and posttraumatic stress disorder, may persist for prolonged periods of time, affecting women's quality of life and resulting in adverse effects to them and their babies. Objective The aims of the present study are to create a nationwide network of scientific cooperation to carry out surveillance and estimate the frequency of maternal near-miss cases, to perform a multicenter investigation into the quality of care for women with severe complications of pregnancy, and to carry out a multidimensional evaluation of these women up to six months. Methods/Design This project has two components: a multicenter, cross-sectional study to be implemented in 27 referral obstetric units in different geographical regions of Brazil, and a concurrent cohort study of multidimensional analysis. Over 12 months, investigators will perform prospective surveillance to identify all maternal complications. The population of the cross-sectional component will consist of all women surviving potentially life-threatening conditions (severe maternal complications or life-threatening conditions (the maternal near miss criteria and maternal deaths according to the new WHO definition and criteria. Data analysis will be performed in case subgroups according to the moment of occurrence and determining cause. Frequencies of near-miss and other severe maternal morbidity and the association between organ dysfunction and maternal death will be estimated. A proportion of cases identified in the cross

  7. Brazilian network for the surveillance of maternal potentially life threatening morbidity and maternal near-miss and a multidimensional evaluation of their long term consequences.

    Science.gov (United States)

    Cecatti, Jose G; Souza, João P; Parpinelli, Mary A; Haddad, Samira M; Camargo, Rodrigo S; Pacagnella, Rodolfo C; Silveira, Carla; Zanardi, Dulce T; Costa, Maria L; Pinto e Silva, João L; Passini, Renato; Surita, Fernanda G; Sousa, Maria H; Calderon, Iracema M P; Say, Lale; Pattinson, Robert C

    2009-09-24

    It has been suggested that the study of women who survive life-threatening complications related to pregnancy (maternal near-miss cases) may represent a practical alternative to surveillance of maternal morbidity/mortality since the number of cases is higher and the woman herself is able to provide information on the difficulties she faced and the long-term repercussions of the event. These repercussions, which may include sexual dysfunction, postpartum depression and posttraumatic stress disorder, may persist for prolonged periods of time, affecting women's quality of life and resulting in adverse effects to them and their babies. The aims of the present study are to create a nationwide network of scientific cooperation to carry out surveillance and estimate the frequency of maternal near-miss cases, to perform a multicenter investigation into the quality of care for women with severe complications of pregnancy, and to carry out a multidimensional evaluation of these women up to six months. This project has two components: a multicenter, cross-sectional study to be implemented in 27 referral obstetric units in different geographical regions of Brazil, and a concurrent cohort study of multidimensional analysis. Over 12 months, investigators will perform prospective surveillance to identify all maternal complications. The population of the cross-sectional component will consist of all women surviving potentially life-threatening conditions (severe maternal complications) or life-threatening conditions (the maternal near miss criteria) and maternal deaths according to the new WHO definition and criteria. Data analysis will be performed in case subgroups according to the moment of occurrence and determining cause. Frequencies of near-miss and other severe maternal morbidity and the association between organ dysfunction and maternal death will be estimated. A proportion of cases identified in the cross-sectional study will comprise the cohort of women for the

  8. Long-term effective population sizes, temporal stability of genetic composition and potential for local adaptation in anadromous brown trout ( Salmo trutta ) populations

    DEFF Research Database (Denmark)

    Hansen, Michael Møller; Ruzzante, D.E.; Eg Nielsen, Einar;

    2002-01-01

    (3 km) river showed Ne greater than or equal to 300. Assuming a stepping-stone model of gene flow we considered the relative roles of gene flow, random genetic drift and selection to assess the possibilities for local adaptation. The requirements for local adaptation were fulfilled, but only......We examined the long-term temporal (1910s to 1990s) genetic variation at eight microsatellite DNA loci in brown trout (Salmo trutta L) collected from five anadromous populations in Denmark to assess the long-term stability of genetic composition and to estimate effective population sizes (N......-e). Contemporary and historical samples consisted of tissue and archived scales, respectively. Pairwise Theta(ST) estimates, a hierarchical analysis of molecular variance (AMOVA) and multidimensional scaling analysis of pairwise genetic distances between samples revealed much closer genetic relationships among...

  9. The E3 Ligase APC/C-Cdh1 Is Required for Associative Fear Memory and Long-Term Potentiation in the Amygdala of Adult Mice

    Science.gov (United States)

    Pick, Joseph E.; Malumbres, Marcos; Klann, Eric

    2013-01-01

    The anaphase promoting complex/cyclosome (APC/C) is an E3 ligase regulated by Cdh1. Beyond its role in controlling cell cycle progression, APC/C-Cdh1 has been detected in neurons and plays a role in long-lasting synaptic plasticity and long-term memory. Herein, we further examined the role of Cdh1 in synaptic plasticity and memory by generating…

  10. Long-term results of a prospective randomized trial evaluating G-CSF priming in intensive induction chemotherapy followed by autologous stem cell transplantation in elderly patients with acute myeloid leukemia.

    Science.gov (United States)

    Bug, Gesine; Koschmieder, Steffen; Krauter, Juergen; Heuser, Michael; Thol, Felicitas; Wiebe, Stefanie; Hofmann, Wolf-Karsten; Klein, Stefan A; Wegener, Gerd; Göhring, Gudrun; Heit, Wolfgang; Hoelzer, Dieter; Ganser, Arnold; Ottmann, Oliver G

    2014-02-01

    Few studies have evaluated granulocyte colony-stimulating factor (G-CSF) priming in elderly patients with intensively treated acute myeloid leukemia (AML), and no data are available for genetically defined AML subgroups. We provide long-term results (median follow-up 7.6 years) of a randomized trial in which 183 patients (median age 67 years) received G-CSF prior to (G-CSF priming) or after two cycles of induction chemotherapy. CR rates with G-CSF priming and G-CSF post-chemotherapy were comparable (57 vs. 67 %, p = 0.153), with overall survival (OS) probabilities of 14 vs. 17 % at 10 years. Induction mortality was significantly higher with G-CSF priming (23 vs. 10 %, p = 0.015), primarily in normal karyotype (NK) AML. In this subgroup, a trend for better relapse-free survival (RFS) was observed with G-CSF priming (44 vs. 22 % at 10 years, p = 0.074) but did not translate into an OS benefit. G-CSF priming had no impact on AML with FLT3-ITD and NPM mutations and did not improve outcome in patients with adverse cytogenetics. In a landmark analysis, late consolidation with autologous stem cell transplantation or a second consolidation cycle significantly improved RFS compared with one consolidation cycle (21.0 vs. 12.8 months, p = 0.046). Future studies on G-CSF priming should be restricted to NK AML and used only in post-remission therapy.

  11. Effects of the ephedra alkaloid methylephedrine on the basal evoked potential transportation and the long-term potentiation (LTP) in the rat hippocampal dentate granule cells in vivo

    Institute of Scientific and Technical Information of China (English)

    PENG Xiao-dong

    2008-01-01

    Objective The effect of the ephedra/ephedrine alkaloid methylephedrine (dl-methylephedrine hydrochloride for testing in this paper) on cognitive related synaptic plasticity was investigated by recording extracellular field evoked potentials and its LTP in hippocampal dentate granule cells in urethane-anaesthetized rats in vivo. Methods Single pathway recording of evoked field potentials was made from the dentate granule cells of hippocampal hemisphere in response to stimulation of the ipsilateral medial perforant path (MPP). Two parameters, the amplitude of population spike (PS amplitude) and the latency of the PS, were employed to evaluate the effects of drug on the overall changes in cellular responses. Results The present study show that methylephedrine 90 mg·kg-1 intraperitoneally, about 1/3 LD50, could increase the latency of the PS in hippocampal dentate granule cells by constant single stimulation of the MPP as the basal ransportation. However, the 30 mg·kg-1 and 10 mg·kg-1 dosage had no effect on the latency, and there are no influences of PS amplitude for all examinational groups. The methylephedrine 90 mg·kg-1 group significant enhanced the development of amplitude LTP in hippocampal dentate granule cells that induced by 60 Hz, 60 pulses conditional tetanus in medial perforant path area. Also, the 30 mg·kg-1 group can promoted the maintenance of LTP induced by this tetanus, but no promotion on PS amplitude LTP appeared in this dosage and no any changes been found in 10 mg·kg-1 dosage group. Conclusions The ephedra/ephedrine alkaloid methylephedrine can modulate the synaptic plasticity in the lateral perforant path. A possible mechanism of methylephedrine on hippocampal LTP is been discussed.

  12. [Fetal pain: immediate and long term consequences].

    Science.gov (United States)

    Houfflin Debarge, Véronique; Dutriez, Isabelle; Pusniak, Benoit; Delarue, Eléonore; Storme, Laurent

    2010-06-01

    Several situations are potentially painful for fetuses, such as malformations and invasive procedures. Nociceptive pathways are known to be functional at 26 weeks. Even if it is not possible to evaluate the fetal experience of pain, it is essential to examine its immediate and long-term consequences. As early as the beginning of the second trimester, hemodynamic and hormonal responses are observed following fetal nociceptive stimulation, In experimental studies, long-term changes have been noted in the corticotrop axis, subsequent responses to pain, and behavior after perinatal nociceptive stimulation.

  13. Projecting marine fish production and catch potential in Bangladesh in the 21st century under long-term environmental change and management scenarios

    OpenAIRE

    Jose A Fernandes; Kay, Susan; Hossain, Mostafa A.R.; Ahmed, Munir; William W L Cheung; Lazar, Attila; Barange, Manuel

    2016-01-01

    The fisheries sector is crucial to the Bangladeshi economy and wellbeing, accounting for 4.4% of national gross domestic product and 22.8% of agriculture sector production, and supplying ca. 60% of the national animal protein intake. Fish is vital to the 16 million Bangladeshis living near the coast, a number that has doubled since the 1980s. Here, we develop and apply tools to project the long-term productive capacity of Bangladesh marine fisheries under climate and fisheries management scen...

  14. Right-sided infective endocarditis as a potentially fatal complication in patients with long-term refractory severe bradyarrhythmia after cervical spinal cord injury: A case report

    Directory of Open Access Journals (Sweden)

    Naoki Miura

    2015-08-01

    Full Text Available Bradyarrhythmia is usually a spontaneously subsiding complication of cervical spinal cord injury. However, in severe cases, it can lead to cardiac arrest. We report a case of cervical spinal cord injury, complicated by right-sided infective endocarditis after the placement of a temporary pacing catheter in the right ventricle for severe bradyarrhythmia that led to cardiac arrest. Although the patient׳s condition was successfully treated by pacing catheter removal and pharmacological therapy, right-sided infective endocarditis would be a fatal complication in cases of cervical spinal cord injury where cardiac pacing is required for long-term refractory severe bradyarrhythmia.

  15. Potential for Local Fertilization: A Benthocosm Test of Long-Term and Short-Term Effects of Mussel Excretion on the Plankton.

    Science.gov (United States)

    Cherif, Mehdi; Granados, Monica; Duffy, Sean; Robert, Pauline; Péquin, Bérangère; Mohit, Vani; McKindsey, Christopher W; Archambault, Philippe; Myrand, Bruno; Lovejoy, Connie; Tremblay, Réjean; Plourde, Stéphane; Fussmann, Gregor F

    2016-01-01

    Mussel aquaculture has expanded worldwide and it is important to assess its impact on the water column and the planktonic food web to determine the sustainability of farming practices. Mussel farming may affect the planktonic food web indirectly by excreting bioavailable nutrients in the water column (a short-term effect) or by increasing nutrient effluxes from biodeposit-enriched sediments (a long-term effect). We tested both of these indirect effects in a lagoon by using plankton-enclosing benthocosms that were placed on the bottom of a shallow lagoon either inside of a mussel farm or at reference sites with no history of aquaculture. At each site, half of the benthocosms were enriched with seawater that had held mussels (excretion treatment), the other half received non-enriched seawater as a control treatment. We monitored nutrients ([PO43-] and [NH4+]), dissolved oxygen and plankton components (bacteria, the phytoplankton and the zooplankton) over 5 days. We found a significant relationship between long-term accumulation of mussel biodeposits in sediments, water-column nutrient concentrations and plankton growth. Effects of mussel excretion were not detected, too weak to be significant given the spatial and temporal variability observed in the lagoon. Effects of mussels on the water column are thus likely to be coupled to benthic processes in such semi-enclosed water bodies.

  16. Potential for Local Fertilization: A Benthocosm Test of Long-Term and Short-Term Effects of Mussel Excretion on the Plankton.

    Directory of Open Access Journals (Sweden)

    Mehdi Cherif

    Full Text Available Mussel aquaculture has expanded worldwide and it is important to assess its impact on the water column and the planktonic food web to determine the sustainability of farming practices. Mussel farming may affect the planktonic food web indirectly by excreting bioavailable nutrients in the water column (a short-term effect or by increasing nutrient effluxes from biodeposit-enriched sediments (a long-term effect. We tested both of these indirect effects in a lagoon by using plankton-enclosing benthocosms that were placed on the bottom of a shallow lagoon either inside of a mussel farm or at reference sites with no history of aquaculture. At each site, half of the benthocosms were enriched with seawater that had held mussels (excretion treatment, the other half received non-enriched seawater as a control treatment. We monitored nutrients ([PO43-] and [NH4+], dissolved oxygen and plankton components (bacteria, the phytoplankton and the zooplankton over 5 days. We found a significant relationship between long-term accumulation of mussel biodeposits in sediments, water-column nutrient concentrations and plankton growth. Effects of mussel excretion were not detected, too weak to be significant given the spatial and temporal variability observed in the lagoon. Effects of mussels on the water column are thus likely to be coupled to benthic processes in such semi-enclosed water bodies.

  17. Realizing the cognitive potential of children 5-7 with a mathematics focus: post-test and long-term effects of a 2-year intervention.

    Science.gov (United States)

    Shayer, Michael; Adhami, Mundher

    2010-09-01

    In the context of the British Government's policy directed on improving standards in schools, this paper presents research on the effects of a programme intended to promote the cognitive development of children in the first 2 years of primary school (Y1 & 2, aged 5-7 years). The programme is based on earlier work dealing with classroom-based interventions with older children at both primary and secondary levels of schooling. The hypothesis tested is that it is possible to increase the cognitive ability of children by assisting teachers towards that aim in the context of mathematics. A corollary hypothesis is that such an increase would result in an increase in long-term school achievement. The participants were 8 teachers in one local education authority (LEA) and 10 teachers in another. Data were analysed on 275 children present at Year 1 pre-test in 2002 and at long-term Key Stage 2 post-test in 2008. Two intervention methods were employed: a Y1 set of interactive activities designed around Piagetian concrete operational schemata, and mathematics lessons in both Y1 and Y2 designed from a theory-base derived from both Piaget and Vygotsky. At post-test in 2004, the mean effect sizes for cognitive development of the children - assessed by the Piagetian test Spatial Relations - were 0.71 SD in one LEA and 0.60 SD in the other. Five classes achieved a median increase of 1.3 SD. The mean gains over pre-test in 2002 for all children in Key Stage 1 English in 2004 were 0.51 SD, and at Key Stage 2 English in 2008 - the long-term effect - were 0.36 SD, an improvement of 14 percentile points. The main hypothesis was supported by the data on cognitive development. The corollary hypothesis is supported by the gains in English. The implications of this study are that relative intelligence can be increased and is not fixed, and that children can be led into collaborating with each other to the benefit of their own thinking, and that there does exist a theory-based methodology

  18. Potential long-term effects of a mind-body intervention for women with major depressive disorder: sustained mental health improvements with a pilot yoga intervention.

    Science.gov (United States)

    Kinser, Patricia Anne; Elswick, R K; Kornstein, Susan

    2014-12-01

    Despite pharmacologic and psychotherapeutic advances over the past decades, many individuals with major depressive disorder (MDD) experience recurrent depressive episodes and persistent depressive symptoms despite treatment with the usual care. Yoga is a mind-body therapeutic modality that has received attention in both the lay and research literature as a possible adjunctive therapy for depression. Although promising, recent findings about the positive mental health effects of yoga are limited because few studies have used standardized outcome measures and none of them have involved long-term follow-up beyond a few months after the intervention period. The goal of our research study was to evaluate the feasibility, acceptability, and effects of a yoga intervention for women with MDD using standardized outcome measures and a long follow-up period (1year after the intervention). The key finding is that previous yoga practice has long-term positive effects, as revealed in both qualitative reports of participants' experiences and in the quantitative data about depression and rumination scores over time. Although generalizability of the study findings is limited because of a very small sample size at the 1-year follow-up assessment, the trends in the data suggest that exposure to yoga may convey a sustained positive effect on depression, ruminations, stress, anxiety, and health-related quality of life. Whether an individual continues with yoga practice, simple exposure to a yoga intervention appears to provide sustained benefits to the individual. This is important because it is rare that any intervention, pharmacologic or non-pharmacologic, for depression conveys such sustained effects for individuals with MDD, particularly after the treatment is discontinued.

  19. Inductively coupled corrosion potential sensor for steel reinforced concrete with time domain gating interrogation

    Science.gov (United States)

    Thomson, D. J.; Perveen, K.; Bridges, G. E.; Bhadra, S.

    2012-04-01

    Corrosion is a major problem for civil infrastructure and is one of the leading factors in infrastructure deterioration. Techniques such as half-cell potential can be used to periodically monitor corrosion, but can be difficult to reliably interpret. Wired systems have large installation cost and long-term reliability issues due to wire corrosion. In this paper an embedded inductively coupled coil sensor able to monitor the corrosion potential of reinforcement steel in concrete is presented. The sensor is based on a coil resonator whose resonant frequency changes due to the corrosion potential being applied across a parallel varactor diode. The corrosion potential can be monitored externally using an inductively coupled coil. An accelerated corrosion test shows that it can measure corrosion potentials with a resolution of less than 10 mV. This sensor will detect corrosion at the initiation stage before observable corrosion has taken place. The wireless sensor is passive and simple in design, making it an inexpensive, battery less option for long-term monitoring of the corrosion potential of reinforcing steel.

  20. A long-term investigation of the anti-hepatocarcinogenic potential of an indigenous medicine comprised of Nigella sativa, Hemidesmus indicus and Smilax glabra

    Directory of Open Access Journals (Sweden)

    Iddamaldeniya SS

    2006-05-01

    Full Text Available Abstract Background A decoction comprised of Nigella sativa seeds, Hemidesmus indicus root bark and Smilax glabra rhizome is being recommended for cancer patients by a family of traditional medical practitioners of Sri Lanka. Previous investigations have demonstrated that a short term (10 weeks treatment with the decoction can significantly inhibit diethylnitrosamine (DEN mediated expression of Glutathione S-transferase P form (GST-P in rat liver. The objective of the present investigation was to determine whether long term (16 months treatment with the decoction would be successful in inhibiting in rat livers, not only DEN- mediated expression of GST-P, but also the carcinogen mediated development of overt tumours (OT or histopathological changes leading to tumour development (HT. Methods Thirty-six male Wistar rats were divided into 3 groups of 12 each. Groups 1 and 2 were injected intraperitoneally (i.p with DEN (200 mg/kg while group 3 was injected normal saline (NS. Twenty-four hours later, decoction (DC; 6 g/kg body weight/day was orally administered to group 1 rats, while groups 2 and 3 (DEN-control and normal control were given distilled water (DW. Treatment with DC or DW continued for 16 months. At the end of the 9th month and 16th months (study 1 and study 2 respectively, six rats from each group were sacrificed, and livers observed for OT or HT, both visually and by subjecting liver sections to staining with Haemotoxylin and Eosin (H & E, Sweet's Silver stain (for reticulin fibers, Periodic Acid Schiff (PAS staining (for glycogen, and immunohistochemical staining (for GST-P. Results At the end of 9 months (study 1 a hepatocellular adenoma (HA developed in one of the rats in the DEN + DW treated group (group 2. At the end of 16 months (study 2, livers of all rats of group 2 developed OT and HT. Large areas of GST-P positive foci were also observed. No OT, HT or GST-P positive foci were detected in any of the other groups. Conclusion

  1. Unilateral lesion of dorsal hippocampus in adult rats impairs contralateral long-term potentiation in vivo and spatial memory in the early postoperative phase.

