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Sample records for differing presynaptic contributions

  1. Presynaptic excitability.

    Science.gov (United States)

    Jackson, M B

    1995-01-01

    + channels. In four of the five preparations reviewed in this chapter--motor nerve, squid giant synapse, ciliary ganglion, and retina bipolar neurons--evidence was presented that supports a location for Ca2+ channels that is very close to active zones of secretion. All of these synapses secrete from clear vesicles, and the speed and specificity of transduction provided by proximity may be a common feature of these rapid synapses. In contrast, the posterior pituitary secretion apparatus may be triggered by higher-affinity Ca2+ receptors and lower concentrations of Ca2+ (Lindau et al., 1992). This would correspond with the slower performance of peptidergic secretion, but because of the large stimuli needed to evoke release from neurosecretosomes, the possibility remains that the threshold for secretion is higher than that reported. While the role of Ca2+ as a trigger of secretion dictates a requirement for voltage-activated Ca2+ channels as universal components of the presynaptic membrane, the presence of other channels is more difficult to predict. Depolarizations caused by voltage-activated Na+ channels activate the presynaptic Ca2+ channels, but whether this depolarization requires Na+ channels in the presynaptic membrane itself may depend on the electrotonic length of the nerve terminal. Variations in density between motor nerve terminals may reflect species differences in geometry. The high Na+ channel density in the posterior pituitary reflects the great electrotonic length of this terminal arbor. Whether Na+ channels are abundant or not in a presynaptic membrane, K+ channels provide the most robust mechanism for limiting depolarization-induced Ca2+ entry. K+ channel blockers enhance transmission at most synapses. In general, K+ channels are abundant in nerve terminals, although their apparent lower priority compared to Ca2+ channels in the eyes of many investigators leaves us with fewer detailed investigations in some preparations. Most nerve terminals have more than

  2. Contribution of presynaptic HCN channels to excitatory inputs of spinal substantia gelatinosa neurons.

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    Peng, S-C; Wu, J; Zhang, D-Y; Jiang, C-Y; Xie, C-N; Liu, T

    2017-09-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are pathological pain-associated voltage-gated ion channels. They are widely expressed in central nervous system including spinal lamina II (also named the substantia gelatinosa, SG). Here, we examined the distribution of HCN channels in glutamatergic synaptic terminals as well as their role in the modulation of synaptic transmission in SG neurons from SD rats and glutamic acid decarboxylase-67 (GAD67)-GFP mice. We found that the expression of the HCN channel isoforms was varied in SG. The HCN4 isoform showed the highest level of co-localization with VGLUT2 (23±3%). In 53% (n=21/40 neurons) of the SG neurons examined in SD rats, application of HCN channel blocker, ZD7288 (10μM), decreased the frequency of spontaneous (s) and miniature (m) excitatory postsynaptic currents (EPSCs) by 37±4% and 33±4%, respectively. Consistently, forskolin (FSK) (an activator of adenylate cyclase) significantly increased the frequency of mEPSCs by 225±34%, which could be partially inhibited by ZD7288. Interestingly, the effects of ZD7288 and FSK on sEPSC frequency were replicated in non-GFP-expressing neurons, but not in GFP-expressing GABAergic SG neurons, in GAD67-GFP transgenic C57/BL6 mice. In summary, our results represent a previously unknown cellular mechanism by which presynaptic HCN channels, especially HCN4, regulate the glutamate release from presynaptic terminals that target excitatory, but not inhibitory SG interneurons. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Homeostatic Presynaptic Plasticity Is Specifically Regulated by P/Q-type Ca2+ Channels at Mammalian Hippocampal Synapses

    OpenAIRE

    Jeans, Alexander F.; van Heusden, Fran C.; Al-Mubarak, Bashayer; Padamsey, Zahid; Emptage, Nigel J.

    2017-01-01

    Voltage-dependent Ca2+ channels (VGCC) represent the principal source of Ca2+ ions driving evoked neurotransmitter release at presynaptic boutons. In mammals, presynaptic Ca2+ influx is mediated mainly via P/Q-type and N-type VGCC, which differ in their properties. Changes in their relative contributions tune neurotransmission both during development and in Hebbian plasticity. However, whether this represents a functional motif also present in other forms of activity-dependent ...

  4. Brain-derived neurotrophic factor (BDNF)-induced mitochondrial motility arrest and presynaptic docking contribute to BDNF-enhanced synaptic transmission.

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    Su, Bo; Ji, Yun-Song; Sun, Xu-lu; Liu, Xiang-Hua; Chen, Zhe-Yu

    2014-01-17

    Appropriate mitochondrial transport and distribution are essential for neurons because of the high energy and Ca(2+) buffering requirements at synapses. Brain-derived neurotrophic factor (BDNF) plays an essential role in regulating synaptic transmission and plasticity. However, whether and how BDNF can regulate mitochondrial transport and distribution are still unclear. Here, we find that in cultured hippocampal neurons, application of BDNF for 15 min decreased the percentage of moving mitochondria in axons, a process dependent on the activation of the TrkB receptor and its downstream PI3K and phospholipase-Cγ signaling pathways. Moreover, the BDNF-induced mitochondrial stopping requires the activation of transient receptor potential canonical 3 and 6 (TRPC3 and TRPC6) channels and elevated intracellular Ca(2+) levels. The Ca(2+) sensor Miro1 plays an important role in this process. Finally, the BDNF-induced mitochondrial stopping leads to the accumulation of more mitochondria at presynaptic sites. Mutant Miro1 lacking the ability to bind Ca(2+) prevents BDNF-induced mitochondrial presynaptic accumulation and synaptic transmission, suggesting that Miro1-mediated mitochondrial motility is involved in BDNF-induced mitochondrial presynaptic docking and neurotransmission. Together, these data suggest that mitochondrial transport and distribution play essential roles in BDNF-mediated synaptic transmission.

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

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    Dickenson Anthony H

    2009-02-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

  7. A presynaptic role for PKA in synaptic tagging and memory

    NARCIS (Netherlands)

    Park, Alan Jung; Havekes, Robbert; Choi, Jennifer H K; Luczak, Vincent; Nie, Ting; Huang, Ted; Abel, Ted

    2014-01-01

    Protein kinase A (PKA) and other signaling molecules are spatially restricted within neurons by A-kinase anchoring proteins (AKAPs). Although studies on compartmentalized PKA signaling have focused on postsynaptic mechanisms, presynaptically anchored PKA may contribute to synaptic plasticity and

  8. Facilitation of neocortical presynaptic terminal development by NMDA receptor activation

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    Sceniak Michael P

    2012-02-01

    Full Text Available Abstract Background Neocortical circuits are established through the formation of synapses between cortical neurons, but the molecular mechanisms of synapse formation are only beginning to be understood. The mechanisms that control synaptic vesicle (SV and active zone (AZ protein assembly at developing presynaptic terminals have not yet been defined. Similarly, the role of glutamate receptor activation in control of presynaptic development remains unclear. Results Here, we use confocal imaging to demonstrate that NMDA receptor (NMDAR activation regulates accumulation of multiple SV and AZ proteins at nascent presynaptic terminals of visual cortical neurons. NMDAR-dependent regulation of presynaptic assembly occurs even at synapses that lack postsynaptic NMDARs. We also provide evidence that this control of presynaptic terminal development is independent of glia. Conclusions Based on these data, we propose a novel NMDAR-dependent mechanism for control of presynaptic terminal development in excitatory neocortical neurons. Control of presynaptic development by NMDARs could ultimately contribute to activity-dependent development of cortical receptive fields.

  9. Presynaptic mechanisms of L-DOPA-induced dyskinesia: the findings, the debate, the therapeutic implications.

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    M Angela eCenci

    2014-12-01

    Full Text Available The dopamine precursor L-DOPA has been the most effective treatment for Parkinson´s disease (PD for over 40 years. However, the response to this treatment changes during the progression of PD, and most patients develop dyskinesias (abnormal involuntary movements and motor fluctuations within a few years of L-DOPA therapy. There is wide consensus that these motor complications depend on both pre- and post-synaptic disturbances of nigrostriatal dopamine transmission. Several presynaptic mechanisms converge to generate large dopamine swings in the brain concomitant with the peaks-and-troughs of plasma L-DOPA levels, while post-synaptic changes engender abnormal functional responses in dopaminoceptive neurons. While this general picture is well-accepted, the relative contribution of different factors remains a matter of debate. A particularly animated debate has been growing around putative players on the presynaptic side of the cascade. To what extent do presynaptic disturbances in dopamine transmission depend on deficiency/dysfunction of the dopamine transporter, aberrant release of dopamine from serotonin neurons, or gliovascular mechanisms? And does noradrenaline (which is synthetized from dopamine play a role? This review article will summarize key findings, controversies, and pending questions regarding the presynaptic mechanisms of L-DOPA-induced dyskinesia. Intriguingly, the debate around these mechanisms has spurred research into previously unexplored facets of brain plasticity that have far-reaching implications to the treatment of neuropsychiatric disease.

  10. Selective synaptic targeting of the excitatory and inhibitory presynaptic organizers FGF22 and FGF7.

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    Terauchi, Akiko; Timmons, Kendall M; Kikuma, Koto; Pechmann, Yvonne; Kneussel, Matthias; Umemori, Hisashi

    2015-01-15

    Specific formation of excitatory and inhibitory synapses is crucial for proper functioning of the brain. Fibroblast growth factor 22 (FGF22) and FGF7 are postsynaptic-cell-derived presynaptic organizers necessary for excitatory and inhibitory presynaptic differentiation, respectively, in the hippocampus. For the establishment of specific synaptic networks, these FGFs must localize to appropriate synaptic locations - FGF22 to excitatory and FGF7 to inhibitory postsynaptic sites. Here, we show that distinct motor and adaptor proteins contribute to intracellular microtubule transport of FGF22 and FGF7. Excitatory synaptic targeting of FGF22 requires the motor proteins KIF3A and KIF17 and the adaptor protein SAP102 (also known as DLG3). By contrast, inhibitory synaptic targeting of FGF7 requires the motor KIF5 and the adaptor gephyrin. Time-lapse imaging shows that FGF22 moves with SAP102, whereas FGF7 moves with gephyrin. These results reveal the basis of selective targeting of the excitatory and inhibitory presynaptic organizers that supports their different synaptogenic functions. Finally, we found that knockdown of SAP102 or PSD95 (also known as DLG4), which impairs the differentiation of excitatory synapses, alters FGF7 localization, suggesting that signals from excitatory synapses might regulate inhibitory synapse formation by controlling the distribution of the inhibitory presynaptic organizer. © 2015. Published by The Company of Biologists Ltd.

  11. Presynaptic Mechanisms of l-DOPA-Induced Dyskinesia: The Findings, the Debate, and the Therapeutic Implications.

    Science.gov (United States)

    Cenci, M Angela

    2014-01-01

    The dopamine (DA) precursor l-DOPA has been the most effective treatment for Parkinson's disease (PD) for over 40 years. However, the response to this treatment changes with disease progression, and most patients develop dyskinesias (abnormal involuntary movements) and motor fluctuations within a few years of l-DOPA therapy. There is wide consensus that these motor complications depend on both pre- and post-synaptic disturbances of nigrostriatal DA transmission. Several presynaptic mechanisms converge to generate large DA swings in the brain concomitant with the peaks-and-troughs of plasma l-DOPA levels, while post-synaptic changes engender abnormal functional responses in dopaminoceptive neurons. While this general picture is well-accepted, the relative contribution of different factors remains a matter of debate. A particularly animated debate has been growing around putative players on the presynaptic side of the cascade. To what extent do presynaptic disturbances in DA transmission depend on deficiency/dysfunction of the DA transporter, aberrant release of DA from serotonin neurons, or gliovascular mechanisms? And does noradrenaline (which is synthetized from DA) play a role? This review article will summarize key findings, controversies, and pending questions regarding the presynaptic mechanisms of l-DOPA-induced dyskinesia. Intriguingly, the debate around these mechanisms has spurred research into previously unexplored facets of brain plasticity that have far-reaching implications to the treatment of neuropsychiatric disease.

  12. Gender Differences among Contributing Leadership Development Resources

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    Thompson, Michael D.

    2012-01-01

    Gender differences among contributing student leadership development resources were examined within the context of theory-based perspectives of leadership-related attributes. The findings suggest that students' increased engagement with institutional constituencies cultivates an environment conducive to students' cognitive development toward…

  13. Levetiracetam Affects Differentially Presynaptic Proteins in Rat Cerebral Cortex

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    Daniele Marcotulli

    2017-12-01

    Full Text Available Presynaptic proteins are potential therapeutic targets for epilepsy and other neurological diseases. We tested the hypothesis that chronic treatment with the SV2A ligand levetiracetam affects the expression of other presynaptic proteins. Results showed that in rat neocortex no significant difference was detected in SV2A protein levels in levetiracetam treated animals compared to controls, whereas levetiracetam post-transcriptionally decreased several vesicular proteins and increased LRRK2, without any change in mRNA levels. Analysis of SV2A interactome indicates that the presynaptic proteins regulation induced by levetiracetam reported here is mediated by this interactome, and suggests that LRRK2 plays a role in forging the pattern of effects.

  14. A presynaptic role for PKA in synaptic tagging and memory.

    Science.gov (United States)

    Park, Alan Jung; Havekes, Robbert; Choi, Jennifer Hk; Luczak, Vince; Nie, Ting; Huang, Ted; Abel, Ted

    2014-10-01

    Protein kinase A (PKA) and other signaling molecules are spatially restricted within neurons by A-kinase anchoring proteins (AKAPs). Although studies on compartmentalized PKA signaling have focused on postsynaptic mechanisms, presynaptically anchored PKA may contribute to synaptic plasticity and memory because PKA also regulates presynaptic transmitter release. Here, we examine this issue using genetic and pharmacological application of Ht31, a PKA anchoring disrupting peptide. At the hippocampal Schaffer collateral CA3-CA1 synapse, Ht31 treatment elicits a rapid decay of synaptic responses to repetitive stimuli, indicating a fast depletion of the readily releasable pool of synaptic vesicles. The interaction between PKA and proteins involved in producing this pool of synaptic vesicles is supported by biochemical assays showing that synaptic vesicle protein 2 (SV2), Rim1, and SNAP25 are components of a complex that interacts with cAMP. Moreover, acute treatment with Ht31 reduces the levels of SV2. Finally, experiments with transgenic mouse lines, which express Ht31 in excitatory neurons at the Schaffer collateral CA3-CA1 synapse, highlight a requirement for presynaptically anchored PKA in pathway-specific synaptic tagging and long-term contextual fear memory. These results suggest that a presynaptically compartmentalized PKA is critical for synaptic plasticity and memory by regulating the readily releasable pool of synaptic vesicles. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Cytosolic Calcium Coordinates Mitochondrial Energy Metabolism with Presynaptic Activity

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    Chouhan, Amit K.; Ivannikov, Maxim V.; Lu, Zhongmin; Sugimori, Mutsuyuki; Llinas, Rodolfo R.; Macleod, Gregory T.

    2012-01-01

    Most neurons fire in bursts, imposing episodic energy demands, but how these demands are coordinated with oxidative phosphorylation is still unknown. Here, using fluorescence imaging techniques on presynaptic termini of Drosophila motor neurons (MNs), we show that mitochondrial matrix pH (pHm), inner membrane potential (Δψm), and NAD(P)H levels ([NAD(P)H]m) increase within seconds of nerve stimulation. The elevations of pHm, Δψm, and [NAD(P)H]m indicate an increased capacity for ATP production. Elevations in pHm were blocked by manipulations which blocked mitochondrial Ca2+ uptake, including replacement of extracellular Ca2+ with Sr2+, and application of either tetraphenylphosphonium chloride or KB-R7943, indicating that it is Ca2+ that stimulates presynaptic mitochondrial energy metabolism. To place this phenomenon within the context of endogenous neuronal activity, the firing rates of a number of individually identified MNs were determined during fictive locomotion. Surprisingly, although endogenous firing rates are significantly different, there was little difference in presynaptic cytosolic Ca2+ levels ([Ca2+]c) between MNs when each fires at its endogenous rate. The average [Ca2+]c level (329±11nM) was slightly above the average Ca2+ affinity of the mitochondria (281±13nM). In summary, we show that when MNs fire at endogenous rates [Ca2+]c is driven into a range where mitochondria rapidly acquire Ca2+. As we also show that Ca2+ stimulates presynaptic mitochondrial energy metabolism, we conclude that [Ca2+]c levels play an integral role in coordinating mitochondrial energy metabolism with presynaptic activity in Drosophila MNs. PMID:22279208

  16. Presynaptic Active Zone Density during Development and Synaptic Plasticity.

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    Clarke, Gwenaëlle L; Chen, Jie; Nishimune, Hiroshi

    2012-01-01

    Neural circuits transmit information through synapses, and the efficiency of synaptic transmission is closely related to the density of presynaptic active zones, where synaptic vesicles are released. The goal of this review is to highlight recent insights into the molecular mechanisms that control the number of active zones per presynaptic terminal (active zone density) during developmental and stimulus-dependent changes in synaptic efficacy. At the neuromuscular junctions (NMJs), the active zone density is preserved across species, remains constant during development, and is the same between synapses with different activities. However, the NMJ active zones are not always stable, as exemplified by the change in active zone density during acute experimental manipulation or as a result of aging. Therefore, a mechanism must exist to maintain its density. In the central nervous system (CNS), active zones have restricted maximal size, exist in multiple numbers in larger presynaptic terminals, and maintain a constant density during development. These findings suggest that active zone density in the CNS is also controlled. However, in contrast to the NMJ, active zone density in the CNS can also be increased, as observed in hippocampal synapses in response to synaptic plasticity. Although the numbers of known active zone proteins and protein interactions have increased, less is known about the mechanism that controls the number or spacing of active zones. The following molecules are known to control active zone density and will be discussed herein: extracellular matrix laminins and voltage-dependent calcium channels, amyloid precursor proteins, the small GTPase Rab3, an endocytosis mechanism including synaptojanin, cytoskeleton protein spectrins and β-adducin, and a presynaptic web including spectrins. The molecular mechanisms that organize the active zone density are just beginning to be elucidated.

  17. Presynaptic DLG regulates synaptic function through the localization of voltage-activated Ca2+ Channels

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    Astorga, César; Jorquera, Ramón A.; Ramírez, Mauricio; Kohler, Andrés; López, Estefanía; Delgado, Ricardo; Córdova, Alex; Olguín, Patricio; Sierralta, Jimena

    2016-01-01

    The DLG-MAGUK subfamily of proteins plays a role on the recycling and clustering of glutamate receptors (GLUR) at the postsynaptic density. discs-large1 (dlg) is the only DLG-MAGUK gene in Drosophila and originates two main products, DLGA and DLGS97 which differ by the presence of an L27 domain. Combining electrophysiology, immunostaining and genetic manipulation at the pre and postsynaptic compartments we study the DLG contribution to the basal synaptic-function at the Drosophila larval neuromuscular junction. Our results reveal a specific function of DLGS97 in the regulation of the size of GLUR fields and their subunit composition. Strikingly the absence of any of DLG proteins at the presynaptic terminal disrupts the clustering and localization of the calcium channel DmCa1A subunit (Cacophony), decreases the action potential-evoked release probability and alters short-term plasticity. Our results show for the first time a crucial role of DLG proteins in the presynaptic function in vivo. PMID:27573697

  18. Presynaptic DLG regulates synaptic function through the localization of voltage-activated Ca(2+) Channels.

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    Astorga, César; Jorquera, Ramón A; Ramírez, Mauricio; Kohler, Andrés; López, Estefanía; Delgado, Ricardo; Córdova, Alex; Olguín, Patricio; Sierralta, Jimena

    2016-08-30

    The DLG-MAGUK subfamily of proteins plays a role on the recycling and clustering of glutamate receptors (GLUR) at the postsynaptic density. discs-large1 (dlg) is the only DLG-MAGUK gene in Drosophila and originates two main products, DLGA and DLGS97 which differ by the presence of an L27 domain. Combining electrophysiology, immunostaining and genetic manipulation at the pre and postsynaptic compartments we study the DLG contribution to the basal synaptic-function at the Drosophila larval neuromuscular junction. Our results reveal a specific function of DLGS97 in the regulation of the size of GLUR fields and their subunit composition. Strikingly the absence of any of DLG proteins at the presynaptic terminal disrupts the clustering and localization of the calcium channel DmCa1A subunit (Cacophony), decreases the action potential-evoked release probability and alters short-term plasticity. Our results show for the first time a crucial role of DLG proteins in the presynaptic function in vivo.

  19. Presynaptic mechanisms of lead neurotoxicity: effects on vesicular release, vesicle clustering and mitochondria number.

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    Zhang, Xiao-Lei; Guariglia, Sara R; McGlothan, Jennifer L; Stansfield, Kirstie H; Stanton, Patric K; Guilarte, Tomás R

    2015-01-01

    Childhood lead (Pb2+) intoxication is a global public health problem and accounts for 0.6% of the global burden of disease associated with intellectual disabilities. Despite the recognition that childhood Pb2+ intoxication contributes significantly to intellectual disabilities, there is a fundamental lack of knowledge on presynaptic mechanisms by which Pb2+ disrupts synaptic function. In this study, using a well-characterized rodent model of developmental Pb2+ neurotoxicity, we show that Pb2+ exposure markedly inhibits presynaptic vesicular release in hippocampal Schaffer collateral-CA1 synapses in young adult rats. This effect was associated with ultrastructural changes which revealed a reduction in vesicle number in the readily releasable/docked vesicle pool, disperse vesicle clusters in the resting pool, and a reduced number of presynaptic terminals with multiple mitochondria with no change in presynaptic calcium influx. These studies provide fundamental knowledge on mechanisms by which Pb2+ produces profound inhibition of presynaptic vesicular release that contribute to deficits in synaptic plasticity and intellectual development.

  20. Exocytosis: using amperometry to study presynaptic mechanisms of neurotoxicity

    NARCIS (Netherlands)

    Westerink, R.H.S.

    2004-01-01

    The development of carbon fiber microelectrode amperometry enabled detailed investigation of the presynaptic response at the single cell level with single vesicle resolution. Consequently, amperometry allowed for detailed studies into the presynaptic mechanisms underlying neurotoxicity. This review

  1. Presynaptic proteoglycans: sweet organizers of synapse development.

    Science.gov (United States)

    Song, Yoo Sung; Kim, Eunjoon

    2013-08-21

    Synaptic adhesion molecules control neuronal synapse development. In this issue of Neuron, Siddiqui et al. (2013) and de Wit et al. (2013) demonstrate that LRRTM4, a postsynaptic adhesion molecule, trans-synaptically interacts with presynaptic heparan sulfate proteoglycans (HSPGs) to promote synapse development. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Immobilization induces changes in presynaptic control of group Ia afferents in healthy humans

    DEFF Research Database (Denmark)

    Jensen, Jesper Lundbye; Nielsen, Jens Bo

    2008-01-01

    immobilized the left foot and ankle joint for 2 weeks in 12 able-bodied subjects. Disynaptic reciprocal inhibition of soleus (SOL) motoneurones and presynaptic control of SOL group Ia afferents was measured before and after the immobilization as well as following 2 weeks of recovery. Following immobilization...... maximal voluntary plantar- and dorsiflexion torque (MVC) was significantly reduced and the maximal SOL H-reflex amplitude increased with no changes in Mmax. Decreased presynaptic inhibition of the Ia afferents likely contributed to the increase of the H-reflex size, since we observed a significant...... decrease in the long-latency depression of the SOL H-reflex evoked by peroneal nerve stimulation (D2 inhibition) and an increase in the size of the monosynaptic Ia facilitation of the SOL H-reflex evoked by femoral nerve stimulation. These two measures provide independent evidence of changes in presynaptic...

  3. Presynaptic calcium signalling in cerebellar mossy fibres

    DEFF Research Database (Denmark)

    Thomsen, Louiza Bohn; Jörntell, Henrik; Midtgaard, Jens

    2010-01-01

    Whole-cell recordings were obtained from mossy fibre terminals in adult turtles in order to characterize the basic membrane properties. Calcium imaging of presynaptic calcium signals was carried out in order to analyse calcium dynamics and presynaptic GABA B inhibition. A tetrodotoxin (TTX......)-sensitive fast Na(+) spike faithfully followed repetitive depolarizing pulses with little change in spike duration or amplitude, while a strong outward rectification dominated responses to long-lasting depolarizations. High-threshold calcium spikes were uncovered following addition of potassium channel blockers....... Calcium imaging using Calcium-Green dextran revealed a stimulus-evoked all-or-none TTX-sensitive calcium signal in simple and complex rosettes. All compartments of a complex rosette were activated during electrical activation of the mossy fibre, while individual simple and complex rosettes along an axon...

  4. Role of the Wnt receptor Frizzled-1 in presynaptic differentiation and function

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    Alvarez Alejandra R

    2009-11-01

    Full Text Available Abstract Background The Wnt signaling pathway regulates several fundamental developmental processes and recently has been shown to be involved in different aspects of synaptic differentiation and plasticity. Some Wnt signaling components are localized at central synapses, and it is thus possible that this pathway could be activated at the synapse. Results We examined the distribution of the Wnt receptor Frizzled-1 in cultured hippocampal neurons and determined that this receptor is located at synaptic contacts co-localizing with presynaptic proteins. Frizzled-1 was found in functional synapses detected with FM1-43 staining and in synaptic terminals from adult rat brain. Interestingly, overexpression of Frizzled-1 increased the number of clusters of Bassoon, a component of the active zone, while treatment with the extracellular cysteine-rich domain (CRD of Frizzled-1 decreased Bassoon clustering, suggesting a role for this receptor in presynaptic differentiation. Consistent with this, treatment with the Frizzled-1 ligand Wnt-3a induced presynaptic protein clustering and increased functional presynaptic recycling sites, and these effects were prevented by co-treatment with the CRD of Frizzled-1. Moreover, in synaptically mature neurons Wnt-3a was able to modulate the kinetics of neurotransmitter release. Conclusion Our results indicate that the activation of the Wnt pathway through Frizzled-1 occurs at the presynaptic level, and suggest that the synaptic effects of the Wnt signaling pathway could be modulated by local activation through synaptic Frizzled receptors.

  5. The effect of coniine on presynaptic nicotinic receptors.

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    Erkent, Ulkem; Iskit, Alper B; Onur, Rustu; Ilhan, Mustafa

    2016-01-01

    Toxicity of coniine, an alkaloid of Conium maculatum (poison hemlock), is manifested by characteristic nicotinic clinical signs including excitement, depression, hypermetria, seizures, opisthotonos via postsynaptic nicotinic receptors. There is limited knowledge about the role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine in the literature. The present study was undertaken to evaluate the possible role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine. For this purpose, the rat anococcygeus muscle and guinea-pig atria were used in vitro. Nicotine (100 μM) elicited a biphasic response composed of a relaxation followed by contraction through the activation of nitrergic and noradrenergic nerve terminals in the phenylephrine-contracted rat anococcygeus muscle. Coniine inhibited both the nitrergic and noradrenergic response in the muscle (-logIC(50) = 3.79 ± 0.11 and -logIC(50) = 4.57 ± 0.12 M, respectively). The effect of coniine on nicotinic receptor-mediated noradrenergic transmission was also evaluated in the guinea-pig atrium (-logIC(50) = 4.47 ± 0.12 M) and did not differ from the -logIC(50) value obtained in the rat anococcygeus muscle. This study demonstrated that coniine exerts inhibitory effects on nicotinic receptor-mediated nitrergic and noradrenergic transmitter response.

  6. Antagonism of presynaptic dopamine receptors by phenothiazine drug metabolites

    International Nuclear Information System (INIS)

    Nowak, J.Z.; Arbilla, S.; Langer, S.Z.; Dahl, S.G.

    1990-01-01

    Electrically evoked release of dopamine from the caudate nucleus is reduced by the dopamine receptor agonists, apomorphine and bromocriptine, and facilitated by neuroleptic drugs, which act as dopamine autoreceptor antagonists. The potencies of chlorpromazine, fluphenazine, levomepromazine and their hydroxy-metabolites in modulating electrically evoked release of dopamine were examined by superfusion of rabbit caudate nucleus slices pre-incubated with 3 H-dopamine. O-Desmethyl levomepromazine, 3-hydroxy- and 7-hydroxy metabolites of chlorpromazine and levomepromazine facilitated electrically evoked release of 3 H-dopamine, having potencies similar to that of the parent compounds. 7-Hydroxy fluphenazine was less active than fluphenazine in this system. These results indicate that phenolic metabolites of chlorpromazine and levomepromazine, but not of fluphenazine, may contribute to effects of the drugs mediated by presynaptic dopamine receptors

  7. Homeostatic Presynaptic Plasticity Is Specifically Regulated by P/Q-type Ca2+ Channels at Mammalian Hippocampal Synapses.

    Science.gov (United States)

    Jeans, Alexander F; van Heusden, Fran C; Al-Mubarak, Bashayer; Padamsey, Zahid; Emptage, Nigel J

    2017-10-10

    Voltage-dependent Ca 2+ channels (VGCC) represent the principal source of Ca 2+ ions driving evoked neurotransmitter release at presynaptic boutons. In mammals, presynaptic Ca 2+ influx is mediated mainly via P/Q-type and N-type VGCC, which differ in their properties. Changes in their relative contributions tune neurotransmission both during development and in Hebbian plasticity. However, whether this represents a functional motif also present in other forms of activity-dependent regulation is unknown. Here, we study the role of VGCC in homeostatic plasticity (HSP) in mammalian hippocampal neurons using optical techniques. We find that changes in evoked Ca 2+ currents specifically through P/Q-type, but not N-type, VGCC mediate bidirectional homeostatic regulation of both neurotransmitter release efficacy and the size of the major synaptic vesicle pools. Selective dependence of HSP on P/Q-type VGCC in mammalian terminals has important implications for phenotypes associated with P/Q-type channelopathies, including migraine and epilepsy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Homeostatic Presynaptic Plasticity Is Specifically Regulated by P/Q-type Ca2+ Channels at Mammalian Hippocampal Synapses

    Directory of Open Access Journals (Sweden)

    Alexander F. Jeans

    2017-10-01

    Full Text Available Voltage-dependent Ca2+ channels (VGCC represent the principal source of Ca2+ ions driving evoked neurotransmitter release at presynaptic boutons. In mammals, presynaptic Ca2+ influx is mediated mainly via P/Q-type and N-type VGCC, which differ in their properties. Changes in their relative contributions tune neurotransmission both during development and in Hebbian plasticity. However, whether this represents a functional motif also present in other forms of activity-dependent regulation is unknown. Here, we study the role of VGCC in homeostatic plasticity (HSP in mammalian hippocampal neurons using optical techniques. We find that changes in evoked Ca2+ currents specifically through P/Q-type, but not N-type, VGCC mediate bidirectional homeostatic regulation of both neurotransmitter release efficacy and the size of the major synaptic vesicle pools. Selective dependence of HSP on P/Q-type VGCC in mammalian terminals has important implications for phenotypes associated with P/Q-type channelopathies, including migraine and epilepsy.

  9. Cellular mechanisms for presynaptic inhibition of sensory afferents

    DEFF Research Database (Denmark)

    Perrier, Jean-Francois Marie; delgado-lezama, rodolfo; Christensen, Rasmus Kordt

    It is well established that presynaptic inhibition of primary afferents involves the activation of GABAA receptors located on presynaptic terminals. However, the source of GABA remains unknown. In an integrated preparation of the spinal cord of the adult turtle, we evoked dorsal root potentials...

  10. Presynaptic signal transduction pathways that modulate synaptic transmission

    NARCIS (Netherlands)

    de Jong, A.P.H.; Verhage, M.

    2009-01-01

    Presynaptic modulation is a crucial factor in the adaptive capacity of the nervous system. The coupling between incoming action potentials and neurotransmitter secretion is modulated by firstly, recent activity of the presynaptic axon that leads to the accumulation of residual calcium in the

  11. Presynaptic G Protein-Coupled Receptors: Gatekeepers of Addiction?

    Directory of Open Access Journals (Sweden)

    Kari A Johnson

    2016-11-01

    Full Text Available Drug abuse and addiction cause widespread social and public health problems, and the neurobiology underlying drug actions and drug use and abuse is an area of intensive research. Drugs of abuse alter synaptic transmission, and these actions contribute to acute intoxication as well as the chronic effects of abused substances. Transmission at most mammalian synapses involves neurotransmitter activation of two receptor subtypes, ligand-gated ion channels that mediate fast synaptic responses, and G protein-coupled receptors (GPCRs that have slower neuromodulatory actions. The GPCRs represent a large proportion of neurotransmitter receptors involved in almost all facets of nervous system function. In addition, these receptors are targets for many pharmacotherapeutic agents. Drugs of abuse directly or indirectly affect neuromodulation mediated by GPCRs, with important consequences for intoxication, drug taking and responses to prolonged drug exposure, withdrawal and addiction. Among the GPCRs are several subtypes involved in presynaptic inhibition, most of which are coupled to the Gi/o class of G protein. There is increasing evidence that these presynaptic Gi/o-coupled GPCRs have important roles in the actions of drugs of abuse, as well as behaviors related to these drugs. This topic will be reviewed, with particular emphasis on receptors for three neurotransmitters, dopamine (D1- and D2-like receptors, endocannabinoids (CB1 receptors and glutamate (group II metabotropic glutamate (mGlu receptors. The focus is on recent evidence from laboratory animal models (and some evidence in humans implicating these receptors in the acute and chronic effects of numerous abused drugs, as well as in the control of drug seeking and taking. The ability of drugs targeting these receptors to modify drug seeking behavior has raised the possibility of using compounds targeting these receptors for addiction pharmacotherapy. This topic is also discussed, with emphasis on

  12. Lateral presynaptic inhibition mediates gain control in an olfactory circuit.

    Science.gov (United States)

    Olsen, Shawn R; Wilson, Rachel I

    2008-04-24

    Olfactory signals are transduced by a large family of odorant receptor proteins, each of which corresponds to a unique glomerulus in the first olfactory relay of the brain. Crosstalk between glomeruli has been proposed to be important in olfactory processing, but it is not clear how these interactions shape the odour responses of second-order neurons. In the Drosophila antennal lobe (a region analogous to the vertebrate olfactory bulb), we selectively removed most interglomerular input to genetically identified second-order olfactory neurons. Here we show that this broadens the odour tuning of these neurons, implying that interglomerular inhibition dominates over interglomerular excitation. The strength of this inhibitory signal scales with total feedforward input to the entire antennal lobe, and has similar tuning in different glomeruli. A substantial portion of this interglomerular inhibition acts at a presynaptic locus, and our results imply that this is mediated by both ionotropic and metabotropic receptors on the same nerve terminal.

  13. PRESYNAPTIC DOPAMINE MODULATION BY STIMULANT SELF ADMINISTRATION

    Science.gov (United States)

    España, Rodrigo A.; Jones, Sara R.

    2013-01-01

    The mesolimbic dopamine system is an essential participant in the initiation and modulation of various forms of goal-directed behavior, including drug reinforcement and addiction processes. Dopamine neurotransmission is increased by acute administration of all drugs of abuse, including the stimulants cocaine and amphetamine. Chronic exposure to these drugs via voluntary self-administration provides a model of stimulant abuse that is useful in evaluating potential behavioral and neurochemical adaptations that occur during addiction. This review describes commonly used methodologies to measure dopamine and baseline parameters of presynaptic dopamine regulation, including exocytotic release and reuptake through the dopamine transporter in the nucleus accumbens core, as well as dramatic adaptations in dopamine neurotransmission and drug sensitivity that occur with acute non-contingent and chronic, contingent self-administration of cocaine and amphetamine. PMID:23277050

  14. Contribution of honeybee drones of different age to colonial thermoregulation.

    Science.gov (United States)

    Kovac, Helmut; Stabentheiner, Anton; Brodschneider, Robert

    2009-01-01

    In addition to honeybee workers, drones also contribute to colonial thermoregulation. We show the drones' contribution to thermoregulation at 5 different experimental temperatures ranging from 15-34 °C. The frequency and the degree of endothermy depended on the drones' local ambient temperature and age. Location on brood or non-brood areas had no influence. The frequency of endothermic drones and the intensity of endothermy increased with decreasing temperature. 30% of drones of 8 days and older heated their thorax by more than 1 °C above the abdomen. The youngest drones (0-2 days) did not exceed this level of endothermy. Though young drones were less often engaged in active heat production, their contribution to brood warming was not insignificant because their abundance on the brood nest was 3.5 times higher than that of the oldest drones (≥13 days). Results suggest that the stimulus for the drones' increased frequency of heating at low experimental temperatures was their low local ambient air and/or comb temperature.

  15. Contribution of honeybee drones of different age to colonial thermoregulation*

    Science.gov (United States)

    Kovac, Helmut; Stabentheiner, Anton; Brodschneider, Robert

    2011-01-01

    In addition to honeybee workers, drones also contribute to colonial thermoregulation. We show the drones’ contribution to thermoregulation at 5 different experimental temperatures ranging from 15–34 °C. The frequency and the degree of endothermy depended on the drones’ local ambient temperature and age. Location on brood or non-brood areas had no influence. The frequency of endothermic drones and the intensity of endothermy increased with decreasing temperature. 30% of drones of 8 days and older heated their thorax by more than 1 °C above the abdomen. The youngest drones (0–2 days) did not exceed this level of endothermy. Though young drones were less often engaged in active heat production, their contribution to brood warming was not insignificant because their abundance on the brood nest was 3.5 times higher than that of the oldest drones (≥13 days). Results suggest that the stimulus for the drones’ increased frequency of heating at low experimental temperatures was their low local ambient air and/or comb temperature. PMID:22140282

  16. Study of axonal dystrophy. II Dystrophy and atrophy of the presynaptic boutons: a dual pathology.

    Science.gov (United States)

    Fujisawa, K; Shiraki, H

    1980-01-01

    In succession to the previous quantitative work, a qualitative study has been carried out on the nature of a dual pathology affecting presynaptic boutons in the posterior tract nuclei of ageing rats. Based on the morphology of dystrophic boutons in early stage, it is concluded that the initial and therefore essential characteristic of dystrophic process is an abnormal increase of normal axonal components within the presynaptic boutons, and that various abnormal substructures of spheroids hitherto reported in the literature are probably the results of their secondary metamorphosis. The dystrophic process within the posterior tract nuclei is a selective one, involving presynaptic boutons and preterminal axons only of the posterior tract fibres. Comparison of the frequency of early dystrophic boutons and of fully grown-up spheroids indicates that a small percentage of boutons deriving from posterior tract fibres become dystrophic and of these dystrophic boutons only a small percentage again continue to develop unto large spheroids, throughout lifespan of the animals. On the other hand, in search of a morphological counterpart for the age-related decrease of volume ratio of presynaptic boutons to the neuropil, some dubious atrophic changes were also found in presynaptic boutons, which could have been easily missed from observation if studied qualitatively alone. Accordingly, no less numerous boutons other than dystrophic ones are supposed to atrophy 'independently' and to disappear 'silently' during the same period. The dystrophic and the atrophic changes involve different boutons (of different or the same terminal axons) within the same gray matter. This dual pathology of boutons needs further elucidation of its neurocytopathological as well as neurobiological background in the future.

  17. Cell-Specific PKM Isoforms Contribute to the Maintenance of Different Forms of Persistent Long-Term Synaptic Plasticity.

    Science.gov (United States)

    Hu, Jiangyuan; Adler, Kerry; Farah, Carole Abi; Hastings, Margaret H; Sossin, Wayne S; Schacher, Samuel

    2017-03-08

    Multiple kinase activations contribute to long-term synaptic plasticity, a cellular mechanism mediating long-term memory. The sensorimotor synapse of Aplysia expresses different forms of long-term facilitation (LTF)-nonassociative and associative LTF-that require the timely activation of kinases, including protein kinase C (PKC). It is not known which PKC isoforms in the sensory neuron or motor neuron L7 are required to sustain each form of LTF. We show that different PKMs, the constitutively active isoforms of PKCs generated by calpain cleavage, in the sensory neuron and L7 are required to maintain each form of LTF. Different PKMs or calpain isoforms were blocked by overexpressing specific dominant-negative constructs in either presynaptic or postsynaptic neurons. Blocking either PKM Apl I in L7, or PKM Apl II or PKM Apl III in the sensory neuron 2 d after 5-hydroxytryptamine (5-HT) treatment reversed persistent nonassociative LTF. In contrast, blocking either PKM Apl II or PKM Apl III in L7, or PKM Apl II in the sensory neuron 2 d after paired stimuli reversed persistent associative LTF. Blocking either classical calpain or atypical small optic lobe (SOL) calpain 2 d after 5-HT treatment or paired stimuli did not disrupt the maintenance of persistent LTF. Soon after 5-HT treatment or paired stimuli, however, blocking classical calpain inhibited the expression of persistent associative LTF, while blocking SOL calpain inhibited the expression of persistent nonassociative LTF. Our data suggest that different stimuli activate different calpains that generate specific sets of PKMs in each neuron whose constitutive activities sustain long-term synaptic plasticity. SIGNIFICANCE STATEMENT Persistent synaptic plasticity contributes to the maintenance of long-term memory. Although various kinases such as protein kinase C (PKC) contribute to the expression of long-term plasticity, little is known about how constitutive activation of specific kinase isoforms sustains long

  18. The structure and function of presynaptic endosomes

    Energy Technology Data Exchange (ETDEWEB)

    Jähne, Sebastian, E-mail: sebastian.jaehne1@stud.uni-goettingen.de [Department of Neuro- and Sensory Physiology, University of Göttingen Medical Center, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Humboldtallee 23, 37073 Göttingen (Germany); International Max Planck Research School for Neurosciences, 37077 Göttingen (Germany); Rizzoli, Silvio O. [Department of Neuro- and Sensory Physiology, University of Göttingen Medical Center, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Humboldtallee 23, 37073 Göttingen (Germany); Helm, Martin S., E-mail: martin.helm@med.uni-goettingen.de [Department of Neuro- and Sensory Physiology, University of Göttingen Medical Center, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Humboldtallee 23, 37073 Göttingen (Germany); International Max Planck Research School for Molecular Biology, 37077 Göttingen (Germany)

    2015-07-15

    The function of endosomes and of endosome-like structures in the presynaptic compartment is still controversial. This is in part due to the absence of a consensus on definitions and markers for these compartments. Synaptic endosomes are sometimes seen as stable organelles, permanently present in the synapse. Alternatively, they are seen as short-lived intermediates in synaptic vesicle recycling, arising from the endocytosis of large vesicles from the plasma membrane, or from homotypic fusion of small vesicles. In addition, the potential function of the endosome is largely unknown in the synapse. Some groups have proposed that the endosome is involved in the sorting of synaptic vesicle proteins, albeit others have produced data that deny this possibility. In this review, we present the existing evidence for synaptic endosomes, we discuss their potential functions, and we highlight frequent technical pitfalls in the analysis of this elusive compartment. We also sketch a roadmap to definitely determine the role of synaptic endosomes for the synaptic vesicle cycle. Finally, we propose a common definition of synaptic endosome-like structures.

  19. The structure and function of presynaptic endosomes

    International Nuclear Information System (INIS)

    Jähne, Sebastian; Rizzoli, Silvio O.; Helm, Martin S.

    2015-01-01

    The function of endosomes and of endosome-like structures in the presynaptic compartment is still controversial. This is in part due to the absence of a consensus on definitions and markers for these compartments. Synaptic endosomes are sometimes seen as stable organelles, permanently present in the synapse. Alternatively, they are seen as short-lived intermediates in synaptic vesicle recycling, arising from the endocytosis of large vesicles from the plasma membrane, or from homotypic fusion of small vesicles. In addition, the potential function of the endosome is largely unknown in the synapse. Some groups have proposed that the endosome is involved in the sorting of synaptic vesicle proteins, albeit others have produced data that deny this possibility. In this review, we present the existing evidence for synaptic endosomes, we discuss their potential functions, and we highlight frequent technical pitfalls in the analysis of this elusive compartment. We also sketch a roadmap to definitely determine the role of synaptic endosomes for the synaptic vesicle cycle. Finally, we propose a common definition of synaptic endosome-like structures

  20. Stereoselectivity of presynaptic autoreceptors modulating dopamine release

    International Nuclear Information System (INIS)

    Arbilla, S.; Langer, S.Z.

    1981-01-01

    The effects of the (R)- and (S)-enantiomers of sulpiride and butaclamol were studied on the spontaneous and field stimulation-evoked release of total radioactivity from slices of rabbit caudate nucleus prelabelled with [ 3 H]dopamine. (S)-Sulpiride in concentrations ranging from 0.01-1μM enhanced the electrically evoked release of [ 3 H]dopamine while (R)-sulpiride was 10 times less potent than (S)-sulpiride. Exposure to (S)-butaclamol (0.1-1 μM) but not to (R)-butaclamol (0.1-10μM) enhanced the field-stimulated release of [ 3 H]dopamine. The facilitatory effects of (S)- and (R)-sulpiride and (S)-butaclamol on the stimulated release of the labelled neurotransmitter were observed under conditions in which these drugs did not modify the spontaneous outflow of radioactivity. Only the active enantiomers of sulpiride and butaclamol antagonized the inhibition by apomorphine (1μM) of the stimulated release of [ 3 H]dopamine. Our results indicate that the presynaptic inhibitory dopamine autoreceptors modulating the stimulation-evoked release of [ 3 H]dopamine in the caudate nucleus are, like the classical postsynaptic dopamine receptors, chemically stereoselective. (Auth.)

  1. The contribution of different information sources for adverse effects data.

    Science.gov (United States)

    Golder, Su; Loke, Yoon K

    2012-04-01

    The aim of this study is to determine the relative value and contribution of searching different sources to identify adverse effects data. The process of updating a systematic review and meta-analysis of thiazolidinedione-related fractures in patients with type 2 diabetes mellitus was used as a case study. For each source searched, a record was made for each relevant reference included in the review noting whether it was retrieved with the search strategy used and whether it was available but not retrieved. The sensitivity, precision, and number needed to read from searching each source and from different combinations of sources were also calculated. There were 58 relevant references which presented sufficient numerical data to be included in a meta-analysis of fractures and bone mineral density. The highest number of relevant references were retrieved from Science Citation Index (SCI) (35), followed by BIOSIS Previews (27) and EMBASE (24). The precision of the searches varied from 0.88% (Scirus) to 41.67% (CENTRAL). With the search strategies used, the minimum combination of sources required to retrieve all the relevant references was; the GlaxoSmithKline (GSK) website, Science Citation Index (SCI), EMBASE, BIOSIS Previews, British Library Direct, Medscape DrugInfo, handsearching and reference checking, AHFS First, and Thomson Reuters Integrity or Conference Papers Index (CPI). In order to identify all the relevant references for this case study a number of different sources needed to be searched. The minimum combination of sources required to identify all the relevant references did not include MEDLINE.

  2. A Glutamate Homeostat Controls the Presynaptic Inhibition of Neurotransmitter Release

    Directory of Open Access Journals (Sweden)

    Xiling Li

    2018-05-01

    Full Text Available Summary: We have interrogated the synaptic dialog that enables the bi-directional, homeostatic control of presynaptic efficacy at the glutamatergic Drosophila neuromuscular junction (NMJ. We find that homeostatic depression and potentiation use disparate genetic, induction, and expression mechanisms. Specifically, homeostatic potentiation is achieved through reduced CaMKII activity postsynaptically and increased abundance of active zone material presynaptically at one of the two neuronal subtypes innervating the NMJ, while homeostatic depression occurs without alterations in CaMKII activity and is expressed at both neuronal subtypes. Furthermore, homeostatic depression is only induced through excess presynaptic glutamate release and operates with disregard to the postsynaptic response. We propose that two independent homeostats modulate presynaptic efficacy at the Drosophila NMJ: one is an intercellular signaling system that potentiates synaptic strength following diminished postsynaptic excitability, while the other adaptively modulates presynaptic glutamate release through an autocrine mechanism without feedback from the postsynaptic compartment. : Homeostatic mechanisms stabilize synaptic strength, but the signaling systems remain enigmatic. Li et al. suggest the existence of a homeostat operating at the Drosophila neuromuscular junction that responds to excess glutamate through an autocrine mechanism to adaptively inhibit presynaptic neurotransmitter release. This system parallels forms of plasticity at central synapses. Keywords: homeostatic synaptic plasticity, glutamate homeostasis, synaptic depression, Drosophila neuromuscular junction

  3. Presynaptic Membrane Receptors Modulate ACh Release, Axonal Competition and Synapse Elimination during Neuromuscular Junction Development.

    Science.gov (United States)

    Tomàs, Josep; Garcia, Neus; Lanuza, Maria A; Santafé, Manel M; Tomàs, Marta; Nadal, Laura; Hurtado, Erica; Simó, Anna; Cilleros, Víctor

    2017-01-01

    During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ) are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon. This peripheral synapse has long been used as a convenient model for synapse development. In the last few years, we have studied transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors (mAChR), adenosine autoreceptors (AR) and trophic factor receptors (TFR, for neurotrophins and trophic cytokines) during the development of NMJ and in the adult. This review article brings together previously published data and proposes a molecular background for developmental axonal competition and loss. At the end of the first week postnatal, these receptors modulate transmitter release in the various nerve terminals on polyinnervated NMJ and contribute to axonal competition and synapse elimination.

  4. Presynaptic Membrane Receptors Modulate ACh Release, Axonal Competition and Synapse Elimination during Neuromuscular Junction Development

    Directory of Open Access Journals (Sweden)

    Josep Tomàs

    2017-05-01

    Full Text Available During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon. This peripheral synapse has long been used as a convenient model for synapse development. In the last few years, we have studied transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors (mAChR, adenosine autoreceptors (AR and trophic factor receptors (TFR, for neurotrophins and trophic cytokines during the development of NMJ and in the adult. This review article brings together previously published data and proposes a molecular background for developmental axonal competition and loss. At the end of the first week postnatal, these receptors modulate transmitter release in the various nerve terminals on polyinnervated NMJ and contribute to axonal competition and synapse elimination.

  5. Calcium microdomains near R-type calcium channels control the induction of presynaptic LTP at parallel fiber to Purkinje cell synapses

    Science.gov (United States)

    Myoga, Michael H.; Regehr, Wade G.

    2011-01-01

    R-type calcium channels in postsynaptic spines signal through functional calcium microdomains to regulate a calcium-calmodulin sensitive potassium channel that in turn regulates postsynaptic hippocampal LTP. Here we ask whether R-type calcium channels in presynaptic terminals also signal through calcium microdomains to control presynaptic LTP. We focus on presynaptic LTP at parallel fiber to Purkinje cell synapses in the cerebellum (PF-LTP), which is mediated by calcium/calmodulin-stimulated adenylyl cyclases. Although most presynaptic calcium influx is through N-type and P/Q-type calcium channels, blocking these channels does not disrupt PF-LTP, but blocking R-type calcium channels does. Moreover, global calcium signaling cannot account for the calcium dependence of PF-LTP because R-type channels contribute modestly to overall calcium entry. These findings indicate that within presynaptic terminals, R-type calcium channels produce calcium microdomains that evoke presynaptic LTP at moderate frequencies that do not greatly increase global calcium levels,. PMID:21471358

  6. Presynaptic Ionotropic Receptors Controlling and Modulating the Rules for Spike Timing-Dependent Plasticity

    Directory of Open Access Journals (Sweden)

    Matthijs B. Verhoog

    2011-01-01

    Full Text Available Throughout life, activity-dependent changes in neuronal connection strength enable the brain to refine neural circuits and learn based on experience. In line with predictions made by Hebb, synapse strength can be modified depending on the millisecond timing of action potential firing (STDP. The sign of synaptic plasticity depends on the spike order of presynaptic and postsynaptic neurons. Ionotropic neurotransmitter receptors, such as NMDA receptors and nicotinic acetylcholine receptors, are intimately involved in setting the rules for synaptic strengthening and weakening. In addition, timing rules for STDP within synapses are not fixed. They can be altered by activation of ionotropic receptors located at, or close to, synapses. Here, we will highlight studies that uncovered how network actions control and modulate timing rules for STDP by activating presynaptic ionotropic receptors. Furthermore, we will discuss how interaction between different types of ionotropic receptors may create “timing” windows during which particular timing rules lead to synaptic changes.

  7. Adolescents' Contribution to Household Production: Male and Female Differences.

    Science.gov (United States)

    Sanik, Margaret Mietus; Stafford, Kathryn

    1985-01-01

    Develops a model to predict the contribution adolescent males and females make to household work, based upon family characteristics, human capital of the adolescent, geographic location, and societal expectations. Adolescent females worked longer than males, regardless of birth order. Time use for household work was largely unaffected by family…

  8. Synapse-specific and compartmentalized expression of presynaptic homeostatic potentiation

    Science.gov (United States)

    Li, Xiling; Goel, Pragya; Chen, Catherine; Angajala, Varun; Chen, Xun

    2018-01-01

    Postsynaptic compartments can be specifically modulated during various forms of synaptic plasticity, but it is unclear whether this precision is shared at presynaptic terminals. Presynaptic homeostatic plasticity (PHP) stabilizes neurotransmission at the Drosophila neuromuscular junction, where a retrograde enhancement of presynaptic neurotransmitter release compensates for diminished postsynaptic receptor functionality. To test the specificity of PHP induction and expression, we have developed a genetic manipulation to reduce postsynaptic receptor expression at one of the two muscles innervated by a single motor neuron. We find that PHP can be induced and expressed at a subset of synapses, over both acute and chronic time scales, without influencing transmission at adjacent release sites. Further, homeostatic modulations to CaMKII, vesicle pools, and functional release sites are compartmentalized and do not spread to neighboring pre- or post-synaptic structures. Thus, both PHP induction and expression mechanisms are locally transmitted and restricted to specific synaptic compartments. PMID:29620520

  9. Contributions of Neuroimaging to Understanding Sex Differences in Cocaine Abuse

    OpenAIRE

    Andersen, ML; Sawyer, EK; Howell, LL

    2011-01-01

    A consistent observation in drug abuse research is that males and females show differences in their response to drugs of abuse. In order to understand the neurobiology underlying cocaine abuse and effective treatments, it is important to consider the role of sex differences. Sex hormones have been investigated in both behavioral and molecular studies, but further evidence addressing drug abuse and dependence in both sexes would expand our knowledge of sex-differences in response to drugs of a...

  10. Sex differences in jealousy: a contribution from attachment theory.

    Science.gov (United States)

    Levy, Kenneth N; Kelly, Kristen M

    2010-02-01

    Studies have found that more men than women endorse sexual infidelity as more distressing than emotional infidelity, whereas more women than men endorse emotional infidelity as more distressing than sexual infidelity. Some evolutionary psychologists have proposed that this sex difference can be best conceptualized as reflecting evolution-based differences in parental investment that produce a need for paternity certainty among men and a need for male investment in offspring among women. Nonetheless, a conspicuous subset of men report emotional infidelity as more distressing than sexual infidelity. Current theorizing explains between-sex differences but not within-sex differences. We hypothesized that attachment-style differences may help to explain both between- and within-sex differences in jealousy. As hypothesized, dismissing avoidant participants reported more jealousy regarding sexual than emotional infidelity (64.8%), and secure participants, including secure men, reported more jealousy regarding emotional than sexual infidelity (77.3%), chi(2)(3, N = 411) = 45.03, p jealousy relationship by attachment style. Implications of an attachment perspective are discussed.

  11. Region-specific changes in presynaptic agmatine and glutamate levels in the aged rat brain.

    Science.gov (United States)

    Jing, Y; Liu, P; Leitch, B

    2016-01-15

    During the normal aging process, the brain undergoes a range of biochemical and structural alterations, which may contribute to deterioration of sensory and cognitive functions. Age-related deficits are associated with altered efficacy of synaptic neurotransmission. Emerging evidence indicates that levels of agmatine, a putative neurotransmitter in the mammalian brain, are altered in a region-specific manner during the aging process. The gross tissue content of agmatine in the prefrontal cortex (PFC) of aged rat brains is decreased whereas levels in the temporal cortex (TE) are increased. However, it is not known whether these changes in gross tissue levels are also mirrored by changes in agmatine levels at synapses and thus could potentially contribute to altered synaptic function with age. In the present study, agmatine levels in presynaptic terminals in the PFC and TE regions (300 terminals/region) of young (3month; n=3) and aged (24month; n=3) brains of male Sprague-Dawley rats were compared using quantitative post-embedding immunogold electron-microscopy. Presynaptic levels of agmatine were significantly increased in the TE region (60%; pagmatine and glutamate were co-localized in the same synaptic terminals, and quantitative analyses revealed significantly reduced glutamate levels in agmatine-immunopositive synaptic terminals in both regions in aged rats compared to young animals. This study, for the first time, demonstrates differential effects of aging on agmatine and glutamate in the presynaptic terminals of PFC and TE. Future research is required to understand the functional significance of these changes and the underlying mechanisms. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Identifying the contribution of different urban highway air pollution sources

    International Nuclear Information System (INIS)

    Peace, H.; Owen, B.; Raper, D.W.

    2004-01-01

    This paper describes the methodology and results, and draws conclusions from a large-scale source apportionment study undertaken in a large urban conurbation in the northwest of England. Annual average oxides of nitrogen (NOx) emission and ambient air pollution contributions have been estimated for road traffic sources. Ground level air pollution concentrations were estimated over a 1552-km 2 area with a resolution of up to 20 m, using emissions estimates and the second generation ADMS-Urban Gaussian dispersion model. Road traffic emissions were split into car and motorcycles; heavy and light goods vehicles; and buses to represent domestic users; commercial users and bus companies. Car related emissions were split further in to journey lengths under 3 km; journeys between 3 and 8 km; and journeys over 8 km to represent journeys which could be either walked or cycled; journeys for which a bus can easily be used and other journeys. These source sections were chosen so that the relevant authorities could target key groups in terms of reducing air pollution. The results confirm that the areas most likely to exceed air quality objectives are typically close to main arterial routes and close to urban centres and that the major culprits of road traffic related air pollution are goods vehicles and car journeys over 8 km. The paper also discusses the implications of the results and suggests how these can be used in the assessment of actions to reduce air pollution concentrations

  13. Identifying the contribution of different urban highway air pollution sources.

    Science.gov (United States)

    Peace, H; Owen, B; Raper, D W

    2004-12-01

    This paper describes the methodology and results, and draws conclusions from a large-scale source apportionment study undertaken in a large urban conurbation in the northwest of England. Annual average oxides of nitrogen (NOx) emission and ambient air pollution contributions have been estimated for road traffic sources. Ground level air pollution concentrations were estimated over a 1552-km(2) area with a resolution of up to 20 m, using emissions estimates and the second generation ADMS-Urban Gaussian dispersion model. Road traffic emissions were split into car and motorcycles; heavy and light goods vehicles; and buses to represent domestic users; commercial users and bus companies. Car related emissions were split further in to journey lengths under 3 km; journeys between 3 and 8 km; and journeys over 8 km to represent journeys which could be either walked or cycled; journeys for which a bus can easily be used and other journeys. These source sections were chosen so that the relevant authorities could target key groups in terms of reducing air pollution. The results confirm that the areas most likely to exceed air quality objectives are typically close to main arterial routes and close to urban centres and that the major culprits of road traffic related air pollution are goods vehicles and car journeys over 8 km. The paper also discusses the implications of the results and suggests how these can be used in the assessment of actions to reduce air pollution concentrations.

  14. Eracing the Simple Certainty of Difference: A Psychoanalytic Contribution.

    Science.gov (United States)

    Lombardi, Karen L.

    2002-01-01

    Asserts that racism, classism, and sexism are fostered not only through material conditions but also through the privileging of difference common to Western intellectual thought. Turns to the unconscious of psychoanalytic theory, especially the theories of Melanie Klein and Ignacio Matter Blanco, recommending an alternative discourse on race,…

  15. Teacher Twitter Chats: Gender Differences in Participants' Contributions

    Science.gov (United States)

    Kerr, Stacey L.; Schmeichel, Mardi J.

    2018-01-01

    Gender differences in participation were examined across four Twitter chats for social studies teachers. Analyses drawing on mixed methods revealed that while there was parity across most kinds of tweets, participants identified as men were more likely to use the examined Twitter chats to share resources, give advice, boast, promote their own…

  16. Contribution of Patient Characteristics to Differences in Readmission Rates

    Science.gov (United States)

    Barnett, Michael L.; Hsu, John; McWilliams, J. Michael

    2016-01-01

    Importance Medicare penalizes hospitals with higher than expected readmission rates by up to 3% of annual inpatient payments. Expected rates are adjusted only for patients’ age, sex, discharge diagnosis, and recent diagnoses. Objective To assess the extent to which a comprehensive set of patient characteristics accounts for differences in hospital readmission rates. Design and Setting Using survey data from the nationally representative Health and Retirement Study (HRS) and linked Medicare claims, we assessed 29 patient characteristics from survey data and claims as potential predictors of 30-day readmission when added to standard Medicare adjustments of hospital readmission rates. We then compared the distribution of these characteristics between participants admitted to hospitals with higher vs. lower hospital-wide readmission rates reported by Medicare. Finally, we estimated differences in the probability of readmission between these groups of participants before vs. after adjusting for the additional patient characteristics. Participants HRS participants enrolled in Medicare who were hospitalized from 2009–2012 (n=8,067 admissions). Main Outcomes and Measures All-cause readmission within 30 days of discharge. Results Of the additional 29 patient characteristics assessed, 22 significantly predicted readmission beyond standard adjustments, and 17 of these were distributed differently between hospitals in the highest vs. lowest quintiles of publicly reported hospital-wide readmission rates (p≤0.04 for all). Almost all of these differences (16 of 17) indicated that participants admitted to hospitals in the highest quintile of readmission rates were more likely to have characteristics that were associated with a higher probability of readmission. The difference in the probability of readmission between participants admitted to hospitals in the highest vs. lowest quintile of hospital-wide readmission rates was reduced by 48% from 4.41 percentage points with

  17. Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks

    Science.gov (United States)

    Letellier, Mathieu; Park, Yun Kyung; Chater, Thomas E.; Chipman, Peter H.; Gautam, Sunita Ghimire; Oshima-Takago, Tomoko; Goda, Yukiko

    2016-01-01

    Dendrites are neuronal structures specialized for receiving and processing information through their many synaptic inputs. How input strengths are modified across dendrites in ways that are crucial for synaptic integration and plasticity remains unclear. We examined in single hippocampal neurons the mechanism of heterosynaptic interactions and the heterogeneity of synaptic strengths of pyramidal cell inputs. Heterosynaptic presynaptic plasticity that counterbalances input strengths requires N-methyl-d-aspartate receptors (NMDARs) and astrocytes. Importantly, this mechanism is shared with the mechanism for maintaining highly heterogeneous basal presynaptic strengths, which requires astrocyte Ca2+ signaling involving NMDAR activation, astrocyte membrane depolarization, and L-type Ca2+ channels. Intracellular infusion of NMDARs or Ca2+-channel blockers into astrocytes, conditionally ablating the GluN1 NMDAR subunit, or optogenetically hyperpolarizing astrocytes with archaerhodopsin promotes homogenization of convergent presynaptic inputs. Our findings support the presence of an astrocyte-dependent cellular mechanism that enhances the heterogeneity of presynaptic strengths of convergent connections, which may help boost the computational power of dendrites. PMID:27118849

  18. Functional mobility and its contributing factors for older adults in different cities in Taiwan

    Directory of Open Access Journals (Sweden)

    Sang-I. Lin

    2017-02-01

    Conclusion: Taiwanese older adults with mobility problems living in different cities performed differently in TUG and the contributing factors were also different. These findings indicate a need of further studies examining older adults in different environments.

  19. Abnormal presynaptic short-term plasticity and information processing in a mouse model of fragile X syndrome.

    Science.gov (United States)

    Deng, Pan-Yue; Sojka, David; Klyachko, Vitaly A

    2011-07-27

    Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and the leading genetic cause of autism. It is associated with the lack of fragile X mental retardation protein (FMRP), a regulator of protein synthesis in axons and dendrites. Studies on FXS have extensively focused on the postsynaptic changes underlying dysfunctions in long-term plasticity. In contrast, the presynaptic mechanisms of FXS have garnered relatively little attention and are poorly understood. Activity-dependent presynaptic processes give rise to several forms of short-term plasticity (STP), which is believed to control some of essential neural functions, including information processing, working memory, and decision making. The extent of STP defects and their contributions to the pathophysiology of FXS remain essentially unknown, however. Here we report marked presynaptic abnormalities at excitatory hippocampal synapses in Fmr1 knock-out (KO) mice leading to defects in STP and information processing. Loss of FMRP led to enhanced responses to high-frequency stimulation. Fmr1 KO mice also exhibited abnormal synaptic processing of natural stimulus trains, specifically excessive enhancement during the high-frequency spike discharges associated with hippocampal place fields. Analysis of individual STP components revealed strongly increased augmentation and reduced short-term depression attributable to loss of FMRP. These changes were associated with exaggerated calcium influx in presynaptic neurons during high-frequency stimulation, enhanced synaptic vesicle recycling, and enlarged readily-releasable and reserved vesicle pools. These data suggest that loss of FMRP causes abnormal STP and information processing, which may represent a novel mechanism contributing to cognitive impairments in FXS.

  20. Drosophila Atlastin in motor neurons is required for locomotion and presynaptic function.

    Science.gov (United States)

    De Gregorio, Cristian; Delgado, Ricardo; Ibacache, Andrés; Sierralta, Jimena; Couve, Andrés

    2017-10-15

    Hereditary spastic paraplegias (HSPs) are characterized by spasticity and weakness of the lower limbs, resulting from length-dependent axonopathy of the corticospinal tracts. In humans, the HSP-related atlastin genes ATL1 - ATL3 catalyze homotypic membrane fusion of endoplasmic reticulum (ER) tubules. How defects in neuronal Atlastin contribute to axonal degeneration has not been explained satisfactorily. Using Drosophila , we demonstrate that downregulation or overexpression of Atlastin in motor neurons results in decreased crawling speed and contraction frequency in larvae, while adult flies show progressive decline in climbing ability. Broad expression in the nervous system is required to rescue the atlastin -null Drosophila mutant ( atl 2 ) phenotype. Importantly, both spontaneous release and the reserve pool of synaptic vesicles are affected. Additionally, axonal secretory organelles are abnormally distributed, whereas presynaptic proteins diminish at terminals and accumulate in distal axons, possibly in lysosomes. Our findings suggest that trafficking defects produced by Atlastin dysfunction in motor neurons result in redistribution of presynaptic components and aberrant mobilization of synaptic vesicles, stressing the importance of ER-shaping proteins and the susceptibility of motor neurons to their mutations or depletion. © 2017. Published by The Company of Biologists Ltd.

  1. Estimating the contribution of genetic variants to difference in incidence of disease between population groups.

    Science.gov (United States)

    Moonesinghe, Ramal; Ioannidis, John P A; Flanders, W Dana; Yang, Quanhe; Truman, Benedict I; Khoury, Muin J

    2012-08-01

    Genome-wide association studies have identified multiple genetic susceptibility variants to several complex human diseases. However, risk-genotype frequency at loci showing robust associations might differ substantially among different populations. In this paper, we present methods to assess the contribution of genetic variants to the difference in the incidence of disease between different population groups for different scenarios. We derive expressions for the contribution of a single genetic variant, multiple genetic variants, and the contribution of the joint effect of a genetic variant and an environmental factor to the difference in the incidence of disease. The contribution of genetic variants to the difference in incidence increases with increasing difference in risk-genotype frequency, but declines with increasing difference in incidence between the two populations. The contribution of genetic variants also increases with increasing relative risk and the contribution of joint effect of genetic and environmental factors increases with increasing relative risk of the gene-environmental interaction. The contribution of genetic variants to the difference in incidence between two populations can be expressed as a function of the population attributable risks of the genetic variants in the two populations. The contribution of a group of genetic variants to the disparity in incidence of disease could change considerably by adding one more genetic variant to the group. Any estimate of genetic contribution to the disparity in incidence of disease between two populations at this stage seems to be an elusive goal.

  2. Estimating the contribution of genetic variants to difference in incidence of disease between population groups

    Science.gov (United States)

    Moonesinghe, Ramal; Ioannidis, John PA; Flanders, W Dana; Yang, Quanhe; Truman, Benedict I; Khoury, Muin J

    2012-01-01

    Genome-wide association studies have identified multiple genetic susceptibility variants to several complex human diseases. However, risk-genotype frequency at loci showing robust associations might differ substantially among different populations. In this paper, we present methods to assess the contribution of genetic variants to the difference in the incidence of disease between different population groups for different scenarios. We derive expressions for the contribution of a single genetic variant, multiple genetic variants, and the contribution of the joint effect of a genetic variant and an environmental factor to the difference in the incidence of disease. The contribution of genetic variants to the difference in incidence increases with increasing difference in risk-genotype frequency, but declines with increasing difference in incidence between the two populations. The contribution of genetic variants also increases with increasing relative risk and the contribution of joint effect of genetic and environmental factors increases with increasing relative risk of the gene–environmental interaction. The contribution of genetic variants to the difference in incidence between two populations can be expressed as a function of the population attributable risks of the genetic variants in the two populations. The contribution of a group of genetic variants to the disparity in incidence of disease could change considerably by adding one more genetic variant to the group. Any estimate of genetic contribution to the disparity in incidence of disease between two populations at this stage seems to be an elusive goal. PMID:22333905

  3. Coupling of exocytosis and endocytosis at the presynaptic active zone.

    Science.gov (United States)

    Maritzen, Tanja; Haucke, Volker

    2018-02-01

    Brain function depends on the ability of neurons to communicate with each other via the regulated exocytosis of neurotransmitter-containing synaptic vesicles (SVs) at specialized presynaptic release sites termed active zones (AZs). The presynaptic AZ comprises an assembly of large multidomain proteins that link the machinery for vesicle fusion to sites of voltage-dependent Ca 2+ entry. Following SV fusion at AZ release sites SV membranes are retrieved by compensatory endocytosis, and SVs are reformed. Recent data suggest that Ca 2+ -triggered SV exocytosis at AZs and endocytic retrieval of SVs may be functionally and physically linked. Here we discuss the evidence supporting such exo-endocytic coupling as well as possible modes and mechanisms that may underlie coupling of exocytosis and endocytosis at and around AZs in presynaptic nerve terminals. As components of the exo-endocytic machinery at synapses have been linked to neurological and neuropsychiatric disorders, understanding the mechanisms that couple exocytosis and endocytosis at AZs may be of importance for developing novel therapies to treat these diseases. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  4. Age-dependent changes of presynaptic neuromodulation via A1-adenosine receptors in rat hippocampal slices.

    Science.gov (United States)

    Sperlágh, B; Zsilla, G; Baranyi, M; Kékes-Szabó, A; Vizi, E S

    1997-10-01

    The presynaptic neuromodulation of stimulation-evoked release of [3H]-acetylcholine by endogenous adenosine, via A1-adenosine receptors, was studied in superfused hippocampal slices taken from 4-, 12- and 24-month-old rats. 8-Cyclopentyl-1,3-dimethylxanthine (0.25 microM), a selective A1-receptor antagonist, increased significantly the electrical field stimulation-induced release of [3H]-acetylcholine in slices prepared from 4- and 12-month-old rats, showing a tonic inhibitory action of endogenous adenosine via stimulation of presynaptic A1-adenosine receptors. In contrast, 8-cyclopentyl-1,3-dimethylxanthine had no effect in 24-month-old rats. 2-Chloroadenosine (10 microM), an adenosine receptor agonist decreased the release of [3H]-acetylcholine in slices taken from 4- and 12-month-old rats, and no significant change was observed in slices taken from 24-month-old rats. In order to show whether the number/or affinity of the A1-receptors was affected in aged rats, [3H]-8-cyclopentyl-1,3-dimethylxanthine binding was studied in hippocampal membranes prepared from rats of different ages. Whereas the Bmax value was significantly lower in 2-year-old rats than in younger counterparts, the dissociation constant (Kd) was not affected by aging, indicating that the density rather than the affinity of adenosine receptors was altered. Endogenous adenosine levels present in the extracellular space were also measured in the superfusate by high performance liquid chromatography (HPLC) coupled with ultraviolet detection, and an age-related increase in the adenosine level was found. In summary, our results indicate that during aging the level of adenosine in the extracellular fluid is increased in the hippocampus. There is a downregulation and reduced responsiveness of presynaptic adenosine A1-receptors, and it seems likely that these changes are due to the enhanced adenosine level in the extracellular space.

  5. Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors.

    Science.gov (United States)

    Vulfius, Catherine A; Kasheverov, Igor E; Kryukova, Elena V; Spirova, Ekaterina N; Shelukhina, Irina V; Starkov, Vladislav G; Andreeva, Tatyana V; Faure, Grazyna; Zouridakis, Marios; Tsetlin, Victor I; Utkin, Yuri N

    2017-01-01

    Phospholipases A2 (PLA2s) are enzymes found throughout the animal kingdom. They hydrolyze phospholipids in the sn-2 position producing lysophospholipids and unsaturated fatty acids, agents that can damage membranes. PLA2s from snake venoms have numerous toxic effects, not all of which can be explained by phospholipid hydrolysis, and each enzyme has a specific effect. We have earlier demonstrated the capability of several snake venom PLA2s with different enzymatic, cytotoxic, anticoagulant and antiproliferative properties, to decrease acetylcholine-induced currents in Lymnaea stagnalis neurons, and to compete with α-bungarotoxin for binding to nicotinic acetylcholine receptors (nAChRs) and acetylcholine binding protein. Since nAChRs are implicated in postsynaptic and presynaptic activities, in this work we probe those PLA2s known to have strong presynaptic effects, namely β-bungarotoxin from Bungarus multicinctus and crotoxin from Crotalus durissus terrificus. We also wished to explore whether mammalian PLA2s interact with nAChRs, and have examined non-toxic PLA2 from porcine pancreas. It was found that porcine pancreatic PLA2 and presynaptic β-bungarotoxin blocked currents mediated by nAChRs in Lymnaea neurons with IC50s of 2.5 and 4.8 μM, respectively. Crotoxin competed with radioactive α-bungarotoxin for binding to Torpedo and human α7 nAChRs and to the acetylcholine binding protein. Pancreatic PLA2 interacted similarly with these targets; moreover, it inhibited radioactive α-bungarotoxin binding to the water-soluble extracellular domain of human α9 nAChR, and blocked acetylcholine induced currents in human α9α10 nAChRs heterologously expressed in Xenopus oocytes. These and our earlier results show that all snake PLA2s, including presynaptically active crotoxin and β-bungarotoxin, as well as mammalian pancreatic PLA2, interact with nAChRs. The data obtained suggest that this interaction may be a general property of all PLA2s, which should be proved by

  6. 'Fractional recovery' analysis of a presynaptic synaptotagmin 1-anchored endocytic protein complex.

    Directory of Open Access Journals (Sweden)

    Rajesh Khanna

    Full Text Available BACKGROUND: The integral synaptic vesicle protein and putative calcium sensor, synaptotagmin 1 (STG, has also been implicated in synaptic vesicle (SV recovery. However, proteins with which STG interacts during SV endocytosis remain poorly understood. We have isolated an STG-associated endocytic complex (SAE from presynaptic nerve terminals and have used a novel fractional recovery (FR assay based on electrostatic dissociation to identify SAE components and map the complex structure. The location of SAE in the presynaptic terminal was determined by high-resolution quantitative immunocytochemistry at the chick ciliary ganglion giant calyx-type synapse. METHODOLOGY/PRINCIPLE FINDINGS: The first step in FR analysis was to immunoprecipitate (IP the complex with an antibody against one protein component (the IP-protein. The immobilized complex was then exposed to a high salt (1150 mM stress-test that caused shedding of co-immunoprecipitated proteins (co-IP-proteins. A Fractional Recovery ratio (FR: recovery after high salt/recovery with control salt as assayed by Western blot was calculated for each co-IP-protein. These FR values reflect complex structure since an easily dissociated protein, with a low FR value, cannot be intermediary between the IP-protein and a salt-resistant protein. The structure of the complex was mapped and a blueprint generated with a pair of FR analyses generated using two different IP-proteins. The blueprint of SAE contains an AP180/X/STG/stonin 2/intersectin/epsin core (X is unknown and epsin is hypothesized, and an AP2 adaptor, H-/L-clathrin coat and dynamin scission protein perimeter. Quantitative immunocytochemistry (ICA/ICQ method at an isolated calyx-type presynaptic terminal indicates that this complex is associated with STG at the presynaptic transmitter release face but not with STG on intracellular synaptic vesicles. CONCLUSIONS/SIGNIFICANCE: We hypothesize that the SAE serves as a recognition site and also as a

  7. Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors.

    Directory of Open Access Journals (Sweden)

    Catherine A Vulfius

    Full Text Available Phospholipases A2 (PLA2s are enzymes found throughout the animal kingdom. They hydrolyze phospholipids in the sn-2 position producing lysophospholipids and unsaturated fatty acids, agents that can damage membranes. PLA2s from snake venoms have numerous toxic effects, not all of which can be explained by phospholipid hydrolysis, and each enzyme has a specific effect. We have earlier demonstrated the capability of several snake venom PLA2s with different enzymatic, cytotoxic, anticoagulant and antiproliferative properties, to decrease acetylcholine-induced currents in Lymnaea stagnalis neurons, and to compete with α-bungarotoxin for binding to nicotinic acetylcholine receptors (nAChRs and acetylcholine binding protein. Since nAChRs are implicated in postsynaptic and presynaptic activities, in this work we probe those PLA2s known to have strong presynaptic effects, namely β-bungarotoxin from Bungarus multicinctus and crotoxin from Crotalus durissus terrificus. We also wished to explore whether mammalian PLA2s interact with nAChRs, and have examined non-toxic PLA2 from porcine pancreas. It was found that porcine pancreatic PLA2 and presynaptic β-bungarotoxin blocked currents mediated by nAChRs in Lymnaea neurons with IC50s of 2.5 and 4.8 μM, respectively. Crotoxin competed with radioactive α-bungarotoxin for binding to Torpedo and human α7 nAChRs and to the acetylcholine binding protein. Pancreatic PLA2 interacted similarly with these targets; moreover, it inhibited radioactive α-bungarotoxin binding to the water-soluble extracellular domain of human α9 nAChR, and blocked acetylcholine induced currents in human α9α10 nAChRs heterologously expressed in Xenopus oocytes. These and our earlier results show that all snake PLA2s, including presynaptically active crotoxin and β-bungarotoxin, as well as mammalian pancreatic PLA2, interact with nAChRs. The data obtained suggest that this interaction may be a general property of all PLA2s, which

  8. MicroRNA-22 Gates Long-Term Heterosynaptic Plasticity in Aplysia through Presynaptic Regulation of CPEB and Downstream Targets

    Directory of Open Access Journals (Sweden)

    Ferdinando Fiumara

    2015-06-01

    Full Text Available The maintenance phase of memory-related long-term facilitation (LTF of synapses between sensory and motor neurons of the gill-withdrawal reflex of Aplysia depends on a serotonin (5-HT-triggered presynaptic upregulation of CPEB, a functional prion that regulates local protein synthesis at the synapse. The mechanisms whereby serotonin regulates CPEB levels in presynaptic sensory neurons are not known. Here, we describe a sensory neuron-specific microRNA 22 (miR-22 that has multiple binding sites on the mRNA of CPEB and inhibits it in the basal state. Serotonin triggers MAPK/Erk-dependent downregulation of miR-22, thereby upregulating the expression of CPEB, which in turn regulates, through functional CPE elements, the presynaptic expression of atypical PKC (aPKC, another candidate regulator of memory maintenance. Our findings support a model in which the neurotransmitter-triggered downregulation of miR-22 coordinates the regulation of genes contributing synergistically to the long-term maintenance of memory-related synaptic plasticity.

  9. MicroRNA-22 Gates Long-Term Heterosynaptic Plasticity in Aplysia through Presynaptic Regulation of CPEB and Downstream Targets.

    Science.gov (United States)

    Fiumara, Ferdinando; Rajasethupathy, Priyamvada; Antonov, Igor; Kosmidis, Stylianos; Sossin, Wayne S; Kandel, Eric R

    2015-06-30

    The maintenance phase of memory-related long-term facilitation (LTF) of synapses between sensory and motor neurons of the gill-withdrawal reflex of Aplysia depends on a serotonin (5-HT)-triggered presynaptic upregulation of CPEB, a functional prion that regulates local protein synthesis at the synapse. The mechanisms whereby serotonin regulates CPEB levels in presynaptic sensory neurons are not known. Here, we describe a sensory neuron-specific microRNA 22 (miR-22) that has multiple binding sites on the mRNA of CPEB and inhibits it in the basal state. Serotonin triggers MAPK/Erk-dependent downregulation of miR-22, thereby upregulating the expression of CPEB, which in turn regulates, through functional CPE elements, the presynaptic expression of atypical PKC (aPKC), another candidate regulator of memory maintenance. Our findings support a model in which the neurotransmitter-triggered downregulation of miR-22 coordinates the regulation of genes contributing synergistically to the long-term maintenance of memory-related synaptic plasticity. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Differences in Binding and Monitoring Mechanisms Contribute to Lifespan Age Differences in False Memory

    Science.gov (United States)

    Fandakova, Yana; Shing, Yee Lee; Lindenberger, Ulman

    2013-01-01

    Based on a 2-component framework of episodic memory development across the lifespan (Shing & Lindenberger, 2011), we examined the contribution of memory-related binding and monitoring processes to false memory susceptibility in childhood and old age. We administered a repeated continuous recognition task to children (N = 20, 10-12 years),…

  11. Presynaptic control of group Ia afferents in relation to acquisition of a visuo-motor skill in healthy humans

    DEFF Research Database (Denmark)

    Perez, Monica A.; Lungholt, Bjarke K.S.; Nielsen, Jens Bo

    2005-01-01

    Sensory information continuously converges on the spinal cord during a variety of motor behaviours. Here, we examined presynaptic control of group Ia afferents in relation to acquisition of a novel motor skill. We tested whether repetition of two motor tasks with different degrees of difficulty......, a novel visuo-motor task involving the ankle muscles, and a control task involving simple voluntary ankle movements, would induce changes in the size of the soleus H-reflex. The slope of the H-reflex recruitment curve and the H-max/M-max ratio were depressed after repetition of the visuo-motor skill task...... of the monosynaptic Ia facilitation of the soleus H-reflex evoked by femoral nerve stimulation. The D1 inhibition was increased and the femoral nerve facilitation was decreased following the visuo-motor skill task, suggesting an increase in presynaptic inhibition of Ia afferents. No changes were observed...

  12. Visualizing presynaptic calcium dynamics and vesicle fusion with a single genetically encoded reporter at individual synapses

    Directory of Open Access Journals (Sweden)

    Rachel E Jackson

    2016-07-01

    Full Text Available Synaptic transmission depends on the influx of calcium into the presynaptic compartment, which drives neurotransmitter release. Genetically encoded reporters are widely used tools to understand these processes, particularly pHluorin-based reporters that report vesicle exocytosis and endocytosis through pH dependent changes in fluorescence, and genetically encoded calcium indicators (GECIs that exhibit changes in fluorescence upon binding to calcium. The recent expansion of the color palette of available indicators has made it possible to image multiple probes simultaneously within a cell. We have constructed a single molecule reporter capable of concurrent imaging of both presynaptic calcium influx and exocytosis, by fusion of sypHy, the vesicle associated protein synaptophysin containing a GFP-based pHluorin sensor, with the red-shifted GECI R-GECO1. Due to the fixed stoichiometry of the two probes, the ratio of the two responses can also be measured, providing an all optical correlate of the calcium dependence of release. Here, we have characterized stimulus-evoked sypHy-RGECO responses of hippocampal synapses in vitro, exploring the effects of different stimulus strengths and frequencies as well as variations in external calcium concentrations. By combining live sypHy-RGECO imaging with post-hoc fixation and immunofluorescence, we have also investigated correlations between structural and functional properties of synapses.

  13. Presynaptic (Type III) cells in mouse taste buds sense sour (acid) taste.

    Science.gov (United States)

    Huang, Yijen A; Maruyama, Yutaka; Stimac, Robert; Roper, Stephen D

    2008-06-15

    Taste buds contain two types of cells that directly participate in taste transduction - receptor (Type II) cells and presynaptic (Type III) cells. Receptor cells respond to sweet, bitter and umami taste stimulation but until recently the identity of cells that respond directly to sour (acid) tastants has only been inferred from recordings in situ, from behavioural studies, and from immunostaining for putative sour transduction molecules. Using calcium imaging on single isolated taste cells and with biosensor cells to identify neurotransmitter release, we show that presynaptic (Type III) cells specifically respond to acid taste stimulation and release serotonin. By recording responses in cells isolated from taste buds and in taste cells in lingual slices to acetic acid titrated to different acid levels (pH), we also show that the active stimulus for acid taste is the membrane-permeant, uncharged acetic acid moiety (CH(3)COOH), not free protons (H(+)). That observation is consistent with the proximate stimulus for acid taste being intracellular acidification, not extracellular protons per se. These findings may also have implications for other sensory receptors that respond to acids, such as nociceptors.

  14. Evidence for presynaptically silent synapses in the immature hippocampus

    International Nuclear Information System (INIS)

    Yoon, Jae Young; Choi, Sukwoo

    2017-01-01

    Silent synapses show NMDA receptor (NMDAR)-mediated synaptic responses, but not AMPAR-mediated synaptic responses. A prevailing hypothesis states that silent synapses contain NMDARs, but not AMPARs. However, alternative presynaptic hypotheses, according to which AMPARs are present at silent synapses, have been proposed; silent synapses show slow glutamate release via a fusion pore, and glutamate spillover from the neighboring synaptic terminals. Consistent with these presynaptic hypotheses, the peak glutamate concentrations at silent synapses have been estimated to be ≪170 μM, much lower than those seen at functional synapses. Glutamate transients predicted based on the two presynaptic mechanisms have been shown to activate only high-affinity NMDARs, but not low-affinity AMPARs. Interestingly, a previous study has developed a new approach to distinguish between the two presynaptic mechanisms using dextran, an inert macromolecule that reduces the diffusivity of released glutamate: postsynaptic responses through the fusion pore mechanism, but not through the spillover mechanism, are potentiated by reduced glutamate diffusivity. Therefore, we reasoned that if the fusion pore mechanism underlies silent synapses, dextran application would reveal AMPAR-mediated synaptic responses at silent synapses. In the present study, we recorded AMPAR-mediated synaptic responses at the CA3-CA1 synapses in neonatal rats in the presence of blockers for NMDARs and GABAARs. Bath application of dextran revealed synaptic responses at silent synapses. GYKI53655, a selective AMPAR-antagonist, completely inhibited the unsilenced synaptic responses, indicating that the unsilenced synaptic responses are mediated by AMPARs. The dextran-mediated reduction in glutamate diffusivity would also lead to the activation of metabotropic glutamate receptors (mGluRs), which might induce unsilencing via the activation of unknown intracellular signaling. Hence, we determined whether mGluR-blockers alter

  15. Sphingosine-1-Phosphate (S1P) Impacts Presynaptic Functions by Regulating Synapsin I Localization in the Presynaptic Compartment.

    Science.gov (United States)

    Riganti, Loredana; Antonucci, Flavia; Gabrielli, Martina; Prada, Ilaria; Giussani, Paola; Viani, Paola; Valtorta, Flavia; Menna, Elisabetta; Matteoli, Michela; Verderio, Claudia

    2016-04-20

    Growing evidence indicates that sphingosine-1-P (S1P) upregulates glutamate secretion in hippocampal neurons. However, the molecular mechanisms through which S1P enhances excitatory activity remain largely undefined. The aim of this study was to identify presynaptic targets of S1P action controlling exocytosis. Confocal analysis of rat hippocampal neurons showed that S1P applied at nanomolar concentration alters the distribution of Synapsin I (SynI), a presynaptic phosphoprotein that controls the availability of synaptic vesicles for exocytosis. S1P induced SynI relocation to extrasynaptic regions of mature neurons, as well as SynI dispersion from synaptic vesicle clusters present at axonal growth cones of developing neurons. S1P-induced SynI relocation occurred in a Ca(2+)-independent but ERK-dependent manner, likely through the activation of S1P3 receptors, as it was prevented by the S1P3 receptor selective antagonist CAY1044 and in neurons in which S1P3 receptor was silenced. Our recent evidence indicates that microvesicles (MVs) released by microglia enhance the metabolism of endogenous sphingolipids in neurons and stimulate excitatory transmission. We therefore investigated whether MVs affect SynI distribution and whether endogenous S1P could be involved in the process. Analysis of SynI immunoreactivity showed that exposure to microglial MVs induces SynI mobilization at presynaptic sites and growth cones, whereas the use of inhibitors of sphingolipid cascade identified S1P as the sphingolipid mediating SynI redistribution. Our data represent the first demonstration that S1P induces SynI mobilization from synapses, thereby indicating the phosphoprotein as a novel target through which S1P controls exocytosis. Growing evidence indicates that the bioactive lipid sphingosine and its metabolite sphingosine-1-P (S1P) stimulate excitatory transmission. While it has been recently clarified that sphingosine influences directly the exocytotic machinery by activating the

  16. Uncovering cognitive processes: Different techniques that can contribute to cognitive load research and instruction

    NARCIS (Netherlands)

    Van Gog, Tamara; Kester, Liesbeth; Nievelstein, Fleurie; Giesbers, Bas; Fred, Paas

    2009-01-01

    Van Gog, T., Kester, L., Nievelstein, F., Giesbers, B., & Paas, F. (2009). Uncovering cognitive processes: Different techniques that can contribute to cognitive load research and instruction. Computers in Human Behavior, 25, 325-331.

  17. Does human presynaptic striatal dopamine function predict social conformity?

    Science.gov (United States)

    Stokes, Paul R A; Benecke, Aaf; Puraite, Julita; Bloomfield, Michael A P; Shotbolt, Paul; Reeves, Suzanne J; Lingford-Hughes, Anne R; Howes, Oliver; Egerton, Alice

    2014-03-01

    Socially desirable responding (SDR) is a personality trait which reflects either a tendency to present oneself in an overly positive manner to others, consistent with social conformity (impression management (IM)), or the tendency to view one's own behaviour in an overly positive light (self-deceptive enhancement (SDE)). Neurochemical imaging studies report an inverse relationship between SDR and dorsal striatal dopamine D₂/₃ receptor availability. This may reflect an association between SDR and D₂/₃ receptor expression, synaptic dopamine levels or a combination of the two. In this study, we used a [¹⁸F]-DOPA positron emission tomography (PET) image database to investigate whether SDR is associated with presynaptic dopamine function. Striatal [¹⁸F]-DOPA uptake, (k(i)(cer), min⁻¹), was determined in two independent healthy participant cohorts (n=27 and 19), by Patlak analysis using a cerebellar reference region. SDR was assessed using the revised Eysenck Personality Questionnaire (EPQ-R) Lie scale, and IM and SDE were measured using the Paulhus Deception Scales. No significant associations were detected between Lie, SDE or IM scores and striatal [¹⁸F]-DOPA k(i)(cer). These results indicate that presynaptic striatal dopamine function is not associated with social conformity and suggests that social conformity may be associated with striatal D₂/₃ receptor expression rather than with synaptic dopamine levels.

  18. Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart

    International Nuclear Information System (INIS)

    Mongillo, Marco; Leccisotti, Lucia; John, Anna S.; Pennell, Dudley J.; Camici, Paolo G.

    2007-01-01

    We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic β-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF. Eight patients (aged 67 ± 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 ± 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [ 11 C]meta-hydroxy-ephedrine (HED) volume of distribution (V d ) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 ± 4 years, p -1 .g -1 ) and dysfunctional (0.49 ± 0.14 μmol.min -1 .g -1 ) segments compared with controls (0.61 ± 0.7 μmol.min -1 .g -1 ; p d was reduced in dysfunctional segments of patients (38.9 ± 21.2 ml.g -1 ) compared with normal segments (52.2 ± 19.6 ml.g -1 ) and compared with controls (62.7 ± 11.3 ml.g -1 ). In patients, regional MGU was correlated with HED V d . The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts. (orig.)

  19. Intra-axonal Synthesis of SNAP25 Is Required for the Formation of Presynaptic Terminals

    Directory of Open Access Journals (Sweden)

    Andreia F.R. Batista

    2017-09-01

    Full Text Available Localized protein synthesis is a mechanism for developing axons to react acutely and in a spatially restricted manner to extracellular signals. As such, it is important for many aspects of axonal development, but its role in the formation of presynapses remains poorly understood. We found that the induced assembly of presynaptic terminals required local protein synthesis. Newly synthesized proteins were detectable at nascent presynapses within 15 min of inducing synapse formation in isolated axons. The transcript for the t-SNARE protein SNAP25, which is required for the fusion of synaptic vesicles with the plasma membrane, was recruited to presynaptic sites and locally translated. Inhibition of intra-axonal SNAP25 synthesis affected the clustering of SNAP25 and other presynaptic proteins and interfered with the release of synaptic vesicles from presynaptic sites. This study reveals a critical role for the axonal synthesis of SNAP25 in the assembly of presynaptic terminals.

  20. The relative labour productivity contribution of different age-skill categories for a developing economy

    Directory of Open Access Journals (Sweden)

    Gerhardus van Zyl

    2013-01-01

    Full Text Available Orientation: The article dealt with the estimation, computation and interpretation of the relative productivity contributions of different age-skill categories. Research purpose: The aim of the article was to estimate and compute, (1 relative productivity contributions and (2 relative productivity contribution–employee remuneration cost levels for different age-skill categories. Motivation for the study: The research was deemed necessary given the current debate on relative productivity levels and possible changes to the retirement age in the South African labour market. No real research in this regard has been published regarding the South African labour market situation. Research design, approach and method: A less restrictive production function was used, allowing for the simultaneous estimation and final computation of relative labour contribution levels of different age-skill categories. Main findings: The lower-skilled segment produced significantly smaller productivity contributions and the relative productivity contribution–employee remuneration cost ratios of the 55 years and older age group were superior in the higher-skilled segment but, at the same time, the lowest in the lower-skilled segment. Practical/managerial implications: It is recommended that human resource practitioners (given the perceived rigidity of labour legislation implement and maintain structures that promote higher productivity levels for all age-skill categories in the workplace. Contribution/value-add: An estimation procedure, which can be applied to the measurement of the relative productivity contribution of different age-skill categories, has been established.

  1. The relative labour productivity contribution of different age-skill categories for a developing economy

    Directory of Open Access Journals (Sweden)

    Gerhardus van Zyl

    2013-01-01

    Full Text Available Orientation: The article dealt with the estimation, computation and interpretation of the relative productivity contributions of different age-skill categories.Research purpose: The aim of the article was to estimate and compute, (1 relative productivity contributions and (2 relative productivity contribution–employee remuneration cost levels for different age-skill categories.Motivation for the study: The research was deemed necessary given the current debate on relative productivity levels and possible changes to the retirement age in the South African labour market. No real research in this regard has been published regarding the South African labour market situation.Research design, approach and method: A less restrictive production function was used, allowing for the simultaneous estimation and final computation of relative labour contribution levels of different age-skill categories.Main findings: The lower-skilled segment produced significantly smaller productivity contributions and the relative productivity contribution–employee remuneration cost ratios of the 55 years and older age group were superior in the higher-skilled segment but, at the same time, the lowest in the lower-skilled segment.Practical/managerial implications: It is recommended that human resource practitioners (given the perceived rigidity of labour legislation implement and maintain structures that promote higher productivity levels for all age-skill categories in the workplace.Contribution/value-add: An estimation procedure, which can be applied to the measurement of the relative productivity contribution of different age-skill categories, has been established.

  2. The contribution of differences in adiposity to educational disparities in mortality in the United States

    Directory of Open Access Journals (Sweden)

    Yana Vierboom

    2017-12-01

    Full Text Available Background: There are large differences in life expectancy by educational attainment in the United States. Previous research has found obesity's contribution to these differences to be small. Those findings may be sensitive to how obesity is estimated. Methods: This analysis uses discrete-time logistic regressions with data from the National Health and Nutrition Examination Survey (NHANES, pooled from 1988 to 1994 and 1999 to 2010, to estimate the contribution of differences in adiposity, or body fat, to educational differences in mortality. I show that results depend upon the measure of adiposity used: body mass index (BMI at the time of survey or lifetime maximum BMI. Results: College graduates were less likely than high school graduates to be obese at the time of survey (25Š vs. 34.6Š, respectively and were also less likely to have ever been obese (35.7Š vs. 49.4Š, respectively. Lifetime maximum BMI performed better than BMI at the time of survey in predicting mortality using criteria for model selection. Differences in maximum BMI were associated with between 10.3Š and 12Š of mortality differences between college graduates and all others, compared to between 3.3Š and 4.6Š for BMI at the time of survey. Among nonsmokers, between 18.4Š and 27.6Š of mortality differences between college graduates and all others were associated with differences in maximum BMI. Contribution: Adiposity is an overlooked contributor to educational differences in mortality. Previous findings that obesity does not contribute to educational disparities were based on BMI at the time of survey, which is less informative than maximum BMI. The contribution of adiposity to educational mortality differences will likely grow as smoking prevalence declines. Health surveys should collect information on weight history.

  3. Learning and retrieval behavior in recurrent neural networks with pre-synaptic dependent homeostatic plasticity

    Science.gov (United States)

    Mizusaki, Beatriz E. P.; Agnes, Everton J.; Erichsen, Rubem; Brunnet, Leonardo G.

    2017-08-01

    The plastic character of brain synapses is considered to be one of the foundations for the formation of memories. There are numerous kinds of such phenomenon currently described in the literature, but their role in the development of information pathways in neural networks with recurrent architectures is still not completely clear. In this paper we study the role of an activity-based process, called pre-synaptic dependent homeostatic scaling, in the organization of networks that yield precise-timed spiking patterns. It encodes spatio-temporal information in the synaptic weights as it associates a learned input with a specific response. We introduce a correlation measure to evaluate the precision of the spiking patterns and explore the effects of different inhibitory interactions and learning parameters. We find that large learning periods are important in order to improve the network learning capacity and discuss this ability in the presence of distinct inhibitory currents.

  4. Synaptic transmission block by presynaptic injection of oligomeric amyloid beta

    Science.gov (United States)

    Moreno, Herman; Yu, Eunah; Pigino, Gustavo; Hernandez, Alejandro I.; Kim, Natalia; Moreira, Jorge E.; Sugimori, Mutsuyuki; Llinás, Rodolfo R.