    Science.gov (United States)

    Li, Hongjie; Wu, Xiaoyan; Bai, Yanrui; Huang, Yan; He, Wenting; Dong, Zhifang

    2012-05-01

    It is well documented that bilateral hippocampal lesions or unilateral hippocampal lesion at birth causes impairment of contralateral LTP and long-term memory. However, effects of unilateral hippocampal lesion in adults on contralateral in vivo LTP and memory are not clear. We here examined the influence of unilateral electrolytic dorsal hippocampal lesion in adult rats on contralateral LTP in vivo and spatial memory during different postoperative phases. We found that acute unilateral hippocampal lesion had no effect on contralateral LTP. However, contralateral LTP was impaired at 1 week after lesion, and was restored to the control level at postoperative week 4. Similarly, spatial memory was also impaired at postoperative week 1, and was restored at postoperative week 4. In addition, the rats at postoperative week 1 showed stronger spatial exploratory behavior in a novel open-field environment. The sham operation had no effects on contralateral LTP, spatial memory and exploration at either postoperative week 1 or week 4. These results suggest that unilateral dorsal hippocampal lesion in adult rats causes transient contralateral LTP impairment and spatial memory deficit. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Evidence that limbic neural plasticity in the right hemisphere mediates partial kindling induced lasting increases in anxiety-like behavior: effects of low frequency stimulation (quenching?) on long term potentiation of amygdala efferents and behavior following kindling.

    Science.gov (United States)

    Adamec, R E

    1999-08-21

    Behavioral and physiological effects of partial kindling of the right ventral hippocampus by perforant path (PP) stimulation were investigated in the cat. Partial kindling produced lasting changes in affect (increased defensive response to rats) and predatory attack (decreased pawing and biting attack). Partial kindling also induced long term potentiation (LTP) of amygdala efferent transmission to ventromedial hypothalamus (VMH) and periaqueductal gray (PAG) in left and right hemispheres. LTP of field population spikes evoked in area CA3 by PP stimulation was also observed. LTP was detected using evoked potential methods. These findings parallel previous studies of left PP-CA3 partial kindling. Analysis of covariance removing effects of LTP from behavioral changes suggests that initiation of increased defensiveness at 2 days after completion of partial kindling depended on LTP of left and right amygdalo-VMH and right amygdalo-PAG transmission. From 6 days after kindling onward, increased defensiveness depended on LTP of right amygdalo-PAG transmission. Depotentiation of amygdala efferent LTP by bilateral low frequency amygdala stimulation (LFS) (900 pulses at 1 Hz, once daily for 7 days) selectively reduced LTP in right amygdala efferents. At the same time, defensive, but not predatory attack behavior, was returned to levels seen prior to partial kindling. Both depotentiation and reduction of defensiveness were transient. Defensiveness increased to post-kindling levels by 76 days after LFS. At the same time, LTP was restored in the right amygdalo-PAG pathway. In contrast LTP in the right amygdalo-VMH pathway remained depotentiated. Effects of LFS were not due to damage, as thresholds to evoke amygdala efferent response were unchanged. These findings suggest that lasting change in affect following partial hippocampal kindling depends on LTP of right amygdala efferent transmission to PAG. The findings parallel studies of non-convulsant pharmacological induction of

  3. Analysing long term discursive processes

    DEFF Research Database (Denmark)

    Horsbøl, Anders

    What do timescales - the notion that processes take place or can be viewed within a shorter or longer temporal range (Lemke 2005) - mean for the analysis of discourse? What are the methodological consequences of analyzing discourse at different timescales? It may be argued that discourse analysis...... in general has favored either the analysis of short term processes such as interviews, discussions, and lessons, or the analysis of non-processual entities such as (multimodal) texts, arguments, discursive repertoires, and discourses (in a Foucaultian sense). In contrast, analysis of long term processes...... which extend beyond the single interaction, for instance negotiations or planning processes, seems to have played a less important role, with studies such as Iedema 2001 and Wodak 2000 as exceptions. These long term processes, however, are central to the constitution and workings of organizations...

  4. Long term immunologic consequences of experimental stroke and mucosal tolerance

    Directory of Open Access Journals (Sweden)

    Gee J Michael

    2009-10-01

    Full Text Available Abstract Background An inflammatory insult following middle cerebral artery occlusion (MCAO is associated with a predisposition to develop a deleterious autoimmune response to the brain antigen myelin basic protein (MBP. Induction of immunologic tolerance to brain antigens prior to MCAO prevents this deleterious autoimmune response and is associated with better functional outcome early after stroke. In this study, we sought to determine the long term immunologic consequences of experimental stroke and induction of mucosal tolerance. Methods Male Lewis rats were tolerized to MBP or ovalbumin (OVA by intranasal administration prior to MCAO and administration of lipopolysaccharide (LPS. Neurological outcome was assessed at set points after MCAO and animals sacrificed at 3 months; the immune response to MBP in brain and spleen was determined using ELISPOT assay and degree of cellular inflammatory brain infiltrate assessed by immunocytochemistry. Results Animals that developed a pro-inflammatory (TH1 response to MBP experienced worse outcome, while those that developed a regulatory response (TREG experienced better outcome. A TREG response in spleen was also associated with decreased inflammation and an increase in the number of FoxP3 positive cells in brain. In this study, tolerization to MBP prior to MCAO was associated with a tendency to develop a TH1 response to MBP by 3 months after MCAO. Conclusion These data show that induction of immunological tolerance to MBP is associated with improved outcome after stroke. This study, however, raises concern about the potential for inadvertent induction of detrimental autoimmunity through mucosal administration of antigen.

  5. Induction Chemotherapy Improved Long-term Outcomes of Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: A Propensity Matched Analysis of 5-year Survival Outcomes in the Era of Intensity-modulated Radiotherapy

    Science.gov (United States)

    Peng, Hao; Chen, Lei; Zhang, Jian; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Yuan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2017-01-01

    Background: The aim of this study is to evaluate the long-term therapeutic gain of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT). Methods: Data on 957 patients with stage T1-2N2-3 or T3-4N1-3 NPC treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance influence of various covariates. Patient survival between IC and non-IC groups were compared. Results: For the 318 pairs selected from the original 957 patients by PSM, the median follow-up duration was 57.13 months (range, 1.27-78.1 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and locoregional relapse-free survival (LRRFS) rates for IC group vs. non-IC group were 87.2% vs. 80.8% (P = 0.023), 88.1% vs. 83.2% (P = 0.071), 80.7% vs. 71.4% (P = 0.011) and 92.1% vs. 86.7% (P = 0.081), respectively. Multivariate analysis identify IC as an independent prognostic factor for OS (HR, 0.595; 95% CI, 0.397-0.891; P = 0.012) and DFS (HR, 0.627; 95% CI, 0.451-0.872; P = 0.006). After excluding the patients not receiving concurrent chemotherapy, IC was found to be an independent prognostic factor for OS (HR, 0.566; 95% CI, 0.368-0.872; P = 0.01), DMFS (HR, 0.580; 95% CI, 0.367-0.916; P = 0.02) and DFS (HR, 0.633; 95% CI, 0.444-0.903; P = 0.012). Conclusions: IC is an effective treatment modality for patients with stage T1-2N2-3 and T3-4N1-3 NPC, and the incorporation of IC with standard CCRT could achieve the best therapeutic gain. PMID:28261337

  6. Leukodepleted blood components do not remove the potential for long-term transfusion-associated microchimerism in Australian major trauma patients.

    Science.gov (United States)

    Hirani, Rena; Balogh, Zsolt J; Lott, Natalie J; Hsu, Jeremy M; Irving, David O

    2014-01-01

    Despite the introduction of leukodepleted blood components, it has been shown that donor leukocyte engraftment (microchimerism) remains a long-term consequence of red blood cell (RBC) transfusion. The incidence of microchimerism may be affected by international disparities in blood processing methods or variations in transfusion practices. This study was conducted to determine the prevalence of microchimerism in Australian trauma patients. A secondary aim was to examine whether any patient complications correlated to the incidence of microchimerism. Australian trauma patients (n = 86) who had been transfused with red blood cell (RBC) units between 2000 and 2012 with an injury severity score (ISS) of greater than 15 were recruited. The prevalence of microchimerism was determined using genetic screening with a panel of insertion/deletion biallelic polymorphisms. The mean storage age of the transfused RBC units was 20 ± 8 days and the mean length of stay (LOS) in hospital was 40 ± 39 days. There were no significant associations in this study sample to bias for patient age, gender, number of transfused RBC units or ISS. Nine of the 55 (16.3%) patients transfused with non-leukodepleted blood components displayed an incidence of microchimerism. Of the 31 patients transfused with leukodepleted RBC units, 3 (9.6%) displayed an incidence of microchimerism. Therefore, despite the universal introduction of leukodepleted blood components in Australia, the prevalence of transfusion-associated microchimerism was found to be unchanged. Furthermore, half of the patients exhibiting microchimerism were recorded to have had splenic injury or required splenectomy at the time of transfusion.

  7. Slug-dependent upregulation of L1CAM is responsible for the increased invasion potential of pancreatic cancer cells following long-term 5-FU treatment.

    Directory of Open Access Journals (Sweden)

    Kaja Lund

    Full Text Available Pancreatic adenocarcinoma is a lethal disease with 5-year survival of less than 5%. 5-fluorouracil (5-FU is a principal first-line therapy, but treatment only extends survival modestly and is seldom curative. Drug resistance and disease recurrence is typical and there is a pressing need to overcome this. To investigate acquired 5-FU resistance in pancreatic adenocarcinoma, we established chemoresistant monoclonal cell lines from the Panc 03.27 cell line by long-term exposure to increasing doses of 5-FU.5-FU-resistant cell lines exhibited increased expression of markers associated with multidrug resistance explaining their reduced sensitivity to 5-FU. In addition, 5-FU-resistant cell lines showed alterations typical for an epithelial-to-mesenchymal transition (EMT, including upregulation of mesenchymal markers and increased invasiveness. Microarray analysis revealed the L1CAM pathway as one of the most upregulated pathways in the chemoresistant clones, and a significant upregulation of L1CAM was seen on the RNA and protein level. In pancreatic cancer, expression of L1CAM is associated with a chemoresistant and migratory phenotype. Using esiRNA targeting L1CAM, or by blocking the extracellular part of L1CAM with antibodies, we show that the increased invasiveness observed in the chemoresistant cells functionally depends on L1CAM. Using esiRNA targeting β-catenin and/or Slug, we demonstrate that in the chemoresistant cell lines, L1CAM expression depends on Slug rather than β-catenin.Our findings establish Slug-induced L1CAM expression as a mediator of a chemoresistant and migratory phenotype in pancreatic adenocarcinoma cells.

  8. Evaluation of guanfacine as a potential medication for alcohol use disorder in long-term drinking rats: behavioral and electrophysiological findings.

    Science.gov (United States)

    Fredriksson, Ida; Jayaram-Lindström, Nitya; Wirf, Malin; Nylander, Erik; Nyström, Erica; Jardemark, Kent; Steensland, Pia

    2015-03-13

    One of the main treatment challenges in alcohol use disorder (AUD) is the high rate of craving in combination with decreased cognitive functioning including impaired decision making and impulse control that often lead to relapse. Recent studies show that guanfacine, an α-2-adrenoceptor agonist and FDA-approved ADHD medication, attenuates stress-induced relapse of several drugs of abuse including alcohol. Here we evaluated guanfacine's effects on voluntary alcohol intake, the alcohol deprivation effect (ADE), alcohol seeking behavior, and cue/priming-induced reinstatement in Wistar rats that had voluntarily consumed alcohol for at least 2 months before treatment. In addition, guanfacine's ability to regulate glutamatergic neurotransmission was evaluated through electrophysiological recordings in medial prefrontal cortex (mPFC) slices prepared from long-term drinking rats (and alcohol-naive controls) that had received three daily guanfacine (0.6 mg/kg/day) or vehicle injections in vivo. Guanfacine decreased alcohol intake in high, but not low, alcohol-consuming rats and the effects were generally more long lasting than that of the AUD medication naltrexone. Repeated guanfacine treatment induced a long-lasting decrease in alcohol intake, persistent up to five drinking sessions after the last injection. In addition, guanfacine attenuated the ADE as well as alcohol seeking and cue/priming-induced reinstatement of alcohol seeking. Finally, subchronic guanfacine treatment normalized an alcohol-induced dysregulated glutamatergic neurotransmission in the mPFC. These results support previous studies showing that guanfacine has the ability to improve prefrontal connectivity through modulation of the glutamatergic system. Together with the fact that guanfacine appears to be clinically safe, these results merit evaluation of guanfacine's clinical efficacy in AUD individuals.

  9. LONG-TERM EFFECT OF HOMOHARRINGTONINE ON CHRONIC GRANULOCYTIC LEUKEMIA

    Institute of Scientific and Technical Information of China (English)

    LI Yu-feng; ZHU Jia-bin; WANG Chun-ling; DING Bang-he; LI Yuan-yuan; XUAN Heng-bao; QIAN Mo-sheng

    2005-01-01

    Objective: To observe the long-term effect of homoharringtonine (HHT) on chronic granulocytic leukemia (CGL) and its pharmacological mechanism. Methods: 76 patients with newly diagnosed early chronic phase CGL received treatment of merely 1.5 mg/m2 daily HHT for induction remission and long-term maintenance treatment. The apoptosis rate of bone marrow CD34+ cells induced by HHT was assayed with flow cytometer. Results: 86.8% patients achieved CHR, 13.2% patients PHR and 31.8% patients got cytogenetic response in HHT treatment group, which was longer than 31 (8-54) months in hydroxyurea (HU) group (P<0.05). The effect of apoptosis induction HHT was stronger on CGL-CP patients bone marrow CD34+ cells than on normal person bone marrow CD34+ cells. Conclusion: HHT is a very effective drug for remission induction and long-term maintenance treatment in early chronic phase CGL patients.

  10. Raw materials potential and long-term raw materials supply in the pit-and-quarry sector: The Niedersachsen experience; Rohstoffpotential sowie Rohstoffsicherung fuer Steine-Erden-Rohstoffe - Erfahrungen in Niedersachsen

    Energy Technology Data Exchange (ETDEWEB)

    Langer, A. [Niedersaechsisches Landesamt fuer Bodenforschung, Hannover (Germany)

    1998-11-01

    The contribution outlines the potential of nometallic minerals in Niedersachsen, e.g. gravel and sand, raw materials for brick and gypsum production, and oil shales. Measures taken to ensure long-term supply and the experience gained in this sector are presented. (orig.) [Deutsch] Der Beitrag beschaeftigt sich mit dem Potential an Steine-Erden-Rohstoffen in Niedersachsen, wie u.a. Kiese und Sande, Rohstoffe der Ziegelindustrie, Rohstoffe fuer die Gipsindustrie und Oelschiefervorkommen. Zudem werden die Massnahmen und die Erfahrungen bei der Rohstoffsicherung geschildert.

  11. Medium and Long-term Opportunities and Risks of the Biotechnological Production of Bulk Chemicals from Renewable Resources. The Potential of White Biotechnology. The BREW Project. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Patel, M.; Crank, M.; Dornburg, V.; Hermann, B.; Roes, L. [Department of Science, Technology and Society NWS, Utrecht University, Utrecht (Netherlands); Huesing, B. [Fraunhofer Institute for Systems and Innovation Research FhG-ISl, Karlsruhe (Germany); Overbeek, L. [Plant Research International PRI, Wageningen (Netherlands); Terragni, F.; Recchia, E. [CERISS, Centro per I' Educazione, la Ricerca, I' lnformazione su Scienza e Society, Milan (Italy)

    2006-09-15

    This study investigates the medium and long-term opportunities and risks of the biotechnological production of organic chemicals. The objective is to gain better understanding of the techno-economic and the societal viability of White Biotechnology in the coming decades. The key research questions are which products could be made with White Biotechnology, whether these products can contribute to savings of energy use and greenhouse gas (GHG) emissions, under which conditions the products become economically viable, which risks may originate from the use of genetically modified organisms (GMO) in fermentation and what the public perception is. The main purpose of Chapter 2 is to provide an overview of emerging key White Biotechnology products and to explain which chemicals could be produced on their basis. For a selection of these products, detailed environmental and economic assessments are conducted in Chapter 3 (in specific terms, i.e. per tonne of product). Chapter 3 discusses also the so-called Generic Approach which is the methodology we developed and applied to assess future processes and processes, for which very little information is available. In Chapter 4, three scenario projections are developed for Europe (EU-25), thereby assuming benign, moderate and disadvantageous conditions for bio-based chemicals. The purpose of this chapter is hence to understand to which extent restructuring of the chemical sector might occur under which conditions. In Chapter 5, the risks related to the use of White Biotechnology are addressed. The main purpose of this chapter is to give insight into the main risk components influencing the overall risk and of the knowledge gaps. Both conventional risks (e.g., human toxicity and accidents) and risks related to generic modification (e.g., horizontal gene transfer) are analyzed. Since the public perception may play an important role for the implementation of White Biotechnology on a large scale, these issues are discussed in

  12. Long term stability of power systems

    Energy Technology Data Exchange (ETDEWEB)

    Kundur, P.; Gao, B. [Powertech Labs. Inc., Surrey, BC (Canada)

    1994-12-31

    Power system long term stability is still a developing subject. In this paper we provide our perspectives and experiences related to long term stability. The paper begins with the description of the nature of the long term stability problem, followed by the discussion of issues related to the modeling and solution techniques of tools for long term stability analysis. Cases studies are presented to illustrate the voltage stability aspect and plant dynamics aspect of long term stability. (author) 20 refs., 11 figs.

  13. Consider long-term care as service alternative.

    Science.gov (United States)

    Loria, L S

    1987-04-01

    The increasing demand for elderly care services, pressures on inpatient average length of stay and payment levels, and potential financial rewards from providing additional services, makes long-term care look attractive to hospitals. Long-term care, however, is not for every hospital. Before deciding to establish long-term care services, management should examine how the service fits within the hospital's strategic plan. The action plan below provides guidance in evaluating a decision to use hospital facilities for long-term care. Examine how long-term care services fit within the hospital's strategic plan. Study area demographics and competitors to assess the need and supply of long-term care services. Survey the medical staff, consumers and payers to determine attitudes, perceptions and interests regarding long-term care services. Develop a facility plan that identifies areas of excess capacity that can be most easily converted into long-term care with minimal effects on hospital operations. Prepare a financial feasibility analysis of the contribution margin and return on investment attributable to long-term care services. Include an impact analysis on hospital operations. Establish a management task force to develop a detailed implementation plan including assigned individual responsibilities and related timetable. Develop an effective marketing plan designed to generate increased patient market share.

  14. Experimental hypothyroidism delays field excitatory post-synaptic potentials and disrupts hippocampal long-term potentiation in the dentate gyrus of hippocampal formation and Y-maze performance in adult rats.