    2009-01-01

    Early Alzheimer's disease (AD) pathophysiology is characterized by synaptic changes induced by degradation products of amyloid precursor protein (APP). The exact mechanisms of such modulation are unknown. Here, we report that nanomolar concentrations of intraaxonal oligomeric (o)Aβ42, but not oAβ40 or extracellular oAβ42, acutely inhibited synaptic transmission at the squid giant synapse. Further characterization of this phenotype demonstrated that presynaptic calcium currents were unaffected. However, electron microscopy experiments revealed diminished docked synaptic vesicles in oAβ42-microinjected terminals, without affecting clathrin-coated vesicles. The molecular events of this modulation involved casein kinase 2 and the synaptic vesicle rapid endocytosis pathway. These findings open the possibility of a new therapeutic target aimed at ameliorating synaptic dysfunction in AD. PMID:19304802

  5. Presynaptic inhibition of spontaneous acetylcholine release induced by adenosine at the mouse neuromuscular junction.

    Science.gov (United States)

    De Lorenzo, Silvana; Veggetti, Mariela; Muchnik, Salomón; Losavio, Adriana

    2004-05-01

    1. At the mouse neuromuscular junction, adenosine (AD) and the A(1) agonist 2-chloro-N(6)-cyclopentyl-adenosine (CCPA) induce presynaptic inhibition of spontaneous acetylcholine (ACh) release by activation of A(1) AD receptors through a mechanism that is still unknown. To evaluate whether the inhibition is mediated by modulation of the voltage-dependent calcium channels (VDCCs) associated with tonic secretion (L- and N-type VDCCs), we measured the miniature end-plate potential (mepp) frequency in mouse diaphragm muscles. 2. Blockade of VDCCs by Cd(2+) prevented the effect of the CCPA. Nitrendipine (an L-type VDCC antagonist) but not omega-conotoxin GVIA (an N-type VDCC antagonist) blocked the action of CCPA, suggesting that the decrease in spontaneous mepp frequency by CCPA is associated with an action on L-type VDCCs only. 3. As A(1) receptors are coupled to a G(i/o) protein, we investigated whether the inhibition of PKA or the activation of PKC is involved in the presynaptic inhibition mechanism. Neither N-(2[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide (H-89, a PKA inhibitor), nor 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine (H-7, a PKC antagonist), nor phorbol 12-myristate 13-acetate (PHA, a PKC activator) modified CCPA-induced presynaptic inhibition, suggesting that these second messenger pathways are not involved. 4. The effect of CCPA was eliminated by the calmodulin antagonist N-(6-aminohexil)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) and by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-acetoxymethyl ester epsilon6TDelta-BM, which suggests that the action of CCPA to modulate L-type VDCCs may involve Ca(2+)-calmodulin. 5. To investigate the action of CCPA on diverse degrees of nerve terminal depolarization, we studied its effect at different external K(+) concentrations. The effect of CCPA on ACh secretion evoked by 10 mm K(+) was prevented by the P/Q-type VDCC antagonist omega-agatoxin IVA. 6. CCPA failed to

  6. How do different components of Effortful Control contribute to children's mathematics achievement?

    Science.gov (United States)

    Sánchez-Pérez, Noelia; Fuentes, Luis J; Pina, Violeta; López-López, Jose A; González-Salinas, Carmen

    2015-01-01

    This work sought to investigate the specific contribution of two different components of Effortful Control (EC) -attentional focusing (AF) and inhibitory control- to children's mathematics achievement. The sample was composed of 142 children aged 9-12 year-old. EC components were measured through the Temperament in Middle Childhood Questionnaire (TMCQ; parent's report); math achievement was measured via teacher's report and through the standard Woodcock-Johnson test. Additionally, the contribution of other cognitive and socio-emotional processes was taken into account. Our results showed that only AF significantly contributed to the variance of children's mathematics achievement; interestingly, mediational models showed that the relationship between effortful attentional self-regulation and mathematics achievement was mediated by academic peer popularity, as well as by intelligence and study skills. Results are discussed in the light of the current theories on the role of children's self-regulation abilities in the context of school.

  7. Phosphorylation of synaptotagmin-1 controls a post-priming step in PKC-dependent presynaptic plasticity

    DEFF Research Database (Denmark)

    de Jong, Arthur P H; Meijer, Marieke; Saarloos, Ingrid

    2016-01-01

    Presynaptic activation of the diacylglycerol (DAG)/protein kinase C (PKC) pathway is a central event in short-term synaptic plasticity. Two substrates, Munc13-1 and Munc18-1, are essential for DAG-induced potentiation of vesicle priming, but the role of most presynaptic PKC substrates is not unde......Presynaptic activation of the diacylglycerol (DAG)/protein kinase C (PKC) pathway is a central event in short-term synaptic plasticity. Two substrates, Munc13-1 and Munc18-1, are essential for DAG-induced potentiation of vesicle priming, but the role of most presynaptic PKC substrates...... is not understood. Here, we show that a mutation in synaptotagmin-1 (Syt1(T112A)), which prevents its PKC-dependent phosphorylation, abolishes DAG-induced potentiation of synaptic transmission in hippocampal neurons. This mutant also reduces potentiation of spontaneous release, but only if alternative Ca(2+)sensors...

  8. New Treatments for Drug-Resistant Epilepsy that Target Presynaptic Transmitter Release

    Science.gov (United States)

    2015-07-01

    may become a key piece in the arsenal of antiepileptic drugs in mesial temporal lobe epilepsy . Thereby, screening for a presynaptic action site may be...neuronal damage, mesial temporal lobe epilepsy (MTLE) in ~30% of patients, and resistance to available anticonvulsant drugs. Therefore, it is of... temporal lobe epilepsy (MTLE) (months 1-12). Working hypothesis: Drugs acting on presynaptic Ca 2+ channels, autoreceptors, and SV2a will be more

  9. Protein dynamics during presynaptic complex assembly on individual ssDNA molecules

    OpenAIRE

    Gibb, Bryan; Ye, Ling F.; Kwon, YoungHo; Niu, Hengyao; Sung, Patrick; Greene, Eric C.

    2014-01-01

    Homologous recombination is a conserved pathway for repairing double?stranded breaks, which are processed to yield single?stranded DNA overhangs that serve as platforms for presynaptic complex assembly. Here we use single?molecule imaging to reveal the interplay between Saccharomyce cerevisiae RPA, Rad52, and Rad51 during presynaptic complex assembly. We show that Rad52 binds RPA?ssDNA and suppresses RPA turnover, highlighting an unanticipated regulatory influence on protein dynamics. Rad51 b...

  10. Sociodemographic differences in fears and mistrust contributing to unwillingness to participate in cancer screenings

    OpenAIRE

    Davis, Jenna L.; Bynum, Shalanda A.; Katz, Ralph V.; Buchanan, Kyrel; Green, B. Lee

    2012-01-01

    Effective provider-patient relationships are vital for positive patient health outcomes. This analysis assessed sociodemographic differences in fears and mistrust related to the provider-patient relationship, which may contribute to unwillingness to participate in cancer screenings (CSs). The data are from a stratified, random-digit dial telephone questionnaire of non-institutionalized households in New York, Maryland, and Puerto Rico. Statistically significant results indicate that Hispanics...

  11. The contribution of general cognitive abilities and number abilities to different aspects of mathematics in children.

    Science.gov (United States)

    Träff, Ulf

    2013-10-01

    This study examined the relative contributions of general cognitive abilities and number abilities to word problem solving, calculation, and arithmetic fact retrieval in a sample of 134 children aged 10 to 13 years. The following tasks were administered: listening span, visual matrix span, verbal fluency, color naming, Raven's Progressive Matrices, enumeration, number line estimation, and digit comparison. Hierarchical multiple regressions demonstrated that number abilities provided an independent contribution to fact retrieval and word problem solving. General cognitive abilities contributed to problem solving and calculation. All three number tasks accounted for a similar amount of variance in fact retrieval, whereas only the number line estimation task contributed unique variance in word problem solving. Verbal fluency and Raven's matrices accounted for an equal amount of variance in problem solving and calculation. The current findings demonstrate, in accordance with Fuchs and colleagues' developmental model of mathematical learning (Developmental Psychology, 2010, Vol. 46, pp. 1731-1746), that both number abilities and general cognitive abilities underlie 10- to 13-year-olds' proficiency in problem solving, whereas only number abilities underlie arithmetic fact retrieval. Thus, the amount and type of cognitive contribution to arithmetic proficiency varies between the different aspects of arithmetic. Furthermore, how closely linked a specific aspect of arithmetic is to the whole number representation systems is not the only factor determining the amount and type of cognitive contribution in 10- to 13-year-olds. In addition, the mathematical complexity of the task appears to influence the amount and type of cognitive support. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Strontium, barium, and manganese metabolism in isolated presynaptic nerve terminals

    International Nuclear Information System (INIS)

    Rasgado-Flores, H.; Sanchez-Armass, S.; Blaustein, M.P.; Nachshen, D.A.

    1987-01-01

    To gain insight into the mechanisms by which the divalent cations Sr, Ba, and Mn affect neurotransmitter release from presynaptic nerve terminals, the authors examined the sequestration of these cations, ion comparison to Ca, by mitochondrial and nonmitochondrial organelles and the extrusion of these cations from isolated nerve terminals. Sequestration was studied in synaptosomes made leaky to small ions by treatment with saponin; efflux was examined in intact synaptosomes that were preloaded with the divalent cations by incubation in depolarizing (K rich) media. The selectivity sequence for ATP-dependent mitochondrial uptake that they observed was Mn>>Ca>Sr>>Ba, whereas that for the SER was Ca ≥ Mn>Sr>>Ba. When synaptosomes that were preloaded with divalent cations were incubated in Na- and Ca-free media, there was little efflux of 45 Ca, 133 Ba, 85 Sr, or 54 Mn. When the incubation was carried out in media containing Na without Ca, there was substantial stimulation of Ca and Sr efflux, but only slight stimulation of Ba or Mn efflux. In Na-free media, the addition of 1 mM Ca promoted the efflux of all four divalent cations, probably via Ca-divalent cation exchange. In summary, the sequestration and extrusion data suggest that, with equal loads, Mn will be buffered to the greatest extent, whereas Ba will be least well buffered. These results may help to explain why Mn has a very long-lasting effect on transmitter release, while the effect of Sr is much briefer

  13. Presynaptic localization of histamine H3-receptors in rat brain

    International Nuclear Information System (INIS)

    Fujimoto, K.; Mizuguchi, H.; Fukui, H.; Wada, H.

    1991-01-01

    The localization of histamine H3-receptors in subcellular fractions from the rat brain was examined in a [3H] (R) alpha-methylhistamine binding assay and compared with those of histamine H1- and adrenaline alpha 1- and alpha 2-receptors. Major [3H](R) alpha-methylhistamine binding sites with increased specific activities ([3H]ligand binding vs. protein amount) were recovered from the P2 fraction by differential centrifugation. Minor [3H](R)alpha-methylhistamine binding sites with increased specific activities were also detected in the P3 fraction. Further subfractionation of the P2 fraction by discontinuous sucrose density gradient centrifugation showed major recoveries of [3H](R)alpha-methylhistamine binding in myelin (MYE) and synaptic plasma membrane (SPM) fractions. A further increase in specific activity was observed in the MYE fraction, but the SPM fraction showed no significant increase in specific activity. Adrenaline alpha 2-receptors, the pre-synaptic autoreceptors, in a [3H] yohimbine binding assay showed distribution patterns similar to histamine H3-receptors. On the other hand, post-synaptic histamine H1- and adrenaline alpha 1-receptors were closely localized and distributed mainly in the SPM fraction with increased specific activity. Only a negligible amount was recovered in the MYE fraction, unlike the histamine H3- and adrenaline alpha 2-receptors

  14. Nondestructive Estimation of Muscle Contributions to STS Training with Different Loadings Based on Wearable Sensor System.

    Science.gov (United States)

    Liu, Kun; Liu, Yong; Yan, Jianchao; Sun, Zhenyuan

    2018-03-25

    Partial body weight support or loading sit-to-stand (STS) rehabilitation can be useful for persons with lower limb dysfunction to achieve movement again based on the internal residual muscle force and external assistance. To explicate how the muscles contribute to the kinetics and kinematics of STS performance by non-invasive in vitro detection and to nondestructively estimate the muscle contributions to STS training with different loadings, a wearable sensor system was developed with ground reaction force (GRF) platforms, motion capture inertial sensors and electromyography (EMG) sensors. To estimate the internal moments of hip, knee and ankle joints and quantify the contributions of individual muscle and gravity to STS movement, the inverse dynamics analysis on a simplified STS biomechanical model with external loading is proposed. The functional roles of the lower limb individual muscles (rectus femoris (RF), gluteus maximus (GM), vastus lateralis (VL), tibialis anterior (TA) and gastrocnemius (GAST)) during STS motion and the mechanism of the muscles' synergies to perform STS-specific subtasks were analyzed. The muscle contributions to the biomechanical STS subtasks of vertical propulsion, anteroposterior (AP) braking and propulsion for body balance in the sagittal plane were quantified by experimental studies with EMG, kinematic and kinetic data.

  15. Urban PM in Eastern Germany: Source apportionment and contributions from different spatial scales

    Science.gov (United States)

    van Pinxteren, D.; Fomba, K. W.; Mothes, F.; Spindler, G.; Herrmann, H.

    2017-12-01

    Understanding the contributions of particulate matter (PM) sources and the source areas impacting total PM levels in a city are important requirements for further developing clean air policies and efficient abatement strategies. This presentation reports on two studies in Eastern Germany providing a detailed picture of present-day urban PM sources and discriminating contributions of local, regional and long-range sources. The "Leipzig Aerosol 2013-15" study yielded contributions of 12 sources to coarse, fine, and ultrafine particles, resolved by Positive Matrix Factorization (PMF) from comprehensive chemical speciation of 5-stage Berner impactor samples at 4 different sites in the Leipzig area. Dominant winter-time sources were traffic exhaust and non-exhaust emissions, secondary aerosol formation, and combustion emissions from both biomass and coal burning with different relative importance in different particle size ranges. Local sources dominated PM levels in ultrafine and coarse particles (60% - 80%) while high mass concentrations in accumulation mode particles mainly resulted from regional import into the city (70%). The "PM-East" study compiled PM10 mass and constituents' concentrations at 10 urban and rural sites in Eastern Germany during winter 2016/17, which included a 3-week episode of frequent exceedances of the PM10 limit value. PMF source apportionment is performed for a subset of the sites, including the city of Berlin. Contributions from short-, mid-, and long-range sources, including trans-boundary pollution import from neighbouring countries, are quantitatively assessed by advanced back trajectory statistical methods. Data analysis in PM-East is ongoing and final results will be available by November. Funding is acknowledged from 4 federal states of Germany: Berlin Senate Department for Environment, Transport and Climate Protection; Saxon State Office for Environment, Agriculture and Geology; State Agency for Environment, Nature Conservation and

  16. Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart

    Energy Technology Data Exchange (ETDEWEB)

    Mongillo, Marco; Leccisotti, Lucia [Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, Imperial College Faculty of Medicine, London (United Kingdom); John, Anna S. [Hammersmith Hospital, National Heart and Lung Institute, Imperial College, London (United Kingdom); Pennell, Dudley J. [Royal Brompton Hospital, National Heart and Lung Institute, Imperial College, London (United Kingdom); Camici, Paolo G. [Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, Imperial College Faculty of Medicine, London (United Kingdom); Hammersmith Hospital, National Heart and Lung Institute, Imperial College, London (United Kingdom)

    2007-08-15

    We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic {beta}-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF. Eight patients (aged 67 {+-} 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 {+-} 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with {sup 18}F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [{sup 11}C]meta-hydroxy-ephedrine (HED) volume of distribution (V{sub d}) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 {+-} 4 years, p < 0.01 vs patients) and HED (n = 8, aged 40 {+-} 6 years, p < 0.01 vs patients) data. MGU in patients was reduced in both normal remote (0.44 {+-} 0.14 {mu}mol.min{sup -1}.g{sup -1}) and dysfunctional (0.49 {+-} 0.14 {mu}mol.min{sup -1}.g{sup -1}) segments compared with controls (0.61 {+-} 0.7 {mu}mol.min{sup -1}.g{sup -1}; p < 0.001 vs both). HED V{sub d} was reduced in dysfunctional segments of patients (38.9 {+-} 21.2 ml.g{sup -1}) compared with normal segments (52.2 {+-} 19.6 ml.g{sup -1}) and compared with controls (62.7 {+-} 11.3 ml.g{sup -1}). In patients, regional MGU was correlated with HED V{sub d}. The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts. (orig.)

  17. The contribution of major diagnostic causes to socioeconomic differences in disability retirement.

    Science.gov (United States)

    Polvinen, Anu; Laaksonen, Mikko; Gould, Raija; Lahelma, Eero; Martikainen, Pekka

    2014-07-01

    The aim of this study was twofold: to investigate socioeconomic differences in disability retirement (DR) due to major diseases and find out which diseases contribute most to the overall socioeconomic differences in DR. The data were longitudinal register-based (10% sample of Finns) from Statistics Finland. These data included 258 428 participants aged 35-64 years during the follow-up. The participants were employed or unemployed before the follow-up period 1997-2010. Of all participants, 14 303 men and 13 188 women ended up in DR during the follow-up. Socioeconomic status was categorized into upper- and lower-class non-manual employees, manual workers, and self-employed persons. Cox models were used to estimate hazard ratios for DR due to different diseases. Compared to upper-class non-manual employees, DR was especially high for manual workers whose retirement diagnoses included psychoactive substance use, musculoskeletal diseases (MSD), or cardiovascular diseases. Socioeconomic differences in DR were stronger for younger age groups and men versus women. For females and males, the largest part of the excess DR among manual workers compared to upper-class non-manual employees was due to MSD. In the age group 54-64 years, the contribution of MSD to the total excess was >50% among male manual workers and 75% among female manual workers. Excess DR due to mental disorders concerned only 35-54-year-old manual workers (among 23% men and 26% women). The contribution of MSD to the total excess DR among lower socioeconomic groups was large. Prevention of MSD among manual workers would likely reduce socioeconomic differences in DR.

  18. Variability in source sediment contributions by applying different statistic test for a Pyrenean catchment.

    Science.gov (United States)

    Palazón, L; Navas, A

    2017-06-01

    Information on sediment contribution and transport dynamics from the contributing catchments is needed to develop management plans to tackle environmental problems related with effects of fine sediment as reservoir siltation. In this respect, the fingerprinting technique is an indirect technique known to be valuable and effective for sediment source identification in river catchments. Large variability in sediment delivery was found in previous studies in the Barasona catchment (1509 km 2 , Central Spanish Pyrenees). Simulation results with SWAT and fingerprinting approaches identified badlands and agricultural uses as the main contributors to sediment supply in the reservoir. In this study the Kruskal-Wallis H-test and (3) principal components analysis. Source contribution results were different between assessed options with the greatest differences observed for option using #3, including the two step process: principal components analysis and discriminant function analysis. The characteristics of the solutions by the applied mixing model and the conceptual understanding of the catchment showed that the most reliable solution was achieved using #2, the two step process of Kruskal-Wallis H-test and discriminant function analysis. The assessment showed the importance of the statistical procedure used to define the optimum composite fingerprint for sediment fingerprinting applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Seeing the same thing differently: mechanisms that contribute to assessor differences in directly-observed performance assessments.

    Science.gov (United States)

    Yeates, Peter; O'Neill, Paul; Mann, Karen; Eva, Kevin

    2013-08-01

    Assessors' scores in performance assessments are known to be highly variable. Attempted improvements through training or rating format have achieved minimal gains. The mechanisms that contribute to variability in assessors' scoring remain unclear. This study investigated these mechanisms. We used a qualitative approach to study assessors' judgements whilst they observed common simulated videoed performances of junior doctors obtaining clinical histories. Assessors commented concurrently and retrospectively on performances, provided scores and follow-up interviews. Data were analysed using principles of grounded theory. We developed three themes that help to explain how variability arises: Differential Salience-assessors paid attention to (or valued) different aspects of the performances to different degrees; Criterion Uncertainty-assessors' criteria were differently constructed, uncertain, and were influenced by recent exemplars; Information Integration-assessors described the valence of their comments in their own unique narrative terms, usually forming global impressions. Our results (whilst not precluding the operation of established biases) describe mechanisms by which assessors' judgements become meaningfully-different or unique. Our results have theoretical relevance to understanding the formative educational messages that performance assessments provide. They give insight relevant to assessor training, assessors' ability to be observationally "objective" and to the educational value of narrative comments (in contrast to numerical ratings).

  20. Whereas Short-Term Facilitation Is Presynaptic, Intermediate-Term Facilitation Involves Both Presynaptic and Postsynaptic Protein Kinases and Protein Synthesis

    Science.gov (United States)

    Jin, Iksung; Kandel, Eric R.; Hawkins, Robert D.

    2011-01-01

    Whereas short-term plasticity involves covalent modifications that are generally restricted to either presynaptic or postsynaptic structures, long-term plasticity involves the growth of new synapses, which by its nature involves both pre- and postsynaptic alterations. In addition, an intermediate-term stage of plasticity has been identified that…

  1. Gender differences in contributions of emotion to psychopathy and antisocial personality disorder.

    Science.gov (United States)

    Rogstad, Jill E; Rogers, Richard

    2008-12-01

    Traditional conceptualizations of psychopathy highlight the importance of affective features as they relate to social deviance; however, little empirical research has actually investigated specific roles of emotion and emotion processing with respect to antisocial conduct. Antisocial personality disorder (APD), prevalent in forensic populations, is commonly associated with psychopathy despite the notable omission of such core affective features in its diagnosis. In this paper, we review the empirical literature on the contribution of emotion to psychopathy and APD, highlighting in particular research on emotion processing and various facets of emotional expression, including empathy and alexithymia. Research findings are discussed on gender differences in emotional functioning and their likely effects on the assessment of psychopathy and APD. Given the known gender differences in the expressions of emotion, the article concludes with recommendations to bridge research for different offender groups, including psychopathy and APD.

  2. Individual differences in memory span: the contribution of rehearsal, access to lexical memory, and output speed.

    Science.gov (United States)

    Tehan, G; Lalor, D M

    2000-11-01

    Rehearsal speed has traditionally been seen to be the prime determinant of individual differences in memory span. Recent studies, in the main using young children as the subject population, have suggested other contributors to span performance, notably contributions from long-term memory and forgetting and retrieval processes occurring during recall. In the current research we explore individual differences in span with respect to measures of rehearsal, output time, and access to lexical memory. We replicate standard short-term phenomena; we show that the variables that influence children's span performance influence adult performance in the same way; and we show that lexical memory access appears to be a more potent source of individual differences in span than either rehearsal speed or output factors.

  3. The translational regulator Cup controls NMJ presynaptic terminal morphology.

    Science.gov (United States)

    Menon, Kaushiki P; Carrillo, Robert A; Zinn, Kai

    2015-07-01

    During oogenesis and early embryonic development in Drosophila, translation of proteins from maternally deposited mRNAs is tightly controlled. We and others have previously shown that translational regulatory proteins that function during oogenesis also have essential roles in the nervous system. Here we examine the role of Cup in neuromuscular system development. Maternal Cup controls translation of localized mRNAs encoding the Oskar and Nanos proteins and binds to the general translation initiation factor eIF4E. In this paper, we show that zygotic Cup protein is localized to presynaptic terminals at larval neuromuscular junctions (NMJs). cup mutant NMJs have strong phenotypes characterized by the presence of small clustered boutons called satellite boutons. They also exhibit an increase in the frequency of spontaneous glutamate release events (mEPSPs). Reduction of eIF4E expression synergizes with partial loss of Cup expression to produce satellite bouton phenotypes. The presence of satellite boutons is often associated with increases in retrograde bone morphogenetic protein (BMP) signaling, and we show that synaptic BMP signaling is elevated in cup mutants. cup genetically interacts with two genes, EndoA and Dap160, that encode proteins involved in endocytosis that are also neuronal modulators of the BMP pathway. Endophilin protein, encoded by the EndoA gene, is downregulated in a cup mutant. Our results are consistent with a model in which Cup and eIF4E work together to ensure efficient localization and translation of endocytosis proteins in motor neurons and control the strength of the retrograde BMP signal. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. How do different components of Effortful Control contribute to children's mathematics achievement?

    Directory of Open Access Journals (Sweden)

    Noelia eSánchez-Pérez

    2015-09-01

    Full Text Available This work sought to investigate the specific contribution of two different components of Effortful Control -attentional focusing and inhibitory control- to children’s mathematics achievement. The sample was composed of 142 children aged 9 to 12 years old. Effortful Control components were measured through the Temperament in Middle Childhood Questionnaire (TMCQ; parent´s report; math achievement was measured via teacher’s report and through the standard Woodcock-Johnson test. Additionally, the contribution of other cognitive and socio-emotional processes was taken into account. Our results showed that only attentional focusing significantly contributed to the variance of children’s mathematics achievement; interestingly, mediational models showed that the relationship between effortful attentional self-regulation and mathematics achievement was mediated by academic peer popularity, as well as by intelligence and study skills. Results are discussed in the light of the current theories on the role of children’ self-regulation abilities in the context of school.

  5. How do different components of Effortful Control contribute to children’s mathematics achievement?

    Science.gov (United States)

    Sánchez-Pérez, Noelia; Fuentes, Luis J.; Pina, Violeta; López-López, Jose A.; González-Salinas, Carmen

    2015-01-01

    This work sought to investigate the specific contribution of two different components of Effortful Control (EC) -attentional focusing (AF) and inhibitory control- to children’s mathematics achievement. The sample was composed of 142 children aged 9–12 year-old. EC components were measured through the Temperament in Middle Childhood Questionnaire (TMCQ; parent’s report); math achievement was measured via teacher’s report and through the standard Woodcock–Johnson test. Additionally, the contribution of other cognitive and socio-emotional processes was taken into account. Our results showed that only AF significantly contributed to the variance of children’s mathematics achievement; interestingly, mediational models showed that the relationship between effortful attentional self-regulation and mathematics achievement was mediated by academic peer popularity, as well as by intelligence and study skills. Results are discussed in the light of the current theories on the role of children’s self-regulation abilities in the context of school. PMID:26441758

  6. Actin and microtubule networks contribute differently to cell response for small and large strains

    Science.gov (United States)

    Kubitschke, H.; Schnauss, J.; Nnetu, K. D.; Warmt, E.; Stange, R.; Kaes, J.

    2017-09-01

    Cytoskeletal filaments provide cells with mechanical stability and organization. The main key players are actin filaments and microtubules governing a cell’s response to mechanical stimuli. We investigated the specific influences of these crucial components by deforming MCF-7 epithelial cells at small (≤5% deformation) and large strains (>5% deformation). To understand specific contributions of actin filaments and microtubules, we systematically studied cellular responses after treatment with cytoskeleton influencing drugs. Quantification with the microfluidic optical stretcher allowed capturing the relative deformation and relaxation of cells under different conditions. We separated distinctive deformational and relaxational contributions to cell mechanics for actin and microtubule networks for two orders of magnitude of drug dosages. Disrupting actin filaments via latrunculin A, for instance, revealed a strain-independent softening. Stabilizing these filaments by treatment with jasplakinolide yielded cell softening for small strains but showed no significant change at large strains. In contrast, cells treated with nocodazole to disrupt microtubules displayed a softening at large strains but remained unchanged at small strains. Stabilizing microtubules within the cells via paclitaxel revealed no significant changes for deformations at small strains, but concentration-dependent impact at large strains. This suggests that for suspended cells, the actin cortex is probed at small strains, while at larger strains; the whole cell is probed with a significant contribution from the microtubules.

  7. Human immunodeficiency virus-1 protein Tat induces excitotoxic loss of presynaptic terminals in hippocampal cultures.

    Science.gov (United States)

    Shin, Angela H; Thayer, Stanley A

    2013-05-01

    Human immunodeficiency virus (HIV) infection of the CNS produces dendritic damage that correlates with cognitive decline in patients with HIV-associated neurocognitive disorders (HAND). HIV-induced neurotoxicity results in part from viral proteins shed from infected cells, including the HIV transactivator of transcription (Tat). We previously showed that Tat binds to the low density lipoprotein receptor-related protein (LRP), resulting in overactivation of NMDA receptors, activation of the ubiquitin-proteasome pathway, and subsequent loss of postsynaptic densities. Here, we show that Tat also induces a loss of presynaptic terminals. The number of presynaptic terminals was quantified using confocal imaging of synaptophysin fused to green fluorescent protein (Syn-GFP). Tat-induced loss of presynaptic terminals was secondary to excitatory postsynaptic mechanisms because treatment with an LRP antagonist or an NMDA receptor antagonist inhibited this loss. Treatment with nutlin-3, an E3 ligase inhibitor, prevented Tat-induced loss of presynaptic terminals. These data suggest that Tat-induced loss of presynaptic terminals is a consequence of excitotoxic postsynaptic activity. We previously found that ifenprodil, an NR2B subunit-selective NMDA receptor antagonist, induced recovery of postsynaptic densities. Here we show that Tat-induced loss of presynaptic terminals was reversed by ifenprodil treatment. Thus, Tat-induced loss of presynaptic terminals is reversible, and this recovery can be initiated by inhibiting a subset of postsynaptic NMDA receptors. Understanding the dynamics of synaptic changes in response to HIV infection of the CNS may lead to the design of improved pharmacotherapies for HAND patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Synapse Formation in Monosynaptic Sensory–Motor Connections Is Regulated by Presynaptic Rho GTPase Cdc42

    Science.gov (United States)

    Imai, Fumiyasu; Ladle, David R.; Leslie, Jennifer R.; Duan, Xin; Rizvi, Tilat A.; Ciraolo, Georgianne M.; Zheng, Yi

    2016-01-01

    Spinal reflex circuit development requires the precise regulation of axon trajectories, synaptic specificity, and synapse formation. Of these three crucial steps, the molecular mechanisms underlying synapse formation between group Ia proprioceptive sensory neurons and motor neurons is the least understood. Here, we show that the Rho GTPase Cdc42 controls synapse formation in monosynaptic sensory–motor connections in presynaptic, but not postsynaptic, neurons. In mice lacking Cdc42 in presynaptic sensory neurons, proprioceptive sensory axons appropriately reach the ventral spinal cord, but significantly fewer synapses are formed with motor neurons compared with wild-type mice. Concordantly, electrophysiological analyses show diminished EPSP amplitudes in monosynaptic sensory–motor circuits in these mutants. Temporally targeted deletion of Cdc42 in sensory neurons after sensory–motor circuit establishment reveals that Cdc42 does not affect synaptic transmission. Furthermore, addition of the synaptic organizers, neuroligins, induces presynaptic differentiation of wild-type, but not Cdc42-deficient, proprioceptive sensory neurons in vitro. Together, our findings demonstrate that Cdc42 in presynaptic neurons is required for synapse formation in monosynaptic sensory–motor circuits. SIGNIFICANCE STATEMENT Group Ia proprioceptive sensory neurons form direct synapses with motor neurons, but the molecular mechanisms underlying synapse formation in these monosynaptic sensory–motor connections are unknown. We show that deleting Cdc42 in sensory neurons does not affect proprioceptive sensory axon targeting because axons reach the ventral spinal cord appropriately, but these neurons form significantly fewer presynaptic terminals on motor neurons. Electrophysiological analysis further shows that EPSPs are decreased in these mice. Finally, we demonstrate that Cdc42 is involved in neuroligin-dependent presynaptic differentiation of proprioceptive sensory neurons in vitro

  9. Contribution of Binaural Masking Release to Improved Speech Intelligibility for different Masker types.

    Science.gov (United States)

    Sutojo, Sarinah; van de Par, Steven; Schoenmaker, Esther

    2018-06-01

    In situations with competing talkers or in the presence of masking noise, speech intelligibility can be improved by spatially separating the target speaker from the interferers. This advantage is generally referred to as spatial release from masking (SRM) and different mechanisms have been suggested to explain it. One proposed mechanism to benefit from spatial cues is the binaural masking release, which is purely stimulus driven. According to this mechanism, the spatial benefit results from differences in the binaural cues of target and masker, which need to appear simultaneously in time and frequency to improve the signal detection. In an alternative proposed mechanism, the differences in the interaural cues improve the segregation of auditory streams, a process, which involves top-down processing rather than being purely stimulus driven. Other than the cues that produce binaural masking release, the interaural cue differences between target and interferer required to improve stream segregation do not have to appear simultaneously in time and frequency. This study is concerned with the contribution of binaural masking release to SRM for three masker types that differ with respect to the amount of energetic masking they exert. Speech intelligibility was measured, employing a stimulus manipulation that inhibits binaural masking release, and analyzed with a metric to account for the number of better-ear glimpses. Results indicate that the contribution of the stimulus-driven binaural masking release plays a minor role while binaural stream segregation and the availability of glimpses in the better ear had a stronger influence on improving the speech intelligibility. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. In vitro culture may be the major contributing factor for transgenic versus nontransgenic proteomic plant differences.

    Science.gov (United States)

    Fonseca, Cátia; Planchon, Sébastien; Serra, Tânia; Chander, Subhash; Saibo, Nelson J M; Renaut, Jenny; Oliveira, M Margarida; Batista, Rita

    2015-01-01

    Identification of differences between genetically modified plants and their original counterparts plays a central role in risk assessment strategy. Our main goal was to better understand the relevance of transgene presence, genetic, and epigenetic changes induced by transgene insertion, and in vitro culture in putative unintended differences between a transgenic and its comparator. Thus, we have used multiplex fluorescence 2DE coupled with MS to characterize the proteome of three different rice lines (Oryza sativa L. ssp. japonica cv. Nipponbare): a control conventional line (C), an Agrobacterium-transformed transgenic line (Ta) and a negative segregant (NSb). We observed that Ta and NSb appeared identical (with only one spot differentially abundant--fold difference ≥ 1.5), contrasting with the control (49 spots with fold difference ≥ 1.5, in both Ta and NSb vs. control). Given that in vitro culture was the only event in common between Ta and NSb, we hypothesize that in vitro culture stress was the most relevant condition contributing for the observed proteomic differences. MS protein identification support our hypothesis, indicating that Ta and NSb lines adjusted their metabolic pathways and altered the abundance of several stress related proteins in order to cope with in vitro culture. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Decarbonising the power sector via technological change – differing contributions from heterogeneous firms

    International Nuclear Information System (INIS)

    Schmidt, Tobias S.; Schneider, Malte; Hoffmann, Volker H.

    2012-01-01

    In the power sector, technological change is a key lever to address the decarbonisation needed to avoid dangerous climate change. Policy makers aim to accelerate and redirect technological change by targeting relevant firms via climate policy, e.g., the European Union Emissions Trading System (EU ETS), and climate-relevant technology policies, e.g., feed-in tariffs. Changes in firm's behaviour, i.e., their research and development (R and D) as well as diffusion activities, are at the heart of technological change. However, firms are heterogeneous actors with varying attributes which perceive policy differently. Hence, they can be expected to react very heterogeneously to these new policies. Based on an original dataset of 201 firms, we perform a cluster analysis grouping firms along their R and D and diffusion activity changes. We then compare these clusters with regards to the characteristics of the contained firms. Our analysis results in seven clusters showing very diverse contributions to low-carbon technological change, suggesting potential for policy to become more effective. A comparison of the firms' characteristics allows us to derive indicative recommendations on how to adjust the policy mix in order to induce contributions from most firms in the power sector. - Highlights: ► Firms differ strongly regarding their contribution low-carbon technological change. ► E.g., about 40% of the surveyed firms have not changed their R and D and diffusion activities. ► These observations cast doubt upon the effectiveness of current policy. ► From the findings recommendations for making policy more effective are derived.

  12. Sex differences in hepatic and intestinal contributions to nevirapine biotransformation in rats.

    Science.gov (United States)

    Pinheiro, P F; Marinho, A T; Antunes, A M M; Marques, M M; Pereira, S A; Miranda, J P

    2015-05-25

    The understanding of the intestine contribution to drug biotransformation improved significantly in recent years. However, the sources of inter-individual variability in intestinal drug biotransformation, namely sex-differences, are still elusive. Nevirapine (NVP) is an orally taken anti-HIV drug associated with severe idiosyncratic reactions elicited by toxic metabolites, with women at increased risk. As such, NVP is a good model to assess sex-dimorphic metabolism. The aim of this study was to perform a comparative profiling of NVP biotransformation in rat intestine and liver and evaluate whether or not it is organ- and sex-dependent. Therefore, nevirapine-containing solutions were perfused through the intestine, in a specially designed chamber, or incubated with liver slices, from male and female Wistar rats. The levels of NVP and its Phase I metabolites were quantified by HPLC-UV. Liver incubation experiments yielded the metabolites 2-, 3-, 8-, and 12-OH-NVP, being 12-OH-NVP and 2-OH-NVP the major metabolites in males and females, respectively. Inter-sex differences in the metabolic profile were also detected in the intestine perfusion experiments. Herein, the metabolites 3- and 12-OH-NVP were only found in male rats, whereas 2-OH-NVP levels were higher in females, both in extraluminal (pbiotransformation was observed, strengthening the relevance of the intestinal contribution in the biotransformation of orally taken-drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Individual differences in forced-choice recognition memory: partitioning contributions of recollection and familiarity.

    Science.gov (United States)

    Migo, Ellen M; Quamme, Joel R; Holmes, Selina; Bendell, Andrew; Norman, Kenneth A; Mayes, Andrew R; Montaldi, Daniela

    2014-01-01

    In forced-choice recognition memory, two different testing formats are possible under conditions of high target-foil similarity: Each target can be presented alongside foils similar to itself (forced-choice corresponding; FCC), or alongside foils similar to other targets (forced-choice noncorresponding; FCNC). Recent behavioural and neuropsychological studies suggest that FCC performance can be supported by familiarity whereas FCNC performance is supported primarily by recollection. In this paper, we corroborate this finding from an individual differences perspective. A group of older adults were given a test of FCC and FCNC recognition for object pictures, as well as standardized tests of recall, recognition, and IQ. Recall measures were found to predict FCNC, but not FCC performance, consistent with a critical role for recollection in FCNC only. After the common influence of recall was removed, standardized tests of recognition predicted FCC, but not FCNC performance. This is consistent with a contribution of only familiarity in FCC. Simulations show that a two-process model, where familiarity and recollection make separate contributions to recognition, is 10 times more likely to give these results than a single-process model. This evidence highlights the importance of recognition memory test design when examining the involvement of recollection and familiarity.

  14. Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities

    DEFF Research Database (Denmark)

    Delaissé, Jean-Marie; Andersen, Thomas L; Engsig, Michael T

    2003-01-01

    The best established proteolytic event of osteoclasts is bone matrix solubilization by the cysteine proteinase cathepsin K. Here, however, we draw the attention on osteoclastic activities depending on matrix metalloproteinases (MMPs). We discuss the observations supporting that MMPs contribute...... significantly to bone matrix solubilization in specific areas of the skeleton and in some developmental and pathological situations. Our discussion takes into account (1) the characteristics of the bone remodeling persisting in the absence of cathepsin K, (2) the ultrastructure of the resorption zone...... in response to inactivation of MMPs and of cathepsin K in different bone types, (3) bone resorption levels in MMP knockout mice compared to wild-type mice, (4) the identification of MMPs in osteoclasts and surrounding cells, and (5) the effect of different bone pathologies on the serum concentrations...

  15. Identification of the different magnetic field contributions during a geomagnetic storm in magnetospheric and ground observations

    Directory of Open Access Journals (Sweden)

    T. Alberti

    2016-11-01

    Full Text Available We used the empirical mode decomposition (EMD to investigate the time variation of the magnetospheric and ground-based observations of the Earth's magnetic field during both quiet and disturbed periods. We found two timescale variations in magnetospheric data which are associated with different magnetospheric current systems and the characteristic diurnal orbital variation, respectively. On the ground we identified three timescale variations related to the solar-wind–magnetosphere high-frequency interactions, the ionospheric processes, and the internal dynamics of the magnetosphere. This approach is able to identify the different physical processes involved in solar-wind–magnetosphere–ionosphere coupling. In addition, the large-timescale contribution can be used as a local index for the identification of the intensity of a geomagnetic storm on the ground.

  16. Circuit motifs for contrast-adaptive differentiation in early sensory systems: the role of presynaptic inhibition and short-term plasticity.

    Science.gov (United States)

    Zhang, Danke; Wu, Si; Rasch, Malte J

    2015-01-01

    In natural signals, such as the luminance value across of a visual scene, abrupt changes in intensity value are often more relevant to an organism than intensity values at other positions and times. Thus to reduce redundancy, sensory systems are specialized to detect the times and amplitudes of informative abrupt changes in the input stream rather than coding the intensity values at all times. In theory, a system that responds transiently to fast changes is called a differentiator. In principle, several different neural circuit mechanisms exist that are capable of responding transiently to abrupt input changes. However, it is unclear which circuit would be best suited for early sensory systems, where the dynamic range of the natural input signals can be very wide. We here compare the properties of different simple neural circuit motifs for implementing signal differentiation. We found that a circuit motif based on presynaptic inhibition (PI) is unique in a sense that the vesicle resources in the presynaptic site can be stably maintained over a wide range of stimulus intensities, making PI a biophysically plausible mechanism to implement a differentiator with a very wide dynamical range. Moreover, by additionally considering short-term plasticity (STP), differentiation becomes contrast adaptive in the PI-circuit but not in other potential neural circuit motifs. Numerical simulations show that the behavior of the adaptive PI-circuit is consistent with experimental observations suggesting that adaptive presynaptic inhibition might be a good candidate neural mechanism to achieve differentiation in early sensory systems.

  17. Acetylcholine-induced inhibition of presynaptic calcium signals and transmitter release in the frog neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Eduard Khaziev

    2016-12-01

    Full Text Available Acetylcholine (ACh, released from axonal terminals of motor neurones in neuromuscular junctions regulates the efficacy of neurotransmission through activation of presynaptic nicotinic and muscarinic autoreceptors. Receptor-mediated presynaptic regulation could reflect either direct action on exocytotic machinery or modulation of Ca2+ entry and resulting intra-terminal Ca2+ dynamics. We have measured free intra-terminal cytosolic Ca2+ ([Ca2+]i using Oregon-Green 488 microfluorimetry, in parallel with voltage-clamp recordings of spontaneous (mEPC and evoked (EPC postsynaptic currents in post-junctional skeletal muscle fibre. Activation of presynaptic muscarinic and nicotinic receptors with exogenous acetylcholine and its non-hydrolized analogue carbachol reduced amplitude of the intra-terminal [Ca2+]i transients and decreased quantal content (calculated by dividing the area under EPC curve by the area under mEPC curve. Pharmacological analysis revealed the role of muscarinic receptors of M2 subtype as well as d-tubocurarine-sensitive nicotinic receptor in presynaptic modulation of [Ca2+]i transients. Modulation of synaptic transmission efficacy by ACh receptors was completely eliminated by pharmacological inhibition of N-type Ca2+ channels. We conclude that ACh receptor-mediated reduction of Ca2+ entry into the nerve terminal through N-type Ca2+ channels represents one of possible mechanism of presynaptic modulation in frog neuromuscular junction.

  18. Electrophysiological signals associated with fluency of different levels of processing reveal multiple contributions to recognition memory.

    Science.gov (United States)

    Li, Bingbing; Taylor, Jason R; Wang, Wei; Gao, Chuanji; Guo, Chunyan

    2017-08-01

    Processing fluency appears to influence recognition memory judgements, and the manipulation of fluency, if misattributed to an effect of prior exposure, can result in illusory memory. Although it is well established that fluency induced by masked repetition priming leads to increased familiarity, manipulations of conceptual fluency have produced conflicting results, variously affecting familiarity or recollection. Some recent studies have found that masked conceptual priming increases correct recollection (Taylor & Henson, 2012), and the magnitude of this behavioural effect correlates with analogous fMRI BOLD priming effects in brain regions associated with recollection (Taylor, Buratto, & Henson, 2013). However, the neural correlates and time-courses of masked repetition and conceptual priming were not compared directly in previous studies. The present study used event-related potentials (ERPs) to identify and compare the electrophysiological correlates of masked repetition and conceptual priming and investigate how they contribute to recognition memory. Behavioural results were consistent with previous studies: Repetition primes increased familiarity, whereas conceptual primes increased correct recollection. Masked repetition and conceptual priming also decreased the latency of late parietal component (LPC). Masked repetition priming was associated with an early P200 effect and a later parietal maximum N400 effect, whereas masked conceptual priming was only associated with a central-parietal maximum N400 effect. In addition, the topographic distributions of the N400 repetition priming and conceptual priming effects were different. These results suggest that fluency at different levels of processing is associated with different ERP components, and contributes differentially to subjective recognition memory experiences. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Relative contribution of different altered motor unit control to muscle weakness in stroke: a simulation study

    Science.gov (United States)

    Shin, Henry; Suresh, Nina L.; Zev Rymer, William; Hu, Xiaogang

    2018-02-01

    Objective. Chronic muscle weakness impacts the majority of individuals after a stroke. The origins of this hemiparesis is multifaceted, and an altered spinal control of the motor unit (MU) pool can lead to muscle weakness. However, the relative contribution of different MU recruitment and discharge organization is not well understood. In this study, we sought to examine these different effects by utilizing a MU simulation with variations set to mimic the changes of MU control in stroke. Approach. Using a well-established model of the MU pool, this study quantified the changes in force output caused by changes in MU recruitment range and recruitment order, as well as MU firing rate organization at the population level. We additionally expanded the original model to include a fatigue component, which variably decreased the output force with increasing length of contraction. Differences in the force output at both the peak and fatigued time points across different excitation levels were quantified and compared across different sets of MU parameters. Main results. Across the different simulation parameters, we found that the main driving factor of the reduced force output was due to the compressed range of MU recruitment. Recruitment compression caused a decrease in total force across all excitation levels. Additionally, a compression of the range of MU firing rates also demonstrated a decrease in the force output mainly at the higher excitation levels. Lastly, changes to the recruitment order of MUs appeared to minimally impact the force output. Significance. We found that altered control of MUs alone, as simulated in this study, can lead to a substantial reduction in muscle force generation in stroke survivors. These findings may provide valuable insight for both clinicians and researchers in prescribing and developing different types of therapies for the rehabilitation and restoration of lost strength after stroke.

  20. Otolith signals contribute to inter-individual differences in the perception of gravity-centered space.

    Science.gov (United States)

    Cian, C; Barraud, P A; Paillard, A C; Hidot, S; Denise, P; Ventre-Dominey, J

    2014-03-01

    The aim of the present study was to investigate (1) the relative contribution of the egocentric reference as well as body orientation perception to visual horizon percept during tilt or during increased gravito-inertial acceleration (GiA, hypergravity environment) conditions and (2) the role of vestibular signals in the inter-individual differences observed in these perceptual modalities. Perceptual estimates analysis showed that backward tilt induced (1) an elevation of the visual horizon, (2) an elevation of the egocentric estimation (visual straight ahead) and (3) an overestimation of body tilt. The increase in the magnitude of GiA induced (1) a lowering of the apparent horizon, (2) a lowering of the straight ahead and (3) a perception of backward tilt. Overall, visual horizon percept can be expressed as the combination of body orientation perception and egocentric estimation. When assessing otolith reactivity using off-vertical axis rotation (OVAR), only visual egocentric estimation was significantly correlated with horizontal OVAR performance. On the one hand, we found a correlation between a low modulation amplitude of the otolith responses and straight ahead accuracy when the head axis was tilted relative to gravity. On the other hand, the bias of otolith responses was significantly correlated with straight ahead accuracy when subjects were submitted to an increase in the GiA. Thus, straight ahead sense would be dependent to some extent to otolith function. These results are discussed in terms of the contribution of otolith inputs in the overall multimodal integration subtending spatial constancy.

  1. CONTRIBUTION OF DIFFERENT PARTICLES MEASURED WITH TRACK ETCHED DETECTORS ONBOARD ISS.

    Science.gov (United States)

    Ambrožová, I; Davídková, M; Brabcová, K Pachnerová; Tolochek, R V; Shurshakov, V A

    2017-09-29

    Cosmic radiation consists of primary high-energy galactic and solar particles. When passing through spacecraft walls and astronauts' bodies, the spectrum becomes even more complex due to generating of secondary particles through fragmentation and nuclear interactions. Total radiation exposure is contributed by both these components. With an advantage, space research uses track etched detectors from the group of passive detectors visualizing the tracks of particles, in this case by etching. The detectors can discriminate between various components of cosmic radiation. A method is introduced for the separation of the different types of particles according to their range using track etched detectors. The method is demonstrated using detectors placed in Russian segment of the International Space Station in 2009. It is shown that the primary high-energy heavy ions with long range contribute up to 56% of the absorbed dose and up to 50% to the dose equivalent. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Liver and Muscle Contribute Differently to the Plasma Acylcarnitine Pool During Fasting and Exercise in Humans

    DEFF Research Database (Denmark)

    Xu, G.; Hansen, J S; Zhao, Jian-xin

    2016-01-01

    BACKGROUND: Plasma acylcarnitine levels are elevated by physiological conditions such as fasting and exercise but also in states of insulin resistance and obesity. AIM: To elucidate the contribution of liver and skeletal muscle to plasma acylcarnitines in the fasting state and during exercise...... in humans. METHODS: In 2 independent studies, young healthy males were fasted overnight and performed an acute bout of exercise to investigate either acylcarnitines in skeletal muscle biopsies and arterial-to-venous plasma differences over the exercising and resting leg (n = 9) or the flux over the hepato......-splanchnic bed (n = 10). RESULTS: In the fasting state, a pronounced release of C2- and C3-carnitines from the hepato-splanchnic bed and an uptake of free carnitine by the legs were detected. Exercise further increased the release of C3-carnitine from the hepato-splanchnic bed and the uptake of free carnitine...

  3. The contribution of mediator-based deficiencies to age differences in associative learning.

    Science.gov (United States)

    Dunlosky, John; Hertzog, Christopher; Powell-Moman, Amy

    2005-03-01

    Production, mediational, and utilization deficiencies, which describe how strategy use may contribute to developmental trends in episodic memory, have been intensively investigated. Using a mediator report-and-retrieval method, the authors present evidence concerning the degree to which 2 previously unexplored mediator-based deficits--retrieval and decoding deficiencies--account for age deficits in learning. During study, older and younger adults were instructed to use a strategy (imagery or sentence generation) to associate words within paired associates. They also reported each mediator and later attempted to retrieve each response and the mediator produced at study. Substantial deficits occurred in mediator recall, and small differences were observed in decoding mediators. Mediator recall also accounted for a substantial proportion of the age deficits in criterion recall independently of fluid or crystallized intelligence. Discussion focuses on mediator-based deficiencies and their implications for theories of age deficits in episodic memory. Copyright 2005 APA, all rights reserved.