    Science.gov (United States)

    Artis, A S; Bitiktas, S; Taşkın, E; Dolu, N; Liman, N; Suer, C

    2012-03-01

    Manipulations of thyroid hormones have been shown to influence learning and memory. Although a large body of literature is available on the effect of thyroid hormone deficiency on learning and memory functions during the developmental stage, electrophysiological and behavioural findings, particularly on propylthiouracil administration to adult normothyroid animals, are not satisfactory. The experiments in the present study were carried out on 12 adult male Wistar rats aged 6-7 months. Hypothyroidism was induced by administering 6-n-propyl-2-thiouracil in their drinking water for 21 days at a concentration of 0.05%. The spatial learning performance of hypothyroid and control rats was studied on a Y-maze. The rats were then placed in a stereotaxic frame under urethane anaesthesia. A bipolar tungsten electrode was used to stimulate the medial perforant path. A glass micropipette was inserted into the granule cell layer of the ipsilateral dentate gyrus to record field excitatory post-synaptic potentials. After a 15-min baseline recording of field potentials, long-term potentiation was induced by four sets of tetanic trains. The propylthiouracil-treated rats showed a significantly attenuated input-output (I/O) relationship when population spike (PS) amplitudes and field excitatory post-synaptic potentials (fEPSP) were compared. fEPSP and PS latencies were found to be longer in the hypothyroid group than in the control group. The PS amplitude and fEPSP slope potentiations in the hypothyroid rats were not statistically different from those in the control rats, except for the field EPSP slope measured in the post-tetanic and maintenance phases. The hypothyroid rats also showed lower thyroxine levels and poor performance in the spatial memory task. The present study provides in vivo evidence for the action of propylthiouracil leading to impaired synaptic plasticity, which might explain deficit in spatial memory tasks in adult hypothyroid rats.

  15. Potential long-term chemical effects of diesel fuel emissions on a mining environment: A preliminary assessment based on data from a deep subsurface tunnel at Rainer Mesa, Nevada test site

    Energy Technology Data Exchange (ETDEWEB)

    Meike, A.; Bourcier, W.L.; Alai, M. [and others

    1995-09-01

    The general purpose of the Yucca Mountain Site Characterization Project (YMSCP) Introduced Materials Task is to understand and predict potential long-term modifications of natural water chemistry related to the construction and operation of a radioactive waste repository that may significantly affect performance of the waste packages. The present study focuses on diesel exhaust. Although chemical information on diesel exhaust exists in the literature, it is either not explicit or incomplete, and none of it establishes mechanisms that might be used to predict long-term behavior. In addition, the data regarding microbially mediated chemical reactions are not well correlated with the abiotic chemical data. To obtain some of the required long-term information, we chose a historical analog: the U12n tunnel at Rainier Mesa, Nevada Test Site. This choice was based on the tunnel`s extended (30-year) history of diesel usage, its geological similarity to Yucca Mountain, and its availability. The sample site within the tunnel was chosen based on visual inspection and on information gathered from miners who were present during tunnel operations. The thick layer of dark deposit at that site was assumed to consist primarily of rock powder and diesel exhaust. Surface samples and core samples were collected with an intent to analyze the deposit and to measure potential migration of chemical components into the rock. X-ray diffraction (XRD), x-ray fluorescence (XRF), scanning electron microscopy (SEM) with energy dispersive spectra (EDS) analysis, secondary-ion mass spectrometry (SIMS), and Fourier transform infrared (FTIR) analysis were used to measure both spatial distribution and concentration for the wide variety of chemical components that were expected based on our literature survey.

  16. IMPAIRMENT IN SHORT-TERM BUT ENHANCED LONG-TERM SYNAPTIC POTENTIATION AND ERK ACTIVATION IN ADULT HIPPOCAMPAL AREA CA1 FOLLOWING DEVELOPMENTAL HYPOTHYROIDISM.

    Science.gov (United States)

    The EPA must evaluate the risk of exposure of the developing brain to chemicals with the potential to disrupt thyroid hormone homeostasis. The existing literature identifies morphological and neurochemical indices of severe neonatal hypothyroidism in the early postnatal period i...

  17. Potential groundwater sampling sites for installation of a well network for long-term monitoring of agricultural chemicals in the High Plains Aquifer, Colorado

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — These data are in support of report DS 456 (Arnold and others, 2009). This dataset includes 90 potential groundwater sampling sites randomly generated using...

  18. Modulation of Long-Term Potentiation and Epileptiform Activity in the Rat Dentate Gyrus by the Group II Metabotropic Glutamate Receptor Subtype mGluR3

    Science.gov (United States)

    2006-05-31

    200 µM) blocked LTP of extracellular excitatory post-synaptic potentials ( EPSPs ) after high-frequency stimulation (100Hz; 2s) of the medial perforant...affect EPSPs recorded in a paired-pulse paradigm which argues against a presynaptic effect. These data are the first to indicate competitive effects...acetylaspartylglutamate (NAAG; 50 and 200 µM) blocked LTP of extracellular excitatory post-synaptic potentials ( EPSPs ) after high-frequency stimulation

  19. High incidence of potentially virus-induced malignancies in systemic lupus erythematosus: a long-term followup study in a Danish cohort

    DEFF Research Database (Denmark)

    Dreyer, Lene; Faurschou, Mikkel; Mogensen, Mette

    2011-01-01

    Patients with systemic lupus erythematosus (SLE) seem to experience an increased prevalence of oncogenic virus infections. The aim of the present study was to investigate whether SLE patients have an increased risk of virus-associated malignancies, defined as malignancies potentially caused...

  20. Effects of neonatal exposure to the flame retardant tetrabromobisphenol-A, aluminum diethylphosphinate or zinc stannate on long-term potentiation and synaptic protein levels in mice

    NARCIS (Netherlands)

    Hendriks, Hester S; Koolen, Lucas A E; Dingemans, Milou M L; Viberg, Henrik; Lee, Iwa; Leonards, Pim E G; Ramakers, Geert M J; Westerink, Remco H S

    2015-01-01

    Brominated flame retardants such as tetrabromobisphenol-A (TBBPA) may exert (developmental) neurotoxic effects. However, data on (neuro)toxicity of halogen-free flame retardants (HFFRs) are scarce. Recent in vitro studies indicated a high neurotoxic potential for some HFFRs, e.g., zinc stannate (ZS)

  1. Effects of neonatal exposure to the flame retardant tetrabromobisphenol-A, aluminum diethylphosphinate or zinc stannate on long-term potentiation and synaptic protein levels in mice

    NARCIS (Netherlands)

    Hendriks, Hester; Koolen, Lucas; Dingemans, Milou; Viberg, Henrik; Lee, Iwa; Leonards, P.E.G.; Ramakers, G.M.J.; Westerink, Remco

    2014-01-01

    Brominated flame retardants such as tetrabromobisphenol-A (TBBPA) may exert (developmental) neurotoxic effects. However, data on (neuro)toxicity of halogen-free flame retardants (HFFRs) are scarce. Recent in vitro studies indicated a high neurotoxic potential for some HFFRs, e.g., zinc stannate (ZS)

  2. Short- and long-term effects on fuels, forest structure, and wildfire potential from prescribed fire and resource benefit fire in southwestern forests, USA

    Science.gov (United States)

    Molly E. Hunter; Jose M. Iniguez; Leigh B. Lentile

    2011-01-01

    Prescribed and resource benefit fires are used to manage fuels in fire-prone landscapes in the Southwest. These practices, however, typically occur under different conditions, potentially leading to differences in fire behavior and effects. The objectives of this study were to investigate the effects of recent prescribed fires, resource benefit fires, and repeated...

  3. Long-Term Corrosion Potential Behavior of Alloy 22 in Hot 5 m CaCl2 + 5 m Ca(NO3)2 Brines

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, M A; Carranza, R M; Stuart, M L; Rebak, R B

    2007-02-20

    Alloy 22 is a nickel base alloy highly resistant to all forms of corrosion. In very aggressive conditions (e.g. hot concentrated chloride containing brines) Alloy 22 could suffer localized attack, namely pitting and crevice corrosion. The occurrence of localized corrosion in a given environment is governed by the values of the critical potential (E{sub crit}) for crevice corrosion and the corrosion potential (E{sub corr}) that the alloy may establish in the studied environment. If E{sub corr} is equal or higher than E{sub crit}, localized corrosion may be expected. This paper discusses the evolution of E{sub corr} of Alloy 22 specimens in 5 m CaCl{sub 2} + 5 m Ca(NO{sub 3}){sub 2} brines at 100 C and 120 C. Two types of specimens were used, polished as-welded (ASW) creviced and noncreviced specimens and as-welded plus solution heat-treated (ASW+SHT) creviced specimens. The latter contained the black annealing oxide film on the surface. Results show that, for all types of Alloy 22 specimens the E{sub corr} was higher at 120 C than at 100 C, probably because a more protective film formed at the higher temperature. Specimens with the black oxide film on the surface showed more oscillations in the potential. None of the tested specimens suffered crevice corrosion probably because of the relatively high concentration of nitrate in the electrolyte, R = [NO3]/[Cl] = 1.

  4. Long-term agricultural land-cover change and potential for cropland expansion in the former Virgin Lands area of Kazakhstan

    DEFF Research Database (Denmark)

    Kraemer, Roland; Prishchepov, Alexander; Müller, Daniel

    2015-01-01

    During the Soviet Virgin Lands Campaign, approximately 23 million hectares (Mha) of Eurasian steppe grassland were converted into cropland in Northern Kazakhstan from 1954 to 1963. As a result Kazakhstan became an important breadbasket of the former Soviet Union. However, the collapse of the Soviet...... of Northern Kazakhstan. Further, we assessed the potential of currently idle cropland for re-cultivation. We reconstructed the cropland extent before and after the Virgin Lands Campaign using archival maps, and we mapped the agricultural land cover in the late Soviet and post-Soviet period using multi...

  5. Long Term Analysis for the BAM device

    Science.gov (United States)

    Bonino, D.; Gardiol, D.

    2011-02-01

    Algorithms aimed at the evaluation of critical quantities are based on models with many parameters, which values are estimated from data. The knowledge, with high accuracy, of these values and the control of their temporal evolution are important features. In this work, we focus on the latter subject, and we show a proposed pipeline for the BAM (Basic Angle Monitoring) Long Term Analysis, aimed at the study of the calibration parameters of the BAM device and of the Basic Angle variation, searching for unwanted trends, cyclic features, or other potential unexpected behaviours.

  6. TiO2 nanotube arrays deposited on Ti substrate by anodic oxidation and their potential as a long-term drug delivery system for antimicrobial agents

    Science.gov (United States)

    Moseke, Claus; Hage, Felix; Vorndran, Elke; Gbureck, Uwe

    2012-05-01

    Nanotube arrays on medical titanium surfaces were fabricated by two different anodization methods and their potential for storage and release of antimicrobial substances was evaluated. The treatment of the Ti surfaces in fluoride containing electrolytes on water as well as on polyethylene glycol basis led to the formation of TiO2 nanotubes with up to 6.54 μm length and average diameters of up to 160 nm. Drug release experiments with the model antibiotic vancomycin and with antibacterial silver ions showed that the increased surface area of the anodized samples enabled them to be loaded with up to 450% more active agent than the untreated Ti surfaces. Significant surface-dependent differences in the release kinetics of vancomycin were observed. In comparison to surfaces anodized in an aqueous electrolyte, the release of the antibiotic from surfaces anodized in an electrolyte based on ethylene glycol was significantly retarded, with a release of noticeable amounts over a period of more than 300 days. Loading of nanotube surfaces fabricated in aqueous electrolyte with silver ions revealed increased amounts of adsorbed silver by up to 230%, while the release kinetics showed significant differences in comparison to untreated Ti. It was concluded that nanotube arrays on favored medical implant materials have a high potential for loading with antimicrobial agents and also provide the possibility of tailored release kinetics by variation of anodization parameters.

  7. Asthma Medicines: Long-Term Control

    Science.gov (United States)

    ... Size Email Print Share Asthma Medicines: Long-term Control Page Content Article Body Corticosteroids Synthetic versions of ... form, they are used exclusively for long-term control; they are not very effective for acute symptoms. ...

  8. Long term complications after radical cystoprostatectomy with ...

    African Journals Online (AJOL)

    Long term complications after radical cystoprostatectomy with orthotopic diversion in male ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING ... Objective: To evaluate the long-term outcomes beyond 1 year, both ...

  9. Long-term agricultural land-cover change and potential for cropland expansion in the former Virgin Lands area of Kazakhstan

    Science.gov (United States)

    Kraemer, Roland; Prishchepov, Alexander V.; Müller, Daniel; Kuemmerle, Tobias; Radeloff, Volker C.; Dara, Andrey; Terekhov, Alexey; Frühauf, Manfred

    2015-05-01

    During the Soviet Virgin Lands Campaign, approximately 23 million hectares (Mha) of Eurasian steppe grassland were converted into cropland in Northern Kazakhstan from 1954 to 1963. As a result Kazakhstan became an important breadbasket of the former Soviet Union. However, the collapse of the Soviet Union in 1991 triggered widespread agricultural abandonment, and much cropland reverted to grasslands. Our goal in this study was to reconstruct and analyze agricultural land-cover change since the eve of the Virgin Lands Campaign, from 1953 to 2010 in Kostanay Province, a region that is representative of Northern Kazakhstan. Further, we assessed the potential of currently idle cropland for re-cultivation. We reconstructed the cropland extent before and after the Virgin Lands Campaign using archival maps, and we mapped the agricultural land cover in the late Soviet and post-Soviet period using multi-seasonal Landsat TM/ETM+ images from circa 1990, 2000 and 2010. Cropland extent peaked at approximately 3.1 Mha in our study area in 1990, 38% of which had been converted from grasslands from 1954 to 1961. After the collapse of the Soviet Union, 45% of the Soviet cropland was abandoned and had reverted to grassland by 2000. After 2000, cropland contraction and re-cultivation were balanced. Using spatial logistic regressions we found that cropland expansion during the Virgin Lands Campaign was significantly associated with favorable agro-environmental conditions. In contrast, cropland expansion after the Campaign until 1990, as well as cropland contraction after 1990, occurred mainly in areas that were less favorable for agriculture. Cropland re-cultivation after 2000 was occurring on lands with relatively favorable agro-environmental conditions in comparison to remaining idle croplands, albeit with much lower agro-environmental endowment compared to stable croplands from 1990 to 2010. In sum, we found that cropland production potentials of the currently uncultivated areas are

  10. A hierarchical porous bowl-like PLA@MSNs-COOH composite for pH-dominated long-term controlled release of doxorubicin and integrated nanoparticle for potential second treatment.

    Science.gov (United States)

    Pan, Jianming; Wu, Runrun; Dai, Xiaohui; Yin, Yijie; Pan, Guoqing; Meng, Minjia; Shi, Weidong; Yan, Yongsheng

    2015-04-13

    We chemically integrated mesoporous silica nanoparticles (MSNs) and macroporous bowl-like polylactic acid (pBPLA) matrix, for noninvasive electrostatic loading and long-term controlled doxorubicin (DOX) release, to prepare a hierarchical porous bowl-like pBPLA@MSNs-COOH composite with a nonspherical and hierarchical porous structure. Strong electrostatic interaction with DOX rendered excellent encapsulation efficiency (up to 90.14%) to the composite. DOX release showed pH-dominated drug release kinetics; thus, maintaining a weak acidic pH (e.g., 5.0) triggered sustained release, suggesting the composite's great potential for long-term therapeutic approaches. In-vitro cell viability assays further confirmed that the composite was biocompatible and that the loaded drugs were pharmacologically active, exhibiting dosage-dependent cytotoxicity. Additionally, a wound-healing assay revealed the composite's intrinsic ability to inhibit cell migration. Moreover, pH- and time-dependent leaching of the integrated MSNs due to pBPLA matrix degradation allow us to infer that the leached (and drug loaded) MSNs may be engulfed by cancer cells contributing to a second wave of DOX-mediated cytotoxicity following pH-triggered DOX release.

  11. Gratitude in Long Term Care

    Directory of Open Access Journals (Sweden)

    Brooke Abrams Sunding

    2015-04-01

    Full Text Available An exploratory study was conducted to examine the effectiveness of a group gratitude intervention with 29 permanent residents at a long term care/skilled nursing facility in improving elder mood, behavior and well- being over a 3 week time period. The sample included individuals diagnosed with dementia, other cognitive impairment, major depressive disorder, insomnia and generalized anxiety disorder. The gratitude intervention consisted of asking elders to share what they are thankful for at the dinner table each day. Measures included the Elder Well Being Scale and The Dinner Rating Scale. On both measures, higher scores indicated better functioning. To test the hypothesis that post treatment elder well-being will be significantly higher than pretreatment elder well-being ratings, a one-way ANOVA was conducted. Post-hoc tests revealed a statistically significant increase in Elder Well Being Scale scores. An ANOVA of comparing Dinner Ratings demonstrated a nonsignificant increase over the 3 week experiment. Implications are discussed.

  12. Long-term variations in outgoing long-wave radiation (OLR), convective available potential energy (CAPE) and temperature in the tropopause region over India

    Indian Academy of Sciences (India)

    R Sapra; S K Dhaka; V Panwar; R Bhatnagar; K Praveen Kumar; Y Shibagaki; M Venkat Ratnam; M Takahashi

    2011-10-01

    Relationship of outgoing long-wave radiation (OLR) with convective available potential energy (CAPE) and temperature at the 100-hPa pressure level is examined using daily radiosonde data for a period 1980–2006 over Delhi (28.3° N, 77.1°E) and Kolkata (22.3°N, 88.2°E), and during 1989–2005 over Cochin (10°N, 77°E) and Trivandrum (8.5°N, 77.0°E), India. Correlation coefficient (xy) between monthly OLR and CAPE shows a significant (∼ −0.45) anti-correlation at Delhi and Kolkata suggesting low OLR associated with high convective activity during summer (seasonal variation). Though, no significant correlation was found between OLR and CAPE at Cochin and Trivandrum (low latitude region); analysis of OLR and temperature (at 100-hPa) association suggests that low OLR peaks appear corresponding to low temperature at Delhi (xy ∼ 0.30) and Kolkata (xy ∼ 0.25) during summer. However, xy between OLR and temperature becomes opposite as we move towards low latitudes (∼8° – 10°N) due to strong solar cycle influence. Large scale components mainly ENSO and quasi-biennial oscillaton (QBO) that contributed to the 100-hPa temperature variability were also analyzed, which showed that ENSO variance is larger by a factor of two in comparison to QBO over Indian region. ENSO warm conditions cause warming at 100-hPa over Delhi and Darwin. However, due to strong QBO and solar signals in the equatorial region, ENSO signal seems less effective. QBO, ENSO, and solar cycle contribution in temperature are found location-dependent (latitudinal variability) responding in consonance with shifting in convective activity regime during El Niño, seasonal variability in the tropical easterly jet, and the solar irradiance.

  13. Japan's Long-term Energy Demand and Supply Scenario to 2050 - Estimation for the Potential of Massive CO2 Mitigation

    Energy Technology Data Exchange (ETDEWEB)

    Komiyama, Ryoichi; Marnay, Chris; Stadler, Michael; Lai, Judy; Borgeson, Sam; Coffey, Brian; Azevedo, Ines Lima

    2009-09-01

    In this analysis, the authors projected Japan's energy demand/supply and energy-related CO{sub 2} emissions to 2050. Their analysis of various scenarios indicated that Japan's CO{sub 2} emissions in 2050 could be potentially reduced by 26-58% from the current level (FY 2005). These results suggest that Japan could set a CO{sub 2} emission reduction target for 2050 at between 30% and 60%. In order to reduce CO{sub 2} emissions by 60% in 2050 from the present level, Japan will have to strongly promote energy conservation at the same pace as an annual rate of 1.9% after the oil crises (to cut primary energy demand per GDP (TPES/GDP) in 2050 by 60% from 2005) and expand the share of non-fossil energy sources in total primary energy supply in 2050 to 50% (to reduce CO{sub 2} emissions per primary energy demand (CO{sub 2}/TPES) in 2050 by 40% from 2005). Concerning power generation mix in 2050, nuclear power will account for 60%, solar and other renewable energy sources for 20%, hydro power for 10% and fossil-fired generation for 10%, indicating substantial shift away from fossil fuel in electric power supply. Among the mitigation measures in the case of reducing CO{sub 2} emissions by 60% in 2050, energy conservation will make the greatest contribution to the emission reduction, being followed by solar power, nuclear power and other renewable energy sources. In order to realize this massive CO{sub 2} abatement, however, Japan will have to overcome technological and economic challenges including the large-scale deployment of nuclear power and renewable technologies.

  14. Studies of breakeven prices and electricity supply potentials of nuclear fusion by a long-term world energy and environment model

    Science.gov (United States)

    Tokimatsu, K.; Asaoka, Y.; Konishi, S.; Fujino, J.; Ogawa, Y.; Okano, K.; Nishio, S.; Yoshida, T.; Hiwatari, R.; Yamaji, K.

    2002-11-01

    In response to social demand, this paper investigates the breakeven price (BP) and potential electricity supply of nuclear fusion energy in the 21st century by means of a world energy and environment model. We set the following objectives in this paper: (i) to reveal the economics of the introduction conditions of nuclear fusion; (ii) to know when tokamak-type nuclear fusion reactors are expected to be introduced cost-effectively into future energy systems; (iii) to estimate the share in 2100 of electricity produced by the presently designed reactors that could be economically selected in the year. The model can give in detail the energy and environment technologies and price-induced energy saving, and can illustrate optimal energy supply structures by minimizing the costs of total discounted energy systems at a discount rate of 5%. The following parameters of nuclear fusion were considered: cost of electricity (COE) in the nuclear fusion introduction year, annual COE reduction rates, regional introduction year, and regional nuclear fusion capacity projection. The investigations are carried out for three nuclear fusion projections one of which includes tritium breeding constraints, four future CO2 concentration constraints, and technological assumptions on fossil fuels, nuclear fission, CO2 sequestration, and anonymous innovative technologies. It is concluded that: (1) the BPs are from 65 to 125 mill kW-1 h-1 depending on the introduction year of nuclear fusion under the 550 ppmv CO2 concentration constraints; those of a business-as-usual (BAU) case are from 51 to 68 mill kW-1h-1. Uncertainties resulting from the CO2 concentration constraints and the technological options influenced the BPs by plus/minus some 10 30 mill kW-1h-1, (2) tokamak-type nuclear fusion reactors (as presently designed, with a COE range around 70 130 mill kW-1h-1) would be favourably introduced into energy systems after 2060 based on the economic criteria under the 450 and 550 ppmv CO2

  15. Long-term aerosol and trace gas measurements in Eastern Lapland, Finland: the impact of Kola air pollution to new particle formation and potential CCN

    Science.gov (United States)

    Kyrö, Ella-Maria; Väänänen, Riikka; Kerminen, Veli-Matti; Virkkula, Aki; Asmi, Ari; Nieminen, Tuomo; Dal Maso, Miikka; Petäjä, Tuukka; Keronen, Petri; Aalto, Pasi; Riipinen, Ilona; Lehtipalo, Katrianne; Hari, Pertti; Kulmala, Markku

    2014-05-01

    Sulphur and primary emissions have been decreasing largely all over Europe, resulting in improved air quality and decreased direct radiation forcing by aerosols. The smelter industry in Kola Peninsula is one of largest sources of anthropogenic SO2 within the Arctic domain and since late 1990s the sulphur emissions have been decreasing rapidly (Paatero et al., 2008; Prank et al., 2010). New particle formation (NPF) is tightly linked with the oxidizing product of SO2, namely sulphuric acid (H2SO4), since it is known to be the key component in atmospheric nucleation (Sipilä et al., 2010). Thus, decreasing sulphur pollution may lead to less NPF. However, low values of condensation sink (CS), which is determined by the amount of pre-existing particles, favours NPF. We used 14 years (1998-2011) of aerosol number size distribution and trace gas data from SMEAR I station in Eastern Lapland, Finland, to investigate these relationships between SO2, NPF and CS. The station is a clean background station with occasional sulphur pollution episodes when the air masses arrive over Kola Peninsula. We found that while SO2 decreased by 11.3 % / year, the number of clear NPF event days was also decreasing by 9.9 % / year. At the same time, CS was decreasing also (-8.0 % / year) leading to formation of more particles per single NPF event (J3 increased by 29.7 % / year in 2006-2011) but the low vapour concentrations of H2SO4 (proxy decreased by 6.2 % / year) did not allow them to grow into climatically relevant sizes. Over the time, concentrations of potential CCN (cloud condensing nuclei) were also decreasing with more moderate pace, -4.0 % / year. The events started on average earlier after sunrise when the SO2 concentration during the start of the event was higher and NPF occurred more frequently in air masses which were travelling over Kola. Despite the total decrease in sulphur pollution originating from Kola there is currently no evidence of cleaning of the emissions, rather the

  16. Climate Predictability and Long Term Memory

    Science.gov (United States)

    Zhu, X.; Blender, R.; Fraedrich, K.; Liu, Z.

    2010-09-01

    The benefit of climate Long Term Memory (LTM) for long term prediction is assessed using data from a millennium control simulation with the atmosphere ocean general circulation model ECHAM5/MPIOM. The forecast skills are evaluated for surface temperature time series at individual grid points. LTM is characterised by the Hurst exponent in the power-law scaling of the fluctuation function which is determined by detrended fluctuation analysis (DFA). LTM with a Hurst exponent close to 0.9 occurs mainly in high latitude oceans, which are also characterized by high potential predictability. Climate predictability is diagnosed in terms of potentially predictable variance fractions. Explicit prediction experiments for various time steps are conducted on a grid point basis using an auto-correlation (AR1) predictor: in regions with LTM, prediction skills are beyond that expected from red noise persistence; exceptions occur in some areas in the southern oceans and over the northern hemisphere continents. Extending the predictability analysis to the fully forced simulation shows large improvement in prediction skills.

  17. Optical quantal analysis indicates that long-term potentiation at single hippocampal mossy fiber synapses is expressed through increased release probability, recruitment of new release sites, and activation of silent synapses.

    Science.gov (United States)

    Reid, Christopher A; Dixon, Don B; Takahashi, Michiko; Bliss, Tim V P; Fine, Alan

    2004-04-01

    It is generally believed that long-term potentiation (LTP) at hippocampal mossy fiber synapses between dentate granule and CA3 pyramidal cells is expressed through presynaptic mechanisms leading to an increase in quantal content. The source of this increase has remained undefined but could include enhanced probability of transmitter release at existing functional release sites or increases in the number of active release sites. We performed optical quantal analyses of transmission at individual mossy fiber synapses in cultured hippocampal slices, using confocal microscopy and intracellular fluorescent Ca(2+) indicators. Our results indicate that LTP is expressed at functional synapses by both increased probability of transmitter release and recruitment of new release sites, including the activation of previously silent synapses here visualized for the first time.

  18. Long term testing of PSI-membranes

    Energy Technology Data Exchange (ETDEWEB)

    Huslage, J.; Brack, H.P.; Geiger, F.; Buechi, F.N.; Tsukada, A.; Scherer, G.G. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1999-08-01

    Long term tests of PSI membranes based on radiation-grafted FEP and ETFE films were carried out and FEP-based membranes were evaluated by monitoring the in-situ membrane area resistance measured by a current pulse method. By modifying our irradiation procedure and using the double crosslinking concept we obtain reproducible membrane cell lifetimes (in term of in-situ membrane resistance) of greater than 5000 hours at 60-65{sup o}C. Preliminary tests at 80-85{sup o}C with lifetimes of greater than 2500 demonstrate the potential long term stability of PSI proton exchange membranes based on FEP over the whole operating temperature range of low-temperature polymer electrolyte fuel cells. Radiation grafted PSI membranes based on ETFE have better mechanical properties than those of the FEP membranes. Mechanical properties are particularly important in large area cells and fuel cell stacks. ETFE membranes have been tested successfully for approximately 1000 h in a 2-cell stack (100 cm{sup 2} active area each cell). (author) 4 figs., 4 refs.

  19. Long-term plasticity in interneurons of the dentate gyrus

    OpenAIRE

    Ross, Stephen T.; Soltesz, Ivan

    2001-01-01

    Single interneurons influence thousands of postsynaptic principal cells, and the control of interneuronal excitability is an important regulator of the computational properties of the hippocampus. However, the mechanisms underlying long-term alterations in the input–output functions of interneurons are not fully understood. We report a mechanism of interneuronal plasticity that leads to the functional enhancement of the gain of glutamatergic inputs in the absence of long-term potentiation of ...

  20. Prediction of Long-Term Treatment Response to Selective Serotonin Reuptake Inhibitors (SSRIs Using Scalp and Source Loudness Dependence of Auditory Evoked Potentials (LDAEP Analysis in Patients with Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Bun-Hee Lee

    2015-03-01

    Full Text Available Background: Animal and clinical studies have demonstrated that the loudness dependence of auditory evoked potentials (LDAEP is inversely related to central serotonergic activity, with a high LDAEP reflecting weak serotonergic neurotransmission and vice versa, though the findings in humans have been less consistent. In addition, a high pretreatment LDAEP appears to predict a favorable response to antidepressant treatments that augment the actions of serotonin. The aim of this study was to test whether the baseline LDAEP is correlated with response to long-term maintenance treatment in patients with major depressive disorder (MDD. Methods: Scalp N1, P2 and N1/P2 LDAEP and standardized low resolution brain electromagnetic tomography-localized N1, P2, and N1/P2 LDAEP were evaluated in 41 MDD patients before and after they received antidepressant treatment (escitalopram (n = 32, 10.0 ± 4.0 mg/day, sertraline (n = 7, 78.6 ± 26.7 mg/day, and paroxetine controlled-release formulation (n = 2, 18.8 ± 8.8 mg/day for more than 12 weeks. A treatment response was defined as a reduction in the Beck Depression Inventory (BDI score of >50% between baseline and follow-up. Results: The responders had higher baseline scalp P2 and N1/P2 LDAEP than nonresponders (p = 0.017; p = 0.036. In addition, changes in total BDI score between baseline and follow-up were larger in subjects with a high baseline N1/P2 LDAEP than those with a low baseline N1/P2 LDAEP (p = 0.009. There were significantly more responders in the high-LDAEP group than in the low-LDAEP group (p = 0.041. Conclusions: The findings of this study reveal that a high baseline LDAEP is associated with a clinical response to long-term antidepressant treatment.

  1. Long- term outcome of paediatric patients with ANCA vasculitis

    Directory of Open Access Journals (Sweden)

    Pusey Charles D

    2011-06-01

    Full Text Available Abstract Background Primary systemic vasculitis presenting in childhood is an uncommon but serious condition. As these patients transfer to adult clinics for continuing care, defining long term outcomes with emphasis on disease and treatment- related morbidity and mortality is important. The aim of this study is to describe the long- term clinical course of paediatric patients with ANCA vasculitis. Methods The adult patients in our vasculitis clinics who had presented in childhood, with a follow up time of greater than 10 years were included. We also reviewed the literature for articles describing the clinical outcome of paediatric patients with ANCA vasculitis. Results We describe the clinical course of 8 adults who presented in childhood with ANCA vasculitis. 7 patients had Wegener's granulomatosis and 1 had microscopic polyangiitis. The median age at presentation was 11.5 years, and follow up time ranged form 11 to 30 years. Induction therapy for all patients was steroids and/or cyclophosphamide. Maintenance therapy was with azathioprine or mycophenolate mofetil. Biological agents were used in 3 patients for relapsed disease in adulthood only. Seven patients achieved complete remission. All patients experienced disease relapse, with a median of 4 episodes. Kidney function was generally well preserved, with median eGFR 76 ml/min. Only one patient developed end-stage renal failure and one patient died after 25 years of disease. Treatment-related morbidity rates were high; 7 suffered from infections, 4 were infertile, 2 had skeletal complications, and 1 developed malignancy. Conclusion Close long- term follow up of paediatric patients with ANCA vasculitis is imperative, as this patient cohort is likely to live long enough to develop significant treatment and disease- related morbidities. Prospective cohort studies with novel therapies including paediatric patients are crucial to help us determine the best approach to managing this complex group

  2. HOME LONG-TERM CARE IN POLAND

    Directory of Open Access Journals (Sweden)

    Ewa Kułagowska

    2011-06-01

    Full Text Available The considerable proportion of the elderly, the chronically ill and the disabled in community is an economic and organizational challenge for the state social policy. It requires a large, steadily increasing financing from the public funds and creating an optional care model to fulfill the needs of citizens and guarantee high quality services. Development of the long-term care is one of the problems to be solved. This paper presents: – a long-term care forms, organization and tasks; – a role of long-term care but particularly home longterm care to protect health in Poland; – problems related with home long-term care functioning.

  3. Long-term dynamics simulation: Modeling requirements

    Energy Technology Data Exchange (ETDEWEB)

    Morched, A.S.; Kar, P.K.; Rogers, G.J.; Morison, G.K. (Ontario Hydro, Toronto, ON (Canada))

    1989-12-01

    This report details the required performance and modelling capabilities of a computer program intended for the study of the long term dynamics of power systems. Following a general introduction which outlines the need for long term dynamic studies, the modelling requirements for the conduct of such studies is discussed in detail. Particular emphasis is placed on models for system elements not normally modelled in power system stability programs, which will have a significant impact in the long term time frame of minutes to hours following the initiating disturbance. The report concludes with a discussion of the special computational and programming requirements for a long term stability program. 43 refs., 36 figs.

  4. Technology for long-term care.

    Science.gov (United States)

    Tak, Sunghee H; Benefield, Lazelle E; Mahoney, Diane Feeney

    2010-01-01

    Severe staff shortages in long-term care (LTC) make it difficult to meet the demands of the growing aging population. Further, technology-savvy Baby Boomers are expected to reshape the current institutional environments toward gaining more freedom and control in their care and lives. Voices from business, academia, research, advocacy organizations, and government bodies suggest that innovative technological approaches are the linchpin that may prepare society to cope with these projected demands. In this article, we review the current state of aging-related technology, identify potential areas for efficacy testing on improving the quality of life of LTC residents in future research, and discuss barriers to implementation of LTC technology. Finally, we present a vision of future technology use that could transform current care practices.

  5. Long-Term Stability of Horseshoe Orbits

    CERN Document Server

    Ćuk, Matija; Holman, Matthew J

    2012-01-01

    Unlike Trojans, horseshoe coorbitals are not generally considered to be long-term stable (Dermott and Murray, 1981; Murray and Dermott, 1999). As the lifetime of Earth's and Venus's horseshoe coorbitals is expected to be about a Gyr, we investigated the possible contribution of late-escaping inner planet coorbitals to the lunar Late Heavy Bombardment. Contrary to analytical estimates, we do not find many horseshoe objects escaping after first 100 Myr. In order to understand this behaviour, we ran a second set of simulations featuring idealized planets on circular orbits with a range of masses. We find that horseshoe coorbitals are generally long lived (and potentially stable) for systems with primary-to-secondary mass ratios larger than about 1200. This is consistent with results of Laughlin and Chambers (2002) for equal-mass pairs or coorbital planets and the instability of Jupiter's horseshoe companions (Stacey and Connors, 2008). Horseshoe orbits at smaller mass ratios are unstable because they must approa...

  6. Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program

    Science.gov (United States)

    Gosz, J.

    2001-12-01

    estuaries below by removing all incoming freshwater. At Toolik Lake, long-term experiments of removing top predators from the good web of lakes showed dramatic alterations of lake populations of small fish and zooplankton. In New Mexico, LTER research on small mammal populations is successfully predicting rodent increases and the potential for increased zoonotic diseases such as Hantavirus and bubonic plague. This ability to forecast based on El Nino prediction is being used to increase scientific awareness and public health awareness through media based communication with the public. In Oregon, the Andrews Forest LTER program has had long, strong links with natural resource policy and management. Basic understanding of forest-stream interactions, characteristics of old-growth forests, roles of woody debris in temperate forest ecosystems, invertebrate biodiversity and ecosystem function have been incorporated in management guidelines, plans and regulations for public and private lands throughout the Pacific Northwest. Other examples of the values of long-term research and monitoring will be presented.

  7. Differential light effects on the dark motility rhythm in Euglena gracilis by series of short light pulses: Induction of long-term fluctuations and holding of the circadian oscillator

    Science.gov (United States)

    Balzer, Ivonne; Hardeland, Rüdiger

    1991-12-01

    Dark motility was measured by means of an infrared beam in stationary, 8- to 10-months-old autotrophic cultures of Euglena gracilis, strain Z. Controls in constant darkness exhibited circadian rhythms for several weeks. Cells were subjected to series of short light pulses of 800 lx covering, in most of the experiments, not more than 1/240 of the intermittent dark periods. When the overall amount of light per day was kept constant, the results of the light treatment strongly depended on the frequency of the light pulses. In light/dard cycles of more than 1 h, the circadian rhythmicity persited, whereas the oscillator was affected by cycles of 40 min or less. Such treatment by a high-frequency series of light pulses led to long-term fluctuations lasting for several days and a subsequent holding of the oscillator. The temporal position of extreme values of the fluctuations correlated with the frequency of the light pulses. The potency of light to suppress rhythmicity, as known from fading-out phenomena in constant illumination, is not restricted to the continuous presence of light, but is also immanent in the Zeitgeber signals of dark/light transitions. Hence, the results reflect differential effects in the action of light.

  8. The fatty acid amide hydrolase inhibitor URB597 exerts anti-inflammatory effects in hippocampus of aged rats and restores an age-related deficit in long-term potentiation

    Directory of Open Access Journals (Sweden)

    Murphy Niamh

    2012-04-01

    Full Text Available Abstract Background Several factors contribute to the deterioration in synaptic plasticity which accompanies age and one of these is neuroinflammation. This is characterized by increased microglial activation associated with increased production of proinflammatory cytokines like interleukin-1β (IL-1β. In aged rats these neuroinflammatory changes are associated with a decreased ability of animals to sustain long-term potentiation (LTP in the dentate gyrus. Importantly, treatment of aged rats with agents which possess anti-inflammatory properties to decrease microglial activation, improves LTP. It is known that endocannabinoids, such as anandamide (AEA, have anti-inflammatory properties and therefore have the potential to decrease the age-related microglial activation. However, endocannabinoids are extremely labile and are hydrolyzed quickly after production. Here we investigated the possibility that inhibiting the degradation of endocannabinoids with the fatty acid amide hydrolase (FAAH inhibitor, URB597, could ameliorate age-related increases in microglial activation and the associated decrease in LTP. Methods Young and aged rats received subcutaneous injections of the FAAH inhibitor URB597 every second day and controls which received subcutaneous injections of 30% DMSO-saline every second day for 28 days. Long-term potentiation was recorded on day 28 and the animals were sacrificed. Brain tissue was analyzed for markers of microglial activation by PCR and for levels of endocannabinoids by liquid chromatography coupled to tandem mass spectrometry. Results The data indicate that expression of markers of microglial activation, MHCII, and CD68 mRNA, were increased in the hippocampus of aged, compared with young, rats and that these changes were associated with increased expression of the proinflammatory cytokines interleukin (IL-1β and tumor necrosis factor-α (TNFα which were attenuated by treatment with URB597. Coupled with these changes, we

  9. Long-term survival after perforated diverticulitis

    NARCIS (Netherlands)

    J. Vermeulen (Jan); M.P. Gosselink (Martijn Pieter); W.C.J. Hop (Wim); E. van der Harst (Erwin); B.E. Hansen (Bettina); G.H.H. Mannaerts (Guido); P-P. Coene (Peter Paul); W.F. Weidema (Wibo); J.F. Lange (Johan)

    2011-01-01

    textabstractAim: Short-term survival after emergency surgery for perforated diverticulitis is poor. Less is known about long-term survival. The aims of this study were to evaluate long-term survival after discharge from hospital and to identify factors associated with prognosis. Method: All patients

  10. Single-crystal elastic properties of (Cs,Na)AlSi2O6.H2O pollucite: A zeolite with potential use for long-term storage of Cs radioisotopes

    Science.gov (United States)

    Sanchez-Valle, Carmen; Chio, Chi-Hong; Gatta, G. Diego

    2010-11-01

    The single-crystal and aggregate elastic properties of the zeolite pollucite (Cs,Na)AlSi2O6ṡH2O, a potential host for Cs radionucleides in geological repositories, have been determined by Brillouin scattering spectroscopy at ambient conditions. The three nonzero individual elastic constants of cubic pollucite are: C11=105.0(1.3) GPa, C44=27.0(3) GPa, and C12=25.7(6) GPa. The Voigt-Reuss-Hill average of the aggregate bulk, shear modulus, Young's modulus and Poisson's ratio are KS=52.2(1.0) GPa, G=31.5(7) GPa, E=78.6(1.0) GPa, and ν =0.248(4), respectively. The bulk modulus of pollucite is 12.7% lower than that of the all-Na isotypic mineral analcime NaAlSi2O6ṡH2O whereas the shear moduli G are identical within mutual uncertainties. The higher compressibility of pollucite results from the weaker Cs-O bonds compared to Na-O bonds, suggesting strong control of the nature and configuration of the extraframework content on the behavior of the structure. The elastic properties of pollucite reported here will help in the prediction of its behavior as a geological barrier and in the modeling of the short-term and long-term safety of the Cs-repositories.