  4. Estrogen signaling modulates allergic inflammation and contributes to sex differences in asthma.

    Directory of Open Access Journals (Sweden)

    Aleksander eKeselman

    2015-11-01

    Full Text Available Asthma is a chronic airway inflammatory disease that afflicts approximately 300 million people worldwide. It is characterized by airway constriction that leads to wheezing, coughing, and shortness of breath. The most common treatments are corticosteroids and β2-adrenergic receptor antagonists, which target inflammation and airway smooth muscle constriction, respectively. The incidence and severity of asthma is greater in women than in men, and women are more prone to develop corticosteroid-resistant or hard-to-treat asthma. Puberty, menstruation, pregnancy, menopause, and oral contraceptives are known to contribute to disease outcome in women, potentially suggesting a role for estrogen and other hormones impacting allergic inflammation. Currently, the mechanisms underlying these sex differences are poorly understood, although the effect of sex hormones, such as estrogen, on allergic inflammation is gaining interest. Asthma presents as a heterogeneous disease. In typical Th2-type allergic asthma, interleukin-4 and interleukin-13 predominate, driving IgE production and recruitment of eosinophils into the lungs. Chronic Th2-inflammation in the lung results in structural changes and activation of multiple immune cell types, leading to a deterioration of lung function over time. Most immune cells express estrogen receptors (ERα, ERβ, or the membrane-bound G-protein-coupled estrogen receptor to varying degrees and can respond to the hormone. Together these receptors have demonstrated the capacity to regulate a spectrum of immune functions, including adhesion, migration, survival, wound healing, and antibody and cytokine production. This review will cover the current understanding of estrogen signaling in allergic inflammation and discuss how this signaling may contribute to sex differences in asthma and allergy.

  5. Speed and lateral inhibition of stimulus processing contribute to individual differences in Stroop-task performance

    Directory of Open Access Journals (Sweden)

    Marnix eNaber

    2016-06-01

    Full Text Available The Stroop task is a popular neuropsychological test that measures executive control. Strong Stroop interference is commonly interpreted in neuropsychology as a diagnostic marker of an impairment in executive control, possibly reflecting executive dysfunction. However, popular models of the Stroop task indicate that several other aspects of colour and word processing may also account for individual differences in the Stroop task, independent of executive control. Here we use new approaches to investigate the degree to which individual differences in Stroop interference correlate with the relative processing speed of word and colour stimuli, and the lateral inhibition between visual stimuli. We conducted an electrophysiological and behavioural experiment to measure (1 how quickly an individual’s brain processes words and colours presented in isolation (P3 latency, and (2 the strength of an individual’s lateral inhibition between visual representations with a visual illusion. Both measures explained at least 40% of the variance in Stroop interference across individuals. As these measures were obtained in contexts not requiring any executive control, we conclude that the Stroop effect also measures an individual’s pre-set way of processing visual features such as words and colours. This study highlights the important contributions of stimulus processing speed and lateral inhibition to individual differences in Stroop interference, and challenges the general view that the Stroop task primarily assesses executive control.

  6. Speed and Lateral Inhibition of Stimulus Processing Contribute to Individual Differences in Stroop-Task Performance.

    Science.gov (United States)

    Naber, Marnix; Vedder, Anneke; Brown, Stephen B R E; Nieuwenhuis, Sander

    2016-01-01

    The Stroop task is a popular neuropsychological test that measures executive control. Strong Stroop interference is commonly interpreted in neuropsychology as a diagnostic marker of impairment in executive control, possibly reflecting executive dysfunction. However, popular models of the Stroop task indicate that several other aspects of color and word processing may also account for individual differences in the Stroop task, independent of executive control. Here we use new approaches to investigate the degree to which individual differences in Stroop interference correlate with the relative processing speed of word and color stimuli, and the lateral inhibition between visual stimuli. We conducted an electrophysiological and behavioral experiment to measure (1) how quickly an individual's brain processes words and colors presented in isolation (P3 latency), and (2) the strength of an individual's lateral inhibition between visual representations with a visual illusion. Both measures explained at least 40% of the variance in Stroop interference across individuals. As these measures were obtained in contexts not requiring any executive control, we conclude that the Stroop effect also measures an individual's pre-set way of processing visual features such as words and colors. This study highlights the important contributions of stimulus processing speed and lateral inhibition to individual differences in Stroop interference, and challenges the general view that the Stroop task primarily assesses executive control.

  7. Phospho-dependent Accumulation of GABABRs at Presynaptic Terminals after NMDAR Activation.

    Science.gov (United States)

    Hannan, Saad; Gerrow, Kim; Triller, Antoine; Smart, Trevor G

    2016-08-16

    Here, we uncover a mechanism for regulating the number of active presynaptic GABAB receptors (GABABRs) at nerve terminals, an important determinant of neurotransmitter release. We find that GABABRs gain access to axon terminals by lateral diffusion in the membrane. Their relative accumulation is dependent upon agonist activation and the presence of the two distinct sushi domains that are found only in alternatively spliced GABABR1a subunits. Following brief activation of NMDA receptors (NMDARs) using glutamate, GABABR diffusion is reduced, causing accumulation at presynaptic terminals in a Ca(2+)-dependent manner that involves phosphorylation of GABABR2 subunits at Ser783. This signaling cascade indicates how synaptically released glutamate can initiate, via a feedback mechanism, increased levels of presynaptic GABABRs that limit further glutamate release and excitotoxicity. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. How Did Cause of Death Contribute to Racial Differences in Life Expectancy in the United States in 2010?

    Science.gov (United States)

    ... Technical Information Service NCHS How Did Cause of Death Contribute to Racial Differences in Life Expectancy in ... National Vital Statistics System, Mortality. What causes of death influenced the difference in life expectancy between the ...

  9. Expression of presynaptic markers in a neurodevelopmental animal model with relevance to schizophrenia

    DEFF Research Database (Denmark)

    Karlsen, Anna S; Kaalund, Sanne Simone; Møller, Morten

    2013-01-01

    Administration of N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) to rat pups at postnatal day (PND) 7, 9, and 11 [neonatal PCP (neoPCP) model] induces cognitive deficits similar to those observed in schizophrenia. Expression of presynaptic SNARE protein, synaptosomal......-associated protein of 25 kDa (Snap25), has been shown to be downregulated in postmortem brains from patients with schizophrenia. The present study was designed to investigate the long-term effects of neoPCP administration on expression of presynaptic markers altered in schizophrenia. Using radioactive in...

  10. Regulatory changes in presynaptic cholinergic function assessed in rapid autopsy material from patients with Alzheimer disease: Implications for etiology and therapy

    International Nuclear Information System (INIS)

    Slotkin, T.A.; Seidler, F.J.; Crain, B.J.; Bell, J.M.; Bissette, G.; Nemeroff, C.B.

    1990-01-01

    Brain regions from patients with or without Alzheimer disease (AD) were obtained within 2 hr of death and examined for indices of presynaptic cholinergic function. Consistent with loss of cholinergic projections, cerebral cortical areas involved in AD exhibited decreased choline acetyltransferase activity. However, remaining nerve terminals in these regions displayed marked up-regulation of synaptosomal high affinity [ 3 H]choline uptake, a result indicative of relative cholinergic hyperactivity. As choline uptake is also rate-limiting in acetylcholine biosynthesis, these findings have implications for both therapy and identification of causes contributing to neuronal death in AD

  11. Double adjoint method for determining the contribution of composition to reactivity at different times

    International Nuclear Information System (INIS)

    Christie, S.A.; Lathouwers, D.; Kloosterman, J.L.

    2013-01-01

    Highlights: ► The double adjoint method is described. ► System reloading is determined so the multiplication factor behaviour is repeated. ► Both fast and thermal systems behave as desired. ► Allowance must be made for indirect effects in thermal systems. ► An alternative definition of breeding ratio is derived. -- Abstract: The double adjoint method uses the adjoint reactivity and transmutation problems to describe how the system composition is related to the system reactivity at different points in time. Values of the contribution to the reactivity are determined using the adjoint reactivity problem, and these are then used as the source function for the adjoint transmutation problem. The method is applied to the problem of determining the contribution of the beginning of cycle composition to the end of cycle reactivity. It is tested in both fast and thermal systems by comparing the behaviour of the multiplication factor at the end of cycle in calculations with perturbed initial compositions to that predicted by the double adjoint method. The results from the fast system are good, while those from the thermal system are less favourable. This is believed to be due to the method neglecting the coupling between the composition and the flux, which plays a more significant role in thermal systems than fast ones. The importance of correcting for the effects of the fuel compound is also established. The values found are used in calculations to determine the appropriate fuel reloading of the systems tested, with the aim of duplicating the behaviour of the multiplication factor of the original system. Again the fast system gives good results, while the thermal system is less accurate. The double adjoint method is also used for a definition of breeding ratio, and some of the features of this definition are illustrated by examining the effects of different feed materials and reprocessing schemes. The method is shown to be a useful tool for the comparison of the

  12. Comparison study between the effects of different terms contributing to viscous dissipation in saturated porous media

    KAUST Repository

    Salama, Amgad

    2013-02-01

    Some sort of controversy is associated with the problem of viscous dissipation in saturated porous media for which we try to present a comparison study between the influences of the different terms contributing to this phenomenon. We consider viscous dissipation by studying the case of semi-infinite flat plate embedded in saturated porous medium and is kept at constant, higher temperature compared with the surrounding fluid. The fluid is induced to move upwards by natural convection during which viscous dissipation is considered. The boundary layer assumptions are considered to simplify the treatment and to highlight the influencing parameters. The behavior of temperature, and velocity fields in the neighborhood of the vertical flat plate were used to highlight the effects of these parameters. Three terms were considered to contribute to viscous dissipation, namely Darcy\\'s term, the Forchheimer term and Al-Hadharami\\'s term. Although there are no unanimous agreements between researchers to include the Forchhemier term in the dissipation function, some researchers argued it might have an indirect effect and hence for this sake and for completion purposes, we include it in this comparison study. Dimensional considerations reveal that Darcy\\'s term is influenced by Gebhart number, the Forchheimer term is controlled by the non-Darcy parameter and Al-Hadharami\\'s term is influenced by Darcy\\'s number. The governing, non-dimensional set of equations together with the imposed boundary conditions is numerically investigated by finite element method. The results for the details of the governing parameters are presented and investigated. It is found that the irreversible process of transforming the kinetic energy of the moving fluid to heat energy via the viscosity of the moving fluid (i.e., viscous dissipation) is very much influenced by the relative magnitude of these dimensionless parameters. © 2012 Elsevier Masson SAS. All rights reserved.

  13. Presynaptic membrane receptors in acetylcholine release modulation in the neuromuscular synapse.

    Science.gov (United States)

    Tomàs, Josep; Santafé, Manel M; Garcia, Neus; Lanuza, Maria A; Tomàs, Marta; Besalduch, Núria; Obis, Teresa; Priego, Mercedes; Hurtado, Erica

    2014-05-01

    Over the past few years, we have studied, in the mammalian neuromuscular junction (NMJ), the local involvement in transmitter release of the presynaptic muscarinic ACh autoreceptors (mAChRs), purinergic adenosine autoreceptors (P1Rs), and trophic factor receptors (TFRs; for neurotrophins and trophic cytokines) during development and in the adult. At any given moment, the way in which a synapse works is largely the logical outcome of the confluence of these (and other) metabotropic signalling pathways on intracellular kinases, which phosphorylate protein targets and materialize adaptive changes. We propose an integrated interpretation of the complementary function of these receptors in the adult NMJ. The activity of a given receptor group can modulate a given combination of spontaneous, evoked, and activity-dependent release characteristics. For instance, P1Rs can conserve resources by limiting spontaneous quantal leak of ACh (an A1 R action) and protect synapse function, because stimulation with adenosine reduces the magnitude of depression during repetitive activity. The overall outcome of the mAChRs seems to contribute to upkeep of spontaneous quantal output of ACh, save synapse function by decreasing the extent of evoked release (mainly an M2 action), and reduce depression. We have also identified several links among P1Rs, mAChRs, and TFRs. We found a close dependence between mAChR and some TFRs and observed that the muscarinic group has to operate correctly if the tropomyosin-related kinase B receptor (trkB) is also to operate correctly, and vice versa. Likewise, the functional integrity of mAChRs depends on P1Rs operating normally. Copyright © 2014 Wiley Periodicals, Inc.

  14. Contribution of smoking and air pollution exposure in urban areas to social differences in respiratory health

    Directory of Open Access Journals (Sweden)

    Ranft Ulrich

    2008-05-01

    Full Text Available Abstract Background Socio-economic status, smoking, and exposure to increased levels of environmental air pollution are associated with adverse effects on respiratory health. We assessed the contribution of occupational exposures, smoking and outdoor air pollution as competing factors for the association between socio-economic status and respiratory health indicators in a cohort of women from the Ruhr area aged 55 at the time of investigation between 1985 and 1990. Methods Data of 1251 women with spirometry and complete questionnaire information about respiratory diseases, smoking and potential confounders were used in the analyses. Exposure to large-scale air pollution was assessed with data from monitoring stations. Exposure to small-scale air pollution was assessed as traffic-related exposure by distance to the nearest major road. Socio-economic status was defined by educational level. Multiple regression models were used to estimate the contribution of occupational exposures, smoking and outdoor air pollution to social differences in respiratory health. Results Women with less than 10 years of school education in comparison to more than 10 years of school education were more often occupationally exposed (16.4% vs. 10.1%, smoked more often (20.3% vs. 13.9%, and lived more often close to major roads (26.0% vs. 22.9%. Long-term exposure to increased levels of PM10 was significantly associated with lower school education. Women with low school education were more likely to suffer from respiratory symptoms and had reduced lung function. In the multivariate analysis the associations between education and respiratory health attenuated after adjusting for occupational exposure, smoking and outdoor air pollution. The crude odds ratio for the association between the lung function indicator FEV1 less than 80% of predicted value and educational level (10 years of school education was 1.83 (95% CI: 1.22–2.74. This changed to 1.56 (95% CI: 1.03–2

  15. COMPULSORY SOCIAL CONTRIBUTIONS IN DIFFERENT COUNTRIES NOT MEMBERS OF THE EUROPEAN UNION

    Directory of Open Access Journals (Sweden)

    MARINEL NEDELUŢ

    2010-01-01

    Full Text Available A proper understanding of the "details" of the pension system in our country can only be known if the essential, defining characteristics of pension systems in European Union countries and most developed countries in the world. Among the defining elements of any pension scheme among the most important are (a the share of social contributions and (2 tax base. In the present social security contributions will be applied in the following countries are not EU Member States: Albania, Bosnia-Herzegovina, Croatia, Iceland, Macedonia, Moldova, Norway, Russia, Serbia, Montenegro, Turkey, Ukraine, Japan, United States of America. For a better comparison and social security contributions are presented in Romania. In the vast majority of these countries (a base contributions is the gross income, (2 are used to calculate the progressive contribution rates for retirement, particularly in most developed countries, (3 pension contribution is supported both by the employee (employee and employer, almost equally.

  16. Distributional structure in language: contributions to noun-verb difficulty differences in infant word recognition.

    Science.gov (United States)

    Willits, Jon A; Seidenberg, Mark S; Saffran, Jenny R

    2014-09-01

    What makes some words easy for infants to recognize, and other words difficult? We addressed this issue in the context of prior results suggesting that infants have difficulty recognizing verbs relative to nouns. In this work, we highlight the role played by the distributional contexts in which nouns and verbs occur. Distributional statistics predict that English nouns should generally be easier to recognize than verbs in fluent speech. However, there are situations in which distributional statistics provide similar support for verbs. The statistics for verbs that occur with the English morpheme -ing, for example, should facilitate verb recognition. In two experiments with 7.5- and 9.5-month-old infants, we tested the importance of distributional statistics for word recognition by varying the frequency of the contextual frames in which verbs occur. The results support the conclusion that distributional statistics are utilized by infant language learners and contribute to noun-verb differences in word recognition. Copyright © 2014. Published by Elsevier B.V.

  17. Quantifying the relative contributions of different solute carriers to aggregate substrate transport

    Science.gov (United States)

    Taslimifar, Mehdi; Oparija, Lalita; Verrey, Francois; Kurtcuoglu, Vartan; Olgac, Ufuk; Makrides, Victoria

    2017-01-01

    Determining the contributions of different transporter species to overall cellular transport is fundamental for understanding the physiological regulation of solutes. We calculated the relative activities of Solute Carrier (SLC) transporters using the Michaelis-Menten equation and global fitting to estimate the normalized maximum transport rate for each transporter (Vmax). Data input were the normalized measured uptake of the essential neutral amino acid (AA) L-leucine (Leu) from concentration-dependence assays performed using Xenopus laevis oocytes. Our methodology was verified by calculating Leu and L-phenylalanine (Phe) data in the presence of competitive substrates and/or inhibitors. Among 9 potentially expressed endogenous X. laevis oocyte Leu transporter species, activities of only the uniporters SLC43A2/LAT4 (and/or SLC43A1/LAT3) and the sodium symporter SLC6A19/B0AT1 were required to account for total uptake. Furthermore, Leu and Phe uptake by heterologously expressed human SLC6A14/ATB0,+ and SLC43A2/LAT4 was accurately calculated. This versatile systems biology approach is useful for analyses where the kinetics of each active protein species can be represented by the Hill equation. Furthermore, its applicable even in the absence of protein expression data. It could potentially be applied, for example, to quantify drug transporter activities in target cells to improve specificity. PMID:28091567

  18. Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia.

    Science.gov (United States)

    Garami, Andras; Shimansky, Yury P; Pakai, Eszter; Oliveira, Daniela L; Gavva, Narender R; Romanovsky, Andrej A

    2010-01-27

    Transient receptor potential vanilloid-1 (TRPV1) antagonists are widely viewed as next-generation pain therapeutics. However, these compounds cause hyperthermia, a serious side effect. TRPV1 antagonists differentially block three modes of TRPV1 activation: by heat, protons, and chemical ligands (e.g., capsaicin). We asked what combination of potencies in these three modes of TRPV1 activation corresponds to the lowest potency of a TRPV1 antagonist to cause hyperthermia. We studied hyperthermic responses of rats, mice, and guinea pigs to eight TRPV1 antagonists with different pharmacological profiles and used mathematical modeling to find a relative contribution of the blockade of each activation mode to the development of hyperthermia. We found that the hyperthermic effect has the highest sensitivity to the extent of TRPV1 blockade in the proton mode (0.43 to 0.65) with no to moderate sensitivity in the capsaicin mode (-0.01 to 0.34) and no sensitivity in the heat mode (0.00 to 0.01). We conclude that hyperthermia-free TRPV1 antagonists do not block TRPV1 activation by protons, even if they are potent blockers of the heat mode, and that decreasing the potency to block the capsaicin mode may further decrease the potency to cause hyperthermia.

  19. Estrogen Signaling Contributes to Sex Differences in Macrophage Polarization during Asthma.

    Science.gov (United States)

    Keselman, Aleksander; Fang, Xi; White, Preston B; Heller, Nicola M

    2017-09-01

    Allergic asthma is a chronic Th2 inflammation in the lungs that constricts the airways and presents as coughing and wheezing. Asthma mostly affects boys in childhood and women in adulthood, suggesting that shifts in sex hormones alter the course of the disease. Alveolar macrophages have emerged as major mediators of allergic lung inflammation in animal models as well as humans. Whether sex differences exist in macrophage polarization and the molecular mechanism(s) that drive differential responses are not well understood. We found that IL-4-stimulated bone marrow-derived and alveolar macrophages from female mice exhibited greater expression of M2 genes in vitro and after allergen challenge in vivo. Alveolar macrophages from female mice exhibited greater expression of the IL-4Rα and estrogen receptor (ER) α compared with macrophages from male mice following allergen challenge. An ERα-specific agonist enhanced IL-4-induced M2 gene expression in macrophages from both sexes, but more so in macrophages from female mice. Furthermore, IL-4-stimulated macrophages from female mice exhibited more transcriptionally active histone modifications at M2 gene promoters than did macrophages from male mice. We found that supplementation of estrogen into ovariectomized female mice enhanced M2 polarization in vivo upon challenge with allergen and that macrophage-specific deletion of ERα impaired this M2 polarization. The effects of estrogen are long-lasting; bone marrow-derived macrophages from ovariectomized mice implanted with estrogen exhibited enhanced IL-4-induced M2 gene expression compared with macrophages from placebo-implanted littermates. Taken together, our findings suggest that estrogen enhances IL-4-induced M2 gene expression and thereby contributes to sex differences observed in asthma. Copyright © 2017 by The American Association of Immunologists, Inc.

  20. Dysfunction of different cellular degradation pathways contributes to specific β-amyloid42-induced pathologies.

    Science.gov (United States)

    Ji, Xuan-Ru; Cheng, Kuan-Chung; Chen, Yu-Ru; Lin, Tzu-Yu; Cheung, Chun Hei Antonio; Wu, Chia-Lin; Chiang, Hsueh-Cheng

    2018-03-01

    The endosomal-lysosomal system (ELS), autophagy, and ubiquitin-proteasome system (UPS) are cellular degradation pathways that each play a critical role in the removal of misfolded proteins and the prevention of the accumulation of abnormal proteins. Recent studies on Alzheimer's disease (AD) pathogenesis have suggested that accumulation of aggregated β-amyloid (Aβ) peptides in the AD brain results from a dysfunction in these cellular clearance systems. However, the specific roles of these pathways in the removal of Aβ peptides and the pathogenesis underlying AD are unclear. Our in vitro and in vivo genetic approaches revealed that ELS mainly removed monomeric β-amyloid42 (Aβ42), while autophagy and UPS clear oligomeric Aβ42. Although overproduction of phosphatidylinositol 4-phosphate-5 increased Aβ42 clearance, it reduced the life span of Aβ42 transgenic flies. Our behavioral studies further demonstrated impaired autophagy and UPS-enhanced Aβ42-induced learning and memory deficits, but there was no effect on Aβ42-induced reduction in life span. Results from genetic fluorescence imaging showed that these pathways were damaged in the following order: UPS, autophagy, and finally ELS. The results of our study demonstrate that different degradation pathways play distinct roles in the removal of Aβ42 aggregates and in disease progression. These findings also suggest that pharmacologic treatments that are designed to stimulate cellular degradation pathways in patients with AD should be used with caution.-Ji, X.-R., Cheng, K.-C., Chen, Y.-R., Lin, T.-Y., Cheung, C. H. A., Wu, C.-L., Chiang, H.-C. Dysfunction of different cellular degradation pathways contributes to specific β-amyloid42-induced pathologies.

  1. Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association

    Directory of Open Access Journals (Sweden)

    Amy Rebecca Bentley

    2012-01-01

    Full Text Available Low levels of high-density cholesterol (HDLc accompany chronic kidney disease, but the association between HDLc and the estimated glomerular filtration rate (eGFR in the general population is unclear. We investigated the HDLc-eGFR association in nondiabetic Han Chinese (HC, n=1100, West Africans (WA, n=1497, and African Americans (AA, n=1539. There were significant differences by ancestry: HDLc was positively associated with eGFR in HC (β=0.13, P<0.0001, but negatively associated among African ancestry populations (WA: −0.19, P<0.0001; AA: −0.09, P=0.02. These differences were also seen in nationally-representative NHANES data (among European Americans: 0.09, P=0.005; among African Americans −0.14, P=0.03. To further explore the findings in African ancestry populations, we investigated the role of an African ancestry-specific nephropathy risk variant, rs73885319, in the gene encoding HDL-associated APOL1. Among AA, an inverse HDLc-eGFR association was observed only with the risk genotype (−0.38 versus 0.001; P=0.03. This interaction was not seen in WA. In summary, counter to expectation, an inverse HDLc-eGFR association was observed among those of African ancestry. Given the APOL1 × HDLc interaction among AA, genetic factors may contribute to this paradoxical association. Notably, these findings suggest that the unexplained mechanism by which APOL1 affects kidney-disease risk may involve HDLc.

  2. Gender Patterns in the Contribution of Different Types of Violence to Posttraumatic Stress Symptoms among South African Urban Youth

    Science.gov (United States)

    Kaminer, Debra; Hardy, Anneli; Heath, Katherine; Mosdell, Jill; Bawa, Umesh

    2013-01-01

    Objective: Identifying the comparative contributions of different forms of violence exposure to trauma sequelae can help to prioritize interventions for polyvictimized youth living in contexts of limited mental health resources. This study aimed to establish gender patterns in the independent and comparative contributions of five types of violence…

  3. A Presynaptic Role for FMRP during Protein Synthesis-Dependent Long-Term Plasticity in "Aplysia"

    Science.gov (United States)

    Till, Sally M.; Li, Hsiu-Ling; Miniaci, Maria Concetta; Kandel, Eric R.; Choi, Yun-Beom

    2011-01-01

    Loss of the Fragile X mental retardation protein (FMRP) is associated with presumed postsynaptic deficits in mouse models of Fragile X syndrome. However, the possible presynaptic roles of FMRP in learning-related plasticity have received little attention. As a result, the mechanisms whereby FMRP influences synaptic function remain poorly…

  4. Presynaptic Glycine Receptors Increase GABAergic Neurotransmission in Rat Periaqueductal Gray Neurons

    Directory of Open Access Journals (Sweden)

    Kwi-Hyung Choi

    2013-01-01

    Full Text Available The periaqueductal gray (PAG is involved in the central regulation of nociceptive transmission by affecting the descending inhibitory pathway. In the present study, we have addressed the functional role of presynaptic glycine receptors in spontaneous glutamatergic transmission. Spontaneous EPSCs (sEPSCs were recorded in mechanically dissociated rat PAG neurons using a conventional whole-cell patch recording technique under voltage-clamp conditions. The application of glycine (100 µM significantly increased the frequency of sEPSCs, without affecting the amplitude of sEPSCs. The glycine-induced increase in sEPSC frequency was blocked by 1 µM strychnine, a specific glycine receptor antagonist. The results suggest that glycine acts on presynaptic glycine receptors to increase the probability of glutamate release from excitatory nerve terminals. The glycine-induced increase in sEPSC frequency completely disappeared either in the presence of tetrodotoxin or Cd2+, voltage-gated Na+, or Ca2+ channel blockers, suggesting that the activation of presynaptic glycine receptors might depolarize excitatory nerve terminals. The present results suggest that presynaptic glycine receptors can regulate the excitability of PAG neurons by enhancing glutamatergic transmission and therefore play an important role in the regulation of various physiological functions mediated by the PAG.

  5. ATM protein is located on presynaptic vesicles and its deficit leads to failures in synaptic plasticity.

    Science.gov (United States)

    Vail, Graham; Cheng, Aifang; Han, Yu Ray; Zhao, Teng; Du, Shengwang; Loy, Michael M T; Herrup, Karl; Plummer, Mark R

    2016-07-01

    Ataxia telangiectasia is a multisystemic disorder that includes a devastating neurodegeneration phenotype. The ATM (ataxia-telangiectasia mutated) protein is well-known for its role in the DNA damage response, yet ATM is also found in association with cytoplasmic vesicular structures: endosomes and lysosomes, as well as neuronal synaptic vesicles. In keeping with this latter association, electrical stimulation of the Schaffer collateral pathway in hippocampal slices from ATM-deficient mice does not elicit normal long-term potentiation (LTP). The current study was undertaken to assess the nature of this deficit. Theta burst-induced LTP was reduced in Atm(-/-) animals, with the reduction most pronounced at burst stimuli that included 6 or greater trains. To assess whether the deficit was associated with a pre- or postsynaptic failure, we analyzed paired-pulse facilitation and found that it too was significantly reduced in Atm(-/-) mice. This indicates a deficit in presynaptic function. As further evidence that these synaptic effects of ATM deficiency were presynaptic, we used stochastic optical reconstruction microscopy. Three-dimensional reconstruction revealed that ATM is significantly more closely associated with Piccolo (a presynaptic marker) than with Homer1 (a postsynaptic marker). These results underline how, in addition to its nuclear functions, ATM plays an important functional role in the neuronal synapse where it participates in the regulation of presynaptic vesicle physiology. Copyright © 2016 the American Physiological Society.

  6. Protein dynamics during presynaptic complex assembly on individual ssDNA molecules

    Science.gov (United States)

    Gibb, Bryan; Ye, Ling F.; Kwon, YoungHo; Niu, Hengyao; Sung, Patrick; Greene, Eric C.

    2014-01-01

    Homologous recombination is a conserved pathway for repairing double–stranded breaks, which are processed to yield single–stranded DNA overhangs that serve as platforms for presynaptic complex assembly. Here we use single–molecule imaging to reveal the interplay between Saccharomyce cerevisiae RPA, Rad52, and Rad51 during presynaptic complex assembly. We show that Rad52 binds RPA–ssDNA and suppresses RPA turnover, highlighting an unanticipated regulatory influence on protein dynamics. Rad51 binding extends the ssDNA, and Rad52–RPA clusters remain interspersed along the presynaptic complex. These clusters promote additional binding of RPA and Rad52. Together, our work illustrates the spatial and temporal progression of RPA and Rad52 association with the presynaptic complex, and reveals a novel RPA–Rad52–Rad51–ssDNA intermediate, which has implications for understanding how the activities of Rad52 and RPA are coordinated with Rad51 during the later stages recombination. PMID:25195049

  7. G-protein-coupled inward rectifier potassium channels involved in corticostriatal presynaptic modulation.

    Science.gov (United States)

    Meneses, David; Mateos, Verónica; Islas, Gustavo; Barral, Jaime

    2015-09-01

    Presynaptic modulation has been associated mainly with calcium channels but recent data suggests that inward rectifier potassium channels (K(IR)) also play a role. In this work we set to characterize the role of presynaptic K(IR) channels in corticostriatal synaptic transmission. We elicited synaptic potentials in striatum by stimulating cortical areas and then determined the synaptic responses of corticostriatal synapsis by using paired pulse ratio (PPR) in the presence and absence of several potassium channel blockers. Unspecific potassium channels blockers Ba(2+) and Cs(+) reduced the PPR, suggesting that these channels are presynaptically located. Further pharmacological characterization showed that application of tertiapin-Q, a specific K(IR)3 channel family blocker, also induced a reduction of PPR, suggesting that K(IR)3 channels are present at corticostriatal terminals. In contrast, exposure to Lq2, a specific K(IR)1.1 inward rectifier potassium channel, did not induce any change in PPR suggesting the absence of these channels in the presynaptic corticostriatal terminals. Our results indicate that K(IR)3 channels are functionally expressed at the corticostriatal synapses, since blockage of these channels result in PPR decrease. Our results also help to explain how synaptic activity may become sensitive to extracellular signals mediated by G-protein coupled receptors. A vast repertoire of receptors may influence neurotransmitter release in an indirect manner through regulation of K(IR)3 channels. © 2015 Wiley Periodicals, Inc.

  8. Queens and Workers Contribute Differently to Adaptive Evolution in Bumble Bees and Honey Bees.

    Science.gov (United States)

    Harpur, Brock A; Dey, Alivia; Albert, Jennifer R; Patel, Sani; Hines, Heather M; Hasselmann, Martin; Packer, Laurence; Zayed, Amro

    2017-09-01

    Eusociality represents a major transition in evolution and is typified by cooperative brood care and reproductive division of labor between generations. In bees, this division of labor allows queens and workers to phenotypically specialize. Worker traits associated with helping are thought to be crucial to the fitness of a eusocial lineage, and recent studies of honey bees (genus Apis) have found that adaptively evolving genes often have worker-biased expression patterns. It is unclear however if worker-biased genes are disproportionately acted on by strong positive selection in all eusocial insects. We undertook a comparative population genomics study of bumble bees (Bombus) and honey bees to quantify natural selection on queen- and worker-biased genes across two levels of social complexity. Despite sharing a common eusocial ancestor, genes, and gene groups with the highest levels of positive selection were often unique within each genus, indicating that life history and the environment, but not sociality per se, drives patterns of adaptive molecular evolution. We uncovered differences in the contribution of queen- and worker-biased genes to adaptive evolution in bumble bees versus honey bees. Unlike honey bees, where worker-biased genes are enriched for signs of adaptive evolution, genes experiencing positive selection in bumble bees were predominately expressed by reproductive foundresses during the initial solitary-founding stage of colonies. Our study suggests that solitary founding is a major selective pressure and that the loss of queen totipotency may cause a change in the architecture of selective pressures upon the social insect genome. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  9. Modulation of TRAIL resistance in colon carcinoma cells: Different contributions of DR4 and DR5

    International Nuclear Information System (INIS)

    Geelen, Caroline MM van; Pennarun, Bodvael; Le, Phuong TK; Vries, Elisabeth GE de; Jong, Steven de

    2011-01-01

    rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5). Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether agonistic DR4 or DR5 antibodies could be used to circumvent rhTRAIL resistance, alone or in combination with various chemotherapies. Our study was performed in an isogenic model comprised of the SW948 human colon carcinoma cell line and its rhTRAIL resistant sub-line SW948-TR. Effects of rhTRAIL and agonistic DR4/DR5 antibodies on cell viability were measured using MTT assays and identification of morphological changes characteristic of apoptosis, after acridine orange staining. Sensitivity to the different death receptor ligands was stimulated using pretreatment with the cytokine IFN-gamma and the proteasome inhibitor MG-132. To investigate the mechanisms underlying the changes in rhTRAIL sensitivity, alterations in expression levels of targets of interest were measured by Western blot analysis. Co-immunoprecipitation was used to determine the composition of the death-inducing signalling complex at the cell membrane. SW948 cells were sensitive to all three of the DR-targeting agents tested, although the agonistic DR5 antibody induced only weak caspase 8 cleavage and limited apoptosis. Surprisingly, agonistic DR4 and DR5 antibodies induced equivalent DISC formation and caspase 8 cleavage at the level of their individual receptors, suggesting impairment of further caspase 8 processing upon DR5 stimulation. SW948-TR cells were cross-resistant to all DR-targeting agents as a result of decreased caspase 8 expression levels. Caspase 8 protein expression was restored by MG-132 and IFN-gamma pretreatment, which also re-established sensitivity to rhTRAIL and agonistic DR4 antibody in SW948-TR. Surprisingly, MG-132 but not IFN-gamma could also increase DR5-mediated apoptosis in SW948

  10. Modulation of TRAIL resistance in colon carcinoma cells: Different contributions of DR4 and DR5

    Directory of Open Access Journals (Sweden)

    de Vries Elisabeth GE

    2011-01-01

    Full Text Available Abstract Background rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5. Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether agonistic DR4 or DR5 antibodies could be used to circumvent rhTRAIL resistance, alone or in combination with various chemotherapies. Methods Our study was performed in an isogenic model comprised of the SW948 human colon carcinoma cell line and its rhTRAIL resistant sub-line SW948-TR. Effects of rhTRAIL and agonistic DR4/DR5 antibodies on cell viability were measured using MTT assays and identification of morphological changes characteristic of apoptosis, after acridine orange staining. Sensitivity to the different death receptor ligands was stimulated using pretreatment with the cytokine IFN-gamma and the proteasome inhibitor MG-132. To investigate the mechanisms underlying the changes in rhTRAIL sensitivity, alterations in expression levels of targets of interest were measured by Western blot analysis. Co-immunoprecipitation was used to determine the composition of the death-inducing signalling complex at the cell membrane. Results SW948 cells were sensitive to all three of the DR-targeting agents tested, although the agonistic DR5 antibody induced only weak caspase 8 cleavage and limited apoptosis. Surprisingly, agonistic DR4 and DR5 antibodies induced equivalent DISC formation and caspase 8 cleavage at the level of their individual receptors, suggesting impairment of further caspase 8 processing upon DR5 stimulation. SW948-TR cells were cross-resistant to all DR-targeting agents as a result of decreased caspase 8 expression levels. Caspase 8 protein expression was restored by MG-132 and IFN-gamma pretreatment, which also re-established sensitivity to rhTRAIL and agonistic DR4 antibody in SW948-TR. Surprisingly, MG-132 but not IFN

  11. Presynaptic dopamine depletion determines the timing of levodopa-induced dyskinesia onset in Parkinson's disease

    International Nuclear Information System (INIS)

    Yoo, Han Soo; Chung, Seok Jong; Chung, Su Jin; Ye, Byoung Seok; Sohn, Young Ho; Lee, Phil Hyu; Moon, Hyojeong; Oh, Jung Su; Kim, Jae Seung; Hong, Jin Yong

    2018-01-01

    Reduced presynaptic dopaminergic activity plays an important role in the development of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). In this study, we investigated whether dopaminergic function in the nigrostriatal system is associated with the timing of LID onset. From among 412 drug-naive PD patients who underwent a dopamine transporter (DAT) PET scan during their baseline evaluation, we enrolled 65 patients who developed LID during a follow-up period of >2 years. Based on the time from PD onset, LID was classified as early, intermediate or late onset. We then compared DAT availability in the striatal subregions of the patients in the three groups. The demographic characteristics did not differ among the three patient groups except for earlier intervention of levodopa therapy in the early LID onset group (p = 0.001). After adjusting for age at PD onset, gender, timing of levodopa therapy from PD onset, and the severity of PD motor symptoms, DAT activity in the posterior putamen was found to be significantly lower in the early LID onset group than in the late LID onset group (p = 0.017). Multivariate linear regression analysis showed that low DAT activity in the posterior putamen was significantly associated with the early appearance of LID in the early LID onset group (β = 16.039, p = 0.033). This study demonstrated that low DAT activity in the posterior putamen at baseline is a major risk factor for the early onset of LID in patients with PD, suggesting that the degree of presynaptic dopaminergic denervation plays an important role in determining the timing of LID onset. (orig.)

  12. Presynaptic dopamine depletion determines the timing of levodopa-induced dyskinesia onset in Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Han Soo; Chung, Seok Jong; Chung, Su Jin; Ye, Byoung Seok; Sohn, Young Ho; Lee, Phil Hyu [Yonsei University College of Medicine, Department of Neurology, Seoul (Korea, Republic of); Moon, Hyojeong; Oh, Jung Su; Kim, Jae Seung [University of Ulsan College of Medicine, Department of Nuclear Medicine, Asan Medical Center, Seoul (Korea, Republic of); Hong, Jin Yong [Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)

    2018-03-15

    Reduced presynaptic dopaminergic activity plays an important role in the development of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). In this study, we investigated whether dopaminergic function in the nigrostriatal system is associated with the timing of LID onset. From among 412 drug-naive PD patients who underwent a dopamine transporter (DAT) PET scan during their baseline evaluation, we enrolled 65 patients who developed LID during a follow-up period of >2 years. Based on the time from PD onset, LID was classified as early, intermediate or late onset. We then compared DAT availability in the striatal subregions of the patients in the three groups. The demographic characteristics did not differ among the three patient groups except for earlier intervention of levodopa therapy in the early LID onset group (p = 0.001). After adjusting for age at PD onset, gender, timing of levodopa therapy from PD onset, and the severity of PD motor symptoms, DAT activity in the posterior putamen was found to be significantly lower in the early LID onset group than in the late LID onset group (p = 0.017). Multivariate linear regression analysis showed that low DAT activity in the posterior putamen was significantly associated with the early appearance of LID in the early LID onset group (β = 16.039, p = 0.033). This study demonstrated that low DAT activity in the posterior putamen at baseline is a major risk factor for the early onset of LID in patients with PD, suggesting that the degree of presynaptic dopaminergic denervation plays an important role in determining the timing of LID onset. (orig.)

  13. Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus.

    Science.gov (United States)

    Rocchetti, Jill; Isingrini, Elsa; Dal Bo, Gregory; Sagheby, Sara; Menegaux, Aurore; Tronche, François; Levesque, Daniel; Moquin, Luc; Gratton, Alain; Wong, Tak Pan; Rubinstein, Marcelo; Giros, Bruno

    2015-03-15

    Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric disorders. Converging evidence from patients with psychiatric disorders and use of antipsychotics suggests that imbalance of dopamine signaling deeply alters hippocampal functions. However, given the lack of full characterization of a functional mesohippocampal pathway, the precise role of dopamine transmission in memory deficits associated with these disorders and their dedicated therapies is unknown. In particular, the positive outcome of antipsychotic treatments, commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and memory impairments remains questionable. Following pharmacologic and genetic manipulation of dopamine transmission, we performed anatomic, neurochemical, electrophysiologic, and behavioral investigations to uncover the role of D2Rs in hippocampal-dependent plasticity and learning. Naïve mice (n = 4-21) were used in the different procedures. Dopamine modulated both long-term potentiation and long-term depression in the temporal hippocampus as well as spatial and recognition learning and memory in mice through D2Rs. Although genetic deletion or pharmacologic blockade of D2Rs led to the loss of long-term potentiation expression, the specific genetic removal of presynaptic D2Rs impaired long-term depression and performances on spatial memory tasks. Presynaptic D2Rs in dopamine fibers of the temporal hippocampus tightly modulate long-term depression expression and play a major role in the regulation of hippocampal learning and memory. This direct role of mesohippocampal dopamine input as uncovered here adds a new dimension to dopamine involvement in the physiology underlying deficits associated with neuropsychiatric disorders. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Triple nitrate isotopes indicate differing nitrate source contributions to streams across a nitrogen saturation gradient

    Science.gov (United States)

    Lucy A. Rose; Emily M. Elliott; Mary Beth. Adams

    2015-01-01

    Nitrogen (N) deposition affects forest biogeochemical cycles worldwide, often contributing to N saturation. Using long-term (>30-year) records of stream nitrate (NO3-) concentrations at Fernow Experimental Forest (West Virginia, USA), we classified four watersheds into N saturation stages ranging from Stage 0 (N-...

  15. Contribution of different livestock species as sources of meat in Bauchi

    African Journals Online (AJOL)

    , 169, 119 and 7 were White Fulani, Red Bororo, Sokoto Gudali and Kuri breeds ... Of the 28,321 goats slaughtered, the contributions of Sokoto Red, Kano brown, Sahel and West African Dwarf were 20,265; 7,469; 575 and 12 respectively.

  16. Other-Sex Relationship Stress and Sex Differences in the Contribution of Puberty to Depression

    Science.gov (United States)

    Llewellyn, Nicole; Rudolph, Karen D.; Roisman, Glenn I.

    2012-01-01

    Research suggests that the pubertal transition, particularly when experienced earlier than age-matched peers, is associated with heightened depression in girls but less depression in boys. This study examined whether stress within other-sex relationships serves as one process through which puberty differentially contributes to depression for girls…

  17. Modulation of TRAIL resistance in colon carcinoma cells : Different contributions of DR4 and DR5

    NARCIS (Netherlands)

    van Geelen, Caroline M. M.; Pennarun, Bodvael; Le, Phuong T. K.; de Vries, Elisabeth G. E.; de Jong, Steven

    2011-01-01

    Background: rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5). Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether

  18. Lower limb joint work and joint work contribution during downhill and uphill walking at different inclinations.

    Science.gov (United States)

    Alexander, Nathalie; Strutzenberger, Gerda; Ameshofer, Lisa Maria; Schwameder, Hermann

    2017-08-16

    Work performance and individual joint contribution to total work are important information for creating training protocols, but were not assessed so far for sloped walking. Therefore, the purpose of this study was to analyze lower limb joint work and joint contribution of the hip, knee and ankle to total lower limb work during sloped walking in a healthy population. Eighteen male participants (27.0±4.7yrs, 1.80±0.05m, 74.5±8.2kg) walked on an instrumented ramp at inclination angles of 0°, ±6°, ±12° and ±18° at 1.1m/s. Kinematic and kinetic data were captured using a motion-capture system (Vicon) and two force plates (AMTI). Joint power curves, joint work (positive, negative, absolute) and each joint's contribution to total lower limb work were analyzed throughout the stance phase using an ANOVA with repeated measures. With increasing inclination positive joint work increased for the ankle and hip joint and in total during uphill walking. Negative joint work increased for each joint and in total work during downhill walking. Absolute work was increased during both uphill (all joints) and downhill (ankle & knee) walking. Knee joint contribution to total negative and absolute work increased during downhill walking while hip and ankle contributions decreased. This study identified, that, when switching from level to a 6° and from 6° to a 12° inclination the gain of individual joint work is more pronounced compared to switching from 12° to an 18° inclination. The results might be used for training recommendations and specific training intervention with respect to sloped walking. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Relative contributions of archaea and bacteria to microbial ammonia oxidation differ under different conditions during agricultural waste composting.

    Science.gov (United States)

    Zeng, Guangming; Zhang, Jiachao; Chen, Yaoning; Yu, Zhen; Yu, Man; Li, Hui; Liu, Zhifeng; Chen, Ming; Lu, Lunhui; Hu, Chunxiao

    2011-10-01

    The aim of this study was to compare the relative contribution of ammonia-oxidizing archaea (AOA) and bacteria (AOB) to nitrification during agricultural waste composting. The AOA and AOB amoA gene abundance and composition were determined by quantitative PCR and denaturing gradient gel electrophoresis (DGGE), respectively. The results showed that the archaeal amoA gene was abundant throughout the composting process, while the bacterial amoA gene abundance decreased to undetectable level during the thermophilic and cooling stages. DGGE showed more diverse archaeal amoA gene composition when the potential ammonia oxidation (PAO) rate reached peak values. A significant positive relationship was observed between the PAO rate and the archaeal amoA gene abundance (R²=0.554; Parchaea dominated ammonia oxidation during the thermophilic and cooling stages. Bacteria were also related to ammonia oxidation activity (R²=0.503; P=0.03) especially during the mesophilic and maturation stages. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Source contribution of PM₂.₅ at different locations on the Malaysian Peninsula.

    Science.gov (United States)

    Ee-Ling, Ooi; Mustaffa, Nur Ili Hamizah; Amil, Norhaniza; Khan, Md Firoz; Latif, Mohd Talib

    2015-04-01

    This study determined the source contribution of PM2.5 (particulate matter heavy metals. Principal component analysis with multilinear regressions were used to identify the possible sources of PM2.5. The range of PM2.5 was between 10 ± 3 and 30 ± 7 µg m(-3). Sulfate (SO4 (2-)) was the major ionic compound detected and zinc was found to dominate the heavy metals. Source apportionment analysis revealed that motor vehicle and soil dust dominated the composition of PM2.5 in the urban area. Domestic waste combustion dominated in the suburban area, while biomass burning dominated in the rural area.

  1. New heavy flavor contributions to DIS at the 3-loop order: different masses and nested topologies

    Energy Technology Data Exchange (ETDEWEB)

    Ablinger, Jakob; Schneider, Carsten [RISC - JKU Linz (Austria); Bluemlein, Johannes; Wissbrock, Fabian [DESY (Germany)

    2013-07-01

    We present recent results on the heavy flavor Wilson coefficients of the deep-inelastic structure function F{sub 2} stemming from diagrams which contain both charm- and bottom-quarks. Starting at 3-loop order these contributions cannot be incorporated into the variable flavor number scheme (VFSN). We also present new results on the computation of diagrams of more advanced topologies (knotted ladder, Benz, and others) which have been obtained via the method of hyperlogarithms. They require the use of extensions to the basic formalism leading to the more general class of generalized hyperlogarithms, resp. the associated nested sums. Both the x- and Mellin N-space representations are discussed.

  2. Subcellular differences in handling Cu excess in three freshwater fish species contributes greatly to their differences in sensitivity to Cu

    International Nuclear Information System (INIS)

    Eyckmans, Marleen; Blust, Ronny; De Boeck, Gudrun

    2012-01-01

    Since changes in metal distribution among tissues and subcellular fractions can provide insights in metal toxicity and tolerance, we investigated this partitioning of Cu in gill and liver tissue of rainbow trout (Oncorhynchus mykiss), common carp (Cyprinus carpio) and gibel carp (Carassius auratus gibelio). These fish species are known to differ in their sensitivity to Cu exposure with gibel carp being the most tolerant and rainbow trout the most sensitive. After an exposure to 50 μg/l (0.79 μM) Cu for 24 h, 3 days, 1 week and 1 month, gills and liver of control and exposed fish were submitted to a differential centrifugation procedure. Interestingly, there was a difference in accumulated Cu in the three fish species, even in control fishes. Where the liver of rainbow trout showed extremely high Cu concentrations under control conditions, the amount of Cu accumulated in their gills was much less than in common and gibel carp. At the subcellular level, the gills of rainbow trout appeared to distribute the additional Cu exclusively in the biologically active metal pool (BAM; contains heat-denaturable fraction and organelle fraction). A similar response could be seen in gill tissue of common carp, although the percentage of Cu in the BAM of common carp was lower compared to rainbow trout. Gill tissue of gibel carp accumulated more Cu in the biologically inactive metal pool (BIM compared to BAM; contains heat-stable fraction and metal-rich granule fraction). The liver of rainbow trout seemed much more adequate in handling the excess Cu (compared to its gills), since the storage of Cu in the BIM increased. Furthermore, the high % of Cu in the metal-rich granule fraction and heat-stable fraction in the liver of common carp and especially gibel carp together with the better Cu handling in gill tissue, pointed out the ability of the carp species to minimize the disadvantages related to Cu stress. The differences in Cu distribution at the subcellular level of gills and

  3. Subcellular differences in handling Cu excess in three freshwater fish species contributes greatly to their differences in sensitivity to Cu

    Energy Technology Data Exchange (ETDEWEB)

    Eyckmans, Marleen, E-mail: marleen.eyckmans@ua.ac.be [Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium); Blust, Ronny; De Boeck, Gudrun [Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium)

    2012-08-15

    Since changes in metal distribution among tissues and subcellular fractions can provide insights in metal toxicity and tolerance, we investigated this partitioning of Cu in gill and liver tissue of rainbow trout (Oncorhynchus mykiss), common carp (Cyprinus carpio) and gibel carp (Carassius auratus gibelio). These fish species are known to differ in their sensitivity to Cu exposure with gibel carp being the most tolerant and rainbow trout the most sensitive. After an exposure to 50 {mu}g/l (0.79 {mu}M) Cu for 24 h, 3 days, 1 week and 1 month, gills and liver of control and exposed fish were submitted to a differential centrifugation procedure. Interestingly, there was a difference in accumulated Cu in the three fish species, even in control fishes. Where the liver of rainbow trout showed extremely high Cu concentrations under control conditions, the amount of Cu accumulated in their gills was much less than in common and gibel carp. At the subcellular level, the gills of rainbow trout appeared to distribute the additional Cu exclusively in the biologically active metal pool (BAM; contains heat-denaturable fraction and organelle fraction). A similar response could be seen in gill tissue of common carp, although the percentage of Cu in the BAM of common carp was lower compared to rainbow trout. Gill tissue of gibel carp accumulated more Cu in the biologically inactive metal pool (BIM compared to BAM; contains heat-stable fraction and metal-rich granule fraction). The liver of rainbow trout seemed much more adequate in handling the excess Cu (compared to its gills), since the storage of Cu in the BIM increased. Furthermore, the high % of Cu in the metal-rich granule fraction and heat-stable fraction in the liver of common carp and especially gibel carp together with the better Cu handling in gill tissue, pointed out the ability of the carp species to minimize the disadvantages related to Cu stress. The differences in Cu distribution at the subcellular level of gills

  4. Contribution of different effluent organic matter fractions to membrane fouling in ultrafiltration of treated domestic wastewater

    KAUST Repository

    Zheng, Xing; Croue, Jean-Philippe

    2012-01-01

    In the present work, effluent organic matter (EfOM) in treated domestic wastewater was separated into hydrophobic neutrals, colloids, hydrophobic acids, transphilic acids and neutrals and hydrophilic compounds. Their contribution to dissolved organic carbon (DOC) was identified. Further characterization was conducted with respect to molecular size and hydrophobicity. Each isolated fraction was dosed into salt solution to identify its fouling potential in ultrafiltration (UF) using a hydrophilized polyethersulfone membrane. The results show that each kind of EfOM leads to irreversible fouling. At similar delivered DOC load to the membrane, colloids present the highest fouling effect in terms of both reversible and irreversible fouling. The hydrophobic organics show much lower reversibility than the biopolymers present. However, as they are of much smaller size than the membrane pore opening, they cannot lead to such severe fouling as biopolymers do. In all of the isolated fractions, hydrophilics show the lowest fouling potential. For either colloids or hydrophobic substances, increasing their content in feedwater leads to worse fouling. The co-effect between biopolymers and other EfOM fractions has also been identified as one of the mechanisms contributing to UF fouling in filtering EfOM-containing waters. © IWA Publishing 2012.