  11. Short-term effects on antioxidant enzymes and long-term genotoxic and carcinogenic potential of CuO nanoparticles compared to bulk CuO and ionic copper in mussels Mytilus galloprovincialis.

    Science.gov (United States)

    Ruiz, Pamela; Katsumiti, Alberto; Nieto, Jose A; Bori, Jaume; Jimeno-Romero, Alba; Reip, Paul; Arostegui, Inmaculada; Orbea, Amaia; Cajaraville, Miren P

    2015-10-01

    The aim of this work was to study short-term effects on antioxidant enzyme activities and long-term genotoxic and carcinogenic potential of CuO nanoparticles (NPs) in comparison to bulk CuO and ionic copper in mussels Mytilus galloprovincialis after 21 days exposure to 10 μg Cu L(-1). Then, mussels were kept for up to 122 days in clean water. Cu accumulation depended on the form of the metal and on the exposure time. CuO NPs were localized in lysosomes of digestive cells, as confirmed by TEM and X ray microanalysis. CuO NPs, bulk CuO and ionic copper produced different effects on antioxidant enzyme activities in digestive glands, overall increasing antioxidant activities. CuO NPs significantly induced catalase and superoxide dismutase activities. Fewer effects were observed in gills. Micronuclei frequency increased significantly in mussels exposed to CuO NPs and one organism treated with CuO NPs showed disseminated neoplasia. However, transcription levels of cancer-related genes did not vary significantly. Thus, short-term exposure to CuO NPs provoked oxidative stress and genotoxicity, but further studies are needed to determine whether these early events can lead to cancer development in mussels.

  12. Vector Potential, Electromagnetic Induction and "Physical Meaning"

    Science.gov (United States)

    Giuliani, G.

    2010-01-01

    A forgotten experiment by Andre Blondel (1914) proves, as held on the basis of theoretical arguments in a previous paper, that the time variation of the magnetic flux is not the cause of the induced emf; the physical agent is instead the vector potential through the term [equation omitted] (when the induced circuit is at rest). The "good…

  13. Effects of electrical acupuncture on long-term potentiation of excitatory postsynaptic potential in rat hippocampus%电针对大鼠海马兴奋性突触后电位长时程增强的作用

    Institute of Scientific and Technical Information of China (English)

    马骋; 闫丽萍; 沈梅红

    2004-01-01

    BACKGROUND: The combination of the researches between long-term potentiation(LTP) of hippocampus and behavioral method of animals has been widely introduced into the researches of improving the functions of study and memory, and the treatments of Alzheimer' s disease including Traditional Chinese Medicine treatments.OBJECTIVE: To observe the impacts of electrical acupuncture(EA) on LTP of excitatory postsynaptic potential(EPSP) in rat hippocampus in normal and scopolamine-induced hypomnesia models under anesthesia conditions.DESIGN: A randomized controlled study.SETTING and MATERIALS; Forty SD rats with a body weight of 270 -310 g were randomly grouped into control group, EA group, model group,and model + EP group with 10 rats each.INTERVENTIONS: EPSPs of granular cell layer at rat hippocampus dentate gyms were induced and recorded. LTP reaction of hippocampal synapse was aroused by high frequency stimulating(HFS) anterior perforated substance of cerebral cortex. Hypomnesia model was established by intraperitoneal injection of scopolamine. Dazhui(DU14) and both Shenshu(BL23) acupoints were acupunctured with EA with 3 - 5 mA of sparse and dense alternation wave for 30 minutes. The impacts of EA on normal and model hippocampal LTP were observed.MAIN OUTCOME MEASURES: Population spike (PS) , latency of EPSP,latency of PS peak, EPSP slope, PS peak value and PS peak area(PSa) of LTP before and at 0, 60 and 120 minutes after HFS.HFS was stronger than that of control group. Compared with control group,EPSP latency significantly shortened[compared with the change rate before HFS, the latencies were( -7.8 ±2.6)% and( - 14.4 ±7.7)% respectively(t=2.568 1, P < 0.05), EPSP slope increased(t=2.436 4, P <0.05); PSa incrensed(t=2.750 8-2.990 9, P < 0.05), with longer synapse LTP induced by HFS, which expressed in the prolongation of latencies of EPSP, PS peak value with significances compared with control group(t =4.564 8 -5.996 5, P <0.01) and, EPSP slope decreased, PS

  14. Methylphenidate amplifies long-term potentiation in rat hippocampus CA1 area involving the insertion of AMPA receptors by activation of β-adrenergic and D1/D5 receptors.

    Science.gov (United States)

    Rozas, C; Carvallo, C; Contreras, D; Carreño, M; Ugarte, G; Delgado, R; Zeise, M L; Morales, B

    2015-12-01

    Methylphenidate (MPH, Ritalin©) is widely used in the treatment of Attention Deficit Hyperactivity Disorder and recently as a drug of abuse. Although the effect of MPH has been studied in brain regions such as striatum and prefrontal cortex (PFC), the hippocampus has received relatively little attention. It is known that MPH increases the TBS-dependent Long Term Potentiation (LTP) in the CA1 area. However, the cellular and molecular mechanisms involved in this process are still unknown. Using field potential recordings and western blot analysis in rat hippocampal slices of young rats, we found that acute application of MPH enhances LTP in CA3-CA1 synapses in a dose-dependent manner with an EC50 of 73.44±6.32 nM. Using specific antagonists and paired-pulse facilitation protocols, we observed that the MPH-dependent increase of LTP involves not only β-adrenergic receptors activation but also post-synaptic D1/D5 dopamine receptors. The inhibition of PKA with PKI, suppressed the facilitation of LTP induced by MPH consistent with an involvement of the adenyl cyclase-cAMP-PKA dependent cascade downstream of the activation of D1/D5 receptors. In addition, samples of CA1 areas taken from slices potentiated with MPH presented an increase in the phosphorylation of the Ser845 residue of the GluA1 subunit of AMPA receptors compared to control slices. This effect was reverted by SCH23390, antagonist of D1/D5 receptors, and PKI. Moreover, we found an increase of surface-associated functional AMPA receptors. We propose that MPH increases TBS-dependent LTP in CA3-CA1 synapses through a polysynaptic mechanism involving activation of β-adrenergic and D1/D5 dopaminergic receptors and promoting the trafficking and insertion of functional AMPA receptors to the plasma membrane.

  15. LONG-TERM MONITORING SENSOR NETWORK

    Energy Technology Data Exchange (ETDEWEB)

    Stephen P. Farrington; John W. Haas; Neal Van Wyck

    2003-10-16

    Long-term monitoring (LTM) associated with subsurface contamination sites is a key element of Long Term Stewardship and Legacy Management across the Department of Energy (DOE) complex. However, both within the DOE and elsewhere, LTM is an expensive endeavor, often exceeding the costs of the remediation phase of a clean-up project. The primary contributors to LTM costs are associated with labor. Sample collection, storage, preparation, analysis, and reporting can add a significant financial burden to project expense when extended over many years. Development of unattended, in situ monitoring networks capable of providing quantitative data satisfactory to regulatory concerns has the potential to significantly reduce LTM costs. But survival and dependable operation in a difficult environment is a common obstacle to widespread use across the DOE complex or elsewhere. Deploying almost any sensor in the subsurface for extended periods of time will expose it to chemical and microbial degradation. Over the time-scales required for in situ LTM, even the most advanced sensor systems may be rendered useless. Frequent replacement or servicing (cleaning) of sensors is expensive and labor intensive, offsetting most, if not all, of the cost savings realized with unattended, in situ sensors. To enable facile, remote monitoring of contaminants and other subsurface parameters over prolonged periods, Applied Research Associates, Inc has been working to develop an advanced LTM sensor network consisting of three key elements: (1) an anti-fouling sensor chamber that can accommodate a variety of chemical and physical measurement devices based on electrochemical, optical and other techniques; (2) two rapid, cost effective, and gentle means of emplacing sensor packages either at precise locations directly in the subsurface or in pre-existing monitoring wells; and (3) a web browser-based data acquisition and control system (WebDACS) utilizing field-networked microprocessor-controlled smart

  16. Long-Term Ownership by Industrial Foundations

    DEFF Research Database (Denmark)

    Børsting, Christa Winther; Kuhn, Johan Moritz; Poulsen, Thomas

    2016-01-01

    Short-termism has become a serious concern for businesses and policy makers and this has inspired a search for governance arrangement to promote long term decision making. In this paper we study a particularly long-term ownership structure, which is fairly common in Northern Europe, particularly...... in Denmark. Industrial foundations are independent legal entities without owners or members typically with the dual objective of preserving the company and using excess profits for charity. We use a unique Danish data set to examine the governance of foundation-owned companies. We show that they are long-term...... in several respects. Foundations hold on to their shares for longer. Foundation-owned companies replace managers less frequently. They have more conservative capital structures with less leverage. Their companies survive longer. Their business decisions appear to be more long term. This paper supports...

  17. Long Term Care Minimum Data Set (MDS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Long-Term Care Minimum Data Set (MDS) is a standardized, primary screening and assessment tool of health status that forms the foundation of the comprehensive...

  18. Long Term Care Minimum Data Set (MDS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Long-Term Care Minimum Data Set (MDS) is a standardized, primary screening and assessment tool of health status that forms the foundation of the comprehensive...

  19. Long-Term Care Ombudsman Program

    Science.gov (United States)

    ... Strategic Plan Federal Initiatives Career Opportunities Contact Us Administration on Aging (AoA) Long-Term Care Ombudsman Program ( ... Prevention HIV/AIDS Nutrition Services Oral Health Elder Justice & Adult Protective Services Elder Justice Coordinating Council Prevention ...

  20. Pituitary diseases : long-term clinical consequences

    NARCIS (Netherlands)

    Klaauw, Agatha Apolonia van der

    2008-01-01

    This thesis describes various studies during the long-term follow-up of patients after treatment for pituitary diseases. The focus of this thesis is acromegaly, growth hormone deficiency, sleep and quality of life. Various aspects are described.

  1. Long-term outcome of meniscectomy

    DEFF Research Database (Denmark)

    Roos, Ewa M.; Ostenberg, A; Roos, H;

    2001-01-01

    To describe the long-term influence of meniscectomy on pain, functional limitations, and muscular performance. To assess the effects of radiographic osteoarthritis (OA), gender and age on these outcomes in patients with meniscectomy....

  2. Pituitary diseases : long-term clinical consequences

    NARCIS (Netherlands)

    Klaauw, Agatha Apolonia van der

    2008-01-01

    This thesis describes various studies during the long-term follow-up of patients after treatment for pituitary diseases. The focus of this thesis is acromegaly, growth hormone deficiency, sleep and quality of life. Various aspects are described.

  3. Differential effects of the histamine H3 receptor agonist methimepip on dentate granule cell excitability, paired-pulse plasticity and long-term potentiation in prenatal alcohol-exposed rats

    Science.gov (United States)

    Varaschin, Rafael K.; Rosenberg, Martina J.; Hamilton, Derek A.; Savage, Daniel D.

    2016-01-01

    We previously reported that prenatal alcohol-induced deficits in dentate gyrus (DG) long-term potentiation (LTP) are ameliorated by the histamine H3 receptor inverse agonist ABT-239. ABT-239 did not enhance LTP in control rats, suggesting a heightened H3 receptor-mediated inhibition of glutamate release in prenatal alcohol-exposed (PAE) offspring. As the modulation of glutamate release is one important facet of LTP, we examined the effect of methimepip, a histamine H3 receptor agonist, on DG granule cell excitability, glutamate release and LTP in control and PAE rats. Long-Evans rat dams voluntarily consumed either a 0% or 5% ethanol solution four hours daily throughout gestation. Male adult offspring were anesthetized with urethane and electrodes implanted into the entorhinal cortex and DG. PAE reduced coupling of excitatory post-synaptic field potentials to population spikes, an effect mimicked in control rats treated with 1 mg/kg methimepip. Methimepip decreased release probability in controls but not in PAE offspring. GABAergic feedback inhibition of granule cell responsiveness was not affected by either PAE or methimepip. PAE reduced LTP in the DG, another effect mimicked in methimepip-treated control rats. Again, methimepip did not exacerbate the PAE-induced LTP deficit. Thus, while methimepip treatment of control rats mimicked some baseline and activity-dependent deficits observed in saline-treated PAE offspring, methimepip treatment of PAE rats did not exacerbate these deficits. Whether the absence of an added methimepip effect in PAE offspring is a consequence of a “floor effect” for the responses measured or is due to differential drug dose responsiveness will require further investigation. Further, more detailed studies of H3 receptor-mediated responses in vitro may provide clearer insights into the role of the H3 receptor regulation of excitatory transmission at the perforant path - DG synapse in PAE rats. PMID:24818819

  4. Long-term outcomes after severe shock.

    Science.gov (United States)

    Pratt, Cristina M; Hirshberg, Eliotte L; Jones, Jason P; Kuttler, Kathryn G; Lanspa, Michael J; Wilson, Emily L; Hopkins, Ramona O; Brown, Samuel M

    2015-02-01

    Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Seventy-six patients who were alive 90 days after severe shock (received ≥1 μg/kg per minute of norepinephrine equivalent) were eligible for the study. We measured 3-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. The mean long-term survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of 5 years after hospital admission. The patients' Physical Functioning scores were below U.S. population norms (P shock had a high 3-year survival rate. Patients' long-term physical and psychological outcomes were similar to those reported for cohorts of less severely ill intensive care unit survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term outcomes. Even extremely critically ill patients have similar outcomes to general intensive care unit survivor populations.

  5. Anticipating Long-Term Stock Market Volatility

    OpenAIRE

    Conrad, Christian; Loch, Karin

    2012-01-01

    We investigate the relationship between long-term U.S. stock market risks and the macroeconomic environment using a two component GARCH-MIDAS model. Our results provide strong evidence in favor of counter-cyclical behavior of long-term stock market volatility. Among the various macro variables in our dataset the term spread, housing starts, corporate profits and the unemployment rate have the highest predictive ability for stock market volatility . While the term spread and housing starts are...

  6. Ubiquitin-Proteasome System Inhibition Promotes Long-Term Depression and Synaptic Tagging/Capture.

    Science.gov (United States)

    Li, Qin; Korte, Martin; Sajikumar, Sreedharan

    2016-06-01

    A balance of protein synthesis and degradation is critical for the dynamic regulation and implementation of long-term memory storage. The role of the ubiquitin-proteasome system (UPS) in regulating the plasticity at potentiated synapses is well studied, but its roles in depressed synaptic populations remain elusive. In this study, we probed the possibility of regulating the UPS by inhibiting the proteasome function during the induction of protein synthesis-independent form of hippocampal long-term depression (early-LTD), an important component of synaptic plasticity. Here, we show that protein degradation is involved in early-LTD induction and interfering with this process facilitates early-LTD to late-LTD. We provide evidence here that under the circumstances of proteasome inhibition brain-derived neurotrophic factor is accumulated as plasticity-related protein and it drives the weakly depressed or potentiated synapses to associativity. Thus, UPS inhibition promotes LTD and establishes associativity between weakly depressed or potentiated synapses through the mechanisms of synaptic tagging/capture or cross-capture.

  7. The Commonwealth Fund Survey of Long-Term Care Specialists.

    Science.gov (United States)

    Miller, Edward Alan; Weissert, William G

    2010-08-01

    The Commonwealth Fund Survey of Long-Term Care of Specialists was administered via the World Wide Web from September 2007 through March 2008. The primary purpose was to characterize the views of those with known or demonstrable experience and expertise with at least one aspect of long-term care. Among 2,577 potential respondents, 1,147 completed the entire survey for an overall response rate of 44.5%. This special supplement of Medical Care Research and Review uses data collected from the survey to explore several issue areas, namely, reforming long-term care financing, improving government oversight, adopting nursing home culture change, and rebalancing long-term care away from institutions toward home- and community-based services. Analyses documenting the opinion networks of long-term care specialists and the relationship between network characteristics and attitudes toward reform are also reported. Two leading experts provide commentary as well. Details of the study's methodology and issue content are described.

  8. LTP的研究进展(Ⅱ)--LTP的转基因研究%Recent advances in the study of long-term potentiation(part II)--transgenic study of LTP

    Institute of Scientific and Technical Information of China (English)

    张嘉伟; 叶桂兰

    2002-01-01

    LTP研究在近十余年来一直是热点课题.尽管LTP是否是学习和记忆的基础仍有争议,肯定性的研究结果日趋增加,所以LTP仍吸引着大量研究工作者.近年来随着分子生物学技术的进步,人们得以借助转基因手段研究疾病相关性基因及其蛋白质,以及不明功能的基因和蛋白.转基因动物模型更是给难以模拟的Alzheimer氏病的研究极大推动.2001年人类基因组序列研究结果报告对医学科学的发展影响深远.应用转基因模型的手段进一步深入各研究领域.近几年来神经工作者借助转基因手段,对LTP的分子机制有了进一步认识.本文概括性介绍了这方面的有趣研究,希望读者能大致了解LTP研究进展,同时领悟转基因技术的推动力.%There is more and more evidence showing long term potentiation (LTP) is underling learning and memory even though it is still controversy and the mechanism behind LTP has not yet been completely understood. It is known that memory processes and long-term potentiation (LTP) are blocked at the time of their initiation by antagonists of glutamate NMDA or metabotropic receptors, and GABA-A receptor agonists. Following initiation, memory and LTP are accompanied by an enhancement of the activity of calcium/calmodulin-dependent protein kinase II and of protein kinase C. At the time of expression, LTP is blocked by antagonists of glutamate AMPA receptors. In recent five years, with advanced molecular biology techniques, scientist could use transgenic and knock out mice to explore what happens to LTP and learning and memory when specific disease related or novel gene was overexpressed or deleted. Therefore cellular and molecular mechanisms of activity-dependent synaptic plasticity are understood in a new level. Here we introduced recent research work on LTP with transgenic approach in hope to inspire interest in genomic and protenomic technology. We will continue to discuss BDNF and LTP and

  9. Intrahepatic haematoma in a patient on long-term haemodialysis.

    Science.gov (United States)

    Lai, K N; Disney, A P; Mathew, T H

    Spontaneous intrahepatic haematoma is an uncommon potentially fatal complication in uraemic patients receiving long-term haemodialysis, particularly in those taking anticoagulant and antiplatelet drugs. Prompt diagnosis, withdrawal of anticoagulant and antiplatelet therapy, cautious transfusion, and careful dialysis with regional heparinisation are essential in the management and may help to avoid surgical intervention in the presence of a tendency to bleed. Noninvasive organ imaging such as ultrasonography and computerised axial tomography are helpful in diagnosis and monitoring of progress. A case of intrahepatic haematoma in a 37-year-old man who had been receiving long-term haemodialysis since 1976 is described.