  5. Contribution of different effluent organic matter fractions to membrane fouling in ultrafiltration of treated domestic wastewater

    KAUST Repository

    Zheng, Xing

    2012-12-01

    In the present work, effluent organic matter (EfOM) in treated domestic wastewater was separated into hydrophobic neutrals, colloids, hydrophobic acids, transphilic acids and neutrals and hydrophilic compounds. Their contribution to dissolved organic carbon (DOC) was identified. Further characterization was conducted with respect to molecular size and hydrophobicity. Each isolated fraction was dosed into salt solution to identify its fouling potential in ultrafiltration (UF) using a hydrophilized polyethersulfone membrane. The results show that each kind of EfOM leads to irreversible fouling. At similar delivered DOC load to the membrane, colloids present the highest fouling effect in terms of both reversible and irreversible fouling. The hydrophobic organics show much lower reversibility than the biopolymers present. However, as they are of much smaller size than the membrane pore opening, they cannot lead to such severe fouling as biopolymers do. In all of the isolated fractions, hydrophilics show the lowest fouling potential. For either colloids or hydrophobic substances, increasing their content in feedwater leads to worse fouling. The co-effect between biopolymers and other EfOM fractions has also been identified as one of the mechanisms contributing to UF fouling in filtering EfOM-containing waters. © IWA Publishing 2012.

  6. Myc contribution to γ-ray induced thymic lymphomas in mice of different genetic predispositions

    International Nuclear Information System (INIS)

    Sato, Toshihiro

    2008-01-01

    Myc gene has been suggested to be one of radiation targets in early genesis of γ ray-induced thymic lymphoma where Myc trisomy often occurs, and Myc activation results in p53 activation and apoptosis. The purpose of this study is to see the effects of radiation and mutation on Myc activation in the mouse. The lymphoma was induced by a single exposure of 3 Gy γ ray in BALB/c Bcl11b/Rit+/- and MSM p53-/- mice at 4 weeks after birth and by 4 weekly exposures of 2.5 Gy in p53+/- mouse. Genetic allele analysis for trisomy identification in the lymphoma was done by quantitative PCR using brain DNA as a control. Myc trisomy was found in the lymphoma of p53+/- mouse in 62% (23/37 animals) and of p53+/+, 66% (23/25), a similar frequency, suggesting that the target of radiation was not only the Myc activation. In addition, Myc trisomy frequency was 15% (4/27) in the lymphoma of Bcl11b+/+p53+/- and 36% (9/25), in heterozygote Bcl11b+/-. This finding suggested that the functional failure of Bcl11b reduced the contribution of Myc trisomy to the genesis. It was concluded that contribution of Myc trisomy to genesis of the lymphoma was dependent on genetic predisposition, and Myc-activated-, Bcl11b/Rit1-signal pathways played a parallel role in the genesis. (R.T.)

  7. 123-I ioflupane (Datscan) presynaptic nigrostriatal imaging in patients with movement disorders

    International Nuclear Information System (INIS)

    Soriano Castrejon, Angel; Garcia Vicente, Ana Maria; Cortes Romera, Montserrat; Rodado Marina, Sonia; Poblete Garcia, Victor Manuel; Ruiz Solis, Sebastian Ruiz; Talavera Rubio, Maria del Prado; Vaamonde Cano, Julia

    2005-01-01

    123-I Ioflupane (Datscan) presynaptic imaging has been shown to have a significant utility in the assessment of patients with movement disorders 123 I Ioflupane SPECT is able to distinguish between Parkinson's disease (PD) and other forms of parkinsonism without degeneration of the nigrostriatal pathway, including a common movement disorder such as essential tremor, and to assess disease progression in PD and other neuro degenerative disorders involving the substantia nigra. (author)

  8. The contribution of childhood circumstances, current circumstances and health behaviour to educational health differences in early adulthood

    Directory of Open Access Journals (Sweden)

    Härkänen Tommi

    2009-05-01

    Full Text Available Abstract Background The life course approach emphasises the contribution of circumstances in childhood and youth to adult health inequalities. However, there is still a lot to know of the contribution of living conditions in childhood and youth to adult health inequalities and how later environmental and behavioural factors are connected with the effects of earlier circumstances. This study aims to assess a how much childhood circumstances, current circumstances and health behaviour contribute to educational health differences and b to which extent the effect of childhood circumstances on educational health differences is shared with the effects of later living conditions and health behaviour in young adults. Methods The data derived from the Health 2000 Survey represent the Finnish young adults aged 18–29 in 2000. The analyses were carried out on 68% (n = 1282 of the sample (N = 1894. The cross-sectional data based on interviews and questionnaires include retrospective information on childhood circumstances. The outcome measure was poor self-rated health. Results Poor self-rated health was much more common among subjects with primary education only than among those in the highest educational category (OR 4.69, 95% CI 2.63 to 8.62. Childhood circumstances contributed substantially (24% to the health differences between these educational groups. Nearly two thirds (63% of this contribution was shared with behavioural factors adopted by early adulthood, and 17% with current circumstances. Health behaviours, smoking especially, were strongly contributed to educational health differences. Conclusion To develop means for avoiding undesirable trajectories along which poor health and health differences develop, it is necessary to understand the pathways to health inequalities and know how to improve the living conditions of families with children.

  9. Presynaptic active zones of mammalian neuromuscular junctions: Nanoarchitecture and selective impairments in aging.

    Science.gov (United States)

    Badawi, Yomna; Nishimune, Hiroshi

    2018-02-01

    Neurotransmitter release occurs at active zones, which are specialized regions of the presynaptic membrane. A dense collection of proteins at the active zone provides a platform for molecular interactions that promote recruitment, docking, and priming of synaptic vesicles. At mammalian neuromuscular junctions (NMJs), muscle-derived laminin β2 interacts with presynaptic voltage-gated calcium channels to organize active zones. The molecular architecture of presynaptic active zones has been revealed using super-resolution microscopy techniques that combine nanoscale resolution and multiple molecular identification. Interestingly, the active zones of adult NMJs are not stable structures and thus become impaired during aging due to the selective degeneration of specific active zone proteins. This review will discuss recent progress in the understanding of active zone nanoarchitecture and the mechanisms underlying active zone organization in mammalian NMJs. Furthermore, we will summarize the age-related degeneration of active zones at NMJs, and the role of exercise in maintaining active zones. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  10. Slit2 as a β-catenin/Ctnnb1-dependent retrograde signal for presynaptic differentiation

    Science.gov (United States)

    Wu, Haitao; Barik, Arnab; Lu, Yisheng; Shen, Chengyong; Bowman, Andrew; Li, Lei; Sathyamurthy, Anupama; Lin, Thiri W; Xiong, Wen-Cheng; Mei, Lin

    2015-01-01

    Neuromuscular junction formation requires proper interaction between motoneurons and muscle cells. β-Catenin (Ctnnb1) in muscle is critical for motoneuron differentiation; however, little is known about the relevant retrograde signal. In this paper, we dissected which functions of muscle Ctnnb1 are critical by an in vivo transgenic approach. We show that Ctnnb1 mutant without the transactivation domain was unable to rescue presynaptic deficits of Ctnnb1 mutation, indicating the involvement of transcription regulation. On the other hand, the cell-adhesion function of Ctnnb1 is dispensable. We screened for proteins that may serve as a Ctnnb1-directed retrograde factor and identified Slit2. Transgenic expression of Slit2 specifically in the muscle was able to diminish presynaptic deficits by Ctnnb1 mutation in mice. Slit2 immobilized on beads was able to induce synaptophysin puncta in axons of spinal cord explants. Together, these observations suggest that Slit2 serves as a factor utilized by muscle Ctnnb1 to direct presynaptic differentiation. DOI: http://dx.doi.org/10.7554/eLife.07266.001 PMID:26159615

  11. Regarding the unitary theory of agonist and antagonist action at presynaptic adrenoceptors.

    Science.gov (United States)

    Kalsner, S; Abdali, S A

    2001-06-01

    1. The linkage between potentiation of field stimulation-induced noradrenaline release and blockade of the presynaptic inhibitory effect of exogenous noradrenaline by a presynaptic antagonist was examined in superfused rabbit aorta preparations. 2. Rauwolscine clearly potentiated the release of noradrenaline in response to 100 pulses at 2 Hz but reduced the capacity of noradrenaline to inhibit transmitter release to a questionable extent, and then only when comparisons were made with untreated, rather then to rauwolscine-treated, controls. 3. Aortic preparations exposed for 60 min to rauwolscine followed by superfusion with antagonist-free Krebs for 60 min retained the potentiation of stimulation-induced transmitter release but no antagonism of the noradrenaline-induced inhibition could be detected at either of two noradrenaline concentrations when comparisons were made with rauwolscine treated controls. 4. Comparisons of the inhibitory effect of exogenous noradrenaline (1.8 x 10-6 M) on transmitter efflux in the presence and absence of rauwolscine pretreatment revealed that the antagonist enhanced rather than antagonized the presynaptic inhibition by noradrenaline. 5 It is concluded that the unitary hypothesis that asserts that antagonist enhancement of transmitter release and its blockade of noradrenaline induced inhibition are manifestations of a unitary event are not supportable.

  12. Localization of Presynaptic Plasticity Mechanisms Enables Functional Independence of Synaptic and Ectopic Transmission in the Cerebellum

    Directory of Open Access Journals (Sweden)

    Katharine L. Dobson

    2015-01-01

    Full Text Available In the cerebellar molecular layer parallel fibre terminals release glutamate from both the active zone and from extrasynaptic “ectopic” sites. Ectopic release mediates transmission to the Bergmann glia that ensheathe the synapse, activating Ca2+-permeable AMPA receptors and glutamate transporters. Parallel fibre terminals exhibit several forms of presynaptic plasticity, including cAMP-dependent long-term potentiation and endocannabinoid-dependent long-term depression, but it is not known whether these presynaptic forms of long-term plasticity also influence ectopic transmission to Bergmann glia. Stimulation of parallel fibre inputs at 16 Hz evoked LTP of synaptic transmission, but LTD of ectopic transmission. Pharmacological activation of adenylyl cyclase by forskolin caused LTP at Purkinje neurons, but only transient potentiation at Bergmann glia, reinforcing the concept that ectopic sites lack the capacity to express sustained cAMP-dependent potentiation. Activation of mGluR1 caused depression of synaptic transmission via retrograde endocannabinoid signalling but had no significant effect at ectopic sites. In contrast, activation of NMDA receptors suppressed both synaptic and ectopic transmission. The results suggest that the signalling mechanisms for presynaptic LTP and retrograde depression by endocannabinoids are restricted to the active zone at parallel fibre synapses, allowing independent modulation of synaptic transmission to Purkinje neurons and ectopic transmission to Bergmann glia.

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

    Science.gov (United States)

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

    2017-09-20

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

  14. Suicidal and Nonsuicidal Adolescents: Different Factors Contribute to Self-Esteem

    Science.gov (United States)

    Groholt, Berit; Ekeberg, Oivind; Wichstrom, Lars; Haldorsen, Tor

    2005-01-01

    Some risk and protective factors differ in their importance to suicidal and nonsuicidal people. In this research we explore the cross-sectional differences between risk factors among suicidal adolescents and nonsuicidal adolescents by focusing on self-esteem. Sixty-five suicidal and 390 nonsuicidal adolescents were compared on Harter's…

  15. The contribution of smoking to regional mortality differences in The Netherlands

    NARCIS (Netherlands)

    Janssen, F.; Spriensma, A.S.

    2012-01-01

    BACKGROUND: Smoking is an important preventable determinant of morbidity and mortality. Knowledge about its role in regional mortality differences can help us to identify relevant policy areas, and to explain national mortality differences. OBJECTIVE: We explored the extent to which the regional

  16. The contribution of smoking to regional mortality differences in the Netherlands

    NARCIS (Netherlands)

    Janssen, Fanny; Spriensma, Alette Sigrid

    2012-01-01

    BACKGROUND Smoking is an important preventable determinant of morbidity and mortality. Knowledge about its role in regional mortality differences can help us to identify relevant policy areas, and to explain national mortality differences. OBJECTIVE We explored the extent to which the regional

  17. Differential effects of presynaptic versus postsynaptic adenosine A2A receptor blockade on Δ9-tetrahydrocannabinol (THC) self-administration in squirrel monkeys.

    Science.gov (United States)

    Justinová, Zuzana; Redhi, Godfrey H; Goldberg, Steven R; Ferré, Sergi

    2014-05-07

    Different doses of an adenosine A2A receptor antagonist MSX-3 [3,7-dihydro-8-[(1E)-2-(3-ethoxyphenyl)ethenyl]-7 methyl-3-[3-(phosphooxy)propyl-1-(2 propynil)-1H-purine-2,6-dione] were found previously to either decrease or increase self-administration of cannabinoids delta-9-tetrahydrocannabinol (THC) or anandamide in squirrel monkeys. It was hypothesized that the decrease observed with a relatively low dose of MSX-3 was related to blockade of striatal presynaptic A2A receptors that modulate glutamatergic neurotransmission, whereas the increase observed with a higher dose was related to blockade of postsynaptic A2A receptors localized in striatopallidal neurons. This hypothesis was confirmed in the present study by testing the effects of the preferential presynaptic and postsynaptic A2A receptor antagonists SCH-442416 [2-(2-furanyl)-7-[3-(4-methoxyphenyl)propyl]-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] and KW-6002 [(E)-1, 3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione], respectively, in squirrel monkeys trained to intravenously self-administer THC. SCH-442416 produced a significant shift to the right of the THC self-administration dose-response curves, consistent with antagonism of the reinforcing effects of THC. Conversely, KW-6002 produced a significant shift to the left, consistent with potentiation of the reinforcing effects of THC. These results show that selectively blocking presynaptic A2A receptors could provide a new pharmacological approach to the treatment of marijuana dependence and underscore corticostriatal glutamatergic neurotransmission as a possible main mechanism involved in the rewarding effects of THC.

  18. Suicidal and nonsuicidal adolescents: different factors contribute to self-esteem.

    Science.gov (United States)

    Grøholt, Berit; Ekeberg, Oivind; Wichstrøm, Lars; Haldorsen, Tor

    2005-10-01

    Some risk and protective factors differ in their importance to suicidal and nonsuicidal people. In this research we explore the cross-sectional differences between risk factors among suicidal adolescents and nonsuicidal adolescents by focusing on self-esteem. Sixty-five suicidal and 390 nonsuicidal adolescents were compared on Harter's Self-Perceived Profile for Adolescents, self-concept stability, seeking support, loneliness, and depression. Self-concept stability, loneliness, and peer support correlated differently with self-esteem. In multivariate regression analyses, variance in self-esteem was explained by depression and loneliness, and among nonsuicidal adolescents also by self-concept stability, support, and competencies. Loneliness and self-concept stability related differently to self-esteem in suicidal and nonsuicidal adolescents. When the aim is to enhance self-esteem, this difference may delineate suicidal subgroups that need special interventions.

  19. Iodine-125 induced DNA strand breakage: Contributions of different physical and chemical radiation action mechanisms

    International Nuclear Information System (INIS)

    Li, W.

    2002-01-01

    The decay of the radioisotope 125 I into 125 Te is typically followed by the emission of two groups of approximately 10 electrons each. In deoxyribonucleic acid (DNA) with 125 I incorporated, these electrons produce various types of damage to DNA, e.g. single and double strand breaks. They occur through direct actions of physical tracks, or indirect actions of radicals produced in water. Among the direct actions one should consider not only the excitation and ionization of DNA by electrons but also the neutralization of highly charged 125m Te ions with electrons from neighboring molecules. The present work begins with a detailed description of electron tracks with the use of the PARTRAC code, compares results with recent experiments, and concludes with a firm assessment of the contribution to the strand break yields from the neutralization effect. (orig.)

  20. Explaining Social Class Inequalities in Educational Achievement in the UK: Quantifying the Contribution of Social Class Differences in School "Effectiveness"

    Science.gov (United States)

    Hobbs, Graham

    2016-01-01

    There are large social class inequalities in educational achievement in the UK. This paper quantifies the contribution of one mechanism to the production of these inequalities: social class differences in school "effectiveness," where "effectiveness" refers to a school's impact on pupils' educational achievement (relative to…

  1. Explaining educational differences in leisure-time physical activity in Europe: the contribution of work-related factors

    NARCIS (Netherlands)

    Mäkinen, T. E.; Sippola, R.; Borodulin, K.; Rahkonen, O.; Kunst, A.; Klumbiene, J.; Regidor, E.; Ekholm, O.; Mackenbach, J.; Prättälä, R.

    2012-01-01

    Although educational differences in leisure-time physical activity (LTPA) exist across Europe, the independent effect of educational level on leisure-time physical activity has rarely been explored. This study examines the relative contribution of occupational class, employment status, and

  2. Explaining educational differences in leisure-time physical activity in Europe: the contribution of work-related factors

    DEFF Research Database (Denmark)

    Mäkinen, T E; Sippola, R; Borodulin, K

    2011-01-01

    Although educational differences in leisure-time physical activity (LTPA) exist across Europe, the independent effect of educational level on leisure-time physical activity has rarely been explored. This study examines the relative contribution of occupational class, employment status...... and employment status had only a modest effect on educational differences in LTPA in most of the examined countries, suggesting that education remains an important predictor of LTPA....

  3. Processed Food Contributions to Energy and Nutrient Intake Differ among US Children by Race/Ethnicity.

    Science.gov (United States)

    Eicher-Miller, Heather A; Fulgoni, Victor L; Keast, Debra R

    2015-12-02

    This study determined and compared the mean daily intake of energy and nutrients from processed foods by level of processing (minimally processed; processed for preservation, nutrient enhancement, and freshness; mixtures of combined ingredients; ready-to-eat processed foods; and prepared foods/meals) among non-Hispanic white, non-Hispanic black, and Mexican American US children. Data from participants 2-18 years old (n = 10,298) of the nationally representative cross-sectional National Health and Nutrition Examination Survey 2003-2008 with a complete one day, 24-h dietary recall were used to determine mean intake of energy and nutrients recommended for increase and decrease, as per the 2010 Dietary Guidelines for Americans, among child race/ethnic groups by category of food processing. Regression analysis was used to estimate and compare covariate-adjusted (gender, age, and poverty-income-level) least square means (p processed foods. Approximately 66% to 84% of total daily energy, saturated fat, cholesterol, fiber, total sugar, added sugars, calcium, vitamin D, potassium, and sodium intake are contributed by one of the five categories of processed foods. Clinicians and policy should primarily advise consideration of the energy and nutrient composition of foods, rather than the processing level, when selecting a healthy diet for children.

  4. Volumetric behaviour of amino acids and their group contributions in aqueous lactose solutions at different temperatures

    International Nuclear Information System (INIS)

    Pal, Amalendu; Chauhan, Nalin

    2011-01-01

    Densities, ρ, for glycine, L-alanine, L-valine, and L-leucine [(0.05 to 0.30) m] in aqueous lactose solutions ranging from pure water to 6 mass% lactose were determined at T = (293.15, 298.15, 303.15, and 308.15) K. The density was used to compute apparent molar volume, V φ , partial molar volume at infinite dilution, V φ o , and experimental slope, S V were obtained and interpreted in terms of solute-solvent and solute-solute interactions. These data were used to calculate the (∂V φ 0 /∂T) P values. The partial molar volume of transfer, ΔV φ 0 from water to aqueous lactose solutions at infinite dilution has also been calculated. In addition to this, the linear correlation of V φ 0 with number of carbon atoms in the alkyl chain of amino acids was utilized to determine the respective contributions of NH 3 + COO - , and CH 2 groups to V φ 0 .

  5. Processed Food Contributions to Energy and Nutrient Intake Differ among US Children by Race/Ethnicity

    Directory of Open Access Journals (Sweden)

    Heather A. Eicher-Miller

    2015-12-01

    Full Text Available This study determined and compared the mean daily intake of energy and nutrients from processed foods by level of processing (minimally processed; processed for preservation, nutrient enhancement, and freshness; mixtures of combined ingredients; ready-to-eat processed foods; and prepared foods/meals among non-Hispanic white, non-Hispanic black, and Mexican American US children. Data from participants 2–18 years old (n = 10,298 of the nationally representative cross-sectional National Health and Nutrition Examination Survey 2003–2008 with a complete one day, 24-h dietary recall were used to determine mean intake of energy and nutrients recommended for increase and decrease, as per the 2010 Dietary Guidelines for Americans, among child race/ethnic groups by category of food processing. Regression analysis was used to estimate and compare covariate-adjusted (gender, age, and poverty-income-level least square means (p < 0.05/3 race/ethnic groups. All children, regardless of race or ethnicity consumed processed foods. Approximately 66% to 84% of total daily energy, saturated fat, cholesterol, fiber, total sugar, added sugars, calcium, vitamin D, potassium, and sodium intake are contributed by one of the five categories of processed foods. Clinicians and policy should primarily advise consideration of the energy and nutrient composition of foods, rather than the processing level, when selecting a healthy diet for children.

  6. Processed Food Contributions to Energy and Nutrient Intake Differ among US Children by Race/Ethnicity

    Science.gov (United States)

    Eicher-Miller, Heather A.; Fulgoni, Victor L.; Keast, Debra R.

    2015-01-01

    This study determined and compared the mean daily intake of energy and nutrients from processed foods by level of processing (minimally processed; processed for preservation, nutrient enhancement, and freshness; mixtures of combined ingredients; ready-to-eat processed foods; and prepared foods/meals) among non-Hispanic white, non-Hispanic black, and Mexican American US children. Data from participants 2–18 years old (n = 10,298) of the nationally representative cross-sectional National Health and Nutrition Examination Survey 2003–2008 with a complete one day, 24-h dietary recall were used to determine mean intake of energy and nutrients recommended for increase and decrease, as per the 2010 Dietary Guidelines for Americans, among child race/ethnic groups by category of food processing. Regression analysis was used to estimate and compare covariate-adjusted (gender, age, and poverty-income-level) least square means (p processed foods. Approximately 66% to 84% of total daily energy, saturated fat, cholesterol, fiber, total sugar, added sugars, calcium, vitamin D, potassium, and sodium intake are contributed by one of the five categories of processed foods. Clinicians and policy should primarily advise consideration of the energy and nutrient composition of foods, rather than the processing level, when selecting a healthy diet for children. PMID:26633491

  7. Volumetric behaviour of amino acids and their group contributions in aqueous lactose solutions at different temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Pal, Amalendu, E-mail: palchem@sify.co [Department of Chemistry, Kurukshetra University, Kurukshetra 136 119 (India); Chauhan, Nalin [Department of Chemistry, Kurukshetra University, Kurukshetra 136 119 (India)

    2011-02-15

    Densities, {rho}, for glycine, L-alanine, L-valine, and L-leucine [(0.05 to 0.30) m] in aqueous lactose solutions ranging from pure water to 6 mass% lactose were determined at T = (293.15, 298.15, 303.15, and 308.15) K. The density was used to compute apparent molar volume, V{sub {phi}}, partial molar volume at infinite dilution, V{sub {phi}}{sup o}, and experimental slope, S{sub V} were obtained and interpreted in terms of solute-solvent and solute-solute interactions. These data were used to calculate the ({partial_derivative}V{sub {phi}}{sup 0}/{partial_derivative}T){sub P} values. The partial molar volume of transfer, {Delta}V{sub {phi}}{sup 0} from water to aqueous lactose solutions at infinite dilution has also been calculated. In addition to this, the linear correlation of V{sub {phi}}{sup 0} with number of carbon atoms in the alkyl chain of amino acids was utilized to determine the respective contributions of NH{sub 3}{sup +}COO{sup -}, and CH{sub 2} groups to V{sub {phi}}{sup 0}.

  8. Sex Differences in the Contribution of Respiratory Sinus Arrhythmia and Trauma to Children's Psychopathology.

    Science.gov (United States)

    Gray, Sarah A O; Theall, Katherine; Lipschutz, Rebecca; Drury, Stacy

    2017-03-01

    Respiratory sinus arrhythmia (RSA), a marker of parasympathetic activity, has been shown to moderate the relation between adversity and child behavioral outcomes; however, this work has been conducted in primarily Caucasian samples and limited in focus to family-level adversity. The current analysis extends the previous literature to examine the co-contribution of exposure to potentially traumatic events (PTEs), baseline RSA, and RSA withdrawal to internalizing and externalizing behavior in a sample of primarily African American youth ( n = 92) recruited using neighborhood mapping techniques from communities high in epidemiological indicators of adversity. Exposure to PTEs was associated with lower baseline RSA. Complex interactions were observed between sex of the child, baseline RSA and RSA withdrawal, and PTE exposure predicting to internalizing behaviors. Among girls with high (4+) levels of PTEs, high baseline RSA and RSA withdrawal predicted higher internalizing; for RSA withdrawal only, the inverse was observed for girls with low PTE exposure, for whom high RSA withdrawal predicted lower internalizing. No associations were observed from RSA to externalizing, or among boys to internalizing. Findings are consistent with distinct patterns among primarily African American samples and suggest the need for sex-specific conceptualizations of the link between environmental adversity, physiological reactivity, and internalizing behaviors.

  9. Sex Differences in the Contribution of Respiratory Sinus Arrhythmia and Trauma to Children’s Psychopathology

    Science.gov (United States)

    Gray, Sarah A. O.; Theall, Katherine; Lipschutz, Rebecca; Drury, Stacy

    2016-01-01

    Respiratory sinus arrhythmia (RSA), a marker of parasympathetic activity, has been shown to moderate the relation between adversity and child behavioral outcomes; however, this work has been conducted in primarily Caucasian samples and limited in focus to family-level adversity. The current analysis extends the previous literature to examine the co-contribution of exposure to potentially traumatic events (PTEs), baseline RSA, and RSA withdrawal to internalizing and externalizing behavior in a sample of primarily African American youth (n = 92) recruited using neighborhood mapping techniques from communities high in epidemiological indicators of adversity. Exposure to PTEs was associated with lower baseline RSA. Complex interactions were observed between sex of the child, baseline RSA and RSA withdrawal, and PTE exposure predicting to internalizing behaviors. Among girls with high (4+) levels of PTEs, high baseline RSA and RSA withdrawal predicted higher internalizing; for RSA withdrawal only, the inverse was observed for girls with low PTE exposure, for whom high RSA withdrawal predicted lower internalizing. No associations were observed from RSA to externalizing, or among boys to internalizing. Findings are consistent with distinct patterns among primarily African American samples and suggest the need for sex-specific conceptualizations of the link between environmental adversity, physiological reactivity, and internalizing behaviors. PMID:28479668

  10. Making sense of differing overdose mortality: contributions to improved understanding of European patterns.

    Science.gov (United States)

    Waal, Helge; Gossop, Michael

    2014-01-01

    The European Monitoring Centre for Drugs and Drug Addiction, EMCDDA, publishes statistics for overdose deaths giving a European mean number, and ranking nations in a national 'league table' for overdose deaths. The interpretation of differing national levels of mortality is more problematic and more complex than is usually recognised. Different systems are used to compile mortality data and this causes problems for cross-national comparisons. Addiction behaviour can only be properly understood within its specific social and environmental ecology. Risk factors for overdose, such as the type of drug consumed, and the route of administration, are known to differ across countries. This paper describes problems associated with ranking and suggests how mortality data might be used in high-level countries aiming at reduction in the number of overdose deaths. Copyright © 2013 S. Karger AG, Basel.

  11. Individual differences in current events knowledge: contributions of ability, personality, and interests.

    Science.gov (United States)

    Hambrick, David Z; Meinz, Elizabeth J; Oswald, Frederick L

    2007-03-01

    What accounts for individual differences in the sort of knowledge that people may draw on in everyday cognitive tasks, such as deciding whom to vote for in a presidential election, how to invest money in the stock market, or what team to bet on in a friendly wager? In a large sample of undergraduate students, we investigated correlates of individual differences in recently acquired knowledge of current events in domains such as politics, business, and sports. Structural equation modeling revealed two predictive pathways: one involving cognitive ability factors and the other involving two major nonability factors (personality and interests). The results of this study add to what is known about the sources of individual differences in knowledge and are interpreted in the context of theoretical conceptions of adult intelligence that emphasize the centrality and importance of knowledge (e.g., Ackerman, 1996; Cattell, 1971).

  12. Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release.

    Directory of Open Access Journals (Sweden)

    Varun K Gupta

    2016-09-01

    Full Text Available Memories are assumed to be formed by sets of synapses changing their structural or functional performance. The efficacy of forming new memories declines with advancing age, but the synaptic changes underlying age-induced memory impairment remain poorly understood. Recently, we found spermidine feeding to specifically suppress age-dependent impairments in forming olfactory memories, providing a mean to search for synaptic changes involved in age-dependent memory impairment. Here, we show that a specific synaptic compartment, the presynaptic active zone (AZ, increases the size of its ultrastructural elaboration and releases significantly more synaptic vesicles with advancing age. These age-induced AZ changes, however, were fully suppressed by spermidine feeding. A genetically enforced enlargement of AZ scaffolds (four gene-copies of BRP impaired memory formation in young animals. Thus, in the Drosophila nervous system, aging AZs seem to steer towards the upper limit of their operational range, limiting synaptic plasticity and contributing to impairment of memory formation. Spermidine feeding suppresses age-dependent memory impairment by counteracting these age-dependent changes directly at the synapse.

  13. Contribution of charge symmetry breaking interactions in binding energy difference of mirror nuclei

    International Nuclear Information System (INIS)

    Asghari, M.

    2006-01-01

    Nolen-Schiffer Anomaly in mirror nuclei due to the NN interactions with isospin mixing between T=0 and T=1 mesons of the same spin and parity are investigated. With the computation of coulomb energy along with the charge symmetry breaking effects provide a reasonably accurate description of binding energy differences between 39 Ca- 39 K , 41 Sc- 41 Ca mirror nuclei

  14. Working Memory and Strategy Use Contribute to Gender Differences in Spatial Ability

    Science.gov (United States)

    Wang, Lu; Carr, Martha

    2014-01-01

    In this review, a new model that is grounded in information-processing theory is proposed to account for gender differences in spatial ability. The proposed model assumes that the relative strength of working memory, as expressed by the ratio of visuospatial working memory to verbal working memory, influences the type of strategies used on spatial…

  15. Role of peptide processing predictions in T cell epitope identification : contribution of different prediction programs

    NARCIS (Netherlands)

    Calis, Jorg J A; Reinink, Peter; Keller, Christin; Kloetzel, Peter M; Kesmir, Can

    2015-01-01

    Proteolysis is the general term to describe the process of protein degradation into peptides. Proteasomes are the main actors in cellular proteolysis, and their activity can be measured in in vitro digestion experiments. However, in vivo proteolysis can be different than what is measured in these

  16. Contribution of screening and survival differences to racial disparities in colorectal cancer rates

    NARCIS (Netherlands)

    I. Lansdorp-Vogelaar (Iris); K.M. Kuntz (Karen); A.B. Knudsen (Amy); M. van Ballegooijen (Marjolein); A. Zauber (Ann); A. Jemal (Ahmedin)

    2012-01-01

    textabstractBackground: Considerable disparities exist in colorectal cancer (CRC) incidence and mortality rates between blacks and whites in the United States. We estimated how much of these disparities could be explained by differences in CRC screening and stage-specific relative CRC survival.

  17. Factors Contributing to Changes in a Deep Approach to Learning in Different Learning Environments

    Science.gov (United States)

    Postareff, Liisa; Parpala, Anna; Lindblom-Ylänne, Sari

    2015-01-01

    The study explored factors explaining changes in a deep approach to learning. The data consisted of interviews with 12 students from four Bachelor-level courses representing different disciplines. We analysed and compared descriptions of students whose deep approach either increased, decreased or remained relatively unchanged during their courses.…

  18. Cause-specific contributions to black-white differences in male mortality from 1960 to 1995

    Directory of Open Access Journals (Sweden)

    2004-04-01

    Full Text Available Between 1960 and 1995 the black-white difference in male life expectancy in the United States increased from 6.7 years to 8.2 years. To provide insights into why mortality trends have been more adverse for black men than for white men, we investigate which causes of death were principally responsible for changes in the black-white difference in male mortality at ages 15-64 between 1960 and 1995. We find that black-white differences in male mortality varied substantially during this period. The gap increased in the 1960s, declined in the 1970s, and widened in the 1980s-early 1990s. Our findings reveal considerable variation in black-white disparities by cause of death and by age, as well as changes in the relative importance of various causes of death to the black-white male mortality disparity over time. The results suggest that consequences of black-white differences in socioeconomic status, access to quality health care, living conditions, and residential segregation vary by cause of death.

  19. Glycosylation differences contribute to distinct catalytic properties among bone alkaline phosphatase isoforms.

    Science.gov (United States)

    Halling Linder, Cecilia; Narisawa, Sonoko; Millán, José Luis; Magnusson, Per

    2009-11-01

    Three circulating human bone alkaline phosphatase (BALP) isoforms (B1, B2, and B/I) can be distinguished in healthy individuals and a fourth isoform (B1x) has been discovered in patients with chronic kidney disease and in bone tissue. The present study was designed to correlate differing glycosylation patterns of each BALP isoform with their catalytic activity towards presumptive physiological substrates and to compare those properties with two recombinant isoforms of the tissue-nonspecific ALP (TNALP) isozyme, i.e., TNALP-flag, used extensively for mutation analysis of hypophosphatasia mutations and sALP-FcD(10), a chimeric enzyme recently used as therapeutic drug in a mouse model of infantile hypophosphatasia. The BALP isoforms were prepared from human osteosarcoma (SaOS-2) cells and the kinetic properties were evaluated using the synthetic substrate p-nitrophenylphosphate (pNPP) at pH 7.4 and 9.8, and the three suggested endogenous physiological substrates, i.e., inorganic pyrophosphate (PP(i)), pyridoxal 5'-phosphate (PLP), and phosphoethanolamine (PEA) at pH 7.4. Qualitative glycosylation differences were also assessed by lectin binding and precipitation. The k(cat)/K(M) was higher for B2 for all the investigated substrates. The catalytic activity towards PEA was essentially undetectable. The kinetic activity for TNALP-flag and sALP-FcD(10) was similar to the activity of the human BALP isoforms. The BALP isoforms differed in their lectin binding properties and dose-dependent lectin precipitation, which also demonstrated differences between native and denatured BALP isoforms. The observed differences in lectin specificity were attributed to N-linked carbohydrates. In conclusion, we demonstrate significantly different catalytic properties among the BALP isoforms due to structural differences in posttranslational glycosylation. Our data also suggests that PEA is not an endogenous substrate for the BALP isoforms or for the recombinant TNALP isoforms. The TNALP

  20. Contribution of screening and survival differences to racial disparities in colorectal cancer rates

    Science.gov (United States)

    Lansdorp-Vogelaar, Iris; Kuntz, Karen M.; Knudsen, Amy B.; van Ballegooijen, Marjolein; Zauber, Ann G.; Jemal, Ahmedin

    2012-01-01

    Background Considerable disparities exist in colorectal cancer (CRC) incidence and mortality rates between blacks and whites in the US. We estimated how much of these disparities could be explained by differences in CRC screening and stage-specific relative CRC survival. Methods We used the MISCAN-Colon microsimulation model to estimate CRC incidence and mortality rates in blacks aged 50 years and older from 1975 to 2007 assuming they had: 1) the same trends in screening rates as whites instead of observed screening rates (incidence and mortality); and 2) the same trends in stage-specific relative CRC survival rates as whites instead of observed (mortality only); and 3) a combination of both. The racial disparities in CRC incidence and mortality rates attributable to differences in screening and/or stage-specific relative CRC survival were then calculated by comparing rates from these scenarios to the observed black rates. Results Differences in screening account for 42% of disparity in CRC incidence and 19% of disparity in CRC mortality between blacks and whites. 36% of the disparity in CRC mortality could be attributed to differences in stage-specific relative CRC survival. Together screening and survival explained a little over 50% of the disparity in CRC mortality between blacks and whites. Conclusion Differences in screening and relative CRC survival are responsible for a considerable proportion of the observed disparities in CRC incidence and mortality rates between blacks and whites. Impact Enabling blacks to achieve equal access to care as whites could substantially reduce the racial disparities in CRC burden. PMID:22514249

  1. Contributions of different degrees of freedom to thermal transport in the C60 molecular crystal

    Science.gov (United States)

    Kumar, Sushant; Shao, Cheng; Lu, Simon; McGaughey, Alan J. H.

    2018-03-01

    Three models of the C60 molecular crystal are studied using molecular dynamics simulations to resolve the roles played by intermolecular and intramolecular degrees of freedom (DOF) in its structural, mechanical, and thermal properties at temperatures between 35 and 400 K. In the full DOF model, all DOF are active. In the rigid body model, the intramolecular DOF are frozen, such that only center of mass (COM) translations and molecular rotations/librations are active. In the point mass model, the molecule is replaced by a point mass, such that only COM translations are active. The zero-pressure lattice constants and bulk moduli predicted from the three models fall within ranges of 0.15 and 20%. The thermal conductivity of the point mass model is the largest across the temperature range, showing a crystal-like temperature dependence (i.e., it decreases with increasing temperature) due to the presence of phonon modes associated with the COM translations. The rigid body model thermal conductivity is the smallest and follows two distinct regimes. It is crystal-like at low temperatures and becomes temperature invariant at high temperatures. The latter is typical of the behavior of an amorphous material. By calculating the rotational diffusion coefficient, the transition between the two regimes is found to occur at the temperature where the molecules begin to rotate freely. Above this temperature, phonons related to COM translations are scattered by the rotational DOF. The full DOF model thermal conductivity is larger than that of the rigid body model, indicating that intramolecular DOF contribute to thermal transport.

  2. Contributions of Different Cloud Types to Feedbacks and Rapid Adjustments in CMIP5*

    Energy Technology Data Exchange (ETDEWEB)

    Zelinka, Mark D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Program for Climate Model Diagnosis and Intercomparison; Klein, Stephen A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Program for Climate Model Diagnosis and Intercomparison; Taylor, Karl E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Program for Climate Model Diagnosis and Intercomparison; Andrews, Timothy [Met Office Hadley Center, Exeter (United Kingdom); Webb, Mark J. [Met Office Hadley Center, Exeter (United Kingdom); Gregory, Jonathan M. [Univ. of Reading, Exeter (United Kingdom). National Center for Atmospheric Science; Forster, Piers M. [Univ. of Leeds (United Kingdom)

    2013-07-01

    When using five climate model simulations of the response to an abrupt quadrupling of CO2, the authors perform the first simultaneous model intercomparison of cloud feedbacks and rapid radiative adjustments with cloud masking effects removed, partitioned among changes in cloud types and gross cloud properties. After CO2 quadrupling, clouds exhibit a rapid reduction in fractional coverage, cloud-top pressure, and optical depth, with each contributing equally to a 1.1 W m-2 net cloud radiative adjustment, primarily from shortwave radiation. Rapid reductions in midlevel clouds and optically thick clouds are important in reducing planetary albedo in every model. As the planet warms, clouds become fewer, higher, and thicker, and global mean net cloud feedback is positive in all but one model and results primarily from increased trapping of longwave radiation. As was true for earlier models, high cloud changes are the largest contributor to intermodel spread in longwave and shortwave cloud feedbacks, but low cloud changes are the largest contributor to the mean and spread in net cloud feedback. The importance of the negative optical depth feedback relative to the amount feedback at high latitudes is even more marked than in earlier models. Furthermore, the authors show that the negative longwave cloud adjustment inferred in previous studies is primarily caused by a 1.3 W m-2 cloud masking of CO2 forcing. Properly accounting for cloud masking increases net cloud feedback by 0.3 W m-2 K-1, whereas accounting for rapid adjustments reduces by 0.14 W m-2 K-1 the ensemble mean net cloud feedback through a combination of smaller positive cloud amount and altitude feedbacks and larger negative optical depth feedbacks.

  3. Postotic and preotic cranial neural crest cells differently contribute to thyroid development.

    Science.gov (United States)

    Maeda, Kazuhiro; Asai, Rieko; Maruyama, Kazuaki; Kurihara, Yukiko; Nakanishi, Toshio; Kurihara, Hiroki; Miyagawa-Tomita, Sachiko

    2016-01-01

    Thyroid development and formation vary among species, but in most species the thyroid morphogenesis consists of five stages: specification, budding, descent, bilobation and folliculogenesis. The detailed mechanisms of these stages have not been fully clarified. During early development, the cranial neural crest (CNC) contributes to the thyroid gland. The removal of the postotic CNC (corresponding to rhombomeres 6, 7 and 8, also known as the cardiac neural crest) results in abnormalities of the cardiovascular system, thymus, parathyroid glands, and thyroid gland. To investigate the influence of the CNC on thyroid bilobation process, we divided the CNC into two regions, the postotic CNC and the preotic CNC (from the mesencephalon to rhombomere 5) regions and examined. We found that preotic CNC-ablated embryos had a unilateral thyroid lobe, and confirmed the presence of a single lobe or the absence of lobes in postotic CNC-ablated chick embryos. The thyroid anlage in each region-ablated embryos was of a normal size at the descent stage, but at a later stage, the thyroid in preotic CNC-ablated embryos was of a normal size, conflicting with a previous report in which the thyroid was reduced in size in the postotic CNC-ablated embryos. The postotic CNC cells differentiated into connective tissues of the thyroid in quail-to-chick chimeras. In contrast, the preotic CNC cells did not differentiate into connective tissues of the thyroid. We found that preotic CNC cells encompassed the thyroid anlage from the specification stage to the descent stage. Finally, we found that endothelin-1 and endothelin type A receptor-knockout mice and bosentan (endothelin receptor antagonist)-treated chick embryos showed bilobation anomalies that included single-lobe formation. Therefore, not only the postotic CNC, but also the preotic CNC plays an important role in thyroid morphogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Gender differences in recognition of toy faces suggest a contribution of experience.

    Science.gov (United States)

    Ryan, Kaitlin F; Gauthier, Isabel

    2016-12-01

    When there is a gender effect, women perform better then men in face recognition tasks. Prior work has not documented a male advantage on a face recognition task, suggesting that women may outperform men at face recognition generally either due to evolutionary reasons or the influence of social roles. Here, we question the idea that women excel at all face recognition and provide a proof of concept based on a face category for which men outperform women. We developed a test of face learning to measures individual differences with face categories for which men and women may differ in experience, using the faces of Barbie dolls and of Transformers. The results show a crossover interaction between subject gender and category, where men outperform women with Transformers' faces. We demonstrate that men can outperform women with some categories of faces, suggesting that explanations for a general face recognition advantage for women are in fact not needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Individual differences in forced-choice recognition memory:Partitioning contributions of recollection and familiarity

    OpenAIRE

    Migo, Ellen M.; Quamme, Joel R.; Holmes, Selina; Bendell, Andrew; Norman, Kenneth A.; Mayes, Andrew R.; Montaldi, Daniela

    2014-01-01

    In forced-choice recognition memory, two different testing formats are possible under conditions of high target-foil similarity: Each target can be presented alongside foils similar to itself (forced-choice corresponding; FCC), or alongside foils similar to other targets (forced-choice noncorresponding; FCNC). Recent behavioural and neuropsychological studies suggest that FCC performance can be supported by familiarity whereas FCNC performance is supported primarily by recollection. In this p...

  6. Factors contributing to the differences in work related injury rates between Danish and Swedish construction workers

    DEFF Research Database (Denmark)

    Spangenberg, S.; Baarts, C.; Dyreborg, J.

    2002-01-01

    of injury risk factors at group and individual level for Danish and Swedish workers. LTI-rates and injury risk factors were compared for Danish and Swedish workers during the construction of the combined rail and road link across the 16-km wide sound, Oresund, between Denmark and Sweden. The comparison...... showed that the LTI-rate of the Danish construction workers was approximately fourfold the LTI-rate of the Swedish construction workers. Factors at the micro-level (group and individual level) e.g. differences in education and experience, training and learning, and attitude were important...

  7. The contribution of social and environmental factors to race differences in dental services use.

    Science.gov (United States)

    Eisen, Colby H; Bowie, Janice V; Gaskin, Darrell J; LaVeist, Thomas A; Thorpe, Roland J

    2015-06-01

    Dental services use is a public health issue that varies by race. African Americans are less likely than whites to make use of these services. While several explanations exist, little is known about the role of segregation in understanding this race difference. Most research does not account for the confounding of race, socioeconomic status, and segregation. Using cross-sectional data from the Exploring Health Disparities in Integrated Communities Study, we examined the relationship between race and dental services use. Our primary outcome of interest was dental services use within 2 years. Our main independent variable was self-identified race. Of the 1408 study participants, 59.3% were African American. More African Americans used dental services within 2 years than whites. After adjusting for age, gender, marital status, income, education, insurance, self-rated health, and number of comorbidities, African Americans had greater odds of having used services (odds ratio = 1.48, 95% confidence interval 1.16, 1.89) within 2 years. Within this low-income racially integrated sample, African Americans participated in dental services more than whites. Place of living is an important factor to consider when seeking to understand race differences in dental service use.

  8. Contribution of caspase-3 differs by p53 status in apoptosis induced by X-irradiation

    International Nuclear Information System (INIS)

    Kobayashi, Daisuke; Tokino, Takashi; Watanabe, Naoki

    2001-01-01

    We investigated the effect of p53 status on involvement of caspase-3 activation in cell death induced by X-irradiation, using rat embryonic fibroblasts (REFs) transduced with a temperature-sensitive mutant (mt) p53 gene. Cells with wild-type (wt) p53 showed greater resistance to X-irradiation than cells with mt p53. In cells with wt p53, X-irradiation-induced apoptosis was not inhibited by the caspase-3 inhibitor acetyl-L-aspartyl-L-methionyl-L-glutaminyl-L-aspartyl-aldehyde (Ac-DMQD-CHO) and caspase-3 activity was not elevated following X-irradiation, although induction of p53 and p21/WAF-1 protein was observed. In contrast, irradiated cells with mt p53 showed 89% inhibition of cell death with Ac-DMQD-CHO and 98% inhibition with the antioxidant N-acetyl-L-cysteine (NAC). In cells with mt p53, caspase-3 activity was increased approximately 5 times beyond baseline activity at 24 h after irradiation. This increase was almost completely inhibited by NAC. However, inhibition of caspase-3 by Ac-DMQD-CHO failed to decrease production of reactive oxygen species by cells with mt p53. Differential involvement of caspase-3 is a reason for differences in sensitivity to X-irradiation in cells with different p53 status. Caspase-3 activation appears to occur downstream from generation of reactive oxygen species occurring independently of wt p53 during X-irradiation-induced cell death. (author)

  9. Individual differences in maternal response to immune challenge predict offspring behavior: Contribution of environmental factors

    Science.gov (United States)

    Bronson, Stefanie L.; Ahlbrand, Rebecca; Horn, Paul S.; Kern, Joseph R.; Richtand, Neil M.

    2011-01-01

    Maternal infection during pregnancy elevates risk for schizophrenia and related disorders in offspring. Converging evidence suggests the maternal inflammatory response mediates the interaction between maternal infection, altered brain development, and behavioral outcome. The extent to which individual differences in the maternal response to immune challenge influence the development of these abnormalities is unknown. The present study investigated the impact of individual differences in maternal response to the viral mimic polyinosinic:polycytidylic acid (poly I:C) on offspring behavior. We observed significant variability in body weight alterations of pregnant rats induced by administration of poly I:C on gestational day 14. Furthermore, the presence or absence of maternal weight loss predicted MK-801 and amphetamine stimulated locomotor abnormalities in offspring. MK-801 stimulated locomotion was altered in offspring of all poly I:C treated dams; however, the presence or absence of maternal weight loss resulted in decreased and modestly increased locomotion, respectively. Adult offspring of poly I:C treated dams that lost weight exhibited significantly decreased amphetamine stimulated locomotion, while offspring of poly I:C treated dams without weight loss performed similarly to vehicle controls. Social isolation and increased maternal age predicted weight loss in response to poly I:C but not vehicle injection. In combination, these data identify environmental factors associated with the maternal response to immune challenge and functional outcome of offspring exposed to maternal immune activation. PMID:21255612

  10. Is there a genetic contribution to cultural differences? Collectivism, individualism and genetic markers of social sensitivity.