  10. Long-term Morbidity of Testicular Cancer Treatment.

    Science.gov (United States)

    Fung, Chunkit; Fossa, Sophie D; Williams, Annalynn; Travis, Lois B

    2015-08-01

    Second malignant neoplasms, cardiovascular disease, neurotoxicity and ototoxicity, pulmonary complications, hypogonadism, and nephrotoxicity are potentially life-threatening long-term complications of testicular cancer and its therapy. This article describes the pathogenesis, risks, and management of these late effects experienced by long-term testicular cancer survivors, who are defined as individuals who are disease free 5 years or more after primary treatment. Testicular cancer survivors should follow applicable national guidelines for cancer screening and management of cardiovascular disease risk factors. In addition, health care providers should capitalize on the time of cancer diagnosis as a teachable moment to introduce and promote lifestyle changes.

  11. 工作记忆和长时记忆共享信息表征的ERP证据%Common Representations between Working Memory and Long-term Memory: Evidence from Event-Related Potentials

    Institute of Scientific and Technical Information of China (English)

    刘兆敏; 郭春彦

    2013-01-01

    Human memory can be characterized as an elaborate network of stored representations. Researchers propose that both working memory (WM) and long-term memory (LTM) utilize same representations, and the representations they activate are in diverse patterns. So the similarity and coherence between WM and LTM are emphasized in the activation-based model, and the priming effect of LTM on WM and vice versa should be both found. By simultaneously recording event-related potentials (ERPs), the present study aimed to investigate two long-term semantic priming effects to illustrate the common representations involved in WM and LTM. Fifteen college students (mean age=20.33±1.91; 7 male) participated in the experiment. The participants were all right-hand, had normal or corrected-to-normal vision and had no neurological or psychological disorders. Each participant signed a consent form prior to experiment and was paid after experiment. We combined a WM component (short-term verbal encoding) and a LTM component (category comparison) into one task, so that WM and LTM processing could be concurrently investigated. LTM priming on WM was manipulated by asking participants to learn before short-term verbal encoding, and the priming effect of WM on related LTM should be found in category comparison. Results revealed two long-term semantic priming effects in behavior data and ERPs. The first effect was found in short-term encoding phase, which was reflected as the priming of LTM on WM. Compared with new targets in WM, the reaction time of studied targets was shorter. They elicitedearlier N2 and P3, and they also decreased N2 amplitude. These may index the so-called neural priming (or repetition suppression) of scalp potentials. However, there was no difference between new and studied distractors in WM. Furthermore, the neural priming of WM on LTM also exhibited in category comparison. Specific contents, which were formerly concerned or ignored in short-term encoding phase, led

  12. Long-term drought severity variations in Morocco

    Science.gov (United States)

    Esper, Jan; Frank, David; Büntgen, Ulf; Verstege, Anne; Luterbacher, Jürg; Xoplaki, Elena

    2007-09-01

    Cedrus atlantica ring width data are used to reconstruct long-term changes in the Palmer Drought Severity Index (PDSI) over the past 953 years in Morocco, NW Africa. The reconstruction captures the dry conditions since the 1980s well and places this extreme period within a millennium-long context. PDSI values were above average for most of the 1450-1980 period, which let recent drought appear exceptional. However, our results also indicate that this pluvial episode of the past millennium was preceded by generally drier conditions back to 1049. Comparison of PDSI estimates with large-scale pressure field reconstructions revealed steady synoptic patterns for drought conditions over the past 350 years. The long-term changes from initially dry to pluvial to recent dry conditions are similar to PDSI trends reported from N America, and we suggest that they are related to long-term temperature changes, potentially teleconnected with ENSO variability and forced by solar irradiance changes.

  13. LTP promotes a selective long-term stabilization and clustering of dendritic spines.

    Directory of Open Access Journals (Sweden)

    Mathias De Roo

    2008-09-01

    Full Text Available Dendritic spines are the main postsynaptic site of excitatory contacts between neurons in the central nervous system. On cortical neurons, spines undergo a continuous turnover regulated by development and sensory activity. However, the functional implications of this synaptic remodeling for network properties remain currently unknown. Using repetitive confocal imaging on hippocampal organotypic cultures, we find that learning-related patterns of activity that induce long-term potentiation act as a selection mechanism for the stabilization and localization of spines. Through a lasting N-methyl-D-aspartate receptor and protein synthesis-dependent increase in protrusion growth and turnover, induction of plasticity promotes a pruning and replacement of nonactivated spines by new ones together with a selective stabilization of activated synapses. Furthermore, most newly formed spines preferentially grow in close proximity to activated synapses and become functional within 24 h, leading to a clustering of functional synapses. Our results indicate that synaptic remodeling associated with induction of long-term potentiation favors the selection of inputs showing spatiotemporal interactions on a given neuron.

  14. Inflammatory markers in relation to long-term air pollution.

    Science.gov (United States)

    Mostafavi, Nahid; Vlaanderen, Jelle; Chadeau-Hyam, Marc; Beelen, Rob; Modig, Lars; Palli, Domenico; Bergdahl, Ingvar A; Vineis, Paolo; Hoek, Gerard; Kyrtopoulos, Soterios Α; Vermeulen, Roel

    2015-08-01

    Long-term exposure to ambient air pollution can lead to chronic health effects such as cancer, cardiovascular and respiratory disease. Systemic inflammation has been hypothesized as a putative biological mechanism contributing to these adverse health effects. We evaluated the effect of long-term exposure to air pollution on blood markers of systemic inflammation. We measured a panel of 28 inflammatory markers in peripheral blood samples from 587 individuals that were biobanked as part of a prospective study. Participants were from Varese and Turin (Italy) and Umea (Sweden). Long-term air pollution estimates of nitrogen oxides (NOx) were available from the European Study of Cohorts for Air Pollution Effects (ESCAPE). Linear mixed models adjusted for potential confounders were applied to assess the association between NOx and the markers of inflammation. Long-term exposure to NOx was associated with decreased levels of interleukin (IL)-2, IL-8, IL-10 and tumor necrosis factor-α in Italy, but not in Sweden. NOx exposure levels were considerably lower in Sweden than in Italy (Sweden: median (5th, 95th percentiles) 6.65 μg/m(3) (4.8, 19.7); Italy: median (5th, 95th percentiles) 94.2 μg/m(3) (7.8, 124.5)). Combining data from Italy and Sweden we only observed a significant association between long-term exposure to NOx and decreased levels of circulating IL-8. We observed some indication for perturbations in the inflammatory markers due to long-term exposure to NOx. Effects were stronger in Italy than in Sweden, potentially reflecting the difference in air pollution levels between the two cohorts.

  15. Long-term human-robot interaction with young users

    NARCIS (Netherlands)

    Baxter, P.; Belpaeme, T.; Canamero, L.; Cosi, P.; Demiris, Y.; Enescu, V.; Et al.

    2011-01-01

    Artificial companion agents have the potential to combine novel means for effective health communication with young patients support and entertainment. However, the theory and practice of long-term child-robot interaction is currently an underdeveloped area of research. This paper introduces an appr

  16. Long-term human-robot interaction with young users

    NARCIS (Netherlands)

    Baxter, P.; Belpaeme, T.; Canamero, L.; Cosi, P.; Demiris, Y.; Enescu, V.; Et al.

    2011-01-01

    Artificial companion agents have the potential to combine novel means for effective health communication with young patients support and entertainment. However, the theory and practice of long-term child-robot interaction is currently an underdeveloped area of research. This paper introduces an appr

  17. Acute mastoiditis in children: presentation and long term consequences.

    LENUS (Irish Health Repository)

    Glynn, F

    2008-03-01

    Acute mastoiditis, a destructive bacterial infection of the mastoid bone and air cell system, is relatively uncommon today but remains a potentially serious condition. There is a lack of information in the literature regarding the long term otological problems that children may face following an episode of this condition.

  18. Dying with Dementia in Long-Term Care

    Science.gov (United States)

    Sloane, Philip D.; Zimmerman, Sheryl; Williams, Christianna S.; Hanson, Laura C.

    2008-01-01

    Purpose: To better understand the experiences and potential unmet need of persons who die in long-term care. Design and Methods: We conducted after-death interviews with staff who had cared for 422 decedents with dementia and 159 who were cognitively intact and received terminal care in U.S. nursing homes (NHs) or residential care-assisted living…

  19. Long term results of kissing stents in the aortic bifurcation

    NARCIS (Netherlands)

    Hinnen, J.W.; Konickx, M.A.; Meerwaldt, Robbert; Kolkert, J.L.P.; van der Palen, Jacobus Adrianus Maria; Huisman, A.B.

    2015-01-01

    BACKGROUND: To evaluate the long-term outcome after aortoiliac kissing stent placement and to analyze variables, which potentially influence the outcome of endovascular reconstruction of the aortic bifurcation. METHODS: All patients treated with aortoiliac kissing stents at our institution between

  20. Global climate change and contaminants--an overview of opportunities and priorities for modelling the potential implications for long-term human exposure to organic compounds in the Arctic.

    Science.gov (United States)

    Armitage, James M; Quinn, Cristina L; Wania, Frank

    2011-06-01

    This overview seeks to provide context and insight into the relative importance of different aspects related to global climate change for the exposure of Northern residents to organic contaminants. A key objective is to identify, from the perspective of researchers engaged in contaminant fate, transport and bioaccumulation modelling, the most useful research questions with respect to projecting the long-term trends in human exposure. Monitoring studies, modelling results, the magnitude of projected changes and simplified quantitative approaches are used to inform the discussion. Besides the influence of temperature on contaminant amplification and distribution, accumulation of organic contaminants in the Arctic is expected to be particularly sensitive to the reduction/elimination of sea-ice cover and also changes to the frequency and intensity of precipitation events (most notably for substances that are highly susceptible to precipitation scavenging). Changes to key food-web interactions, in particular the introduction of additional trophic levels, have the potential to exert a relatively high influence on contaminant exposure but the likelihood of such changes is difficult to assess. Similarly, changes in primary productivity and dynamics of organic matter in aquatic systems could be influential for very hydrophobic contaminants, but the magnitude of change that may occur is uncertain. Shifts in the amount and location of chemical use and emissions are key considerations, in particular if substances with relatively low long range transport potential are used in closer proximity to, or even within, the Arctic in the future. Temperature-dependent increases in emissions via (re)volatilization from primary and secondary sources outside the Arctic are also important in this regard. An increased frequency of boreal forest fires has relevance for compounds emitted via biomass burning and revolatilization from soil during/after burns but compound-specific analyses are

  1. Long-term follow-up study and long-term care of childhood cancer survivors

    Directory of Open Access Journals (Sweden)

    Hyeon Jin Park

    2010-04-01

    Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

  2. 小胶质细胞活化对海马长时程增强影响的研究进展%Recent advance in effect of microglial activation on long-term potentiation of hippocampus

    Institute of Scientific and Technical Information of China (English)

    张占刚; 付岩; 杨拼; 董献文; 徐颖

    2016-01-01

    在对神经退行性疾病如阿尔茨海默病、帕金森病等的研究中,人们提出了神经炎症假说,认为是小胶质细胞活化导致炎症介质持续释放,并损伤神经元结构和功能,出现学习记忆障碍等临床表现.其中神经元突触结构的破坏导致突触可塑性下降,出现长时程增强(LTP)改变,表现为高频刺激后兴奋性突触后电位幅值减小、持续时间缩短等现象.活化的小胶质细胞本身及其释放的炎症因子如白介素-1β、肿瘤坏死因子-α、一氧化氮等都参与了疾病中LTP损伤的病理过程.本文对近几年神经退行性疾病中小胶质细胞活化与LTP损伤关系的研究进展作一综述,希望能为神经退行性疾病的临床诊治和科学研究提供一定的指导.%In the study of neurodegenerative diseases,a hypothesis of inflammation in central nervous system is raised:the activated microglia leads to sustained release of preinflammatory cytokines and injury of normal neural structures and function,resulting in learning and memory deficits,such as Alzheimer's disease (AD) and Parkinson's disease (PD).Synapses structural disorders are responsible for deficit of synaptic plasticity;after high frequency stimulation,changes of long-term potentiation (LTP) are most obvious in synaptic plasticity,characterized by decrease of amplitude and excitatory postsynaptic potential duration.Activated microglia and inflammatory cytokines released by activated microglia,such as interleukin-1β,tumor necrosis factor-α and nitric oxide are involved in the pathological process of LTP changes in these kinds of disease.The aim of this paper is to give a review about progress in the relations between microglia activation and LTP in neurodegenerative diseases researches in recent years and hope to have something to guide the research of neurodegenerative disease.

  3. Long-term Multiwavelength Observations of Polars

    Science.gov (United States)

    Santana, Joshua; Mason, Paul A.

    2016-06-01

    Polars are cataclysmic variables with the highest magnetic field strengths (10-250 MG). Matter is accreted after being funneled by the strong magnetic field of the white dwarf. We perform a meta-study of multi-wavelength data of polars. Many polars have been observed in surveys, such as SDSS, 2MASS, ROSAT, just to name a few. Some polars have now been detected by the JVLA, part of an expanding class of radio CVs. A large subset of polars have long-term optical light curves from CRTS and AAVSO. We suggest that the long term light curves of polars display a variety of signature behaviors and may be grouped accordingly. Additional characteristics such a binary period, magnetic field strengths, X-ray properties, and distance estimates are examined in context with long-term observations.

  4. Metformin ameliorates ionizing irradiation-induced long-term hematopoietic stem cell injury in mice

    Science.gov (United States)

    Xu, Guoshun; Wu, Hongying; Zhang, Junling; Li, Deguan; Wang, Yueying; Wang, Yingying; Zhang, Heng; Lu, Lu; Li, Chengcheng; Huang, Song; Xing, Yonghua; Zhou, Daohong; Meng, Aimin

    2016-01-01

    Exposure to ionizing radiation (IR) increases the production of reactive oxygen species (ROS) not only by the radiolysis of water but also through IR-induced perturbation of the cellular metabolism and disturbance of the balance of reduction/oxidation reactions. Our recent studies showed that the increased production of intracellular ROS induced by IR contributes to IR-induced late effects, particularly in the hematopoietic system, because inhibition of ROS production with an antioxidant after IR exposure can mitigate IR-induced long-term bone marrow (BM) injury. Metformin is a widely used drug for the treatment of type 2 diabetes. Metformin also has the ability to regulate cellular metabolism and ROS production by activating AMP-activated protein kinase. Therefore, we examined whether metformin can ameliorate IR-induced long-term BM injury in a total-body irradiation (TBI) mouse model. Our results showed that the administration of metformin significantly attenuated TBI-induced increases in ROS production and DNA damage and upregulation of NADPH oxidase 4 expression in BM hematopoietic stem cells (HSCs). These changes were associated with a significant increase in BM HSC frequency, a considerable improvement in in vitro and in vivo HSC function, and complete inhibition of upregulation of p16Ink4a in HSCs after TBI. These findings demonstrate that metformin can attenuate TBI-induced long-term BM injury at least in part by inhibiting the induction of chronic oxidative stress in HSCs and HSC senescence. Therefore, metformin has the potential to be used as a novel radioprotectant to ameliorate TBI-induced long-term BM injury. PMID:26086617

  5. Long-term home care scheduling

    DEFF Research Database (Denmark)

    Gamst, Mette; Jensen, Thomas Sejr

    In several countries, home care is provided for certain citizens living at home. The long-term home care scheduling problem is to generate work plans spanning several days such that a high quality of service is maintained and the overall cost is kept as low as possible. A solution to the problem...... provides detailed information on visits and visit times for each employee on each of the covered days. We propose a branch-and-price algorithm for the long-term home care scheduling problem. The pricing problem generates one-day plans for an employee, and the master problem merges the plans with respect...

  6. Keratoprosthesis: a long-term review.

    Science.gov (United States)

    Barnham, J J; Roper-Hall, M J

    1983-07-01

    A keratoprosthesis (KP), is an artificial cornea which is inserted into an opacified cornea in an attempt to restore useful vision or, less commonly, to make the eye comfortable in painful keratopathy. Results o a retrospective study of 35 patients, with 55 KP insertions, are reviewed with regard to visual acuity, length of time vision is maintained, retention time, and complication. Overall there were a number of long-term real successes, eith retention of the KP and maintenance of improved vision in eyes not amenable to conventional treatment. Careful long-term follow-up was needed, with further surgical procedures often being necessary.

  7. Role of the Phosphoinositide 3-Kinase-Akt-Mammalian Target of the Rapamycin Signaling Pathway in Long-Term Potentiation and Trace Fear Conditioning Memory in Rat Medial Prefrontal Cortex

    Science.gov (United States)

    Sui, Li; Wang, Jing; Li, Bao-Ming

    2008-01-01

    Phosphatidylinositol 3-kinase (PI3K) and its downstream targets, including Akt (also known as protein kinase B, PKB), mammalian target of rapamycin (mTOR), the 70-kDa ribosomal S6 kinase (p70S6k), and the eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1), may play important roles in long-term synaptic plasticity and memory in many…

  8. Effects of Patterned Sound Deprivation on Short- and Long-Term Plasticity in the Rat Thalamocortical Auditory System In Vivo

    Directory of Open Access Journals (Sweden)

    Chloe N. Soutar

    2016-01-01

    Full Text Available Postnatal sensory experience plays a significant role in the maturation and synaptic stabilization of sensory cortices, such as the primary auditory cortex (A1. Here, we examined the effects of patterned sound deprivation (by rearing in continuous white noise, WN during early postnatal life on short- and long-term plasticity of adult male rats using an in vivo preparation (urethane anesthesia. Relative to age-matched control animals reared under unaltered sound conditions, rats raised in WN (from postnatal day 5 to 50–60 showed greater levels of long-term potentiation (LTP of field potentials in A1 induced by theta-burst stimulation (TBS of the medial geniculate nucleus (MGN. In contrast, analyses of short-term plasticity using paired-pulse stimulation (interstimulus intervals of 25–1000 ms did not reveal any significant effects of WN rearing. However, LTP induction resulted in a significant enhancement of paired-pulse depression (PPD for both rearing conditions. We conclude that patterned sound deprivation during early postnatal life results in the maintenance of heightened, juvenile-like long-term plasticity (LTP into adulthood. Further, the enhanced PPD following LTP induction provides novel evidence that presynaptic mechanisms contribute to thalamocortical LTP in A1 under in vivo conditions.