    Science.gov (United States)

    Way, Baldwin M; Lieberman, Matthew D

    2010-06-01

    Genes and culture are often thought of as opposite ends of the nature-nurture spectrum, but here we examine possible interactions. Genetic association studies suggest that variation within the genes of central neurotransmitter systems, particularly the serotonin (5-HTTLPR, MAOA-uVNTR) and opioid (OPRM1 A118G), are associated with individual differences in social sensitivity, which reflects the degree of emotional responsivity to social events and experiences. Here, we review recent work that has demonstrated a robust cross-national correlation between the relative frequency of variants in these genes and the relative degree of individualism-collectivism in each population, suggesting that collectivism may have developed and persisted in populations with a high proportion of putative social sensitivity alleles because it was more compatible with such groups. Consistent with this notion, there was a correlation between the relative proportion of these alleles and lifetime prevalence of major depression across nations. The relationship between allele frequency and depression was partially mediated by individualism-collectivism, suggesting that reduced levels of depression in populations with a high proportion of social sensitivity alleles is due to greater collectivism. These results indicate that genetic variation may interact with ecological and social factors to influence psychocultural differences.

  11. Multimodal retrieval of autobiographical memories: sensory information contributes differently to the recollection of events.

    Science.gov (United States)

    Willander, Johan; Sikström, Sverker; Karlsson, Kristina

    2015-01-01

    Previous studies on autobiographical memory have focused on unimodal retrieval cues (i.e., cues pertaining to one modality). However, from an ecological perspective multimodal cues (i.e., cues pertaining to several modalities) are highly important to investigate. In the present study we investigated age distributions and experiential ratings of autobiographical memories retrieved with unimodal and multimodal cues. Sixty-two participants were randomized to one of four cue-conditions: visual, olfactory, auditory, or multimodal. The results showed that the peak of the distributions depends on the modality of the retrieval cue. The results indicated that multimodal retrieval seemed to be driven by visual and auditory information to a larger extent and to a lesser extent by olfactory information. Finally, no differences were observed in the number of retrieved memories or experiential ratings across the four cue-conditions.

  12. Multimodal Retrieval of Autobiographical Memories: Sensory Information Contributes Differently to the Recollection of Events

    Directory of Open Access Journals (Sweden)

    Johan eWillander

    2015-11-01

    Full Text Available Previous studies on autobiographical memory have focused on unimodal retrieval cues (i.e., cues pertaining to one modality. However, from an ecological perspective multimodal cues (i.e., cues pertaining to several modalities are highly important to investigate. In the present study we investigated age distributions and experiential ratings of autobiographical memories retrieved with unimodal and multimodal cues. Sixty-two participants were randomized to one of four cue-conditions: visual, olfactory, auditory, and multimodal. The results showed that the peak of the distributions depend on the modality of the retrieval cue. The results indicated that multimodal retrieval seemed to be driven by visual and auditory information to a larger extent and to a lesser extent by olfactory information. Finally, no differences were observed in the number of retrieved memories or experiential ratings across the four cue-conditions.

  13. The contribution of attentional lapses to individual differences in visual working memory capacity.

    Science.gov (United States)

    Adam, Kirsten C S; Mance, Irida; Fukuda, Keisuke; Vogel, Edward K

    2015-08-01

    Attentional control and working memory capacity are important cognitive abilities that substantially vary between individuals. Although much is known about how attentional control and working memory capacity relate to each other and to constructs like fluid intelligence, little is known about how trial-by-trial fluctuations in attentional engagement impact trial-by-trial working memory performance. Here, we employ a novel whole-report memory task that allowed us to distinguish between varying levels of attentional engagement in humans performing a working memory task. By characterizing low-performance trials, we can distinguish between models in which working memory performance failures are caused by either (1) complete lapses of attention or (2) variations in attentional control. We found that performance failures increase with set-size and strongly predict working memory capacity. Performance variability was best modeled by an attentional control model of attention, not a lapse model. We examined neural signatures of performance failures by measuring EEG activity while participants performed the whole-report task. The number of items correctly recalled in the memory task was predicted by frontal theta power, with decreased frontal theta power associated with poor performance on the task. In addition, we found that poor performance was not explained by failures of sensory encoding; the P1/N1 response and ocular artifact rates were equivalent for high- and low-performance trials. In all, we propose that attentional lapses alone cannot explain individual differences in working memory performance. Instead, we find that graded fluctuations in attentional control better explain the trial-by-trial differences in working memory that we observe.

  14. The Contribution of Numerical Magnitude Comparison and Phonological Processing to Individual Differences in Fourth Graders' Multiplication Fact Ability.

    Directory of Open Access Journals (Sweden)

    Tamara M J Schleepen

    Full Text Available Although numerical magnitude processing has been related to individual differences in arithmetic, its role in children's multiplication performance remains largely unknown. On the other hand, studies have indicated that phonological awareness is an important correlate of individual differences in children's multiplication performance, but the involvement of phonological memory, another important phonological processing skill, has not been studied in much detail. Furthermore, knowledge about the relative contribution of above mentioned processes to the specific arithmetic operation of multiplication in children is lacking. The present study therefore investigated for the first time the unique contributions of numerical magnitude comparison and phonological processing in explaining individual differences in 63 fourth graders' multiplication fact ability (mean age = 9.6 years, SD = .67. The results showed that children's multiplication fact competency correlated significantly with symbolic and nonsymbolic magnitude comparison as well as with phonological short-term memory. A hierarchical regression analysis revealed that, after controlling for intellectual ability and general reaction time, both symbolic and nonsymbolic magnitude comparison and phonological short-term memory accounted for unique variance in multiplication fact performance. The ability to compare symbolic magnitudes was found to contribute the most, indicating that the access to numerical magnitudes by means of Arabic digits is a key factor in explaining individual differences in children's multiplication fact ability.

  15. Phylogeny, life history, and ecology contribute to differences in amphibian susceptibility to ranaviruses.

    Science.gov (United States)

    Hoverman, Jason T; Gray, Matthew J; Haislip, Nathan A; Miller, Debra L

    2011-09-01

    Research that identifies the potential host range of generalist pathogens as well as variation in host susceptibility is critical for understanding and predicting the dynamics of infectious diseases within ecological communities. Ranaviruses have been linked to amphibian die-off events worldwide with the greatest number of reported mortality events occurring in the United States. While reports of ranavirus-associated mortality events continue to accumulate, few data exist comparing the relative susceptibility of different species. Using a series of laboratory exposure experiments and comparative phylogenetics, we compared the susceptibilities of 19 amphibian species from two salamander families and five anurans families for two ranavirus isolates: frog virus 3 (FV3) and an FV3-like isolate from an American bullfrog culture facility. We discovered that ranaviruses were capable of infecting 17 of the 19 larval amphibian species tested with mortality ranging from 0 to 100%. Phylogenetic comparative methods demonstrated that species within the anuran family Ranidae were generally more susceptible to ranavirus infection compared to species from the other five families. We also found that susceptibility to infection was associated with species that breed in semi-permanent ponds, develop rapidly as larvae, and have limited range sizes. Collectively, these results suggest that phylogeny, life history characteristics, and habitat associations of amphibians have the potential to impact susceptibility to ranaviruses.

  16. Differences in oncologist communication across age groups and contributions to adjuvant decision outcomes.

    Science.gov (United States)

    Step, Mary M; Siminoff, Laura A; Rose, Julia H

    2009-11-01

    The objective of this study was to assess potential age-related differences in oncologist communication during conversations about adjuvant therapy decisions and subsequent patient decision outcomes. Communication was observed between a cross-section of female patients aged 40 to 80 with early-stage breast cancer (n=180) and their oncologists (n=36) in 14 academic and community oncology practices in two states. Sources of data included audio recordings of visits, followed by post-visit patient interviews. Communication during the visit was assessed using the Siminoff Communication Content and Affect Program. Patient outcome measures included self-reported satisfaction with decision, decision conflict, and decision regret. Results showed that oncologists were significantly more fluent and more direct with older than middle-aged patients and trended toward expressing their own treatment preferences more with older patients. Satisfaction with treatment decisions was highest for women in their 50s and 60s. Decision conflict was significantly associated with more discussion of oncologist treatment preferences and prognosis. Decision regret was significantly associated with patient age and education. Older adults considering adjuvant therapy may find that oncologists' communication accommodations to perceived deficiencies in older adult cognition or communication challenge their decision-making involvement. Oncologists should carefully assess patient decision-making preferences and be mindful of accommodating their speech to age-related stereotypes.

  17. Spin dependence in the neutralization of He+ ions in metals: An analysis of different contributions

    International Nuclear Information System (INIS)

    Alducin, M.

    2005-01-01

    We study the spin polarization of the Auger electrons produced during the neutralization of He + ions in a free electron gas. In this process, one metal electron decays to the unoccupied state and a second electron is promoted to a continuum excited state. Although the spin of the decaying electron is fixed, both spins are allowed for the excited one. The states of the electrons involved in this Auger capture process are described by the spin-dependent Kohn-Sham orbitals obtained from density functional theory and the local spin approximation. The Auger capture rates indicate a strong polarization of the excited electron. In a paramagnetic free electron gas, there are two mechanisms accounting for this effect, the spin-dependent screening and the interference between indistinguishable processes when the involved electrons are in the same spin state. In a spin-polarized medium, the difference in the density of spin-up and spin-down electrons is a new ingredient to be considered. As a result, the excited electrons preferably come from the majority band, even in the case of He + ions with spin opposite to that of the majority band embedded in a low spin-polarized free electron gas

  18. Differences of Rotavirus Vaccine Effectiveness by Country: Likely Causes and Contributing Factors

    Directory of Open Access Journals (Sweden)

    Ulrich Desselberger

    2017-12-01

    Full Text Available Rotaviruses are a major cause of acute gastroenteritis in infants and young children worldwide and in many other mammalian and avian host species. Since 2006, two live-attenuated rotavirus vaccines, Rotarix® and RotaTeq®, have been licensed in >100 countries and are applied as part of extended program of vaccination (EPI schemes of childhood vaccinations. Whereas the vaccines have been highly effective in high-income countries, they were shown to be considerably less potent in low- and middle-income countries. Rotavirus-associated disease was still the cause of death in >200,000 children of <5 years of age worldwide in 2013, and the mortality is concentrated in countries of sub-Saharan Africa and S.E. Asia. Various factors that have been identified or suggested as being involved in the differences of rotavirus vaccine effectiveness are reviewed here. Recognition of these factors will help to achieve gradual worldwide improvement of rotavirus vaccine effectiveness.

  19. Contribution of trees and grasses to ecosystem fluxes of water, carbon, and energy throughout the seasons under different nutrient availability

    Science.gov (United States)

    El-Madany, T. S.; Migliavacca, M.; Perez-Priego, O.; Luo, Y.; Moreno, G.; Carrara, A.; Kolle, O.; Reichstein, M.

    2017-12-01

    In semi-arid savanna type ecosystems, the carbon and water cycle are closely related to each other. Water availability is the main driver for the development and phenology of the vegetation, especially for annual plants. Depending on tree density, nutrient availability and species the contribution of the tree- and the herbaceous layer to ecosystem fluxes can vary substantially. We present data from an ecosystem scale nutrient manipulation experiment within a Mediterranean savanna type ecosystem which is used for cattle. The footprint areas of two out of three ecosystem eddy co-variance (EC) towers were fertilized with nitrogen (NT) and nitrogen plus phosphorous (NPT) while the third one served as the control tower (CT). At each ecosystem EC-tower an additional herbaceous layer tower was installed that only sampled fluxes from the herbaceous layer. Under certain assumptions flux differences between the ecosystem EC and the herbaceous layer EC systems can be considered as the contribution of the trees to the ecosystem fluxes. Based on phenology of the herbaceous layer estimated through green-chromatic-coordinates from digital imagery the year was separated into spring, senescence, regreening, and winter. The focus of the analysis is (i) the evaluation of the method and how it works throughout the different seasons and (ii) the quantification of the contribution of trees and grasses to ecosystem fluxes of water, carbon, and energy under different environmental conditions and nutrient stoichiometry. The contribution of the trees to total ecosystem fluxes is variable in time. Especially, during the beginning of the senescence period high evapotranspiration rates and largest carbon uptake are measured while the contribution to sensible heat fluxes is largest during the end of the summer. During the regreening and winter the contribution of ET is relatively constant around 0.25 mm d-1. During the peak of the greenness ET and carbon flux of the herbaceous EC tower are

  20. Monaural and binaural contributions to interaural-level-difference sensitivity in human auditory cortex.

    Science.gov (United States)

    Stecker, G Christopher; McLaughlin, Susan A; Higgins, Nathan C

    2015-10-15

    Whole-brain functional magnetic resonance imaging was used to measure blood-oxygenation-level-dependent (BOLD) responses in human auditory cortex (AC) to sounds with intensity varying independently in the left and right ears. Echoplanar images were acquired at 3 Tesla with sparse image acquisition once per 12-second block of sound stimulation. Combinations of binaural intensity and stimulus presentation rate were varied between blocks, and selected to allow measurement of response-intensity functions in three configurations: monaural 55-85 dB SPL, binaural 55-85 dB SPL with intensity equal in both ears, and binaural with average binaural level of 70 dB SPL and interaural level differences (ILD) ranging ±30 dB (i.e., favoring the left or right ear). Comparison of response functions equated for contralateral intensity revealed that BOLD-response magnitudes (1) generally increased with contralateral intensity, consistent with positive drive of the BOLD response by the contralateral ear, (2) were larger for contralateral monaural stimulation than for binaural stimulation, consistent with negative effects (e.g., inhibition) of ipsilateral input, which were strongest in the left hemisphere, and (3) also increased with ipsilateral intensity when contralateral input was weak, consistent with additional, positive, effects of ipsilateral stimulation. Hemispheric asymmetries in the spatial extent and overall magnitude of BOLD responses were generally consistent with previous studies demonstrating greater bilaterality of responses in the right hemisphere and stricter contralaterality in the left hemisphere. Finally, comparison of responses to fast (40/s) and slow (5/s) stimulus presentation rates revealed significant rate-dependent adaptation of the BOLD response that varied across ILD values. Copyright © 2015. Published by Elsevier Inc.

  1. Contribution of different scintigraphic techniques to the management of medullary thyroid carcinoma

    International Nuclear Information System (INIS)

    Sandrock, D.; Blossey, H.C.; Steinroeder, M.; Munz, D.L.

    1989-01-01

    We compared three different scintigraphic techniques for the localization of neck recurrences and metastases in seven patients with medullary thyroid carcinoma one month to eight years after the first surgical intervention. Three successive scintigraphic studies were performed in five patients (6 x 3 studies) within two weeks using 201Tl chloride, 111In-labeled F(ab')2 fragments of the anti-carcinoembryonic antigen (anti-CEA) monoclonal antibody (MoAb) BW 431/31, and 131I meta-iodo-benzylguanidine (MIBG). Additionally, 11 studies were performed with the 111In-labeled MoAb fragment BW 431/31 (seven studies) or the 99mTc-labeled intact anti-CEA MoAb BW 431/26 (four studies). The gold standards for classifying scintigraphic results were biopsy, histology, surgery, and cytology. Six regions were classified as positive or negative in each study: thyroid region, four quadrants (lymph node regions) around the thyroid, and the region of the upper mediastinum. Of 36 sites, 201Tl was true positive (TP) in seven sites, false-positive (FP) in one site, true negative (TN) in 22 sites, and false-negative (FN) in six sites, resulting in a sensitivity of 54% and a specificity of 96%. 131I MIBG was TP in four sites, FP in none of the sites, TN in 23 sites, and FN in nine sites, with a sensitivity of 31% and a specificity of 100%. Immunoscintigraphy (102 sites overall) was TP in 16 sites, FP in five sites, TN in 77 sites, and FN in four sites, resulting in a sensitivity of 80% and a specificity of 94%. Immunoscintigraphy with 111In/99mTc anti-CEA F(ab')2 fragment/intact antibody is superior to scintigraphy with 201Tl and 131I MIBG

  2. Differences in Breast Cancer Survival between Public and Private Care in New Zealand: Which Factors Contribute?

    Science.gov (United States)

    Tin Tin, Sandar; Elwood, J Mark; Lawrenson, Ross; Campbell, Ian; Harvey, Vernon; Seneviratne, Sanjeewa

    2016-01-01

    Patients who received private health care appear to have better survival from breast cancer compared to those who received public care. This study investigated if this applied to New Zealand women and identified factors that could explain such disparities. This study involved all women who were diagnosed with primary breast cancer in two health regions in New Zealand, covering about 40% of the national population, between June 2000 and May 2013. Patients who received public care for primary treatment, mostly surgical treatment, were compared with those who received private care in terms of demographics, mode of presentation, disease factors, comorbidity index and treatment factors. Cox regression modelling was performed with stepwise adjustments, and hazards of breast cancer specific mortality associated with the type of health care received was assessed. Of the 14,468 patients, 8,916 (61.6%) received public care. Compared to patients treated in private care facilities, they were older, more likely to be Māori, Pacifika or Asian and to reside in deprived neighbourhoods and rural areas, and less likely to be diagnosed with early staged cancer and to receive timely cancer treatments. They had a higher risk of mortality from breast cancer (hazard ratio: 1.95; 95% CI: 1.75, 2.17), of which 80% (95% CI: 63%, 100%) was explained by baseline differences, particularly related to ethnicity, stage at diagnosis and type of loco-regional therapy. After controlling for these demographic, disease and treatment factors, the risk of mortality was still 14% higher in the public sector patients. Ethnicity, stage at diagnosis and type of loco-regional therapy were the three key contributors to survival disparities between patients treated in public and private health care facilities in New Zealand. The findings underscore the need for more efforts to improve the quality, timeliness and equitability of public cancer care services.

  3. Forebrain deletion of αGDI in adult mice worsens the pre-synaptic deficit at cortico-lateral amygdala synaptic connections.

    Directory of Open Access Journals (Sweden)

    Veronica Bianchi

    Full Text Available The GDI1 gene encodes αGDI, which retrieves inactive GDP-bound RAB from membranes to form a cytosolic pool awaiting vesicular release. Mutations in GDI1 are responsible for X-linked Intellectual Disability. Characterization of the Gdi1-null mice has revealed alterations in the total number and distribution of hippocampal and cortical synaptic vesicles, hippocampal short-term synaptic plasticity and specific short-term memory deficits in adult mice, which are possibly caused by alterations of different synaptic vesicle recycling pathways controlled by several RAB GTPases. However, interpretation of these studies is complicated by the complete ablation of Gdi1 in all cells in the brain throughout development. In this study, we generated conditionally gene-targeted mice in which the knockout of Gdi1 is restricted to the forebrain, hippocampus, cortex and amygdala and occurs only during postnatal development. Adult mutant mice reproduce the short-term memory deficit previously reported in Gdi1-null mice. Surprisingly, the delayed ablation of Gdi1 worsens the pre-synaptic phenotype at cortico-amygdala synaptic connections compared to Gdi1-null mice. These results suggest a pivotal role of αGDI via specific RAB GTPases acting specifically in forebrain regions at the pre-synaptic sites involved in memory formation.

  4. The effects of manipulation of presynaptic 5-HT nerve terminals of postsynaptic 5-HT1 and 5-HT2 binding sites of the rat brain

    International Nuclear Information System (INIS)

    Hall, H.; Wedel, I.

    1985-01-01

    The effects of long-term treatment of rats with alaproclate and amiflamine on the number and kinetics of 5-HT 1 and 5-HT 2 binding sites were investigated using in vitro receptor binding techniques. Some other studies have reported down-regulatory effects of alaproclate and amiflamine on 5-HT 2 binding sites in certain regions of the rat forebrain, but no such effects could be detected in the present study. Induction of a high-affinity binding site for 3 H-5-HT after long-term antidepressant treatment, as has been reported elsewhere, was not obtained in the present study. The results are compared to the effects obtained by treatment of rats with para-chloroamphetamine (PCA), which depletes the presynaptic neurons of monoamines. These different types of treatment do not cause any change in the binding properties of the specific 5-HT binding sites. It is thus concluded that such manipulations of the presynaptic 5-HT neurons do not affect the postsynaptic 5-HT 1 and 5-HT 2 binding sites. (Author)

  5. Ecologically Different Fungi Affect Arabidopsis Development: Contribution of Soluble and Volatile Compounds

    Science.gov (United States)

    Casarrubia, Salvatore; Sapienza, Sara; Fritz, Héma; Daghino, Stefania; Rosenkranz, Maaria; Schnitzler, Jörg-Peter; Martin, Francis; Perotto, Silvia

    2016-01-01

    Plant growth and development can be influenced by mutualistic and non-mutualistic microorganisms. We investigated the ability of the ericoid endomycorrhizal fungus Oidiodendron maius to influence growth and development of the non-host plant Arabidopsis thaliana. Different experimental setups (non-compartmented and compartmented co-culture plates) were used to investigate the influence of both soluble and volatile fungal molecules on the plant phenotype. O. maius promoted growth of A. thaliana in all experimental setups. In addition, a peculiar clumped root phenotype, characterized by shortening of the primary root and by an increase of lateral root length and number, was observed in A. thaliana only in the non-compartmented plates, suggesting that soluble diffusible molecules are responsible for this root morphology. Fungal auxin does not seem to be involved in plant growth promotion and in the clumped root phenotype because co-cultivation with O. maius did not change auxin accumulation in plant tissues, as assessed in plants carrying the DR5::GUS reporter construct. In addition, no correlation between the amount of fungal auxin produced and the plant root phenotype was observed in an O. maius mutant unable to induce the clumped root phenotype in A. thaliana. Addition of active charcoal, a VOC absorbant, in the compartmented plates did not modify plant growth promotion, suggesting that VOCs are not involved in this phenomenon. The low VOCs emission measured for O. maius further corroborated this hypothesis. By contrast, the addition of CO2 traps in the compartmented plates drastically reduced plant growth, suggesting involvement of fungal CO2 in plant growth promotion. Other mycorrhizal fungi, as well as a saprotrophic and a pathogenic fungus, were also tested with the same experimental setups. In the non-compartmented plates, most fungi promoted A. thaliana growth and some could induce the clumped root phenotype. In the compartmented plate experiments, a general

  6. Source contributions and mass loadings for chemicals of emerging concern: Chemometric application of pharmaco-signature in different aquatic systems

    International Nuclear Information System (INIS)

    Jiang, Jheng-Jie; Lee, Chon-Lin; Brimblecombe, Peter; Vydrova, Lucie; Fang, Meng-Der

    2016-01-01

    To characterize the source contributions of chemicals of emerging concern (CECs) from different aquatic environments of Taiwan, we collected water samples from different aquatic systems, which were screened for 30 pharmaceuticals and illicit drugs. The total estimated mass loadings of CECs were 23.1 g/d in southern aquatic systems and 133 g/d in central aquatic systems. We developed an analytical framework combining pollutant fingerprinting, hierarchical cluster analysis (HCA), and principal component analysis with multiple linear regression (PCA-MLR) to infer the pharmaco-signature and source contributions of CECs. Based on this approach, we estimate source contributions of 62.2% for domestic inputs, 16.9% for antibiotics application, and 20.9% for drug abuse/medication in southern aquatic system, compared with 47.3% domestic, 35.1% antibiotic, and 17.6% drug abuse/medication inputs to central aquatic systems. The proposed pharmaco-signature method provides initial insights into the profile and source apportionment of CECs in complex aquatic systems, which are of importance for environmental management. - Highlights: • Pharmaco-signature provides first insights into the profile and source apportionment of CECs. • Performing HCA and PCA-MLR can discern the potential source of CECs in different aquatic systems. • Chemometric results resolved 3 factors: domestic inputs, antibiotic application and drug abuse. - The proposed pharmaco-signature method provides initial insights into the profile and source apportionment of CECs in complex aquatic systems.

  7. Presynaptic dystroglycan-pikachurin complex regulates the proper synaptic connection between retinal photoreceptor and bipolar cells.

    Science.gov (United States)

    Omori, Yoshihiro; Araki, Fumiyuki; Chaya, Taro; Kajimura, Naoko; Irie, Shoichi; Terada, Koji; Muranishi, Yuki; Tsujii, Toshinori; Ueno, Shinji; Koyasu, Toshiyuki; Tamaki, Yasuhiro; Kondo, Mineo; Amano, Shiro; Furukawa, Takahisa

    2012-05-02

    Dystroglycan (DG) is a key component of the dystrophin-glycoprotein complex (DGC) at the neuromuscular junction postsynapse. In the mouse retina, the DGC is localized at the presynapse of photoreceptor cells, however, the function of presynaptic DGC is poorly understood. Here, we developed and analyzed retinal photoreceptor-specific DG conditional knock-out (DG CKO) mice. We found that the DG CKO retina showed a reduced amplitude and a prolonged implicit time of the ERG b-wave. Electron microscopic analysis revealed that bipolar dendrite invagination into the photoreceptor terminus is perturbed in the DG CKO retina. In the DG CKO retina, pikachurin, a DG ligand in the retina, is markedly decreased at photoreceptor synapses. Interestingly, in the Pikachurin(-/-) retina, the DG signal at the ribbon synaptic terminus was severely reduced, suggesting that pikachurin is required for the presynaptic accumulation of DG at the photoreceptor synaptic terminus, and conversely DG is required for pikachurin accumulation. Furthermore, we found that overexpression of pikachurin induces formation and clustering of a DG-pikachurin complex on the cell surface. The Laminin G repeats of pikachurin, which are critical for its oligomerization and interaction with DG, were essential for the clustering of the DG-pikachurin complex as well. These results suggest that oligomerization of pikachurin and its interaction with DG causes DG assembly on the synapse surface of the photoreceptor synaptic terminals. Our results reveal that the presynaptic interaction of pikachurin with DG at photoreceptor terminals is essential for both the formation of proper photoreceptor ribbon synaptic structures and normal retinal electrophysiology.

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

    Science.gov (United States)

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

    2007-12-01

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

  9. LKB1 Regulates Mitochondria-Dependent Presynaptic Calcium Clearance and Neurotransmitter Release Properties at Excitatory Synapses along Cortical Axons.

    Science.gov (United States)

    Kwon, Seok-Kyu; Sando, Richard; Lewis, Tommy L; Hirabayashi, Yusuke; Maximov, Anton; Polleux, Franck

    2016-07-01

    Individual synapses vary significantly in their neurotransmitter release properties, which underlie complex information processing in neural circuits. Presynaptic Ca2+ homeostasis plays a critical role in specifying neurotransmitter release properties, but the mechanisms regulating synapse-specific Ca2+ homeostasis in the mammalian brain are still poorly understood. Using electrophysiology and genetically encoded Ca2+ sensors targeted to the mitochondrial matrix or to presynaptic boutons of cortical pyramidal neurons, we demonstrate that the presence or absence of mitochondria at presynaptic boutons dictates neurotransmitter release properties through Mitochondrial Calcium Uniporter (MCU)-dependent Ca2+ clearance. We demonstrate that the serine/threonine kinase LKB1 regulates MCU expression, mitochondria-dependent Ca2+ clearance, and thereby, presynaptic release properties. Re-establishment of MCU-dependent mitochondrial Ca2+ uptake at glutamatergic synapses rescues the altered neurotransmitter release properties characterizing LKB1-null cortical axons. Our results provide novel insights into the cellular and molecular mechanisms whereby mitochondria control neurotransmitter release properties in a bouton-specific way through presynaptic Ca2+ clearance.

  10. H-reflex amplitude depression as a marker of presynaptic inhibition in Painful Diabetic Neuropathy (PDN.

    Directory of Open Access Journals (Sweden)

    Ahmad Asmedi

    2016-02-01

    Full Text Available ABSTRACT Painful Diabetic Neuropathy (PDN is a common complication of diabetes mellitus (DM. Disruption in presynaptic inhibition in dorsal horn of the spinal cord has been proposed as one of the pathomechanism of PDN. Previous research showed that presynaptic inhibition can be detected by H-reflex examination. The aim of this study was to know whether the reduction of presynaptic inhibition in spinal dorsal horn of PDN patients really exist, and detectable by H-reflex examination. It was cohort prospective involving 141 (58 men, 83 women patients with DM and impaired glucose tolerance (IGT between the ages of 40 and 61 years from several health facilities in Yogyakarta. All patients underwent clinical, laboratory and electrodiagnostic examination. Demographic, clinical and electrodiagnostic data were collected and analyzed. By survival analysis there were 25 new cases of PDN (12.12% cumulative incidence. Using survival Kaplan Meier analysis, the significant hazard ratio for PDN were 12.81 for median motor nerve amplitude, 5.74 for median nerve distal latency, 3.71 for median sensory nerve amplitude, 6.33 for median sensory latency, 3.4 for tibial nerve amplitude, 3.48 for tibial nerve distal latency, 2.29 for sural nerve amplitude, 4.47 for sural nerve latency, 3.99 for H-reflex latency, 5.88 for H-reflex amplitude, and 17.83 for Diabetic Neuropathy (DN status. Using hazard proportional cox analysis, only H amplitude and DN status (DNS score were significantly correlated with PDN (p= 0.026; hazard ratio = 15.450; CI 95%= 1.39 – 171.62 for H amplitude and p= 0.030; hazard ratio = 10.766; CI 95%=1.26 – 92.09 for DN status. This study showed that depression of H-reflex amplitude was correlated with the occurrence of PDN. This result proves that there was presynaptic inhibition process in PDN that manifests as low H-reflex amplitude.

  11. SPECT 123-I-[FP-CIT] diagnostic in the presynaptic parkinsonism

    International Nuclear Information System (INIS)

    Piperkova, E.; Georgiev, R.; Dimitrova, M.; Daskalov, M.; Orosova, M.; Milanova, M.; Danon, S.

    2005-01-01

    were normal. Results: Visually, the striatal radiopharmaceutical activity was found to be lower on the left striatum in 5 patients with tremor, rigidity or other movement disorders on the right extremities. In 2 patients with motor impairment on the left part of the body the [ 123 I] FP-CIT hypofixation was found on the right striatum and in one female the scintigraphic changes involved the striatum bilaterally. In all these patients the [ 123 I] FP-CIT uptake ratio was lower in the contralateral striatum of the clinical symptoms. In these patients good L - Dopa treatment effect was established in the clinical follow-up. In one female without DaTSCAN brain SPECT abnormality and 99mTc-HMPAO perfusion changes, essential tremor and arteriosclerotic pseodoparkinsonism was accepted. To achieve good quality of the images it is recommended that the filters should be individually selected for each case. We consider that Butterworth filter of 3 th -5 th order and normalised cutoff frequency of 0.25-0.45 and Low Pass Cosine filter with normalised cutoff frequency of 0.25 are most effective at the image processing step. Conclusion: 123 I - Ioflupane SPECT can be very useful for early diagnostics of patients with clinically uncertain Parkinsonism. It could contribute to initial diagnosis, differential diagnosis between presynaptic parkinsonian syndromes (Progressive Supranuclear Palsy and Multiple System Atrophy) and ET and better subsequent therapeutic management

  12. Estimation of scattering contribution in the calibration of neutron devices with radionuclide sources in rooms of different sizes

    Directory of Open Access Journals (Sweden)

    Khabaz Rahim

    2015-01-01

    Full Text Available Calibrations of neutron devices used in area monitoring are often performed by radionuclide neutron sources. Device readings increase due to neutrons scattered by the surroundings and the air. The influence of said scattering effects have been investigated in this paper by performing Monte Carlo simulations for ten different radionuclide neutron sources inside several sizes of concrete wall spherical rooms (Rsp = 200 to 1500 cm. In order to obtain the parameters that relate the additional contribution from scattered neutrons, calculations using a polynomial fit model were evaluated. Obtained results show that the contribution of scattering is roughly independent of the geometric shape of the calibration room. The parameter that relates the room-return scattering has been fitted in terms of the spherical room radius, so as to reasonably accurately estimate the scattering value for each radionuclide neutron source in any geometry of the calibration room.

  13. Reduction of delayed-neutron contribution to variance-to-mean ratio by application of difference filter technique

    International Nuclear Information System (INIS)

    Hashimoto, Kengo; Mouri, Tomoaki; Ohtani, Nobuo

    1999-01-01

    The difference-filtering correlation analysis was applied to time-sequence neutron count data measured in a slightly subcritical assembly, where the Feynman-α analysis suffered from large contribution of delayed neutron to the variance-to-mean ratio of counts. The prompt-neutron decay constant inferred from the present filtering analysis agreed very closely with that by pulsed neutron experiment, and no dependence on the gate-time range specified could be observed. The 1st-order filtering was sufficient for the reduction of the delayed-neutron contribution. While the conventional method requires a choice of analysis formula appropriate to a gate-time range, the present method is applicable to a wide variety of gate-time ranges. (author)

  14. Deformation of attractor landscape via cholinergic presynaptic modulations: a computational study using a phase neuron model.

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    Takashi Kanamaru

    Full Text Available Corticopetal acetylcholine (ACh is released transiently from the nucleus basalis of Meynert (NBM into the cortical layers and is associated with top-down attention. Recent experimental data suggest that this release of ACh disinhibits layer 2/3 pyramidal neurons (PYRs via muscarinic presynaptic effects on inhibitory synapses. Together with other possible presynaptic cholinergic effects on excitatory synapses, this may result in dynamic and temporal modifications of synapses associated with top-down attention. However, the system-level consequences and cognitive relevance of such disinhibitions are poorly understood. Herein, we propose a theoretical possibility that such transient modifications of connectivity associated with ACh release, in addition to top-down glutamatergic input, may provide a neural mechanism for the temporal reactivation of attractors as neural correlates of memories. With baseline levels of ACh, the brain returns to quasi-attractor states, exhibiting transitive dynamics between several intrinsic internal states. This suggests that top-down attention may cause the attention-induced deformations between two types of attractor landscapes: the quasi-attractor landscape (Q-landscape, present under low-ACh, non-attentional conditions and the attractor landscape (A-landscape, present under high-ACh, top-down attentional conditions. We present a conceptual computational model based on experimental knowledge of the structure of PYRs and interneurons (INs in cortical layers 1 and 2/3 and discuss the possible physiological implications of our results.

  15. G protein betagamma-subunits activated by serotonin mediate presynaptic inhibition by regulating vesicle fusion properties.

    Science.gov (United States)

    Photowala, Huzefa; Blackmer, Trillium; Schwartz, Eric; Hamm, Heidi E; Alford, Simon

    2006-03-14

    Neurotransmitters are thought to be released as quanta, where synaptic vesicles deliver packets of neurotransmitter to the synaptic cleft by fusion with the plasma membrane. However, synaptic vesicles may undergo incomplete fusion. We provide evidence that G protein-coupled receptors inhibit release by causing such incomplete fusion. 5-hydroxytryptamine (5-HT) receptor signaling potently inhibits excitatory postsynaptic currents (EPSCs) between lamprey reticulospinal axons and their postsynaptic targets by a direct action on the vesicle fusion machinery. We show that 5-HT receptor-mediated presynaptic inhibition, at this synapse, involves a reduction in EPSC quantal size. Quantal size was measured directly by comparing unitary quantal amplitudes of paired EPSCs before and during 5-HT application and indirectly by determining the effect of 5-HT on the relationship between mean-evoked EPSC amplitude and variance. Results from FM dye-labeling experiments indicate that 5-HT prevents full fusion of vesicles. 5-HT reduces FM1-43 staining of vesicles with a similar efficacy to its effect on the EPSC. However, destaining of FM1-43-labeled vesicles is abolished by lower concentrations of 5-HT that leave a substantial EPSC. The use of a water-soluble membrane impermeant quenching agent in the extracellular space reduced FM1-43 fluorescence during stimulation in 5-HT. Thus vesicles contact the extracellular space during inhibition of synaptic transmission by 5-HT. We conclude that 5-HT, via free Gbetagamma, prevents the collapse of synaptic vesicles into the presynaptic membrane.

  16. Crimpy enables discrimination of presynaptic and postsynaptic pools of a BMP at the Drosophila neuromuscular junction.

    Science.gov (United States)

    James, Rebecca E; Hoover, Kendall M; Bulgari, Dinara; McLaughlin, Colleen N; Wilson, Christopher G; Wharton, Kristi A; Levitan, Edwin S; Broihier, Heather T

    2014-12-08

    Distinct pools of the bone morphogenetic protein (BMP) Glass bottom boat (Gbb) control structure and function of the Drosophila neuromuscular junction. Specifically, motoneuron-derived Gbb regulates baseline neurotransmitter release, whereas muscle-derived Gbb regulates neuromuscular junction growth. Yet how cells differentiate between these ligand pools is not known. Here we present evidence that the neuronal Gbb-binding protein Crimpy (Cmpy) permits discrimination of pre- and postsynaptic ligand by serving sequential functions in Gbb signaling. Cmpy first delivers Gbb to dense core vesicles (DCVs) for activity-dependent release from presynaptic terminals. In the absence of Cmpy, Gbb is no longer associated with DCVs and is not released by activity. Electrophysiological analyses demonstrate that Cmpy promotes Gbb's proneurotransmission function. Surprisingly, the Cmpy ectodomain is itself released upon DCV exocytosis, arguing that Cmpy serves a second function in BMP signaling. In addition to trafficking Gbb to DCVs, we propose that Gbb/Cmpy corelease from presynaptic terminals defines a neuronal protransmission signal. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Pre-synaptic control of remote fear extinction in the neocortex

    Directory of Open Access Journals (Sweden)

    Gisella eVetere

    2012-06-01

    Full Text Available Consolidation of remote memory enhances immediate early genes induction (IEGs, augments the expression of the presynaptic growth associated protein 43 (GAP-43, and increases the density and size of dendritic spines in anterior cingulate (aCC and infra-limbic (ILC cortices. Remote memory extinction, however, does not uniformly alter consolidation-induced structural changes. In the aCC, the density, but not the size, of spines is reset to pseudo-conditioning levels while novel thin spines are formed in the ILC. Whether IEGs and GAP-43 also undergo region-specific changes upon remote memory extinction is undetermined. Here we confirm in the same batch of mice that c-Fos induction and GAP-43 expression are increased in both the aCC and the ILC 36 days after contextual fear conditioning. We then show that, in both regions, remote memory extinction is associated with decrease of c-Fos induction but no change in GAP-43 expression thus revealing similar, although protein-specific, pre-synaptic adaptations in aCC and ILC neurons. These observations, in addition to our previous report of region-specific post-synaptic structural changes, disclose a complex pattern of extinction-driven neocortical alterations suitable to support erasure or reinstatement of fear according to the environment demand.

  18. Translating neuronal activity at the synapse: presynaptic calcium sensors in short-term plasticity

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    Arthur P.H. De Jong

    2014-10-01

    Full Text Available The complex manner in which patterns of presynaptic neural activity are translated into short-term plasticity (STP suggests the existence of multiple presynaptic calcium (Ca2+ sensors, which regulate the amplitude and time-course of STP and are the focus of this review. We describe two canonical Ca2+-binding protein domains (C2 domains and EF-hands and define criteria that need to be met for a protein to qualify as a Ca2+ sensor mediating STP. With these criteria in mind, we discuss various forms of STP and identify established and putative Ca2+ sensors. We find that despite the multitude of proposed sensors, only three are well established in STP: Munc13, protein kinase C and synaptotagmin-7. For putative sensors, we pinpoint open questions and potential pitfalls. Finally, we discuss how the molecular properties and modes of action of Ca2+ sensors can explain their differential involvement in STP and shape net synaptic output.

  19. Inhibition of presynaptic activity by zinc released from mossy fiber terminals during tetanic stimulation.

    Science.gov (United States)

    Minami, Akira; Sakurada, Naomi; Fuke, Sayuri; Kikuchi, Kazuya; Nagano, Tetsuo; Oku, Naoto; Takeda, Atsushi

    2006-01-01

    Zinc exists in high densities in the giant boutons of hippocampal mossy fibers. On the basis of the evidence that zinc decreases extracellular glutamate concentration in the hippocampus, the presynaptic action of zinc released from mossy fibers during high-frequency (tetanic) stimulation was examined using hippocampal slices. The increase in zinc-specific fluorescent signals was observed in both extracellular and intracellular compartments in the mossy fiber terminals during the delivery of tetanic stimuli (100 Hz, 1 sec) to the dentate granule cell layer, suggesting that zinc released from mossy fibers is immediately retaken up by mossy fibers. When mossy fiber terminals were preferentially double-stained with zinc and calcium indicators and tetanic stimuli (100 Hz, 1 sec) were delivered to the dentate granule cell layer, the increase in calcium orange signal during the stimulation was enhanced in mossy fiber terminals by addition of CaEDTA, a membrane-impermeable zinc chelator, and was suppressed by addition of zinc. The decrease in FM4-64 signal (vesicular exocytosis) during tetanic stimulation (10 Hz, 180 sec), which induced mossy fiber long-term potentiation, was also enhanced in mossy fiber terminals by addition of CaEDTA and was suppressed by addition of zinc. The present study demonstrates that zinc released from mossy fibers may be a negative-feedback factor against presynaptic activity during tetanic stimulation.

  20. Different contributions of internal reviewers and external experts to labelling decisions on therapeutic indications in new drug reviews in Japan.

    Science.gov (United States)

    Yokota, M; Kusama, M; Matsuki, N; Ono, S

    2013-12-01

    External experts play an important role in shaping regulatory decisions in the new drug review process in the United States, Europe and Japan. No rigorous study has been performed addressing how and to what extent external experts, in contrast to internal reviewers in the agency, influence the regulatory decisions during new drug reviews. We examined their contributions in Japanese regulatory reviews in contrast to the internal reviewers, focusing on the labelling decision on therapeutic indications. With the data set of 219 new molecular entities (NMEs) approved in Japan from 2000 to 2009, we observed how proposed indications in labelling were modified in a stepwise manner during the review process and conducted multinomial logistic analysis to examine the possible mechanism behind. We found that interim assessment of indications by the internal reviewers was modified substantially by the influence of the external experts in about 20% of the 219 NMEs. Our analysis suggested that internal reviewers provided their opinion mainly based on strict review discipline, whereas external experts added flexibility and reality to their reviews. Our analysis revealed different evaluations between internal reviewers and external experts during regulatory discussions in new drug reviews and how the external panel contributes to changing internal decisions. This study provides a new and quantitative approach to better label setting by emphasizing the contributions of each stakeholder in new drug reviews, which would improve the efficiency, quality and transparency of new drug reviews to enhance public health. © 2013 John Wiley & Sons Ltd.

  1. The contribution of three components of nutrition knowledge to socio-economic differences in food purchasing choices.

    Science.gov (United States)

    McKinnon, Loretta; Giskes, Katrina; Turrell, Gavin

    2014-08-01

    To assess socio-economic differences in three components of nutrition knowledge, i.e. knowledge of (i) the relationship between diet and disease, (ii) the nutrient content of foods and (iii) dietary guideline recommendations; furthermore, to determine if socio-economic differences in nutrition knowledge contribute to inequalities in food purchasing choices. The cross-sectional study considered household food purchasing, nutrition knowledge, socio-economic and demographic information. Household food purchasing choices were summarised by three indices, based on self-reported purchasing of sixteen groceries, nineteen fruits and twenty-one vegetables. Socio-economic position (SEP) was measured by household income and education. Associations between SEP, nutrition knowledge and food purchasing were examined using general linear models adjusted for age, gender, household type and household size. Brisbane, Australia in 2000. Main household food shoppers (n 1003, response rate 66·4 %), located in fifty small areas (Census Collectors Districts). Shoppers in households of low SEP made food purchasing choices that were less consistent with dietary guideline recommendations: they were more likely to purchase grocery foods comparatively higher in salt, sugar and fat, and lower in fibre, and they purchased a narrower range of fruits and vegetables. Those of higher SEP had greater nutrition knowledge and this factor attenuated most associations between SEP and food purchasing choices. Among nutrition knowledge factors, knowledge of the relationship between diet and disease made the greatest and most consistent contribution to explaining socio-economic differences in food purchasing. Addressing inequalities in nutrition knowledge is likely to reduce socio-economic differences in compliance with dietary guidelines. Improving knowledge of the relationship between diet and disease appears to be a particularly relevant focus for health promotion aimed to reduce socio

  2. The contribution of gender-based violence and network trauma to gender differences in Post-Traumatic Stress Disorder

    Science.gov (United States)

    Silove, Derrick; Baker, Jess R.; Mohsin, Mohammed; Teesson, Maree; Creamer, Mark; O'Donnell, Meaghan; Forbes, David; Carragher, Natacha; Slade, Tim; Mills, Katherine; Bryant, Richard; McFarlane, Alexander; Steel, Zachary; Felmingham, Kim; Rees, Susan

    2017-01-01

    Background Posttraumatic stress disorder (PTSD) occurs twice as commonly amongst women as men. Two common domains of trauma, network trauma and gender based violence (GBV), may contribute to this gender difference in PTSD rates. We examined data from a nationally representative sample of the Australian population to clarify the characteristics of these two trauma domains in their contributions to PTSD rates in men and women. Methods We drew on data from the 2007 Australian National Survey of Mental Health and Well-being to assess gender differences across a comprehensive range of trauma domains, including (1) prevalence of lifetime exposure; (2) identification of an index trauma or DSM-IV Criterion A event; and (3) the likelihood of developing full DSM-IV PTSD symptoms once an index trauma was identified. Results Men reported more traumatic events (TEs) overall but women reported twice the prevalence of lifetime PTSD (women, 13.4%; men, 6.3%). Women reported a threefold higher level of exposure to GBV and were seven times more likely to nominate GBV as the index trauma as compared to men. Women were twice more likely than men to identify a network trauma as the index trauma and more likely to meet full PTSD symptoms in relation to that event (women, 20.6%; men, 14.6%). Conclusion Women are more likely to identify GBV and network trauma as an index trauma. Women’s far greater exposure to GBV contributes to their higher prevalence of PTSD. Women are markedly more likely to develop PTSD when network trauma is identified as the index trauma. Preventing exposure to GBV and providing timely interventions for acute psychological reactions following network trauma may assist in reducing PTSD rates amongst women. PMID:28207775

  3. The contribution of gender-based violence and network trauma to gender differences in Post-Traumatic Stress Disorder.

    Directory of Open Access Journals (Sweden)

    Derrick Silove

    Full Text Available Posttraumatic stress disorder (PTSD occurs twice as commonly amongst women as men. Two common domains of trauma, network trauma and gender based violence (GBV, may contribute to this gender difference in PTSD rates. We examined data from a nationally representative sample of the Australian population to clarify the characteristics of these two trauma domains in their contributions to PTSD rates in men and women.We drew on data from the 2007 Australian National Survey of Mental Health and Well-being to assess gender differences across a comprehensive range of trauma domains, including (1 prevalence of lifetime exposure; (2 identification of an index trauma or DSM-IV Criterion A event; and (3 the likelihood of developing full DSM-IV PTSD symptoms once an index trauma was identified.Men reported more traumatic events (TEs overall but women reported twice the prevalence of lifetime PTSD (women, 13.4%; men, 6.3%. Women reported a threefold higher level of exposure to GBV and were seven times more likely to nominate GBV as the index trauma as compared to men. Women were twice more likely than men to identify a network trauma as the index trauma and more likely to meet full PTSD symptoms in relation to that event (women, 20.6%; men, 14.6%.Women are more likely to identify GBV and network trauma as an index trauma. Women's far greater exposure to GBV contributes to their higher prevalence of PTSD. Women are markedly more likely to develop PTSD when network trauma is identified as the index trauma. Preventing exposure to GBV and providing timely interventions for acute psychological reactions following network trauma may assist in reducing PTSD rates amongst women.

  4. Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques

    Science.gov (United States)

    Siciliano, Cody A.; Calipari, Erin S.; Yorgason, Jordan T.; Lovinger, David M.; Mateo, Yolanda; Jimenez, Vanessa A.; Helms, Christa M.; Grant, Kathleen A.; Jones, Sara R.

    2016-01-01

    Rationale Hypofunction of striatal dopamine neurotransmission, or hypodopaminergia, is a consequence of excessive ethanol use, and is hypothesized to be a critical component of alcoholism, driving alcohol intake in an attempt to restore dopamine levels; however, the neurochemical mechanisms involved in these dopaminergic deficiencies are unknown. Objective Here we examined the specific dopaminergic adaptations that produce hypodopaminergia and contribute to alcohol use disorders using direct, sub-second measurements of dopamine signaling in nonhuman primates following chronic ethanol self-administration. Methods Female rhesus macaques completed one year of daily (22 hr/day) ethanol self-administration. Subsequently, fast-scan cyclic voltammetry was used in nucleus accumbens core brain slices to determine alterations in dopamine terminal function, including release and uptake kinetics, and sensitivity to quinpirole (D2/D3 dopamine receptor agonist) and U50,488 (kappa-opioid receptor agonist) induced inhibition of dopamine release. Results Ethanol drinking greatly increased uptake rates, which were positively correlated with lifetime ethanol intake. Furthermore, the sensitivity of dopamine D2/D3 autoreceptors and kappa-opioid receptors, which both act as negative regulators of presynaptic dopamine release, were moderately and robustly enhanced in ethanol drinkers. Conclusions Greater uptake rates and sensitivity to D2-type autoreceptor and kappa-opioid receptor agonists could converge to drive a hypodopaminergic state, characterized by reduced basal dopamine and an inability to mount appropriate dopaminergic responses to salient stimuli. Together, we outline the specific alterations to dopamine signaling that may drive ethanol-induced hypofunction of the dopamine system, and suggest that the dopamine and dynorphin/kappa-opioid receptor systems may be efficacious pharmcotherapeutic targets in the treatment of alcohol use disorders. PMID:26892380

  5. Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques.

    Science.gov (United States)

    Siciliano, Cody A; Calipari, Erin S; Yorgason, Jordan T; Lovinger, David M; Mateo, Yolanda; Jimenez, Vanessa A; Helms, Christa M; Grant, Kathleen A; Jones, Sara R

    2016-04-01

    Hypofunction of striatal dopamine neurotransmission, or hypodopaminergia, is a consequence of excessive ethanol use and is hypothesized to be a critical component of alcoholism, driving alcohol intake in an attempt to restore dopamine levels; however, the neurochemical mechanisms involved in these dopaminergic deficiencies are not fully understood. Here we examined the specific dopaminergic adaptations that produce hypodopaminergia and contribute to alcohol use disorders using direct, sub-second measurements of dopamine signaling in nonhuman primates following chronic ethanol self-administration. Female rhesus macaques completed 1 year of daily (22 h/day) ethanol self-administration. Subsequently, fast-scan cyclic voltammetry was used in nucleus accumbens core brain slices to determine alterations in dopamine terminal function, including release and uptake kinetics, and sensitivity to quinpirole (D2/D3 dopamine receptor agonist) and U50,488 (kappa opioid receptor agonist) induced inhibition of dopamine release. Ethanol drinking greatly increased uptake rates, which were positively correlated with lifetime ethanol intake. Furthermore, the sensitivity of dopamine D2/D3 autoreceptors and kappa opioid receptors, which both act as negative regulators of presynaptic dopamine release, was moderately and robustly enhanced in ethanol drinkers. Greater uptake rates and sensitivity to D2-type autoreceptor and kappa opioid receptor agonists could converge to drive a hypodopaminergic state, characterized by reduced basal dopamine and an inability to mount appropriate dopaminergic responses to salient stimuli. Together, we outline the specific alterations to dopamine signaling that may drive ethanol-induced hypofunction of the dopamine system and suggest that the dopamine and dynorphin/kappa opioid receptor systems may be efficacious pharmacotherapeutic targets in the treatment of alcohol use disorders.

  6. The contributions of differing degrees of acute and chronic malnutrition to the intellectual development of Jamaican boys.

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    Richardson, S A; Koller, H; Katz, M; Albert, K

    1978-07-01

    The purpose of this paper is to determine whether differing degrees and types of malnutrition cause differing degrees of mental impairment. Subjects were 59 Jamaican boys hospitalized for malnutrition in infancy and whose intelligence was assessed at school age. The measure used for degree of chronic malnutrition was height for age and for acute malnutrition weight for height. The measure of intelligence was the I.Q. (WISC). Because the social environment in which a child lives influences his intellectual development, a measure of social background was used as an independent variable in addition to the nutrition measures. Social background showed a significant effect on I.Q. but neither measure of nutrition was significant. A further analysis using comparisons who had not been hospitalized for malnutrition suggests that malnutrition may contribute to mental impairment, through a threshold effect rather than acting as a continuous variable where increasing degrees of malnutrition cause increasing degrees of mental impairment.

  7. Comparison of different statistical methods for estimation of extreme sea levels with wave set-up contribution

    Science.gov (United States)

    Kergadallan, Xavier; Bernardara, Pietro; Benoit, Michel; Andreewsky, Marc; Weiss, Jérôme

    2013-04-01

    Estimating the probability of occurrence of extreme sea levels is a central issue for the protection of the coast. Return periods of sea level with wave set-up contribution are estimated here in one site : Cherbourg in France in the English Channel. The methodology follows two steps : the first one is computation of joint probability of simultaneous wave height and still sea level, the second one is interpretation of that joint probabilities to assess a sea level for a given return period. Two different approaches were evaluated to compute joint probability of simultaneous wave height and still sea level : the first one is multivariate extreme values distributions of logistic type in which all components of the variables become large simultaneously, the second one is conditional approach for multivariate extreme values in which only one component of the variables have to be large. Two different methods were applied to estimate sea level with wave set-up contribution for a given return period : Monte-Carlo simulation in which estimation is more accurate but needs higher calculation time and classical ocean engineering design contours of type inverse-FORM in which the method is simpler and allows more complex estimation of wave setup part (wave propagation to the coast for example). We compare results from the two different approaches with the two different methods. To be able to use both Monte-Carlo simulation and design contours methods, wave setup is estimated with an simple empirical formula. We show advantages of the conditional approach compared to the multivariate extreme values approach when extreme sea-level occurs when either surge or wave height is large. We discuss the validity of the ocean engineering design contours method which is an alternative when computation of sea levels is too complex to use Monte-Carlo simulation method.

  8. Ethnic differences in grains consumption and their contribution to intake of B-vitamins: results of the Multiethnic Cohort Study

    Science.gov (United States)

    2013-01-01

    Background Research indicates that a diet rich in whole grains may reduce the risk of prevalent chronic diseases, including cardiovascular disease, diabetes, and some cancers, and that risk for these diseases varies by ethnicity. The objective of the current study was to identify major dietary sources of grains and describe their contribution to B vitamins in five ethnic groups. Methods A cross-sectional mail survey was used to collect data from participants in the Multiethnic Cohort Study in Hawaii and Los Angeles County, United States, from 1993 to 1996. Dietary intake data collected using a quantitative food frequency questionnaire was available for 186,916 participants representing five ethnic groups (African American, Latino, Japanese American, Native Hawaiian and Caucasian) aged 45–75 years. The top sources of grain foods were determined, and their contribution to thiamin, riboflavin, niacin, vitamin B6, and folic acid intakes were analyzed. Results The top source of whole grains was whole wheat/rye bread for all ethnic-sex groups, followed by popcorn and cooked cereals, except for Native Hawaiian men and Japanese Americans, for whom brown/wild rice was the second top source; major contributors of refined grains were white rice and white bread, except for Latinos. Refined grain foods contributed more to grain consumption (27.1-55.6%) than whole grain foods (7.4-30.8%) among all ethnic-sex groups, except African American women. Grain foods made an important contribution to the intakes of thiamin (30.2-45.9%), riboflavin (23.1-29.2%), niacin (27.1-35.8%), vitamin B6 (22.9-27.5%), and folic acid (23.3-27.7%). Conclusions This is the first study to document consumption of different grain sources and their contribution to B vitamins in five ethnic groups in the U.S. Findings can be used to assess unhealthful food choices, to guide dietary recommendations, and to help reduce risk of chronic diseases in these populations. PMID:23688109

  9. Endoplasmic reticulum stress in the brain subfornical organ contributes to sex differences in angiotensin-dependent hypertension in rats.

    Science.gov (United States)

    Dai, S-Y; Fan, J; Shen, Y; He, J-J; Peng, W

    2016-05-01

    Endoplasmic reticulum (ER) stress in the brain subfornical organ (SFO), a key cardiovascular regulatory centre, has been implicated in angiotensin (ANG) II-induced hypertension in males; however, the contribution of ER stress to ANG II-induced hypertension in females is unknown. Female hormones have been shown to prevent ER stress in the periphery. We tested the hypothesis that females are less susceptible to ANG II-induced SFO ER stress than males, leading to sex differences in hypertension. Male, intact and ovariectomized (OVX) female rats received a continuous 2-week subcutaneous infusion of ANG II or saline. Additional male, intact and OVX female rats received intracerebroventricular (ICV) injection of ER stress inducer tunicamycin. ANG II, but not saline, increased blood pressure (BP) in both males and females, but intact females exhibited smaller increase in BP and less depressor response to ganglionic blockade compared with males or OVX females. Molecular studies revealed that ANG II elevated expression of ER stress biomarkers and Fra-like activity in the SFO in both males and females; however, elevations in these parameters were less in intact females than in males or OVX females. Moreover, ICV tunicamycin induced smaller elevation in BP and less increase in expression of ER stress biomarkers in the SFO in intact females compared with males or OVX females. The results suggest that differences in ANG II-induced brain ER stress between males and females contribute to sex differences in ANG II-mediated hypertension and that oestrogen protects females against ANG II-induced brain ER stress. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  10. Presynaptic CRF1 Receptors Mediate the Ethanol Enhancement of GABAergic Transmission in the Mouse Central Amygdala

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    Zhiguo Nie

    2009-01-01

    Full Text Available Corticotropin-releasing factor (CRF is a 41-amino-acid neuropeptide involved in stress responses initiated from several brain areas, including the amygdala formation. Research shows a strong relationship between stress, brain CRF, and excessive alcohol consumption. Behavioral studies suggest that the central amygdala (CeA is significantly involved in alcohol reward and dependence. We recently reported that the ethanol augmentation of GABAergic synaptic transmission in rat CeA involves CRF1 receptors, because both CRF and ethanol significantly enhanced the amplitude of evoked GABAergic inhibitory postsynaptic currents (IPSCs in CeA neurons from wild-type (WT and CRF2 knockout (KO mice, but not in neurons of CRF1 KO mice. The present study extends these findings using selective CRF receptor ligands, gene KO models, and miniature IPSC (mIPSC analysis to assess further a presynaptic role for the CRF receptors in mediating ethanol effects in the CeA. In whole-cell patch recordings of pharmacologically isolated GABAAergic IPSCs from slices of mouse CeA, both CRF and ethanol augmented evoked IPSCs in a concentration-dependent manner, with low EC50s. A CRF1 (but not CRF2 KO construct and the CRF1-selective nonpeptide antagonist NIH-3 (LWH-63 blocked the augmenting effect of both CRF and ethanol on evoked IPSCs. Furthermore, the new selective CRF1 agonist stressin1, but not the CRF2 agonist urocortin 3, also increased evoked IPSC amplitudes. Both CRF and ethanol decreased paired-pulse facilitation (PPF of evoked IPSCs and significantly enhanced the frequency, but not the amplitude, of spontaneous miniature GABAergic mIPSCs in CeA neurons of WT mice, suggesting a presynaptic site of action. The PPF effect of ethanol was abolished in CeA neurons of CRF1 KO mice. The CRF1 antagonist NIH-3 blocked the CRF- and ethanol-induced enhancement of mIPSC frequency in CeA neurons. These data indicate that presynaptic CRF1 receptors play a critical role in permitting

  11. Spatiotemporal variability and contribution of different aerosol types to the aerosol optical depth over the Eastern Mediterranean

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    A. K. Georgoulias

    2016-11-01

    Full Text Available This study characterizes the spatiotemporal variability and relative contribution of different types of aerosols to the aerosol optical depth (AOD over the Eastern Mediterranean as derived from MODIS (Moderate Resolution Imaging Spectroradiometer Terra (March 2000–December 2012 and Aqua (July 2002–December 2012 satellite instruments. For this purpose, a 0.1° × 0.1° gridded MODIS dataset was compiled and validated against sun photometric observations from the AErosol RObotic NETwork (AERONET. The high spatial resolution and long temporal coverage of the dataset allows for the determination of local hot spots like megacities, medium-sized cities, industrial zones and power plant complexes, seasonal variabilities and decadal averages. The average AOD at 550 nm (AOD550 for the entire region is ∼ 0.22 ± 0.19, with maximum values in summer and seasonal variabilities that can be attributed to precipitation, photochemical production of secondary organic aerosols, transport of pollution and smoke from biomass burning in central and eastern Europe and transport of dust from the Sahara and the Middle East. The MODIS data were analyzed together with data from other satellite sensors, reanalysis projects and a chemistry–aerosol-transport model using an optimized algorithm tailored for the region and capable of estimating the contribution of different aerosol types to the total AOD550. The spatial and temporal variability of anthropogenic, dust and fine-mode natural aerosols over land and anthropogenic, dust and marine aerosols over the sea is examined. The relative contribution of the different aerosol types to the total AOD550 exhibits a low/high seasonal variability over land/sea areas, respectively. Overall, anthropogenic aerosols, dust and fine-mode natural aerosols account for ∼ 51, ∼ 34 and ∼ 15 % of the total AOD550 over land, while, anthropogenic aerosols, dust and marine aerosols account ∼ 40, ∼ 34

  12. Indoor Air Quality Assessment and Study of Different VOC Contributions within a School in Taranto City, South of Italy

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    Annalisa Marzocca

    2017-03-01

    Full Text Available Children spend a large amount of time in school environments and when Indoor Air Quality (IAQ is poor, comfort, productivity and learning performances may be affected. The aim of the present study is to characterize IAQ in a primary school located in Taranto city (south of Italy. Because of the proximity of a large industrial complex to the urban settlement, this district is one of the areas identified as being at high environmental risk in Italy. The study carried out simultaneous monitoring of indoor and outdoor Volatile Organic Compounds (VOC concentrations and assessed different pollutants’ contributions on the IAQ of the investigated site. A screening study of VOC and determination of Benzene, Toluene, Ethylbenzene, Xylenes (BTEX, sampled with Radiello® diffusive samplers suitable for thermal desorption, were carried out in three classrooms, in the corridor and in the yard of the school building. Simultaneously, Total VOC (TVOC concentration was measured by means of real-time monitoring, in order to study the activation of sources during the monitored days. The analysis results showed a prevalent indoor contribution for all VOC except for BTEX which presented similar concentrations in indoor and outdoor air. Among the determined VOC, Terpenes and 2-butohxyethanol were shown to be an indoor source, the latter being the indoor pollutant with the highest concentration.

  13. Contributions of Sensory Coding and Attentional Control to Individual Differences in Performance in Spatial Auditory Selective Attention Tasks.

    Science.gov (United States)

    Dai, Lengshi; Shinn-Cunningham, Barbara G

    2016-01-01

    Listeners with normal hearing thresholds (NHTs) differ in their ability to steer attention to whatever sound source is important. This ability depends on top-down executive control, which modulates the sensory representation of sound in the cortex. Yet, this sensory representation also depends on the coding fidelity of the peripheral auditory system. Both of these factors may thus contribute to the individual differences in performance. We designed a selective auditory attention paradigm in which we could simultaneously measure envelope following responses (EFRs, reflecting peripheral coding), onset event-related potentials (ERPs) from the scalp (reflecting cortical responses to sound) and behavioral scores. We performed two experiments that varied stimulus conditions to alter the degree to which performance might be limited due to fine stimulus details vs. due to control of attentional focus. Consistent with past work, in both experiments we find that attention strongly modulates cortical ERPs. Importantly, in Experiment I, where coding fidelity limits the task, individual behavioral performance correlates with subcortical coding strength (derived by computing how the EFR is degraded for fully masked tones compared to partially masked tones); however, in this experiment, the effects of attention on cortical ERPs were unrelated to individual subject performance. In contrast, in Experiment II, where sensory cues for segregation are robust (and thus less of a limiting factor on task performance), inter-subject behavioral differences correlate with subcortical coding strength. In addition, after factoring out the influence of subcortical coding strength, behavioral differences are also correlated with the strength of attentional modulation of ERPs. These results support the hypothesis that behavioral abilities amongst listeners with NHTs can arise due to both subcortical coding differences and differences in attentional control, depending on stimulus characteristics

  14. Contributions of sensory coding and attentional control to individual differences in performance in spatial auditory selective attention tasks

    Directory of Open Access Journals (Sweden)

    Lengshi Dai

    2016-10-01

    Full Text Available Listeners with normal hearing thresholds differ in their ability to steer attention to whatever sound source is important. This ability depends on top-down executive control, which modulates the sensory representation of sound in cortex. Yet, this sensory representation also depends on the coding fidelity of the peripheral auditory system. Both of these factors may thus contribute to the individual differences in performance. We designed a selective auditory attention paradigm in which we could simultaneously measure envelope following responses (EFRs, reflecting peripheral coding, onset event-related potentials from the scalp (ERPs, reflecting cortical responses to sound, and behavioral scores. We performed two experiments that varied stimulus conditions to alter the degree to which performance might be limited due to fine stimulus details vs. due to control of attentional focus. Consistent with past work, in both experiments we find that attention strongly modulates cortical ERPs. Importantly, in Experiment I, where coding fidelity limits the task, individual behavioral performance correlates with subcortical coding strength (derived by computing how the EFR is degraded for fully masked tones compared to partially masked tones; however, in this experiment, the effects of attention on cortical ERPs were unrelated to individual subject performance. In contrast, in Experiment II, where sensory cues for segregation are robust (and thus less of a limiting factor on task performance, inter-subject behavioral differences correlate with subcortical coding strength. In addition, after factoring out the influence of subcortical coding strength, behavioral differences are also correlated with the strength of attentional modulation of ERPs. These results support the hypothesis that behavioral abilities amongst listeners with normal hearing thresholds can arise due to both subcortical coding differences and differences in attentional control, depending on

  15. Effects of thyroid status on presynaptic. cap alpha. 2-adrenoceptor and. beta. -adrenoceptor binding in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Atterwill, C.K.; Bunn, S.J.; Atkinson, D.J. (Development Neurobiology Unit, London (UK). Inst. of Neurology); Smith, S.L.; Heal, D.J. (Radcliffe Infirmary, Oxford (UK))

    1984-01-01

    The effect of thyroid status on noradrenergic synaptic function in the mature brain was examined by measuring presynaptic ..cap alpha..2- and postsynaptic ..beta..-adrenoceptors. Repeated triiodothyronine (T/sub 3/) administration to rats (100..mu..g/kg x 14 days hyperthyroid) caused an 18% increase in striatal ..beta..-adrenoceptors as shown by (/sup 3/H)-dihydroalprenolol binding with no change in membranes from cerebral cortex or hypothalamus. In contrast, hypothyroidism (propylthiouracil, PTU x 14 days) produced significant 12% and 30% reductions in striatal and hypothalamic ..beta..-adrenoceptors respectively with no change in the cerebral cortex. Presynaptic ..cap alpha..2-adrenoceptor function was measured in the two dysthyroid states using the clonidine-induced hypoactivity model. Experimental hyperthyroidism increased the degree of clonidine-induced hypoactivity, and suggests increased presynaptic ..cap alpha..2-adrenoceptor function compared with control rats, whereas hypothyroidism suppressed presynaptic ..cap alpha..2-adrenoceptor function. These results show firstly that changes of thyroid status in the mature rat may produce homeostatic alterations at central noradrenergic synapses as reflected by changes in pre- and postsynaptic adrenoceptor function. Secondly, there appear to be T/sub 3/-induced changes in ..beta..-adrenoceptors in the striatum where changes in dopaminergic neuronal activity have previously been demonstrated.

  16. Effects of thyroid status on presynaptic α2-adrenoceptor and β-adrenoceptor binding in the rat brain

    International Nuclear Information System (INIS)

    Atterwill, C.K.; Bunn, S.J.; Atkinson, D.J.

    1984-01-01

    The effect of thyroid status on noradrenergic synaptic function in the mature brain was examined by measuring presynaptic α2- and postsynaptic β-adrenoceptors. Repeated triiodothyronine (T 3 ) administration to rats (100μg/kg X 14 days hyperthyroid) caused an 18% increase in striatal β-adrenoceptors as shown by [ 3 H]-dihydroalprenolol binding with no change in membranes from cerebral cortex or hypothalamus. In contrast, hypothyroidism (propylthiouracil, PTU X 14 days) produced significant 12% and 30% reductions in striatal and hypothalamic β-adrenoceptors respectively with no change in the cerebral cortex. Presynaptic α2-adrenoceptor function was measured in the two dysthyroid states using the clonidine-induced hypoactivity model. Experimtal hyperthyroidism increased the degree of clonidine-induced hypoactivity, and suggests increased presynaptic α2-adrenoceptor function compared with control rats, whereas hypothyroidism suppressed presynaptic α2-adrenoceptor function. These results show firstly that changes of thyroid status in the mature rat may produce homeostatic alterations at central noradrenergic synapses as reflected by changes in pre- and postsynaptic adrenoceptor function. Secondly, there appear to be T 3 -induced changes in β-adrenoceptors in the striatum where changes in dopaminergic neuronal activity have previously been demonstrated. (Author)

  17. Contribution of estradiol levels and hormonal contraceptives to sex differences within the fear network during fear conditioning and extinction.

    Science.gov (United States)

    Hwang, Moon Jung; Zsido, Rachel G; Song, Huijin; Pace-Schott, Edward F; Miller, Karen Klahr; Lebron-Milad, Kelimer; Marin, Marie-France; Milad, Mohammed R

    2015-11-18

    Findings about sex differences in the field of fear conditioning and fear extinction have been mixed. At the psychophysiological level, sex differences emerge only when taking estradiol levels of women into consideration. This suggests that this hormone may also influence sex differences with regards to activations of brain regions involved in fear conditioning and its extinction. Importantly, the neurobiological correlates associated with the use of hormonal oral contraceptives in women have not been fully contrasted against men and against naturally cycling women with different levels of estradiol. In this study, we begin to fill these scientific gaps. We recruited 37 healthy men and 48 healthy women. Of these women, 16 were using oral contraceptives (OC) and 32 were naturally cycling. For these naturally cycling women, a median split was performed on their serum estradiol levels to create a high estradiol (HE) group (n = 16) and a low estradiol (LE) group (n = 16). All participants underwent a 2-day fear conditioning and extinction paradigm in a 3 T MR scanner. Using the 4 groups (men, HE women, LE women, and OC users) and controlling for age and coil type, one-way ANCOVAs were performed to look at significant activations within the nodes of the fear circuit. Using post-hoc analyses, beta-weights were extracted in brain regions showing significant effects in order to unveil the differences based on hormonal status (men, HE, LE, OC). Significant main effect of hormonal status group was found across the different phases of the experiment and in different sub-regions of the insular and cingulate cortices, amygdala, hippocampus, and hypothalamus. During conditioning, extinction and recall, most of the observed differences suggested higher activations among HE women relative to men. During the unconditioned response, however, a different pattern was observed with men showing significantly higher brain activations. Our data further support the important contribution

  18. The social determinants of health: a contribution to the analysis of gender differences in health and illness.

    Science.gov (United States)

    Ballantyne, P J

    1999-12-01

    While it is established that socioeconomic status and social integration influence the distribution of health and illness among men and women, little attention has been paid to the different ways in which women and men experience socioeconomic opportunities and social attachments to others. Drawing on evidence from the literature, the position developed in this article is that gender mediates the influence of both socioeconomic status and social integration on health, and for women, these are intricately linked. Women's relationship to the labour market establishes and perpetuates their socioeconomic inequality relative to men, and may produce contradictory influences on women's health. Furthermore, for women, the marital relationship is paradoxical: marriage may at once improve economic and social support opportunities, while diminishing control over paid and unpaid work--potentially increasing as well as compromising the health status of women. The article is intended to contribute to the growing body of literature on gender and the determinants of health.

  19. Streptococcus pneumoniae PspC Subgroup Prevalence in Invasive Disease and Differences in Contribution to Complement Evasion.

    Science.gov (United States)

    van der Maten, Erika; van den Broek, Bryan; de Jonge, Marien I; Rensen, Kim J W; Eleveld, Marc J; Zomer, Aldert L; Cremers, Amelieke J H; Ferwerda, Gerben; de Groot, Ronald; Langereis, Jeroen D; van der Flier, Michiel

    2018-04-01

    The pneumococcal capsular serotype is an important determinant of complement resistance and invasive disease potential, but other virulence factors have also been found to contribute. Pneumococcal surface protein C (PspC), a highly variable virulence protein that binds complement factor H to evade C3 opsonization, is divided into two subgroups: choline-bound subgroup I and LPxTG-anchored subgroup II. The prevalence of different PspC subgroups in invasive pneumococcal disease (IPD) and functional differences in complement evasion are unknown. The prevalence of PspC subgroups in IPD isolates was determined in a collection of 349 sequenced strains of Streptococcus pneumoniae isolated from adult patients. pspC deletion mutants and isogenic pspC switch mutants were constructed to study differences in factor H binding and complement evasion in relation to capsule thickness. Subgroup I pspC was far more prevalent in IPD isolates than subgroup II pspC The presence of capsule was associated with a greater ability of bound factor H to reduce complement opsonization. Pneumococcal subgroup I PspC bound significantly more factor H and showed more effective complement evasion than subgroup II PspC in isogenic encapsulated pneumococci. We conclude that variation in the PspC subgroups, independent of capsule serotypes, affects pneumococcal factor H binding and its ability to evade complement deposition. Copyright © 2018 American Society for Microbiology.

  20. Resolving the infection process reveals striking differences in the contribution of environment, genetics and phylogeny to host-parasite interactions.

    Science.gov (United States)

    Duneau, David; Luijckx, Pepijn; Ben-Ami, Frida; Laforsch, Christian; Ebert, Dieter

    2011-02-22

    Infection processes consist of a sequence of steps, each critical for the interaction between host and parasite. Studies of host-parasite interactions rarely take into account the fact that different steps might be influenced by different factors and might, therefore, make different contributions to shaping coevolution. We designed a new method using the Daphnia magna - Pasteuria ramosa system, one of the rare examples where coevolution has been documented, in order to resolve the steps of the infection and analyse the factors that influence each of them. Using the transparent Daphnia hosts and fluorescently-labelled spores of the bacterium P. ramosa, we identified a sequence of infection steps: encounter between parasite and host; activation of parasite dormant spores; attachment of spores to the host; and parasite proliferation inside the host. The chances of encounter had been shown to depend on host genotype and environment. We tested the role of genetic and environmental factors in the newly described activation and attachment steps. Hosts of different genotypes, gender and species were all able to activate endospores of all parasite clones tested in different environments; suggesting that the activation cue is phylogenetically conserved. We next established that parasite attachment occurs onto the host oesophagus independently of host species, gender and environmental conditions. In contrast to spore activation, attachment depended strongly on the combination of host and parasite genotypes. Our results show that different steps are influenced by different factors. Host-type-independent spore activation suggests that this step can be ruled out as a major factor in Daphnia-Pasteuria coevolution. On the other hand, we show that the attachment step is crucial for the pronounced genetic specificities of this system. We suggest that this one step can explain host population structure and could be a key force behind coevolutionary cycles. We discuss how different

  1. Resolving the infection process reveals striking differences in the contribution of environment, genetics and phylogeny to host-parasite interactions

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    Laforsch Christian

    2011-02-01

    Full Text Available Abstract Background Infection processes consist of a sequence of steps, each critical for the interaction between host and parasite. Studies of host-parasite interactions rarely take into account the fact that different steps might be influenced by different factors and might, therefore, make different contributions to shaping coevolution. We designed a new method using the Daphnia magna - Pasteuria ramosa system, one of the rare examples where coevolution has been documented, in order to resolve the steps of the infection and analyse the factors that influence each of them. Results Using the transparent Daphnia hosts and fluorescently-labelled spores of the bacterium P. ramosa, we identified a sequence of infection steps: encounter between parasite and host; activation of parasite dormant spores; attachment of spores to the host; and parasite proliferation inside the host. The chances of encounter had been shown to depend on host genotype and environment. We tested the role of genetic and environmental factors in the newly described activation and attachment steps. Hosts of different genotypes, gender and species were all able to activate endospores of all parasite clones tested in different environments; suggesting that the activation cue is phylogenetically conserved. We next established that parasite attachment occurs onto the host oesophagus independently of host species, gender and environmental conditions. In contrast to spore activation, attachment depended strongly on the combination of host and parasite genotypes. Conclusions Our results show that different steps are influenced by different factors. Host-type-independent spore activation suggests that this step can be ruled out as a major factor in Daphnia-Pasteuria coevolution. On the other hand, we show that the attachment step is crucial for the pronounced genetic specificities of this system. We suggest that this one step can explain host population structure and could be a key

  2. Presynaptic inhibition of GABAergic synaptic transmission by adenosine in mouse hypothalamic hypocretin neurons.

    Science.gov (United States)

    Xia, J X; Xiong, J X; Wang, H K; Duan, S M; Ye, J N; Hu, Z A

    2012-01-10

    Hypocretin neurons in the lateral hypothalamus, a new wakefulness-promoting center, have been recently regarded as an important target involved in endogenous adenosine-regulating sleep homeostasis. The GABAergic synaptic transmissions are the main inhibitory afferents to hypocretin neurons, which play an important role in the regulation of excitability of these neurons. The inhibitory effect of adenosine, a homeostatic sleep-promoting factor, on the excitatory glutamatergic synaptic transmissions in hypocretin neurons has been well documented, whether adenosine also modulates these inhibitory GABAergic synaptic transmissions in these neurons has not been investigated. In this study, the effect of adenosine on inhibitory postsynaptic currents (IPSCs) in hypocretin neurons was examined by using perforated patch-clamp recordings in the acute hypothalamic slices. The findings demonstrated that adenosine suppressed the amplitude of evoked IPSCs in a dose-dependent manner, which was completely abolished by 8-cyclopentyltheophylline (CPT), a selective antagonist of adenosine A1 receptor but not adenosine A2 receptor antagonist 3,7-dimethyl-1-(2-propynyl) xanthine. A presynaptic origin was suggested as following: adenosine increased paired-pulse ratio as well as reduced GABAergic miniature IPSC frequency without affecting the miniature IPSC amplitude. Further findings demonstrated that when the frequency of electrical stimulation was raised to 10 Hz, but not 1 Hz, a time-dependent depression of evoked IPSC amplitude was detected in hypocretin neurons, which could be partially blocked by CPT. However, under a higher frequency at 100 Hz stimulation, CPT had no action on the depressed GABAergic synaptic transmission induced by such tetanic stimulation in these hypocretin neurons. These results suggest that endogenous adenosine generated under certain stronger activities of synaptic transmissions exerts an inhibitory effect on GABAergic synaptic transmission in hypocretin

  3. Trapping of Syntaxin1a in Presynaptic Nanoclusters by a Clinically Relevant General Anesthetic

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    Adekunle T. Bademosi

    2018-01-01

    Full Text Available Summary: Propofol is the most commonly used general anesthetic in humans. Our understanding of its mechanism of action has focused on its capacity to potentiate inhibitory systems in the brain. However, it is unknown whether other neural mechanisms are involved in general anesthesia. Here, we demonstrate that the synaptic release machinery is also a target. Using single-particle tracking photoactivation localization microscopy, we show that clinically relevant concentrations of propofol and etomidate restrict syntaxin1A mobility on the plasma membrane, whereas non-anesthetic analogs produce the opposite effect and increase syntaxin1A mobility. Removing the interaction with the t-SNARE partner SNAP-25 abolishes propofol-induced syntaxin1A confinement, indicating that syntaxin1A and SNAP-25 together form an emergent drug target. Impaired syntaxin1A mobility and exocytosis under propofol are both rescued by co-expressing a truncated syntaxin1A construct that interacts with SNAP-25. Our results suggest that propofol interferes with a step in SNARE complex formation, resulting in non-functional syntaxin1A nanoclusters. : Bademosi et al. use single-molecule imaging microscopy to understand how general anesthetics might affect presynaptic release mechanisms. They find that a clinically relevant concentration of propofol targets the presynaptic release machinery by specifically restricting syntaxin1A mobility on the plasma membrane. This suggests an alternate target process for these drugs. Keywords: super-resolution microscopy, sptPALM, propofol, etomidate, SNARE, Drosophila melanogaster, PC12, syntaxin1A, SNAP-25, neurotransmission

  4. Super-resolution microscopy reveals presynaptic localization of the ALS / FTD related protein FUS in hippocampal neurons

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    Michael eSchoen

    2016-01-01

    Full Text Available Fused in Sarcoma (FUS is a multifunctional RNA- / DNA-binding protein, which is involved in the pathogenesis of the neurodegenerative disorders amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD. A common hallmark of these disorders is the abnormal accumulation of mutated FUS protein in the cytoplasm. Under normal conditions FUS is confined to the nuclear compartment, in neurons however, additional somatodendritic localization can be observed. In this study, we carefully analyzed the subcellular localization of endogenous FUS at synaptic sites of hippocampal neurons which are among the most affected cell types in frontotemporal dementia with FUS pathology. We could confirm a strong nuclear localization of FUS as well as its prominent and widespread neuronal expression throughout the adult and developing rat brain, particularly in the hippocampus, the cerebellum and the outer layers of the cortex. Intriguingly, FUS was also consistently observed at synaptic sites as detected by neuronal subcellular fractionation as well as by immunolabeling. To define a pre- and / or postsynaptic localization of FUS, we employed super-resolution fluorescence localization microscopy. FUS was found to be localized within the axon terminal in close proximity to the presynaptic vesicle protein Synaptophysin1 and adjacent to the active zone protein Bassoon, but well separated from the postsynaptic protein PSD-95. Having shown the presynaptic localization of FUS in the nervous system, a novel extranuclear role of FUS at neuronal contact sites has to be considered. Since there is growing evidence that local presynaptic translation might also be an important mechanism for plasticity, FUS - like the fragile X mental retardation protein FMRP - might act as one of the presynaptic RNA-binding proteins regulating this machinery. Our observation of presynaptic FUS should foster further investigations to determine its role in neurodegenerative diseases such as

  5. Presynaptic selectivity of a ligand for serotonin 1A receptors revealed by in vivo PET assays of rat brain.

    Directory of Open Access Journals (Sweden)

    Takeaki Saijo

    Full Text Available A novel investigational antidepressant with high affinity for the serotonin transporter and the serotonin 1A (5-HT(1A receptor, called Wf-516 (structural formula: (2S-1-[4-(3,4-dichlorophenylpiperidin-1-yl]-3-[2-(5-methyl-1,3,4-oxadiazol-2-ylbenzo[b]furan-4-yloxy]propan-2-ol monohydrochloride, has been found to exert a rapid therapeutic effect, although the mechanistic basis for this potential advantage remains undetermined. We comparatively investigated the pharmacokinetics and pharmacodynamics of Wf-516 and pindolol by positron emission tomographic (PET and autoradiographic assays of rat brains in order to elucidate their molecular interactions with presynaptic and postsynaptic 5-HT(1A receptors. In contrast to the full receptor occupancy by pindolol in PET measurements, the binding of Wf-516 to 5-HT(1A receptors displayed limited capacity, with relatively high receptor occupancy being achieved in regions predominantly containing presynaptic receptors. This selectivity was further proven by PET scans of neurotoxicant-treated rats deficient in presynaptic 5-HT(1A receptors. In addition, [(35S]guanosine 5'-O-[γ-thio]triphosphate autoradiography indicated a partial agonistic ability of Wf-516 for 5-HT(1A receptors. This finding has lent support to reports that diverse partial agonists for 5-HT(1A receptors exert high sensitivity for presynaptic components. Thus, the present PET data suggest a relatively high capacity of presynaptic binding sites for partial agonists. Since our in vitro and ex vivo autoradiographies failed to illustrate these distinct features of Wf-516, in vivo PET imaging is considered to be, thus far, the sole method capable of pharmacokinetically demonstrating the unique actions of Wf-516 and similar new-generation antidepressants.

  6. Presynaptic selectivity of a ligand for serotonin 1A receptors revealed by in vivo PET assays of rat brain.

    Science.gov (United States)

    Saijo, Takeaki; Maeda, Jun; Okauchi, Takashi; Maeda, Jun-ichi; Morio, Yasunori; Kuwahara, Yasuhiro; Suzuki, Masayuki; Goto, Nobuharu; Fukumura, Toshimitsu; Suhara, Tetsuya; Higuchi, Makoto

    2012-01-01

    A novel investigational antidepressant with high affinity for the serotonin transporter and the serotonin 1A (5-HT(1A)) receptor, called Wf-516 (structural formula: (2S)-1-[4-(3,4-dichlorophenyl)piperidin-1-yl]-3-[2-(5-methyl-1,3,4-oxadiazol-2-yl)benzo[b]furan-4-yloxy]propan-2-ol monohydrochloride), has been found to exert a rapid therapeutic effect, although the mechanistic basis for this potential advantage remains undetermined. We comparatively investigated the pharmacokinetics and pharmacodynamics of Wf-516 and pindolol by positron emission tomographic (PET) and autoradiographic assays of rat brains in order to elucidate their molecular interactions with presynaptic and postsynaptic 5-HT(1A) receptors. In contrast to the full receptor occupancy by pindolol in PET measurements, the binding of Wf-516 to 5-HT(1A) receptors displayed limited capacity, with relatively high receptor occupancy being achieved in regions predominantly containing presynaptic receptors. This selectivity was further proven by PET scans of neurotoxicant-treated rats deficient in presynaptic 5-HT(1A) receptors. In addition, [(35)S]guanosine 5'-O-[γ-thio]triphosphate autoradiography indicated a partial agonistic ability of Wf-516 for 5-HT(1A) receptors. This finding has lent support to reports that diverse partial agonists for 5-HT(1A) receptors exert high sensitivity for presynaptic components. Thus, the present PET data suggest a relatively high capacity of presynaptic binding sites for partial agonists. Since our in vitro and ex vivo autoradiographies failed to illustrate these distinct features of Wf-516, in vivo PET imaging is considered to be, thus far, the sole method capable of pharmacokinetically demonstrating the unique actions of Wf-516 and similar new-generation antidepressants.

  7. Age and Gender Differences in Facial Attractiveness, but Not Emotion Resemblance, Contribute to Age and Gender Stereotypes

    Directory of Open Access Journals (Sweden)

    Rocco Palumbo

    2017-09-01

    Full Text Available Considerable research has shown effects of facial appearance on trait impressions and group stereotypes. We extended those findings in two studies that investigated the contribution of resemblance to emotion expressions and attractiveness to younger adults (YA and older adults (OA age and gender stereotypes on the dimensions of warmth and competence. Using connectionist modeling of facial metrics of 240 neutral younger and older faces, Study 1 found that, neutral expression older faces or female faces showed greater structural resemblance to happy expressions and less resemblance to angry expressions than did younger or male faces, respectively. In addition, neutral female faces showed greater resemblance to surprise expressions. In Study 2, YA and OA rated the faces of Study 1 for attractiveness and for 4 traits that we aggregated on the dimensions of competence (competent, healthy and warmth (trustworthy, not shrewd. We found that YA, but not OA, age stereotypes replicated previous research showing higher perceived warmth and lower perceived competence in older adults. In addition, previously documented gender stereotypes were moderated by face age for both YA and OA. The greater attractiveness of younger than older faces and female than male faces influenced age and gender stereotypes, including these deviations from prior research findings using category labels rather than faces. On the other hand, face age and face sex differences in emotion resemblance did not influence age or gender stereotypes, contrary to prediction. Our results provide a caveat to conclusions about age and gender stereotypes derived from responses to category labels, and they reveal the importance of assessing stereotypes with a methodology that is sensitive to influences of group differences in appearance that can exacerbate or mitigate stereotypes in more ecologically valid contexts. Although the gender differences in attractiveness in the present study may not have

  8. Age and Gender Differences in Facial Attractiveness, but Not Emotion Resemblance, Contribute to Age and Gender Stereotypes.

    Science.gov (United States)

    Palumbo, Rocco; Adams, Reginald B; Hess, Ursula; Kleck, Robert E; Zebrowitz, Leslie

    2017-01-01

    Considerable research has shown effects of facial appearance on trait impressions and group stereotypes. We extended those findings in two studies that investigated the contribution of resemblance to emotion expressions and attractiveness to younger adults (YA) and older adults (OA) age and gender stereotypes on the dimensions of warmth and competence. Using connectionist modeling of facial metrics of 240 neutral younger and older faces, Study 1 found that, neutral expression older faces or female faces showed greater structural resemblance to happy expressions and less resemblance to angry expressions than did younger or male faces, respectively. In addition, neutral female faces showed greater resemblance to surprise expressions. In Study 2, YA and OA rated the faces of Study 1 for attractiveness and for 4 traits that we aggregated on the dimensions of competence (competent, healthy) and warmth (trustworthy, not shrewd). We found that YA, but not OA, age stereotypes replicated previous research showing higher perceived warmth and lower perceived competence in older adults. In addition, previously documented gender stereotypes were moderated by face age for both YA and OA. The greater attractiveness of younger than older faces and female than male faces influenced age and gender stereotypes, including these deviations from prior research findings using category labels rather than faces. On the other hand, face age and face sex differences in emotion resemblance did not influence age or gender stereotypes, contrary to prediction. Our results provide a caveat to conclusions about age and gender stereotypes derived from responses to category labels, and they reveal the importance of assessing stereotypes with a methodology that is sensitive to influences of group differences in appearance that can exacerbate or mitigate stereotypes in more ecologically valid contexts. Although the gender differences in attractiveness in the present study may not have generalizability

  9. Evaluating the contribution of differences in lean mass compartments for resting energy expenditure in African American and Caucasian American children.

    Science.gov (United States)

    Broadney, M M; Shareef, F; Marwitz, S E; Brady, S M; Yanovski, S Z; DeLany, J P; Yanovski, J A

    2018-04-26

    Resting energy expenditure (REE), adjusted for total lean mass (LM), is lower in African American (AA) than Caucasian American (CA) children. Some adult studies suggest that AA-CA differences in lean mass compartments explain this REE difference. Similar data are limited in children. To evaluate differences in compartment-specific lean mass between AA and CA children and examine the individual contributions of high-metabolic rate-at-rest trunk lean mass (TrLM) and low-metabolic-rate-at-rest appendicular lean mass (AppLM) for AA-CA differences in REE. We studied a convenience sample of 594 AA (n = 281) and CA (n = 313) children. REE was measured by using indirect calorimetry; dual-energy X-ray absorptiometry was used to assess body composition. ANCOVAs were performed to examine AA-CA differences in TrLM, AppLM and REE. After accounting for age, sex, height, pubertal development, bone mass and adiposity, REE was evaluated adjusting for total LM (model A) and separately adjusting for TrLM and AppLM (model B). African American children had greater adjusted AppLM (17.8 ± 0.2 [SE] vs. 16.0 ± 0.2 kg, p < 0.001) and lower TrLM (17.2 ± 0.2 vs. 17.7 ± 0.2 kg, p = 0.022) than CA children. REE adjusted for total LM was 77 ± 16 kcal/d lower in AA than CA (p < 0.001). However, after accounting separately for AppLM and TrLM, the discrepancy in REE between the groups declined to 28 ± 19 kcal/d (p = 0.14). In the adjusted model, both TrLM (p < 0.001) and AppLM (p < 0.027) were independently associated with REE. In children, AA-CA differences in REE appear mostly attributable to differences in body composition. Lower REE in AA children is likely due to lower TrLM and greater AppLM. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

  10. New Insights into Different Reproductive Effort and Sexual Recruitment Contribution between Two Geographic Zostera marina L. Populations in Temperate China.

    Science.gov (United States)

    Xu, Shaochun; Wang, Pengmei; Zhou, Yi; Zhang, Xiaomei; Gu, Ruiting; Liu, Xujia; Liu, Bingjian; Song, Xiaoyue; Xu, Shuai; Yue, Shidong

    2018-01-01

    Seagrasses are important components of global coastal ecosystems, and the eelgrass Zostera marina L. is widely distributed along the Atlantic and Pacific coasts in the temperate northern hemisphere, but limited datum related to the contribution of sexual reproduction to population recruitment have been reported. This study aimed to understand eelgrass sexual reproduction and population recruitment in Swan Lake (SLL), and Huiquan Bay (HQB) was included for comparison. Random sampling, permanent quadrats or cores and laboratory seed germination-based experimental methods were employed. The flowering, seed production, seed banks, seed germination, seedling survival, and seedling growth of eelgrass were investigated from July 2014 to December 2015 to evaluate the contribution of sexual reproduction to population recruitment. Results indicated a dominant role of asexual reproduction in HQB, while sexual reproduction played a relatively important role in SLL. The highest flowering shoot density in SLL was 517.27 ± 504.29 shoots m -2 (June) and represented 53.34% of the total shoots at the center site. The potential seed output per reproductive shoot and per unit area in SLL were 103.67 ± 37.95 seeds shoot -1 and 53,623.66 ± 19,628.11 seeds m -2 , respectively. The maximum seed bank density in SLL was 552.21 ± 204.94 seeds m -2 (October). Seed germination mainly occurred from the middle of March to the end of May, and the highest seedling density was 296.88 ± 274.27 seedlings m -2 in April. The recruitment from seedlings accounted for 41.36% of the Z. marina population recruitment at the center site, while the sexual recruitment contribution at the patch site (50.52%) was greater than that at the center site. Seeds in SLL were acclimated to spring germination, while in HQB, they were acclimated to autumn germination (early October-late November). Seed bank density in HQB was very low, with a value of 254.35 ± 613.34 seeds m -2 (early October). However, seeds in HQB

  11. Interaction of NANOS2 and NANOS3 with different components of the CNOT complex may contribute to the functional differences in mouse male germ cells

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    Atsushi Suzuki

    2014-11-01

    Full Text Available NANOS2 and NANOS3 belong to the Nanos family of proteins that contain a conserved zinc finger domain, which consists of two consecutive CCHC-type zinc finger motifs, and contribute to germ cell development in mice. Previous studies indicate that there are redundant and distinct functions of these two proteins. NANOS2 rescues NANOS3 functions in the maintenance of primordial germ cells, whereas NANOS3 fails to replace NANOS2 functions in the male germ cell pathway. However, the lack of a conditional allele of Nanos3 has hampered delineation of each contribution of NANOS2 and NANOS3 to the male germ cell pathway. In addition, the molecular mechanism underlying the distinct functions of these proteins remains unexplored. Here, we report an unexpected observation of a transgenic mouse line expressing a NANOS2 variant harboring mutations in the zinc finger domain. Transcription of Nanos2 and Nanos3 was strongly compromised in the presence of this transgene, which resulted in the mimicking of the Nanos2/Nanos3 double-null condition in the male gonad. In these transgenic mice, P-bodies involved in RNA metabolism had disappeared and germ cell differentiation was more severely affected than that in Nanos2-null mice, indicating that NANOS3 partially substitutes for NANOS2 functions. In addition, similar to NANOS2, we found that NANOS3 associated with the CCR4-NOT deadenylation complex but via a direct interaction with CNOT8, unlike CNOT1 in the case of NANOS2. This alternate interaction might account for the molecular basis of the functional redundancy and differences in NANOS2 and NANOS3 functions.

  12. New Insights into Different Reproductive Effort and Sexual Recruitment Contribution between Two Geographic Zostera marina L. Populations in Temperate China

    Directory of Open Access Journals (Sweden)

    Shaochun Xu

    2018-02-01

    Full Text Available Seagrasses are important components of global coastal ecosystems, and the eelgrass Zostera marina L. is widely distributed along the Atlantic and Pacific coasts in the temperate northern hemisphere, but limited datum related to the contribution of sexual reproduction to population recruitment have been reported. This study aimed to understand eelgrass sexual reproduction and population recruitment in Swan Lake (SLL, and Huiquan Bay (HQB was included for comparison. Random sampling, permanent quadrats or cores and laboratory seed germination-based experimental methods were employed. The flowering, seed production, seed banks, seed germination, seedling survival, and seedling growth of eelgrass were investigated from July 2014 to December 2015 to evaluate the contribution of sexual reproduction to population recruitment. Results indicated a dominant role of asexual reproduction in HQB, while sexual reproduction played a relatively important role in SLL. The highest flowering shoot density in SLL was 517.27 ± 504.29 shoots m−2 (June and represented 53.34% of the total shoots at the center site. The potential seed output per reproductive shoot and per unit area in SLL were 103.67 ± 37.95 seeds shoot−1 and 53,623.66 ± 19,628.11 seeds m−2, respectively. The maximum seed bank density in SLL was 552.21 ± 204.94 seeds m−2 (October. Seed germination mainly occurred from the middle of March to the end of May, and the highest seedling density was 296.88 ± 274.27 seedlings m−2 in April. The recruitment from seedlings accounted for 41.36% of the Z. marina population recruitment at the center site, while the sexual recruitment contribution at the patch site (50.52% was greater than that at the center site. Seeds in SLL were acclimated to spring germination, while in HQB, they were acclimated to autumn germination (early October–late November. Seed bank density in HQB was very low, with a value of 254.35 ± 613.34 seeds m−2 (early October

  13. Differences in cancer awareness and beliefs between Australia, Canada, Denmark, Norway, Sweden and the UK (the International Cancer Benchmarking Partnership): do they contribute to differences in cancer survival?

    Science.gov (United States)

    Forbes, L J L; Simon, A E; Warburton, F; Boniface, D; Brain, K E; Dessaix, A; Donnelly, C; Haynes, K; Hvidberg, L; Lagerlund, M; Lockwood, G; Tishelman, C; Vedsted, P; Vigmostad, M N; Ramirez, A J; Wardle, J

    2013-01-01

    Background: There are wide international differences in 1-year cancer survival. The UK and Denmark perform poorly compared with other high-income countries with similar health care systems: Australia, Canada and Sweden have good cancer survival rates, Norway intermediate survival rates. The objective of this study was to examine the pattern of differences in cancer awareness and beliefs across these countries to identify where these might contribute to the pattern of survival. Methods: We carried out a population-based telephone interview survey of 19 079 men and women aged ⩾50 years in Australia, Canada, Denmark, Norway, Sweden and the UK using the Awareness and Beliefs about Cancer measure. Results: Awareness that the risk of cancer increased with age was lower in the UK (14%), Canada (13%) and Australia (16%) but was higher in Denmark (25%), Norway (29%) and Sweden (38%). Symptom awareness was no lower in the UK and Denmark than other countries. Perceived barriers to symptomatic presentation were highest in the UK, in particular being worried about wasting the doctor's time (UK 34% Canada 21% Australia 14% Denmark 12% Norway 11% Sweden 9%). Conclusion: The UK had low awareness of age-related risk and the highest perceived barriers to symptomatic presentation, but symptom awareness in the UK did not differ from other countries. Denmark had higher awareness of age-related risk and few perceived barriers to symptomatic presentation. This suggests that other factors must be involved in explaining Denmark's poor survival rates. In the UK, interventions that address barriers to prompt presentation in primary care should be developed and evaluated. PMID:23370208

  14. Feeding condition and the relative contribution of different dopamine receptor subtypes to the discriminative stimulus effects of cocaine in rats.

    Science.gov (United States)

    Baladi, Michelle G; Newman, Amy H; France, Charles P

    2014-02-01

    The contribution of dopamine receptor subtypes in mediating the discriminative stimulus effects of cocaine is not fully established. Many drug discrimination studies use food to maintain responding, necessitating food restriction, which can alter drug effects. This study established stimulus control with cocaine (10 mg/kg) in free-feeding and food-restricted rats responding under a schedule of stimulus shock termination (SST) and in food-restricted rats responding under a schedule of food presentation to examine whether feeding condition or the reinforcer used to maintain responding impacts the effects of cocaine. Dopamine receptor agonists and antagonists were examined for their ability to mimic or attenuate, respectively, the effects of cocaine. Apomorphine, quinpirole, and lisuride occasioned >90 % responding on the cocaine-associated lever in free-feeding rats responding under a schedule of SST; apomorphine, but not quinpirole or lisuride, occasioned >90 % responding on the cocaine lever in food-restricted rats responding under a schedule of SST. In food-restricted rats responding for food these drugs occasioned little cocaine lever responding and were comparatively more potent in decreasing responding. In free-feeding rats, the effects of cocaine were attenuated by the D2/D3 receptor antagonist raclopride and the D3 receptor-selective antagonist PG01037. In food-restricted rats, raclopride and the D2 receptor-selective antagonist L-741,626 attenuated the effects of cocaine. Raclopride antagonized quinpirole in all groups while PG01037 antagonized quinpirole only in free-feeding rats. These results demonstrate significant differences in the discriminative stimulus of cocaine that are due to feeding conditions and not to the use of different reinforcers across procedures.