  9. Consequences of long-term hyperparathyroidism

    NARCIS (Netherlands)

    Graal, M B; Wolffenbuttel, B H

    1998-01-01

    We describe a young woman with long-term untreated hyperparathyroidism with a superimposed vitamin D deficiency and an extremely decreased bone mineral density that was complicated by a vertebral fracture. Despite pretreatment with intravenous pamidronate and short-term vitamin D supplementation, se

  10. Long-term prevention of diabetic nephropathy

    DEFF Research Database (Denmark)

    Schjoedt, K J; Hansen, H P; Tarnow, L

    2008-01-01

    AIMS/HYPOTHESIS: In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary AER (UAER) of 6-14%/year and a risk of developing diabetic nephropathy (DN) of 3-30%/year have been reported. We audited the long-term effect of blocking the renin-a...

  11. Long Term Transfer Effect of Metaphoric Allusion.

    Science.gov (United States)

    Hayes, David A.; Mateja, John A.

    A study was conducted to investigate the long term transfer effect of metaphoric allusion used to clarify unfamiliar subject matter. Forty-nine high school students were given unfamiliar prose materials variously augmented by metaphoric allusion. The subjects' immediate performance on a transfer task was compared to their performance on an…

  12. Long-Term Memory and Learning

    Science.gov (United States)

    Crossland, John

    2011-01-01

    The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

  13. Long-Term Stability of Social Participation

    Science.gov (United States)

    Hyyppa, Markku T.; Maki, Juhani; Alanen, Erkki; Impivaara, Olli; Aromaa, Arpo

    2008-01-01

    The long-term stability of social participation was investigated in a representative urban population of 415 men and 579 women who had taken part in the nationwide Mini-Finland Health Survey in the years 1978-1980 and were re-examined 20 years later. Stability was assessed by means of the following tracking coefficients: kappa, proportion of…

  14. The long term characteristics of greenschist

    Science.gov (United States)

    Jang, Bo-An

    2016-04-01

    The greenschist in the Jinping II Hydropower Station in southwest China exhibits continuous creep behaviour because of the geological conditions in the region. This phenomenon illustrates the time-dependent deformation and progressive damage that occurs after excavation. In this study, the responses of greenschist to stress over time were determined in a series of laboratory tests on samples collected from the access tunnel walls at the construction site. The results showed that the greenschist presented time-dependent behaviour under long-term loading. The samples generally experienced two stages: transient creep and steady creep, but no accelerating creep. The periods of transient creep and steady creep increased with increasing stress levels. The long-term strength of the greenschist was identified based on the variation of creep strain and creep rate. The ratio of long-term strength to conventional strength was around 80% and did not vary much with confining pressures. A quantitative method for predicting the failure period of greenschist, based on analysis of the stress-strain curve, is presented and implemented. At a confining pressure of 40 MPa, greenschist was predicted to fail in 5000 days under a stress of 290 MPa and to fail in 85 days under the stress of 320 MPa, indicating that the long-term strength identified by the creep rate and creep strain is a reliable estimate.

  15. Pituitary diseases : long-term psychological consequences

    NARCIS (Netherlands)

    Tiemensma, Jitske

    2012-01-01

    Nowadays, pituitary adenomas can be appropriately treated, but patients continue to report impaired quality of life (QoL) despite long-term remission or cure. In patients with Cushing’s disease, Cushing’s syndrome or acromegaly, doctors should be aware of subtle cognitive impairments and the

  16. 血管性痴呆大鼠海马区的长时程增强变化%Changes of long-term potentiation of hippocampus in vascular dementia rats

    Institute of Scientific and Technical Information of China (English)

    姚国恩; 王景周; 陈曼娥; 蒋晓江

    2004-01-01

    BACKGROUND: Long term potentiation(LTP) of CA1 region in the hippocampus of rats has been widely accepted as the cell model of learning and memory. However, there are few reports on its mechanism and pathological changes.OBJECTIVE: To observe the changes of LTP in CA1 region of rat' s hippocampus when blocking four blood vessels and explore the possible mechanism.DESIGN: Randomized case controlled study.SETTING, PARTICIPANTS and INTERVENTIONS: This experimentwas completed in the Experimental Animal Center of Field Operation Surgery Research Institute, Third Military Medical University of Chinese PLA. 60 Wistar rats were divided into control group and model group by random digits table method. Each group was divided into three subgroups by time phase which was 2 weeks, 4 weeks and 2 months, with each of 10 rats. Vascular dementia was produced in rats using a modification of Pulsinelli' s four-vessel occlusion model. Shuttle box system controlled by computer was used to test the learning and memory of rats. LTP of CA1 region induced by extracorporeal hippocampus slices was used to test the electricity changes of leaning and memory of rats. Ultrastructure of CA1 region of rat' s hippocampus was observed by transmission electron microscope.MAIN OUTCOME MEASURES: Active avoidance reaction(AAR); LTPdetection; ultramicro observation of CA1 region of hippocampus.RESULTS: Compared with control group, the AAR in model group declined more prominent than that of control group in the 2nd week( P < 0.05) . It reduced much greater in the 4th week and 2nd months( P < 0.01 ) . In the control group, the slices of hippocampus could obviously induce the LTP waveform while there was no LTP induced in all time phases in model groups. There were differences on the percentage changes of fEPSP slope before and after conditioned stimulus and between model groups and control groups( P < 0.05) . However, there was no difference among different time phases. There were some chronically

  17. Role of Atypical Protein Kinases in Maintenance of Long-Term Memory and Synaptic Plasticity.

    Science.gov (United States)

    Borodinova, A A; Zuzina, A B; Balaban, P M

    2017-03-01

    Investigation of biochemical mechanisms underlying the long-term storage of information in nervous system is one of main problems of modern neurobiology. As a molecular basis of long-term memory, long-term changes in kinase activities, increase in the level and changes in the subunit composition of receptors in synaptic membranes, local activity of prion-like proteins, and epigenetic modifications of chromatin have been proposed. Perhaps a combination of all or of some of these factors underlies the storage of long-term memory in the brain. Many recent studies have shown an exclusively important role of atypical protein kinases (PKCζ, PKMζ, and PKCι/λ) in processes of learning, consolidation and maintenance of memory. The present review is devoted to consideration of mechanisms of transcriptional and translational control of atypical protein kinases and their roles in induction and maintenance of long-term synaptic plasticity and memory in vertebrates and invertebrates.

  18. A modified potential probe for induction charging risk assessment

    Science.gov (United States)

    Fast, Lars; Paasi, Jaakko

    2008-12-01

    Practical assessment of risks for Electrostatic Discharge (ESD) failures of semiconductor devices, due to charges induced on devices in a manufacturing or repair environment of electronics has been difficult, because easily measurable parameters such as the electrostatic field and the potential of a charged surface do not directly quantify the risk. In this paper a new method of assessing the risks with induction charging of a sensitive device is presented by introducing a well-defined dummy device, which is a simple modification of the probe of DC type non-contacting electrostatic voltmeter. By placing the modified potential probe (mimicking large sensitive device) in front of charged surface, risks of ESD failure for a device due to induction charging can be assessed. The electrostatic response of the probe at different distances between charged surface and the probe has been verified by numerical model calculations.

  19. 锌缺乏对小鼠海马长时程增强的影响%Effect of Zinc deficiency on the formation of hippocampal long term potentiation

    Institute of Scientific and Technical Information of China (English)

    王佐周; 高慧玲; 徐赫; 王涛; 王占友

    2011-01-01

    Objective To investigate the effect of zinc deficiency on hippocampal zinc content and long term potentiation (LTP) in the mouse. Methods CD-1 mice at 3 weeks of age were fed with zinc-deficient diet (O.85mg/kg) for 5 weeks. Autometallography (AMG) was carried out to analyze the zinc content in the hippocampus. A concentric bipolar stimulating electrode was placed in the orientation of the mossy fiber lamellae of the fight dentate gyrus (DG) and a glass capillary recording electrode was placed ipsilaterally in the stratum pyramidal of the CA3 region of the hippecampus. LTP was evoked by a train of high frequency stimulations (HFS), and the changes of population spike (PS) and field excitatory postsynapfic potential (f-EPSP) were recorded, in order to analyze the effect of LTP under zinc deficiency. Results AMG staining showed that treatment with zinc-deficient diet reduced the level of zinc in hippocampal CA1, CA3 and dentate gyrus (p<0.05-0.O1). Electrophysiological in vivo recordings showed that zinc deficiency resulted in impairments of mossy fiber LTP (p<O.01). Conclusion Zinc deficiency results in a decreased level of free zinc ions in the hippocampus, which is associated with the inhibition of the formation of LTP.%目的 探讨锌缺乏对小鼠海马区域锌离子含量以及长时程增强(LTP)的影响.方法 3周龄CD-1小鼠饲以低锌饲料(0.85mg/kg)和去离子水5周进行实验.应用金属自显影技术(AMG)检测低锌饲料喂养对小鼠海马游离锌离子含量的影响;在小鼠海马齿状回的苔藓纤维层插入刺激电极,在CA3区锥体细胞层插入记录电极,记录高频刺激后海马苔藓纤维CA3区引起的峰电位(PS)和兴奋性突触后电位(f-EPSP)的变化,分析锌缺乏对小鼠海马LTP形成的影响.结果 AMG结果显示锌缺乏小鼠海马CA1,CA3和齿状回区域的锌离子含量明显降低(P<0.05-0.01);电生理检测结果表明锌缺乏小鼠在高频刺激后海马苔藓纤

  20. A technique for long term continent gastrostomy.

    Science.gov (United States)

    Locker, D L; Foster, J E; Craun, M L; Torma, M J

    1985-01-01

    The use of the continent gastrostomy described herein offers several advantages: 1, the elimination of an indwelling catheter; 2, prevention of soiling at skin level; 3, long term access to the normal gastrointestinal track for alimentation without fear of tube erosion; 4, little compromise to gastric volume, and 5, ease of stoma care. We recommend this operation in instances when long term tube feedings are indicated either because of damage to the central nervous system or as a palliative treatment for patients with higher obstructing gastrointestinal malignant disease. The procedure may also be useful for patients in whom esophagogastric continuity has been interrupted (surgically or traumatically) and in whom reconstruction of the gastrointestinal tract would not seem feasible within a three to six month interval.

  1. Long-term opioid therapy in Denmark

    DEFF Research Database (Denmark)

    Birke, H; Ekholm, O; Sjøgren, P

    2017-01-01

    BACKGROUND: Longitudinal population-based studies of long-term opioid therapy (L-TOT) in chronic non-cancer pain (CNCP) patients are sparse. Our study investigated incidence and predictors for initiating L-TOT and changes in self-rated health, pain interference and physical activities in long......-term opioid users. METHODS: Data were obtained from the national representative Danish Health and Morbidity Surveys and The Danish National Prescription Registry. Respondents with no dispensed opioids the year before the survey were followed from 2000 and from 2005 until the end of 2012 (n = 12...... defined as those who were dispensed at least one opioid prescription in six separate months within a year. RESULTS: The incidence of L-TOT was substantially higher in CNCP patients at baseline than in others (9/1000 vs. 2/1000 person-years). Smoking behaviour and dispensed benzodiazepines were...

  2. Case presentation: long-term treatment.

    Science.gov (United States)

    Glucksman, Myron L

    2013-01-01

    The long-term (14 years) psychodynamic psychotherapy and pharmacotherapy of a depressed, suicidal, self-mutilating female patient is described. Her diagnoses included Chronic Posttraumatic Stress Disorder, Borderline Personality Disorder, and Recurrent Major Depression. Treatment was punctuated with repeated hospitalizations for self-mutilation (cutting) and suicidal ideation. A major determinant for her psychopathology was sexual abuse by her father from ages 6 to 14. This resulted in feelings of guilt and rage that she repressed and acted out through self-mutilating and suicidal behavior. A prolonged negative transference gradually became ambivalent, then positive. This was associated with her internalization of the healing qualities of the therapeutic relationship. She also gained insight into the reasons for her need to punish herself. Her initial self-representation as unworthy and bad was transformed into perceiving herself as a worthwhile, loving person. This case illustrates the role of long-term treatment for a complex, life-threatening, psychiatric disorder.

  3. Forecasting for Long-term Development Potential of Electricity Consumption in Energy-Intensive Industries of China%我国高耗能行业电力消费中长期发展潜力预测

    Institute of Scientific and Technical Information of China (English)

    柳瑞禹; 叶子菀

    2012-01-01

    利用1985-2009年的年度数据,对我国高耗能行业用电量与GDP、行业产值、行业投资、城市化水平、行业投资结构等之间的相关关系进行了实证研究,采用情景分析法对2011-2020年7个情景下的我国高耗能用电的发展潜力及行业发展前景进行了预测。结果表明:高耗能用电与宏、微观经济变量之间存在长期均衡和短期偏离关系;城市化水平、高耗能行业投资结构是影响高耗能用电的重要因素;高耗能用电对GDP的发展速度比较敏感,在高耗能行业的投资与产值保持目前增长速度的情景下,高耗能用电走势与基准情景比较接近;2011-2020年高耗能行业继续发挥对经济的拉动作用,但巨大的资源消耗与能源环境代价呼唤高耗能行业进行绿色转型。%Using the annual data during 1985-2009,this paper empirically studies the correlations between electricity consumption of energy-intensive industries and GDP,investment as well output value of energy-intensive industries, urbanization level,and investment structure of ener- gy-intensive industries. Then it subsequently predicts the electricity consumption potential and development prospect of energy-intensive industries in 7 scenarios hypothesis by the scenario analysis method. The results show as follows:there exists the long-term equilibrium and the short- term deviation between electricity consumption of energy-intensive industries and GDP,industrial output value and investment;industrial invest- ment structure and urbanization level are the important factors influencing the electricity consumption of energy-intensive industries;the comparative scenario analysis result indicates that the electricity consumption of energy-intensive industries is sensitive to the growth rate of GDP,and the electricity consumption under the scenario of industrial investment and output value maintaining as the current growth rate,is closer to that under

  4. Long-Term Hearing Results After Ossiculoplasty.

    Science.gov (United States)

    Cox, Matthew D; Trinidade, Aaron; Russell, James Shep; Dornhoffer, John L

    2017-04-01

    To determine if the OOPS index is predictive of long-term hearing results after ossiculoplasty. Case series with retrospective chart review. Tertiary care otology practice. Adult and pediatric patients (3-88 years of age). Ossiculoplasty with cartilage tympanoplasty, with or without mastoidectomy. Primary outcome measures included short-term hearing results (pure-tone average air-bone gap [PTA-ABG] measured between 60 days and 1 year after surgery), long-term hearing results (PTA-ABG measured ≥5 years after surgery), and the rate of successful ABG closure to ≤20 dB. Secondary measures included the need for revision surgery, delayed tympanic membrane graft failure, worsening conductive hearing loss (after an initially satisfactory hearing result), and recurrence of cholesteatoma. There was no significant difference between adults and children for short-term hearing results (average post-op PTA-ABG was 18.9 dB vs. 19.8 dB, respectively; p = 0.544), long-term hearing results (average final PTA-ABG was 19.3 dB vs. 19.4 dB, respectively; p = 0.922), or rate of ABG closure to less than 20 dB (63.1% vs. 58.0%, p = 0.282). Spearman's rank-order correlation (ρ) identified a strong positive correlation between OOPS index score and average post-operative PTA-ABG (ρ = 0.983; p hearing outcomes in adult and pediatric patients undergoing ossiculoplasty in both the short term and the long term.

  5. Timber joints under long-term loading

    DEFF Research Database (Denmark)

    Feldborg, T.; Johansen, M.

    This report describes tests and results from stiffness and strength testing of splice joints under long-term loading. During two years of loading the spicimens were exposed to cyclically changing relative humidity. After the loading period the specimens were short-term tested. The connectors were...... integral nail-plates and nailed steel and plywood gussets. The report is intended for designers and researchers in timber engineering....

  6. Cutaneous oxalosis after long-term hemodialysis.

    Science.gov (United States)

    Abuelo, J G; Schwartz, S T; Reginato, A J

    1992-07-01

    A 27-year-old woman undergoing long-term hemodialysis developed cutaneous calcifications on her fingers. A skin biopsy specimen showed that the deposits were calcium oxalate. To our knowledge, only one previous article has reported pathologic and crystallographic studies on calcifications of the skin resulting from dialysis oxalosis. We speculate that vitamin C supplements, liberal tea consumption, an increased serum ionized calcium concentration, and the long duration of hemodialysis contributed to the production of these deposits.

  7. Long term evolution 4G and beyond

    CERN Document Server

    Yacoub, Michel; Figueiredo, Fabrício; Tronco, Tania

    2016-01-01

    This book focus on Long Term Evolution (LTE) and beyond. The chapters describe different aspects of research and development in LTE, LTE-Advanced (4G systems) and LTE-450 MHz such as telecommunications regulatory framework, voice over LTE, link adaptation, power control, interference mitigation mechanisms, performance evaluation for different types of antennas, cognitive mesh network, integration of LTE network and satellite, test environment, power amplifiers and so on. It is useful for researchers in the field of mobile communications.

  8. Consequences of long-term hyperparathyroidism.

    Science.gov (United States)

    Graal, M B; Wolffenbuttel, B H

    1998-07-01

    We describe a young woman with long-term untreated hyperparathyroidism with a superimposed vitamin D deficiency and an extremely decreased bone mineral density that was complicated by a vertebral fracture. Despite pretreatment with intravenous pamidronate and short-term vitamin D supplementation, severe and long-standing hypocalcaemia ('hungry bone syndrome') developed after parathyroidectomy. We discuss the consequences of hyperparathyroidism, especially the effects on bone, the complications of parathyroidectomy and the possibilities of preoperative treatment with bisphosphonates.

  9. Long-term behaviour of GRP pipes

    OpenAIRE

    Faria, H; A Vieira; Reis, J; Marques, A. T.; Guedes, R.M.; Ferreira, A. J. M.

    2005-01-01

    The main objective of the research programme /1/ described is the study of creep and relaxation behaviour of glass-rein forced thermosetting (GRP) pipes, in order to find alternative methods to predict the long-term properties, rendering a considerable reduction of the time needed for testing and assuring, as far as possible, equivalent reliability when compared to the existing methods. Experimental procedures were performed and are presented here, together with discussion of results, as well...

  10. Early Life Environments and Long Term Outcomes

    OpenAIRE

    Bolbocean, Corneliu

    2015-01-01

    A large literature has linked “in utero” environment to health and socio-economic outcomes in adulthood. We consider the effect of early life environments on health and skill formation outcomes. We first evaluate the impact of perinatal-neonatal level of technology at birth, which varies across delivery institutions, on the long-term neurodevelopmental outcomes of children with Cerebral Palsy. The level of technology at delivery determines the type of therapy newborns receive immediately afte...

  11. Long term economic relationships from cointegration maps

    Science.gov (United States)

    Vicente, Renato; Pereira, Carlos de B.; Leite, Vitor B. P.; Caticha, Nestor

    2007-07-01

    We employ the Bayesian framework to define a cointegration measure aimed to represent long term relationships between time series. For visualization of these relationships we introduce a dissimilarity matrix and a map based on the sorting points into neighborhoods (SPIN) technique, which has been previously used to analyze large data sets from DNA arrays. We exemplify the technique in three data sets: US interest rates (USIR), monthly inflation rates and gross domestic product (GDP) growth rates.

  12. TANK S-109 LONG TERM HUMAN HEALTH RISK CALCULATIONS

    Energy Technology Data Exchange (ETDEWEB)

    CARLSON, S.E.

    2003-12-16

    This document provides Tank S-109 long-term human risks calculations, in support of Functions and Requirements document (RPP-18812) as required by milestone M-45-00 of the Hanford Federal Facility Agreement and Consent Order. This calculation was performed to provide a screening-level assessment of long-term human health risk associated with potential leakage that could occur during waste retrieval operations for tank S-109 This calculation supports the development of tank S-109 waste retrieval functions and requirements as documented in RPP-18812. Risks associated with current waste and potential residual waste in tank S-109, as well as risk associated with other S farm tanks, were not of interest and were not evaluated.

  13. Long-term care and hospital collaboration. To survive in a reformed healthcare system, long-term care facilities can initiate hospital-based SNFs.

    Science.gov (United States)

    Hume, S K

    1993-06-01

    Establishing relationships with hospitals may be critical for long-term care facilities facing financial pressures and uncertain futures. One option is to initiate collaborative efforts to develop hospital-based skilled nursing facilities (SNFs). Hospitals, under pressure to move patients to less intensive settings and to diversify, are naturally drawn to long-term care as a related business where they can make limited personnel and financial commitments and extend their continuum of care. Before approaching hospitals to initiate collaborative efforts, long-term care providers should understand how they think and what their strengths and weaknesses are. Long-term and acute care providers have many options for collaboration, including management contracts and joint ventures. In a traditional management contract, the long-term care provider furnishes the administrator and a few key staff in exchange for direct reimbursement for those staff plus a management fee. Another option is for the long-term care facility to provide all the staff for a fee or percentage of revenue. Joint venture options are to form a subsidiary corporation to renovate a floor of the hospital or to have the hospital buy a large percentage of the long-term care facility and share the profits. All these options have potential pitfalls, including differing financial expectations and the threat of unionization at the SNF. Nevertheless, for long-term care facilities struggling under reimbursement cutbacks and other pressures, the benefits may outweigh the risks.

  14. The Reintegration of Military Families Following Long Term Separation

    Science.gov (United States)

    2005-05-01

    again during reunion most dramatically lead to successful reintegration and what leads to negative outcomes such as domestic violence or divorce...best as possible to adapt to separation and reunion. Potentially, programs can be developed that foster traits associated with successful reintegration ...reunifies, it must be discovered what successful reintegration is for AF families after they experienced a long-term separation. Since single parenting

  15. Long-term resightings of humpback whales off Ecuador

    OpenAIRE

    Castro, C.; J. Acevedo; Aguayo-Lobo, A.; Allen, J.; Capella, J.; Rosa, Dalla, L.; Flores-González, L.; Kaufman, G.; Forestell, P.; Scheidat, M.; Secchi, E.R.; Stevick, P.; Santos, M.C.O.

    2012-01-01

    This paper reports on the long-term re-sight histories of fifteen photo-identified humpback whales encountered to date transiting Ecuadorian waters. It also provides information about connections to feeding area destinations. Whale EC1261 has been resighted over a 26 year span and provides insight into age and potential longevity of this species in the stock G. The resighting of whale EC1261 provides the earliest connection from Ecuador to Antarctica. and supports previous findings that Antar...

  16. [Acute and long-term effects of ecstasy

    OpenAIRE

    Salzmann, Julie; Marie-Claire, Cynthia; Noble, Florence

    2004-01-01

    International audience; Side effects in the short term Recreational use of Ecstasy (3,4-methylenedioxymethamphetamine or MDMA), a synthetic drug, has considerably increased over the last decade. Since its appearance it is associated with the rave culture, but its use has spread to other social settings. The drug produces euphoria and empathy, but can lead to side effects, notably acute, potentially lethal, toxicity (malignant hyperthermia and/or hepatitis). Neurotoxicity in the long-term More...

  17. Related Studies in Long Term Lithium Battery Stability

    Science.gov (United States)

    Horning, R. J.; Chua, D. L.

    1984-01-01

    The continuing growth of the use of lithium electrochemical systems in a wide variety of both military and industrial applications is primarily a result of the significant benefits associated with the technology such as high energy density, wide temperature operation and long term stability. The stability or long term storage capability of a battery is a function of several factors, each important to the overall storage life and, therefore, each potentially a problem area if not addressed during the design, development and evaluation phases of the product cycle. Design (e.g., reserve vs active), inherent material thermal stability, material compatibility and self-discharge characteristics are examples of factors key to the storability of a power source.

  18. Long-term security of energy supply and climate change

    Energy Technology Data Exchange (ETDEWEB)

    Turton, H. [International Institute for Applied Systems Analysis, Laxenburg (Austria). ECS; Barreto, L. [Paul Scherrer Institute, Villigen (Switzerland). Energy Economics Group

    2006-10-15

    Security of energy supply and climate change are central concerns for policy makers and important dimensions of the long-term quest for a sustainable global energy system. This paper examines the role of several policy instruments in managing energy security and climate risks and stimulating technological change towards a more secure and climate-benign global energy system in the long-term future. The analysis has been conducted with ERIS, a multi-regional energy-systems ''bottom-up'' optimization model with technology learning. Our analysis provides some policy insights and identifies synergies and trade-offs relating to the potential for security of supply policies to promote the uptake of new technologies, reduce the cost of pursuing climate change mitigation policies, and facilitate a possible transition to a hydrogen economy. (author)

  19. Long-term security of energy supply and climate change

    Energy Technology Data Exchange (ETDEWEB)

    Hal Turton; Leonardo Barreto [International Institute for Applied Systems Analysis (IIASA), Laxenburg (Austria). Environmentally Compatible Energy Strategies (ECS)

    2006-10-15

    Security of energy supply and climate change are central concerns for policy makers and important dimensions of the long-term quest for a sustainable global energy system. This paper examines the role of several policy instruments in managing energy security and climate risks and stimulating technological change towards a more secure and climate-benign global energy system in the long-term future. The analysis has been conducted with ERIS, a multi-regional energy-systems 'bottom-up' optimization model with technology learning. The analysis provides some policy insights and identifies synergies and trade-offs relating to the potential for security of supply policies to promote the uptake of new technologies, reduce the cost of pursuing climate change mitigation policies, and facilitate a possible transition to a hydrogen economy. 44 refs., 13 figs., 1 tab.

  20. Noncontact ECG system for unobtrusive long-term monitoring.

    Science.gov (United States)

    McDonald, Neil J; Anumula, Harini A; Duff, Eric; Soussou, Walid

    2012-01-01

    This paper describes measurements made using an ECG system with QUASAR's capacitive bioelectrodes integrated into a pad system that is placed over a chair. QUASAR's capacitive bioelectrode has the property of measuring bioelectric potentials at a small separation from the body. This enables the measurement of ECG signals through fabric, without the removal of clothing or preparation of skin. The ECG was measured through the subject's clothing while the subject sat in the chair without any supporting action from the subject. The ECG pad system is an example of a high compliance system that places minimal requirements upon the subject and, consequently, can be used to generate a long-term record from ECG segments collected on a daily basis, providing valuable information on long-term trends in cardiac health.

  1. [Acute and long-term effects of ecstasy].

    Science.gov (United States)

    Salzmann, Julie; Marie-Claire, Cynthia; Noble, Florence

    2004-10-23

    Side effects in the short term Recreational use of Ecstasy (3,4-methylenedioxymethamphetamine or MDMA), a synthetic drug, has considerably increased over the last decade. Since its appearance it is associated with the rave culture, but its use has spread to other social settings. The drug produces euphoria and empathy, but can lead to side effects, notably acute, potentially lethal, toxicity (malignant hyperthermia and/or hepatitis). Neurotoxicity in the long-term Moreover, MDMA has been shown to induce long-term deleterious effects and provoke neurotoxic affecting the serotoninergic system. However, the psychopathological consequences of such neurotoxicity are still controversial, particularly since many ecstasy consumers are multi-drug users. A complex pharmacological profile The mechanism of action of MDMA involves various neurobiological systems (serotonin, dopamine, noradrenalin), that may all interact.

  2. New Developments in Long-Term Downhole Monitoring Arrays

    Directory of Open Access Journals (Sweden)

    Jochem Kück

    2006-03-01

    Full Text Available The long-term observation of active geological processes is a major research goal in an increasing number of scientific drilling projects. An extended monitoring phase within a potentially hostile environment (e.g., temperature, pressure, salinity requires new long-lasting and robust instrumentation currently unavailable from either industry or academia. Extended exposure of instrument packages to extreme conditions will typically cause seals to weaken and fail,electronic parts to break under permanent load, and sensors to degrade or develop strong drift. In the framework of scientific exploration, there are currently several major research projects targeting fault zone drilling and in situ measurements to monitor physical and chemical conditions before, during, and after seismic events. Planning has now begun for tool development, testing, and continuous long-term monitoring for the San Andreas Fault Zone Observatory at Depth, SAFOD (Parkfi eld, Calif., U.S.A.; See article on page 32..

  3. Capsosomes as Long-Term Delivery Vehicles for Protein Therapeutics.

    Science.gov (United States)

    Maina, James W; Richardson, Joseph J; Chandrawati, Rona; Kempe, Kristian; van Koeverden, Martin P; Caruso, Frank

    2015-07-21

    We report the preparation of polymer capsules containing liposomal subcompartments, termed capsosomes, and their ability for the sustained delivery of protein therapeutics. Capsosomes were formed through the layer-by-layer (LbL) assembly of polymers and protein-loaded liposomes, followed by the formation of a capsule membrane based on disulfide cross-linked poly(methacrylic acid). The loading capacities of a model cargo (lysozyme) and brain-derived neurotrophic factor (BDNF), an important neurotrophin that has significant physiological functions on the nervous system, were determined, and the long-term release kinetics of the proteins was investigated in simulated physiological conditions. The capsosomes exhibited protein loading and release behavior that can be tuned by the lipid composition of the liposomal compartments, where inclusion of anionic lipids resulted in enhanced protein loading and slower release over the course of 80 days. These findings highlight the potential of capsosomes for the long-term delivery of protein therapeutics.

  4. Long-Term Recency in Anterograde Amnesia.

    Directory of Open Access Journals (Sweden)

    Deborah Talmi

    Full Text Available Amnesia is usually described as an impairment of a long-term memory (LTM despite an intact short-term memory (STM. The intact recency effect in amnesia had supported this view. Although dual-store models of memory have been challenged by single-store models based on interference theory, this had relatively little influence on our understanding and treatment of amnesia, perhaps because the debate has centred on experiments in the neurologically intact population. Here we tested a key prediction of single-store models for free recall in amnesia: that people with amnesia will exhibit a memory advantage for the most recent items even when all items are stored in and retrieved from LTM, an effect called long-term recency. People with amnesia and matched controls studied, and then free-recalled, word lists with a distractor task following each word, including the last (continual distractor task, CDFR. This condition was compared to an Immediate Free Recall (IFR, no distractors and a Delayed Free Recall (DFR, end-of-list distractor only condition. People with amnesia demonstrated the full long-term recency pattern: the recency effect was attenuated in DFR and returned in CDFR. The advantage of recency over midlist items in CDFR was comparable to that of controls, confirming a key prediction of single-store models. Memory deficits appeared only after the first word recalled in each list, suggesting the impairment in amnesia may emerge only as the participant's recall sequence develops, perhaps due to increased susceptibility to output interference. Our findings suggest that interference mechanisms are preserved in amnesia despite the overall impairment to LTM, and challenge strict dual-store models of memory and their dominance in explaining amnesia. We discuss the implication of our findings for rehabilitation.

  5. Long-Term Recency in Anterograde Amnesia.

    Science.gov (United States)

    Talmi, Deborah; Caplan, Jeremy B; Richards, Brian; Moscovitch, Morris

    2015-01-01

    Amnesia is usually described as an impairment of a long-term memory (LTM) despite an intact short-term memory (STM). The intact recency effect in amnesia had supported this view. Although dual-store models of memory have been challenged by single-store models based on interference theory, this had relatively little influence on our understanding and treatment of amnesia, perhaps because the debate has centred on experiments in the neurologically intact population. Here we tested a key prediction of single-store models for free recall in amnesia: that people with amnesia will exhibit a memory advantage for the most recent items even when all items are stored in and retrieved from LTM, an effect called long-term recency. People with amnesia and matched controls studied, and then free-recalled, word lists with a distractor task following each word, including the last (continual distractor task, CDFR). This condition was compared to an Immediate Free Recall (IFR, no distractors) and a Delayed Free Recall (DFR, end-of-list distractor only) condition. People with amnesia demonstrated the full long-term recency pattern: the recency effect was attenuated in DFR and returned in CDFR. The advantage of recency over midlist items in CDFR was comparable to that of controls, confirming a key prediction of single-store models. Memory deficits appeared only after the first word recalled in each list, suggesting the impairment in amnesia may emerge only as the participant's recall sequence develops, perhaps due to increased susceptibility to output interference. Our findings suggest that interference mechanisms are preserved in amnesia despite the overall impairment to LTM, and challenge strict dual-store models of memory and their dominance in explaining amnesia. We discuss the implication of our findings for rehabilitation.

  6. Long-term policy on gas composition

    Energy Technology Data Exchange (ETDEWEB)

    Verhagen, M.J.M.

    2012-03-13

    This letter sets out the policy of the Dutch cabinet on the long-term change to the composition of low calorific gas that is distributed via the public gas grid. The title of a separate attachment to this letter is 'The composition of low calorific gas in the more distant future and the requirements for gas appliances covered by the Gas Appliances Directive'. The attachment sets out the composition of low calorific gas as network operators can distribute it via the public gas grid from 2021 (or from a later date). This relates to the changes in the 'exit specification' of the gas.

  7. Safety of long-term PPI therapy

    DEFF Research Database (Denmark)

    Reimer, Christina

    2013-01-01

    Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been published...... is based on a relevant indication. The concern for complications should primarily be directed at elderly, malnourished with significant co-morbidity. In this population an increased risk for enteric infections, fractures and nutritional deficiencies might have clinical consequences and should lead...

  8. Long-term space flights - personal impressions

    Science.gov (United States)

    Polyakov, V. V.

    During a final 4-month stage of a 1-year space flight of cosmonauts Titov and Manarov, a physician, Valery Polyakov was included on a crew for the purpose of evaluating their health, correcting physical status to prepare for the spacecraft reentry and landing operations. The complex program of scientific investigations and experiments performed by the physician included an evaluation of adaptation reactions of the human body at different stages of space mission using clinicophysiological and biochemical methods; testing of alternative regimes of exercise and new countermeasures to prevent an unfavourable effect of long-term weightlessness.

  9. The long term stability of lidar calibrations

    DEFF Research Database (Denmark)

    Courtney, Michael; Gayle Nygaard, Nicolai

    Wind lidars are now used extensively for wind resource measurements. One of the requirements for the data to be accepted in support of project financing (so-called ‘banka-bility’) is to demonstrate the long-term stability of lidar cali-brations. Calibration results for six Leosphere WindCube li-dars......-ters pertaining in the different calibration periods. This is supported by sliding-window analyses of one lidar at one location where the same order of variation is observed as between pre-service and post-service calibrations....

  10. Long-term effects of sibling incest.

    Science.gov (United States)

    Daie, N; Witztum, E; Eleff, M

    1989-11-01

    Although sexual abuse of children is recognized as a serious problem, sibling incest has received relatively little attention. A distinction has been made between power-oriented sibling incest and nurturance-oriented incest. The authors review the relevant literature and present four clinical examples. The cases illustrate the broad range of sibling incest and demonstrate its effects, including the long-term consequences for the perpetrator. Lasting difficulties in establishing and maintaining close relationships, especially sexual ones, are prominent features of each case. Without denying the occurrences of benign sex-play between siblings, the authors emphasize exploitation and abuse as pathogenic aspects of sibling incest.

  11. Long-Term Wind Power Variability

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Y. H.

    2012-01-01

    The National Renewable Energy Laboratory started collecting wind power data from large commercial wind power plants (WPPs) in southwest Minnesota with dedicated dataloggers and communication links in the spring of 2000. Over the years, additional WPPs in other areas were added to and removed from the data collection effort. The longest data stream of actual wind plant output is more than 10 years. The resulting data have been used to analyze wind power fluctuations, frequency distribution of changes, the effects of spatial diversity, and wind power ancillary services. This report uses the multi-year wind power data to examine long-term wind power variability.

  12. Terminating a long-term clinical trial.

    Science.gov (United States)

    Klimt, C R

    1981-05-01

    Long-term clinical trials often include more than one active treatment group. These may be discontinued independently if found to be ineffective or possibly harmful. Certain subgroups of patients may be discovered, in the course of a clinical trial, who do not respond satisfactorily and are, therefore, excluded during the course of a trial. Yet another kind of termination comes when we have a therapeutic breakthrough or when hope has to be abandoned for demonstrating beneficial effects for one, several, or all treatments included in a trial. Examples from the authors' experience are presented, as are successful and unsuccessful techniques in managing terminations of various types.

  13. Transplant Tolerance Induction in Newborn Infants: Mechanisms, Advantages, and Potential Strategies

    Science.gov (United States)

    Pan, Hua; Gazarian, Aram; Dubernard, Jean-Michel; Belot, Alexandre; Michallet, Marie-Cécile; Michallet, Mauricette

    2016-01-01

    Although several tolerance induction protocols have been successfully implemented in adult renal transplantation, no tolerance induction approach has, as yet, been defined for solid organ transplantations in young infants. Pediatric transplant recipients have a pressing demand for the elaboration of tolerance induction regimens. Indeed, since they display a longer survival time, they are exposed to a higher level of risks linked to long-term immunosuppression (IS) and to chronic rejection. Interestingly, central tolerance induction may be of great interest in newborns, because of their immunological immaturity and the important role of the thymus at this early stage in life. The present review aims to clarify mechanisms and strategies of tolerance induction in these immunologically premature recipients. We first introduce the discovery and mechanisms of neonatal tolerance in murine experimental models and subsequently analyze tolerance induction in human newborn infants. Hematopoietic mixed chimerism in neonates is also discussed based on in utero hematopoietic stem cell (HSC) transplant studies. Then, we review the recent advances in tolerance induction approaches in adults, including the infusion of HSCs associated with less toxic conditioning regimens, regulatory T cells/facilitating cells/mesenchymal stem cells transplantation, costimulatory blockade, and thymus manipulation. Finally, IS withdrawal in pediatric solid organ transplant is discussed. In conclusion, the establishment of transplant tolerance induction in infants is promising and deserves further investigations. Future studies could focus on the selection of patients, on less toxic conditioning regimens, and on biomarkers for IS minimization or withdrawal. PMID:27092138

  14. Long-Term Monitoring Research Needs: A DOE Perspective

    Science.gov (United States)

    Moore, B.; Davis, C. B.

    2002-05-01

    critically on the validity and uncertainty in models used to predict contaminant fate and transport. This is an area of active research at the present time. We survey joint research initiatives in this area involving DOE along with USGS, U.S. EPA, U.S. NRC, and U.S. DOA and non-Federal collaborators, and explore their potential for furthering DOE long-term monitoring needs and objectives.

  15. Fatigue and quality of life in breast cancer survivors: temporal courses and long-term pattern

    NARCIS (Netherlands)

    Schmidt, M.E.; Chang-Claude, J.; Vrieling, A.; Heinz, J.; Flesch-Janys, D.; Steindorf, K.

    2012-01-01

    INTRODUCTION: Fatigue is a frequent problem during and after cancer treatment. We investigated different courses of fatigue from pre-diagnosis, through therapy, to long-term survivorship and evaluated potential implications on long-term quality of life (QoL). METHODS: Breast cancer patients diagnose

  16. Presynaptic Spike Timing-Dependent Long-Term Depression in the Mouse Hippocampus

    Science.gov (United States)

    Andrade-Talavera, Yuniesky; Duque-Feria, Paloma; Paulsen, Ole; Rodríguez-Moreno, Antonio

    2016-01-01

    Spike timing-dependent plasticity (STDP) is a Hebbian learning rule important for synaptic refinement during development and for learning and memory in the adult. Given the importance of the hippocampus in memory, surprisingly little is known about the mechanisms and functions of hippocampal S