  15. Macroglia-derived thrombospondin 2 regulates alterations of presynaptic proteins of retinal neurons following elevated hydrostatic pressure.

    Science.gov (United States)

    Wang, Shuchao; Hu, Tu; Wang, Zhen; Li, Na; Zhou, Lihong; Liao, Lvshuang; Wang, Mi; Liao, Libin; Wang, Hui; Zeng, Leping; Fan, Chunling; Zhou, Hongkang; Xiong, Kun; Huang, Jufang; Chen, Dan

    2017-01-01

    Many studies on retinal injury and repair following elevated intraocular pressure suggest that the survival ratio of retinal neurons has been improved by various measures. However, the visual function recovery is far lower than expected. The homeostasis of retinal synapses in the visual signal pathway is the key structural basis for the delivery of visual signals. Our previous studies found that complicated changes in the synaptic structure between retinal neurons occurred much earlier than obvious degeneration of retinal ganglion cells in rat retinae. The lack of consideration of these earlier retinal synaptic changes in the rescue strategy may be partly responsible for the limited visual function recovery with the types of protective methods for retinal neurons used following elevated intraocular pressure. Thus, research on the modulatory mechanisms of the synaptic changes after elevated intraocular pressure injury may give new light to visual function rescue. In this study, we found that thrombospondin 2, an important regulator of synaptogenesis in central nervous system development, was distributed in retinal macroglia cells, and its receptor α2δ-1 was in retinal neurons. Cell cultures including mixed retinal macroglia cells/neuron cultures and retinal neuron cultures were exposed to elevated hydrostatic pressure for 2 h. The expression levels of glial fibrillary acidic protein (the marker of activated macroglia cells), thrombospondin 2, α2δ-1 and presynaptic proteins were increased following elevated hydrostatic pressure in mixed cultures, but the expression levels of postsynaptic proteins were not changed. SiRNA targeting thrombospondin 2 could decrease the upregulation of presynaptic proteins induced by the elevated hydrostatic pressure. However, in retinal neuron cultures, elevated hydrostatic pressure did not affect the expression of presynaptic or postsynaptic proteins. Rather, the retinal neuron cultures with added recombinant thrombospondin 2

  16. The contribution of radioisotopes in secular equilibrium in the transport index of fissile uranium compounds in different enrichments

    International Nuclear Information System (INIS)

    Silva, Teresinha de Moraes da; Sordi, Gian M.A.A.

    2008-01-01

    Full text: This work shows the contribution of radioisotopes in secular equilibrium in the transport index (TI) of some fissile uranium compounds: uranium oxides UO 2 , U 3 O 8 and uranium silicide U 3 Si 2 , taking into account the different enrichment grades.The range of enrichment (E%) studied was 3,4,5,7,10,20,30,40,50,93 and 100. Initially, the cell of optimum moderation ratio was built, since it represents the most reactive of the system (consisting of uranium), with maximum infinitive multiplication factor k∞, in certain concentration of uranium for each enrichment. This was made using the computer program Gamtec II. The critical radius of a sphere was calculated for a cell of optimum moderation ratio, in order to calculate the critical mass of the uranium compound or of the uranium element for each specific enrichment. For this the program Citation was used. In this study it was calculated the smallest critical mass of the uranium compound or the smallest critical mass of the uranium element. The objective was to match the largest mass of the uranium with each specific enrichment. The largest safety mass corresponds to 45% the critical mass the compound uranium or uranium element. Then, we calculated the uranium element safety mass, which it related to a fifth of this mass to the value 50, which corresponds to criticality safety index (CSI). That is, 20% of the safety mass is the value where the transport is carried out with subcritical mass, going in favor of the security. From the uranium element safety mass (USM) was determined for each enrichment , and it was calculated the mass of 235 U, activity 235 U and dose rate of 235 U, the same items were calculated for the isotope 238 U. The total dose rate was calculated for two isotopes, and applying the transport index definition as the gamma dose rate for the distance of 1 m from the packed, it was determined the TI for 20% of the safety mass for each enrichment of the compound studied. The study of

  17. Functional Differences between Global Pre- and Postsynaptic Inhibition in the Drosophila Olfactory Circuit.

    Science.gov (United States)

    Oizumi, Masafumi; Satoh, Ryota; Kazama, Hokto; Okada, Masato

    2012-01-01

    The Drosophila antennal lobe is subdivided into multiple glomeruli, each of which represents a unique olfactory information processing channel. In each glomerulus, feedforward input from olfactory receptor neurons (ORNs) is transformed into activity of projection neurons (PNs), which represent the output. Recent investigations have indicated that lateral presynaptic inhibitory input from other glomeruli controls the gain of this transformation. Here, we address why this gain control acts "pre"-synaptically rather than "post"-synaptically. Postsynaptic inhibition could work similarly to presynaptic inhibition with regard to regulating the firing rates of PNs depending on the stimulus intensity. We investigate the differences between pre- and postsynaptic gain control in terms of odor discriminability by simulating a network model of the Drosophila antennal lobe with experimental data. We first demonstrate that only presynaptic inhibition can reproduce the type of gain control observed in experiments. We next show that presynaptic inhibition decorrelates PN responses whereas postsynaptic inhibition does not. Due to this effect, presynaptic gain control enhances the accuracy of odor discrimination by a linear decoder while its postsynaptic counterpart only diminishes it. Our results provide the reason gain control operates "pre"-synaptically but not "post"-synaptically in the Drosophila antennal lobe.

  18. Functional differences between global pre- and postsynaptic inhibition in the Drosophila olfactory circuit

    Directory of Open Access Journals (Sweden)

    Masafumi eOizumi

    2012-03-01

    Full Text Available The Drosophila antennal lobe is subdivided into multiple glomeruli, each of which represents a unique olfactory information processing channel. In each glomerulus, feedforward input from olfactory receptor neurons (ORNs is transformed into activity of projection neurons (PNs, which represent the output. Recent investigations have indicated that lateral pre-synaptic inhibitory input from other glomeruli controls the gain of this transformation. Here, we address why this gain control acts `pre'-synaptically rather than `post'-synaptically. Postsynaptic inhibition could work similarly to presynaptic inhibition with regard to regulating the firing rates of PNs depending on the stimulus intensity. We investigate the differences between pre- and postsynaptic gain control in terms of odor discriminability by simulating a network model of the Drosophila antennal lobe with experimental data. We first demonstrate that only presynaptic inhibition can reproduce the type of gain control observed in experiments. We next show that presynaptic inhibition decorrelates PN responses whereas postsynaptic inhibition does not. Due to this effect, presynaptic gain control enhances the accuracy of odor discrimination by a linear decoder while its postsynaptic counterpart only diminishes it. Our results provide the reason gain control operates `pre'-synaptically but not `post'-synaptically in the Drosophila antennal lobe.

  19. Na+K+-ATPase activity and K+ channels differently contribute to vascular relaxation in male and female rats.

    Directory of Open Access Journals (Sweden)

    Fernanda Moura Vargas Dias

    Full Text Available Gender associated differences in vascular reactivity regulation might contribute to the low incidence of cardiovascular disease in women. Cardiovascular protection is suggested to depend on female sex hormones' effects on endothelial function and vascular tone regulation. We tested the hypothesis that potassium (K+ channels and Na+K+-ATPase may be involved in the gender-based vascular reactivity differences. Aortic rings from female and male rats were used to examine the involvement of K+ channels and Na+K+-ATPase in vascular reactivity. Acetylcholine (ACh-induced relaxation was analyzed in the presence of L-NAME (100 µM and the following K+ channels blockers: tetraethylammonium (TEA, 2 mM, 4-aminopyridine (4-AP, 5 mM, iberiotoxin (IbTX, 30 nM, apamin (0.5 µM and charybdotoxin (ChTX, 0.1 µM. The ACh-induced relaxation sensitivity was greater in the female group. After incubation with 4-AP the ACh-dependent relaxation was reduced in both groups. However, the dAUC was greater in males, suggesting that the voltage-dependent K+ channel (Kv participates more in males. Inhibition of the three types of Ca2+-activated K+ channels induced a greater reduction in Rmax in females than in males. The functional activity of the Na+K+-ATPase was evaluated by KCl-induced relaxation after L-NAME and OUA incubation. OUA reduced K+-induced relaxation in female and male groups, however, it was greater in males, suggesting a greater Na+K+-ATPase functional activity. L-NAME reduced K+-induced relaxation only in the female group, suggesting that nitric oxide (NO participates more in their functional Na+K+-ATPase activity. These results suggest that the K+ channels involved in the gender-based vascular relaxation differences are the large conductance Ca2+-activated K+ channels (BKCa in females and Kv in males and in the K+-induced relaxation and the Na+K+-ATPase vascular functional activity is greater in males.

  20. Sex differences in factors contributing to family-to-work and work-to-family conflict in Japanese civil servants.

    Science.gov (United States)

    Fujimura, Yuko; Sekine, Michikazu; Tatsuse, Takashi

    2014-01-01

    As the number of dual-earner couples in Japan has increased, work-life balance has become important. This study aimed to examine the factors that contribute to work-family conflict. The participants included 3,594 (2,332 men and 1,262 women) civil servants aged 20-59 working for local government on the west coast of Japan. Logistic regression analysis was used to evaluate whether work, family, or lifestyle characteristics were associated with work-family conflict. For men, family-to-work conflict was associated with being elderly, having low-grade employment, working long hours, raising children, and sleeping shorter hours. For women, being married and raising children were strong determinants of family-to-work conflict, and being middle-aged, working long hours, and sleeping shorter hours were also associated with this type of conflict. Regarding work-to-family conflict, working long hours was the strongest determinant of conflict in both sexes. In men, being elderly, living with family, eating dinner late, and sleeping shorter hours were also associated with work-to-family conflict. In women, having high-grade employment, being married, raising children, and eating dinner late were associated with work-to-family conflict. This study showed that working long hours was the primary determinant of work-to-family conflict in both sexes and that being married and raising children were strong factors of family-to-work conflict in women only. Sex differences may reflect divergence of the social and domestic roles of men and women in Japanese society. To improve the work-life balance, general and sex-specific health policies may be required.

  1. Distinct adiponectin profiles might contribute to differences in susceptibility to type 2 diabetes in dogs and humans.

    Science.gov (United States)

    Verkest, K R; Rand, J S; Fleeman, L M; Morton, J M; Richards, A A; Rose, F J; Whitehead, J P

    2011-08-01

    Dogs develop obesity-associated insulin resistance but not type 2 diabetes mellitus. Low adiponectin is associated with progression to type 2 diabetes in obese humans. The aims of this study were to compare total and high molecular weight (HMW) adiponectin and the ratio of HMW to total adiponectin (S(A)) between dogs and humans and to examine whether total or HMW adiponectin or both are associated with insulin resistance in naturally occurring obese dogs. We compared adiponectin profiles between 10 lean dogs and 10 lean humans and between 6 lean dogs and 6 age- and sex-matched, client-owned obese dogs. Total adiponectin was measured with assays validated in each species. We measured S(A) with velocity centrifugation on sucrose gradients. The effect of total and HMW adiponectin concentrations on MINMOD-estimated insulin sensitivity was assessed with linear regression. Lean dogs had total and HMW adiponectin concentrations three to four times higher than lean humans (total: dogs 32 ± 5.6 mg/L, humans 10 ± 1.3 mg/L, Pobese dogs (0.76 ± 0.05 in both groups; P=1). Total adiponectin, HMW adiponectin, and S(A) were not associated with insulin sensitivity in dogs. We propose that differences in adiponectin profiles between humans and dogs might contribute to the propensity of humans but not dogs to develop type 2 diabetes. Dogs with chronic, naturally occurring obesity do not have selectively reduced HMW adiponectin, and adiponectin does not appear to be important in the development of canine obesity-associated insulin resistance. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Contribution of the different erosion processes to material release from the vessel walls of fusion devices during plasma operation

    International Nuclear Information System (INIS)

    Behrisch, R.

    2002-01-01

    In high temperature plasma experiments several processes contribute to erosion and loss of material from the vessel walls. This material may enter the plasma edge and the central plasma where it acts as impurities. It will finally be re-deposited at other wall areas. These erosion processes are: evaporation due to heating of wall areas. At very high power deposition evaporation may become very large, which has been named ''blooming''. Large evaporation and melting at some areas of the vessel wall surface may occur during heat pulses, as observed in plasma devices during plasma disruptions. At tips on the vessel walls and/or hot spots on the plasma exposed solid surfaces electrical arcs between the plasma and the vessel wall may ignite. They cause the release of ions, atoms and small metal droplets, or of carbon dust particles. Finally, atoms from the vessel walls are removed by physical and chemical sputtering caused by the bombardment of the vessel walls with ions as well as energetic neutral hydrogen atoms from the boundary plasma. All these processes have been, and are, observed in today's plasma experiments. Evaporation can in principle be controlled by very effective cooling of the wall tiles, arcing is reduced by very stable plasma operation, and sputtering by ions can be reduced by operating with a cold plasma in front of the vessel walls. However, sputtering by energetic neutrals, which impinge on all areas of the vessel walls, is likely to be the most critical process because ions lost from the plasma recycle as neutrals or have to be refuelled by neutrals leading to the charge exchange processes in the plasma. In order to quantify the wall erosion, ''materials factors'' (MF) have been introduced in the following for the different erosion processes. (orig.)

  3. Contributing factors to VEP grating acuity deficit and inter-ocular acuity difference in children with cerebral visual impairment.

    Science.gov (United States)

    Cavascan, Nívea Nunes; Salomão, Solange Rios; Sacai, Paula Yuri; Pereira, Josenilson Martins; Rocha, Daniel Martins; Berezovsky, Adriana

    2014-04-01

    To investigate contributing factors to visual evoked potential (VEP) grating acuity deficit (GAD) and inter-ocular acuity difference (IAD) measured by sweep-VEPs in children with cerebral visual impairment (CVI). VEP GAD was calculated for the better acuity eye by subtracting acuity thresholds from mean normal VEP grating acuity according to norms from our own laboratory. Deficits were categorized as mild (0.17 ≤ deficit children (66 males-57 %) with ages ranging from 1.2 to 166.5 months (median = 17.7) was examined. VEP GAD ranged from 0.17 to 1.28 log units (mean = 0.68 ± 0.27; median = 0.71), and it was mild in 23 (20 %) children, moderate in 32 (28 %) and severe in 60 (52 %). Severe deficit was significantly associated with older age and anti-seizure drug therapy. IAD ranged from 0 to 0.49 log units (mean = 0.06 ± 0.08; median = 0.04) and was acceptable in 96 (83 %) children. Children with strabismus and nystagmus had IAD significantly larger compared to children with orthoposition. In a large cohort of children with CVI, variable severity of VEP GAD was found, with more than half of the children with severe deficits. Older children and those under anti-seizure therapy were at higher risk for larger deficits. Strabismus and nystagmus provided larger IADs. These results should be taken into account on the clinical management of children with this leading cause of bilateral visual impairment.

  4. SAD-B kinase regulates pre-synaptic vesicular dynamics at hippocampal Schaffer collateral synapses and affects contextual fear memory.

    Science.gov (United States)

    Watabe, Ayako M; Nagase, Masashi; Hagiwara, Akari; Hida, Yamato; Tsuji, Megumi; Ochiai, Toshitaka; Kato, Fusao; Ohtsuka, Toshihisa

    2016-01-01

    Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, such as axon specifications and maturation in central and peripheral nervous systems. At mature pre-synaptic terminals, SAD-B is associated with synaptic vesicles and the active zone cytomatrix; however, how SAD-B regulates neurotransmission and synaptic plasticity in vivo remains unclear. Thus, we used SAD-B knockout (KO) mice to study the function of this pre-synaptic kinase in the brain. We found that the paired-pulse ratio was significantly enhanced at Shaffer collateral synapses in the hippocampal CA1 region in SAD-B KO mice compared with wild-type littermates. We also found that the frequency of the miniature excitatory post-synaptic current was decreased in SAD-B KO mice. Moreover, synaptic depression following prolonged low-frequency synaptic stimulation was significantly enhanced in SAD-B KO mice. These results suggest that SAD-B kinase regulates vesicular release probability at pre-synaptic terminals and is involved in vesicular trafficking and/or regulation of the readily releasable pool size. Finally, we found that hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice. These observations suggest that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, but their roles in mature brains were only partially known. Here, we demonstrated, at mature pre-synaptic terminals, that SAD-B regulates vesicular release probability and synaptic plasticity. Moreover, hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice, suggesting that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. © 2015 International

  5. Dopamine synapse is a neuroligin-2–mediated contact between dopaminergic presynaptic and GABAergic postsynaptic structures

    Science.gov (United States)

    Uchigashima, Motokazu; Ohtsuka, Toshihisa; Kobayashi, Kazuto; Watanabe, Masahiko

    2016-01-01

    Midbrain dopamine neurons project densely to the striatum and form so-called dopamine synapses on medium spiny neurons (MSNs), principal neurons in the striatum. Because dopamine receptors are widely expressed away from dopamine synapses, it remains unclear how dopamine synapses are involved in dopaminergic transmission. Here we demonstrate that dopamine synapses are contacts formed between dopaminergic presynaptic and GABAergic postsynaptic structures. The presynaptic structure expressed tyrosine hydroxylase, vesicular monoamine transporter-2, and plasmalemmal dopamine transporter, which are essential for dopamine synthesis, vesicular filling, and recycling, but was below the detection threshold for molecules involving GABA synthesis and vesicular filling or for GABA itself. In contrast, the postsynaptic structure of dopamine synapses expressed GABAergic molecules, including postsynaptic adhesion molecule neuroligin-2, postsynaptic scaffolding molecule gephyrin, and GABAA receptor α1, without any specific clustering of dopamine receptors. Of these, neuroligin-2 promoted presynaptic differentiation in axons of midbrain dopamine neurons and striatal GABAergic neurons in culture. After neuroligin-2 knockdown in the striatum, a significant decrease of dopamine synapses coupled with a reciprocal increase of GABAergic synapses was observed on MSN dendrites. This finding suggests that neuroligin-2 controls striatal synapse formation by giving competitive advantage to heterologous dopamine synapses over conventional GABAergic synapses. Considering that MSN dendrites are preferential targets of dopamine synapses and express high levels of dopamine receptors, dopamine synapse formation may serve to increase the specificity and potency of dopaminergic modulation of striatal outputs by anchoring dopamine release sites to dopamine-sensing targets. PMID:27035941

  6. A postsynaptic PI3K-cII dependent signaling controller for presynaptic homeostatic plasticity

    Science.gov (United States)

    Hauswirth, Anna G; Ford, Kevin J; Wang, Tingting; Fetter, Richard D; Tong, Amy

    2018-01-01

    Presynaptic homeostatic plasticity stabilizes information transfer at synaptic connections in organisms ranging from insect to human. By analogy with principles of engineering and control theory, the molecular implementation of PHP is thought to require postsynaptic signaling modules that encode homeostatic sensors, a set point, and a controller that regulates transsynaptic negative feedback. The molecular basis for these postsynaptic, homeostatic signaling elements remains unknown. Here, an electrophysiology-based screen of the Drosophila kinome and phosphatome defines a postsynaptic signaling platform that includes a required function for PI3K-cII, PI3K-cIII and the small GTPase Rab11 during the rapid and sustained expression of PHP. We present evidence that PI3K-cII localizes to Golgi-derived, clathrin-positive vesicles and is necessary to generate an endosomal pool of PI(3)P that recruits Rab11 to recycling endosomal membranes. A morphologically distinct subdivision of this platform concentrates postsynaptically where we propose it functions as a homeostatic controller for retrograde, trans-synaptic signaling. PMID:29303480

  7. 123-I ioflupane (Datscan® presynaptic nigrostriatal imaging in patients with movement disorders

    Directory of Open Access Journals (Sweden)

    Angel Soriano Castrejón

    2005-10-01

    Full Text Available 123-I Ioflupane (Datscan® presynaptic imaging has been shown to have a significant utility in the assessment of patients with movement disorders 123-I Ioflupane SPECT is able to distinguish between Parkinson’s disease (PD and other forms of parkinsonism without degeneration of the nigrostriatal pathway, including a common movement disorder such as essential tremor, and to assess disease progression in PD and other neurodegenerative disorders involving the substantia nigra.A imagem pré-sináptica através de 123-I Ioflupane (Datscan® tem mostrado um papel significante na avaliação de pacientes com distúrbios do movimento. 123-I Ioflupane SPECT é capaz de distinguir entre Mal de Parkinson (MP e outras formas de parkinsonismo sem degenerações da via nigroestriatal incluindo um distúrbio comum de movimento parecido com o tremor essencial e para medir a evolução da doença no Mal de Parkinson e outros distúrbios neurodegenerativos envolvendo a substantia nigra.

  8. Presynaptic protein synthesis required for NT-3-induced long-term synaptic modulation

    Directory of Open Access Journals (Sweden)

    Je H

    2011-01-01

    Full Text Available Abstract Background Neurotrophins elicit both acute and long-term modulation of synaptic transmission and plasticity. Previously, we demonstrated that the long-term synaptic modulation requires the endocytosis of neurotrophin-receptor complex, the activation of PI3K and Akt, and mTOR mediated protein synthesis. However, it is unclear whether the long-term synaptic modulation by neurotrophins depends on protein synthesis in pre- or post-synaptic cells. Results Here we have developed an inducible protein translation blocker, in which the kinase domain of protein kinase R (PKR is fused with bacterial gyrase B domain (GyrB-PKR, which could be dimerized upon treatment with a cell permeable drug, coumermycin. By genetically targeting GyrB-PKR to specific cell types, we show that NT-3 induced long-term synaptic modulation requires presynaptic, but not postsynaptic protein synthesis. Conclusions Our results provide mechanistic insights into the cell-specific requirement for protein synthesis in the long-term synaptic modulation by neurotrophins. The GyrB-PKR system may be useful tool to study protein synthesis in a cell-specific manner.

  9. Tracers tor the investigation of cerebral presynaptic dopaminergic function with positron emission tomography

    International Nuclear Information System (INIS)

    Firnau, G.; Chirakal, R.; Nahmias, C.; Garnett, E.S.

    1991-01-01

    Two pharmacologic concepts, open-quotes metabolic precursorsclose quotes and open-quotes enzyme inhibitorsclose quotes have been applied to the design of PET tracers for the metabolic aspects of the neurotransmitter dopamine. As the result, highly useful, positron-emitting radiotracers have been developed with which to visualize and measure the cerebral distribution and metabolism of dopaminergic neurons. Positron emitter-labeled DOPA, particularly 6-[ 18 F]fluoro-L-DOPA, is being used to obtain information about the neurochemical anatomy of the dopamine system, and potentially, the rate constant of dopamine biosynthesis. 6-[ 18 F]Fluoro-L- meta-tyrosine delineates the dopaminergic structures even better than 6-[ 18 F]fluoro-L-DOPA but cannot provide kinetic information about dopamine biosynthesis. The in vivo activity of the enzyme aromatic L-aminoacid decarboxylase and that of monoamine oxidase types A and B can be measured with a-fluoro-methyl-6-[ 18 F]fluoro-L-DOPA, [ 11 C]clorgyline and L-[ 11 C]deprenyl, respectively. Thus, neuropharmacologic investigations of human presynaptic dopamine pharmacology are now possible in vivo

  10. In vivo and in vitro studies on a muscarinic presynaptic antagonist and postsynaptic agonist: BM-5

    International Nuclear Information System (INIS)

    Nordstrom, O.; Bartafi, T.; Frieder, B.; Grimm, V.; Ladinsky, H.; Unden, A.

    1986-01-01

    This paper reports on in vitro and in vivo studies with compound BM-5 which, at proper dosage, could have great potential since it could enhance cholinergic transmission by being a presynaptic antagonist and postsynaptic agonist. Binding studies are described in which tritium-4-NMPB, a muscarinic antagonist, was displaced by compound BM-5 in membranes from striatum, cerebral cortex, cerebellum and hippocampus. The binding data are summarized, which for each brain area involved 86-92 data points evaluated by means of nonlinear regression methods. Compound BM-5 recognized in each brain region a population of high and a population of low affinity binding sites; both of which were labelled with tritium-4-NMPB. It is shown that compound BM-5 causes muscarinic cholinergic agonist-like effects such as redness of the eye, increased motility in the gut, and impairment of locomotor behavior. It also produces muscarinic super-sensitivity upon chronic treatment, and decreases rat striatial ACh content by acute treatment

  11. Contribution of different antiretroviral regimens containing zidovudine, lamivudine and ritonavir-boosted lopinavir on HIV viral load reduction during pregnancy.

    Science.gov (United States)

    Sripan, Patumrat; Le Coeur, Sophie; Ingsrisawang, Lily; Cressey, Tim R; Bouazza, Naïm; Foissac, Frantz; Ngo-Giang-Huong, Nicole; Traisathit, Patrinee; Srirompotong, Ussanee; Ayudhaya, Orada Patamasingh Na; Puangsombat, Achara; Jungpipun, Jantana; Jittayanun, Kanokwan; Tréluyer, Jean-Marc; Jourdain, Gonzague; Lallemant, Marc; Urien, Saïk

    2016-01-01

    Antiretroviral (ARV) regimens used for the prevention of mother-to-child transmission of HIV have evolved over time. We evaluated the contribution of different ARV regimens on the reduction of the plasma HIV RNA viral load (VL) during pregnancy. A total of 1,833 VL measurements from ARV-naive pregnant women participating in perinatal prevention trials in Thailand were included. Women received either zidovudine (ZDV) monotherapy, ZDV plus lopinavir/ritonavir (LPV/r), or ZDV plus lamivudine (3TC) plus LPV/r. VL time-course during pregnancy was described as a function of pretreatment VL and treatment duration using an Emax non-linear mixed-effect model. VL reduction and median time to achieve a VL<50 copies/ml were estimated for each regimen. Among 745 women, 279 (37%), 145 (20%) and 321 (43%) received ZDV monotherapy, ZDV+LPV/r and ZDV+3TC+LPV/r, respectively. The predicted VL reduction from baseline to delivery after a median of 10 weeks of treatment were 0.5, 2.7 and 2.9 log10 copies/ml with ZDV monotherapy, ZDV+LPV/r and ZDV+3TC+LPV/r, respectively. At delivery, 1%, 57% and 63% of women receiving ZDV monotherapy, ZDV+LPV/r or ZDV+3TC+LPV/r had a VL<50 copies/ml. The addition of 3TC to ZDV+LPV/r reduced the time to achieve a VL<50 copies/ml and the higher the pretreatment VL, the larger the effect 3TC had on reducing the time to VL<50 copies/ml. The addition of 3TC to ZDV+LPV/r was associated with a slight further VL reduction but the time to reach a VL<50 copies/ml was shorter. This beneficial effect of 3TC is crucial for prevention of mother-to-child transmission in women who receive ARVs late and with high pretreatment VL.

  12. The Less Things Change, the More They Are Different: Contributions of Long-Term Synaptic Plasticity and Homeostasis to Memory

    Science.gov (United States)

    Schacher, Samuel; Hu, Jiang-Yuan

    2014-01-01

    An important cellular mechanism contributing to the strength and duration of memories is activity-dependent alterations in the strength of synaptic connections within the neural circuit encoding the memory. Reversal of the memory is typically correlated with a reversal of the cellular changes to levels expressed prior to the stimulation. Thus, for…

  13. Intersectionality and feminist thought: historical contributions and contemporary debates about the interlocking of social markers of difference

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Henning

    2015-12-01

    Full Text Available This article presents a brief review of the debates concerning the concept of intersectionality among various approaches of the contemporary feminist thought, the women’s studies and the gender theories. Based on the initial contributions of the “Black Feminisms”, this text aims to propose a panorama of the emergent context of the intersectional debate and its main strands of work in the US and UK. Grounded in a literature review of dozens of recent articles, essays and books published in the US and Europe, this text seeks to offer a “summarization” of some of the major contributions that the intersectional analysis has offered to the feminist thought and the social theory as a whole, as well as to propose the notion of “intersectional agency”. Finally, the text presents some critical considerations regarding certain characteristics that cross the field and that are still generating some important questions.

  14. Study of the contribution of the different components of atmospheric cosmic radiation in dose received by the aircraft crew

    International Nuclear Information System (INIS)

    Pereira, Marlon A.; Prado, Adriane C.M.; Federico, Claudio A.; Goncalez, Odair L.

    2014-01-01

    The crews and aircraft passengers are exposed to atmospheric cosmic radiation. The flow of this radiation is modulated by the solar cycle and space weather, varying with the geomagnetic latitude and altitude. This paper presents a study of the contributions of radiation in total ambient dose equivalent of the crews depending on flight altitude up to 20 km, during maximum and minimum solar and in equatorial and polar regions. The results of calculations of the particle flows generated by the EXPACS and QARM codes are used. The particles evaluated that contributing significantly in the ambient dose equivalent are neutrons, protons, electrons, positrons, alphas, photons, muons and charged pions. This review allows us to characterize the origin of the dose received by crews and also support a project of a dosimetric system suitable for this ionizing radiation field in aircraft and on the ground

  15. Ubiquitin–Synaptobrevin Fusion Protein Causes Degeneration of Presynaptic Motor Terminals in Mice

    Science.gov (United States)

    Liu, Yun; Li, Hongqiao; Sugiura, Yoshie; Han, Weiping; Gallardo, Gilbert; Khvotchev, Mikhail; Zhang, Yinan; Kavalali, Ege T.; Südhof, Thomas C.

    2015-01-01

    Protein aggregates containing ubiquitin (Ub) are commonly observed in neurodegenerative disorders, implicating the involvement of the ubiquitin proteasome system (UPS) in their pathogenesis. Here, we aimed to generate a mouse model for monitoring UPS function using a green fluorescent protein (GFP)-based substrate that carries a “noncleavable” N-terminal ubiquitin moiety (UbG76V). We engineered transgenic mice expressing a fusion protein, consisting of the following: (1) UbG76V, GFP, and a synaptic vesicle protein synaptobrevin-2 (UbG76V-GFP-Syb2); (2) GFP-Syb2; or (3) UbG76V-GFP-Syntaxin1, all under the control of a neuron-specific Thy-1 promoter. As expected, UbG76V-GFP-Syb2, GFP-Syb2, and UbG76V-GFP-Sytaxin1 were highly expressed in neurons, such as motoneurons and motor nerve terminals of the neuromuscular junction (NMJ). Surprisingly, UbG76V-GFP-Syb2 mice developed progressive adult-onset degeneration of motor nerve terminals, whereas GFP-Syb2 and UbG76V-GFP-Syntaxin1 mice were normal. The degeneration of nerve terminals in UbG76V-GFP-Syb2 mice was preceded by a progressive impairment of synaptic transmission at the NMJs. Biochemical analyses demonstrated that UbG76V-GFP-Syb2 interacted with SNAP-25 and Syntaxin1, the SNARE partners of synaptobrevin. Ultrastructural analyses revealed a marked reduction in synaptic vesicle density, accompanying an accumulation of tubulovesicular structures at presynaptic nerve terminals. These morphological defects were largely restricted to motor nerve terminals, as the ultrastructure of motoneuron somata appeared to be normal at the stages when synaptic nerve terminals degenerated. Furthermore, synaptic vesicle endocytosis and membrane trafficking were impaired in UbG76V-GFP-Syb2 mice. These findings indicate that UbG76V-GFP-Syb2 may compete with endogenous synaptobrevin, acting as a gain-of-function mutation that impedes SNARE function, resulting in the depletion of synaptic vesicles and degeneration of the nerve

  16. Cortical Presynaptic Control of Dorsal Horn C–Afferents in the Rat

    Science.gov (United States)

    Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rojas-Piloni, Gerardo

    2013-01-01

    Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C–fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C–fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C–fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C–fibers by means of GABAergic inhibitory

  17. Presynaptic plasticity as a hallmark of rat stress susceptibility and antidepressant response.

    Directory of Open Access Journals (Sweden)

    Jose Luis Nieto-Gonzalez

    Full Text Available Two main questions are important for understanding and treating affective disorders: why are certain individuals susceptible or resilient to stress, and what are the features of treatment response and resistance? To address these questions, we used a chronic mild stress (CMS rat model of depression. When exposed to stress, a fraction of rats develops anhedonic-like behavior, a core symptom of major depression, while another subgroup of rats is resilient to CMS. Furthermore, the anhedonic-like state is reversed in about half the animals in response to chronic escitalopram treatment (responders, while the remaining animals are resistant (non-responder animals. Electrophysiology in hippocampal brain slices was used to identify a synaptic hallmark characterizing these groups of animals. Presynaptic properties were investigated at GABAergic synapses onto single dentate gyrus granule cells. Stress-susceptible rats displayed a reduced probability of GABA release judged by an altered paired-pulse ratio of evoked inhibitory postsynaptic currents (IPSCs (1.48 ± 0.25 compared with control (0.81 ± 0.05 and stress-resilient rats (0.78 ± 0.03. Spontaneous IPSCs (sIPSCs occurred less frequently in stress-susceptible rats compared with control and resilient rats. Finally, a subset of stress-susceptible rats responding to selective serotonin reuptake inhibitor (SSRI treatment showed a normalization of the paired-pulse ratio (0.73 ± 0.06 whereas non-responder rats showed no normalization (1.2 ± 0.2. No changes in the number of parvalbumin-positive interneurons were observed. Thus, we provide evidence for a distinct GABAergic synaptopathy which associates closely with stress-susceptibility and treatment-resistance in an animal model of depression.

  18. APP Is a Context-Sensitive Regulator of the Hippocampal Presynaptic Active Zone.

    Directory of Open Access Journals (Sweden)

    Melanie Laßek

    2016-04-01

    Full Text Available The hallmarks of Alzheimer's disease (AD are characterized by cognitive decline and behavioral changes. The most prominent brain region affected by the progression of AD is the hippocampal formation. The pathogenesis involves a successive loss of hippocampal neurons accompanied by a decline in learning and memory consolidation mainly attributed to an accumulation of senile plaques. The amyloid precursor protein (APP has been identified as precursor of Aβ-peptides, the main constituents of senile plaques. Until now, little is known about the physiological function of APP within the central nervous system. The allocation of APP to the proteome of the highly dynamic presynaptic active zone (PAZ highlights APP as a yet unknown player in neuronal communication and signaling. In this study, we analyze the impact of APP deletion on the hippocampal PAZ proteome. The native hippocampal PAZ derived from APP mouse mutants (APP-KOs and NexCreAPP/APLP2-cDKOs was isolated by subcellular fractionation and immunopurification. Subsequently, an isobaric labeling was performed using TMT6 for protein identification and quantification by high-resolution mass spectrometry. We combine bioinformatics tools and biochemical approaches to address the proteomics dataset and to understand the role of individual proteins. The impact of APP deletion on the hippocampal PAZ proteome was visualized by creating protein-protein interaction (PPI networks that incorporated APP into the synaptic vesicle cycle, cytoskeletal organization, and calcium-homeostasis. The combination of subcellular fractionation, immunopurification, proteomic analysis, and bioinformatics allowed us to identify APP as structural and functional regulator in a context-sensitive manner within the hippocampal active zone network.

  19. Distinct presynaptic control of dopamine release in striosomal and matrix areas of the cat caudate nucleus

    International Nuclear Information System (INIS)

    Kemel, M.L.; Desban, M.; Glowinski, J.; Gauchy, C.

    1989-01-01

    By use of a sensitive in vitro microsuperfusion method, the cholinergic presynaptic control of dopamine release was investigated in a prominent striosome (areas poor in acetylcholinesterase activity) located within the core of cat caudate nucleus and also in adjacent matrix area. The spontaneous release of [ 3 H]dopamine continuously synthesized from [ 3 H]tyrosine in the matrix area was found to be twice that in the striosomal area; the spontaneous and potassium-evoked releases of [ 3 H]dopamine were calcium-dependent in both compartments. With 10 -6 M tetrodotoxin, 5 x 10 -5 M acetylcholine stimulated [ 3 H]dopamine release in both striosomal and matrix areas, effects completely antagonized by atropine, thus showing the involvement of muscarinic receptors located on dopaminergic nerve terminals. Experiments without tetrodotoxin revealed a more complex regulation of dopamine release in the matrix: (i) in contrast to results seen in the striosome, acetylcholine induced only a transient stimulatory effect on matrix dopamine release. (ii) Although 10 -6 M atropine completely abolished the cholinergic stimulatory effect on [ 3 H]dopamine release in striosomal area, delayed and prolonged stimulation of [ 3 H] dopamine release was seen with atropine in the matrix. The latter effect was completely abolished by the nicotinic antagonist pempidine. Therefore, in the matrix, in addition to its direct (tetrodotoxin-insensitive) facilitatory action on [ 3 H]dopamine release, acetylcholine exerts two indirect (tetrodotoxin-sensitive) opposing effects: an inhibition and a stimulation of [ 3 H]dopamine release mediated by muscarinic and nicotinic receptors, respectively

  20. Interaction of NANOS2 and NANOS3 with different components of the CNOT complex may contribute to the functional differences in mouse male germ cells

    OpenAIRE

    Atsushi Suzuki; Yuki Niimi; Yumiko Saga

    2014-01-01

    ABSTRACT NANOS2 and NANOS3 belong to the Nanos family of proteins that contain a conserved zinc finger domain, which consists of two consecutive CCHC-type zinc finger motifs, and contribute to germ cell development in mice. Previous studies indicate that there are redundant and distinct functions of these two proteins. NANOS2 rescues NANOS3 functions in the maintenance of primordial germ cells, whereas NANOS3 fails to replace NANOS2 functions in the male germ cell pathway. However, the lack o...

  1. Significant contribution of stacking faults to the strain hardening behavior of Cu-15%Al alloy with different grain sizes.

    Science.gov (United States)

    Tian, Y Z; Zhao, L J; Chen, S; Shibata, A; Zhang, Z F; Tsuji, N

    2015-11-19

    It is commonly accepted that twinning can induce an increase of strain-hardening rate during the tensile process of face-centered cubic (FCC) metals and alloys with low stacking fault energy (SFE). In this study, we explored the grain size effect on the strain-hardening behavior of a Cu-15 at.%Al alloy with low SFE. Instead of twinning, we detected a significant contribution of stacking faults (SFs) irrespective of the grain size even in the initial stage of tensile process. In contrast, twinning was more sensitive to the grain size, and the onset of deformation twins might be postponed to a higher strain with increasing the grain size. In the Cu-15 at.%Al alloy with a mean grain size of 47 μm, there was a stage where the strain-hardening rate increases with strain, and this was mainly induced by the SFs instead of twinning. Thus in parallel with the TWIP effect, we proposed that SFs also contribute significantly to the plasticity of FCC alloys with low SFE.

  2. Quantification of the relative contribution of the different right ventricular wall motion components to right ventricular ejection fraction: the ReVISION method.

    Science.gov (United States)

    Lakatos, Bálint; Tősér, Zoltán; Tokodi, Márton; Doronina, Alexandra; Kosztin, Annamária; Muraru, Denisa; Badano, Luigi P; Kovács, Attila; Merkely, Béla

    2017-03-27

    Three major mechanisms contribute to right ventricular (RV) pump function: (i) shortening of the longitudinal axis with traction of the tricuspid annulus towards the apex; (ii) inward movement of the RV free wall; (iii) bulging of the interventricular septum into the RV and stretching the free wall over the septum. The relative contribution of the aforementioned mechanisms to RV pump function may change in different pathological conditions.Our aim was to develop a custom method to separately assess the extent of longitudinal, radial and anteroposterior displacement of the RV walls and to quantify their relative contribution to global RV ejection fraction using 3D data sets obtained by echocardiography.Accordingly, we decomposed the movement of the exported RV beutel wall in a vertex based manner. The volumes of the beutels accounting for the RV wall motion in only one direction (either longitudinal, radial, or anteroposterior) were calculated at each time frame using the signed tetrahedron method. Then, the relative contribution of the RV wall motion along the three different directions to global RV ejection fraction was calculated either as the ratio of the given direction's ejection fraction to global ejection fraction and as the frame-by-frame RV volume change (∆V/∆t) along the three motion directions.The ReVISION (Right VentrIcular Separate wall motIon quantificatiON) method may contribute to a better understanding of the pathophysiology of RV mechanical adaptations to different loading conditions and diseases.

  3. Different contributions of HtrA protease and chaperone activities to Campylobacter jejuni stress tolerance and physiology

    DEFF Research Database (Denmark)

    Bæk, Kristoffer Torbjørn; Vegge, Christina Skovgaard; Skórko-Glonek, Joanna

    2011-01-01

    activity is sufficient for growth at high temperature or oxidative stress, whereas the HtrA protease activity is only essential at conditions close to the growth limit for C. jejuni. However, the protease activity was required to prevent induction of the cytoplasmic heat-shock response even at optimal......The microaerophilic bacterium Campylobacter jejuni is the most common cause of bacterial food-borne infections in the developed world. Tolerance to environmental stress relies on proteases and chaperones in the cell envelope such as HtrA and SurA. HtrA displays both chaperone and protease activity......, but little is known about how each of these activities contributes to stress tolerance in bacteria. In vitro experiments showed temperature dependent protease and chaperone activities of C. jejuni HtrA. A C. jejuni mutant lacking only the protease activity of HtrA was used to show that the HtrA chaperone...

  4. Ruminal protozoal contribution to the duodenal flow of fatty acids following feeding of steers on forages differing in chloroplast content.

    Science.gov (United States)

    Huws, S A; Lee, M R F; Kingston-Smith, A H; Kim, E J; Scott, M B; Tweed, J K S; Scollan, N D

    2012-12-28

    Ruminant products are criticised for their SFA content relative to PUFA, although n-6:n-3 PUFA is desirable for human health ( content of rumen protozoa offers a potentially novel approach to enhance PUFA flow to the duodenum and subsequent incorporation into meat and milk. We evaluated protozoal contribution to duodenal n-3 PUFA flow due to intracellular chloroplast content. A total of six Holstein × Friesian steers were fed, in a two-period changeover design, either straw:concentrate (S:C, 60:40; DM basis; S:C, low chloroplast) or fresh perennial ryegrass (PRG; high chloroplast). Following 12 d adaptation to diet, ruminal protozoal and whole duodenal samples were obtained. N and fatty acid content of whole duodenum and rumen protozoal samples were assessed and protozoal 18S rDNA quantitative PCR performed, enabling calculation of protozoal N flow. The ratio of individual fatty acids:N in rumen protozoal samples was calculated to obtain protozoal fatty acid flows. Based on total fatty acid flow, contribution (%) of protozoa to individual fatty acid flows was calculated. Protozoal fatty acid data and microscopical observations revealed that protozoa were enriched with 18 : 3n-3 following PRG feeding, compared with the S:C diet, due to increased intracellular chloroplast content. However, duodenal protozoal 18S rDNA concentration post PRG feeding was low, indicating rumen retention of the protozoa. Nutrition influences the 18 : 3n-3 content of protozoa; the challenge is to increase protozoal flow to the small intestine, while maintaining sustainable rumen densities.

  5. Role of allosteric switch residue histidine 195 in maintaining active-site asymmetry in presynaptic filaments of bacteriophage T4 UvsX recombinase.

    Science.gov (United States)

    Farb, Joshua N; Morrical, Scott W

    2009-01-16

    Recombinases of the highly conserved RecA/Rad51 family play central roles in homologous recombination and DNA double-stranded break repair. RecA/Rad51 enzymes form presynaptic filaments on single-stranded DNA (ssDNA) that are allosterically activated to catalyze ATPase and DNA strand-exchange reactions. Information is conveyed between DNA- and ATP-binding sites, in part, by a highly conserved glutamine residue (Gln194 in Escherichia coli RecA) that acts as an allosteric switch. The T4 UvsX protein is a divergent RecA ortholog and contains histidine (His195) in place of glutamine at the allosteric switch position. UvsX and RecA catalyze similar strand-exchange reactions, but differ in other properties. UvsX produces both ADP and AMP as products of its ssDNA-dependent ATPase activity--a property that is unique among characterized recombinases. Details of the kinetics of ssDNA-dependent ATP hydrolysis reactions indicate that UvsX-ssDNA presynaptic filaments are asymmetric and contain two classes of ATPase active sites: one that generates ADP, and another that generates AMP. Active-site asymmetry is reduced by mutations at the His195 position, since UvsX-H195Q and UvsX-H195A mutants both exhibit stronger ssDNA-dependent ATPase activity, with lower cooperativity and markedly higher ADP/AMP product ratios, than wild-type UvsX. Reduced active-site asymmetry correlates strongly with reduced ssDNA-binding affinity and DNA strand-exchange activity in both H195Q and H195A mutants. These and other results support a model in which allosteric switch residue His195 controls the formation of an asymmetric conformation of UvsX-ssDNA filaments that is active in DNA strand exchange. The implications of our findings for UvsX recombination functions, and for RecA functions in general, are discussed.

  6. Do private sustainability standards contribute to income growth and poverty alleviation? A comparison of different coffee certification schemes in Ethiopia

    NARCIS (Netherlands)

    Mitiku, Fikadu; Mey, de Yann; Nyssen, Jan; Maertens, Miet

    2017-01-01

    Private sustainability standards are increasingly important in food trade with developing countries, but the implications for smallholder farmers are still poorly understood. We analyze the implications of different coffee certification schemes in Ethiopia using cross-sectional survey data, and

  7. The Contributions of the on and off Gain Difference to the Contextual Effect in Macaque Monkey V1

    Directory of Open Access Journals (Sweden)

    Kuo-Sheng Lee

    2012-10-01

    Full Text Available In macaque monkey V1, the response amplitudes of ON and OFF sub-regions of simple receptive fields are about equal for cells in the input layer 4c, but the OFF responses tend to be greater than the ON responses for layer-2/3 cells. This OFF-over-ON bias is evident when receptive fields are mapped with sparse noise (a series of dark or bright squares shown in different space and time but is weaker with Hartleys (gratings shown briefly at different orientations and spatial frequencies. One possible mechanism for the receptive-field mismatch in layer 2/3 of V1 is the difference between ON and OFF response gains caused by different degrees of sparseness between Hartleys and sparse noise. Here we manipulated the relative strength of ON and OFF sparse-noise responses until the receptive field similarity (RFS, quantified as the pixel-by-pixel correlation between two maps between sparse-noise and Hartley maps reached the maximum. On average, the relative strength of ON/OFF responses in sparse-noise maps should be increased to approximately two times of their origins in order to match closely their Hartley compartments for layer-2/3 neurons (1.93±0.19; mean±S.E.M.. The sole change in response gain largely increased the RFS between Hartley and sparse-noise maps (on average the RFS increases from 0.35 to 0.58, and it could account for approximately 81% of the overall differences between the two maps. In summary, the difference in ON and OFF gains under different visual stimulations is one critical mechanism underlying the contextual effect in the superficial layer of V1.

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

    Science.gov (United States)

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

    2018-05-02

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

  9. Single or in Combination Antimicrobial Resistance Mechanisms of Klebsiella pneumoniae Contribute to Varied Susceptibility to Different Carbapenems

    Science.gov (United States)

    Tsai, Yu-Kuo; Liou, Ci-Hong; Fung, Chang-Phone; Lin, Jung-Chung; Siu, L. Kristopher

    2013-01-01

    Resistance to carbapenems has been documented by the production of carbapenemase or the loss of porins combined with extended-spectrum β-lactamases or AmpC β-lactamases. However, no complete comparisons have been made regarding the contributions of each resistance mechanism towards carbapenem resistance. In this study, we genetically engineered mutants of Klebsiella pneumoniae with individual and combined resistance mechanisms, and then compared each resistance mechanism in response to ertapenem, imipenem, meropenem, doripenem and other antibiotics. Among the four studied carbapenems, ertapenem was the least active against the loss of porins, cephalosporinases and carbapenemases. In addition to the production of KPC-2 or NDM-1 alone, resistance to all four carbapenems could also be conferred by the loss of two major porins, OmpK35 and OmpK36, combined with CTX-M-15 or DHA-1 with its regulator AmpR. Because the loss of OmpK35/36 alone or the loss of a single porin combined with bla CTX-M-15 or bla DHA-1-ampR expression was only sufficient for ertapenem resistance, our results suggest that carbapenems other than ertapenem should still be effective against these strains and laboratory testing for non-susceptibility to other carbapenems should improve the accurate identification of these isolates. PMID:24265784

  10. Computational model to investigate the relative contributions of different neuromuscular properties of tibialis anterior on force generated during ankle dorsiflexion.

    Science.gov (United States)

    Siddiqi, Ariba; Poosapadi Arjunan, Sridhar; Kumar, Dinesh Kant

    2018-01-16

    This study describes a new model of the force generated by tibialis anterior muscle with three new features: single-fiber action potential, twitch force, and pennation angle. This model was used to investigate the relative effects and interaction of ten age-associated neuromuscular parameters. Regression analysis (significance level of 0.05) between the neuromuscular properties and corresponding simulated force produced at the footplate was performed. Standardized slope coefficients were computed to rank the effect of the parameters. The results show that reduction in the average firing rate is the reason for the sharp decline in the force and other factors, such as number of muscle fibers, specific force, pennation angle, and innervation ratio. The fast fiber ratio affects the simulated force through two significant interactions. This study has ranked the individual contributions of the neuromuscular factors to muscle strength decline of the TA and identified firing rate decline as the biggest cause followed by decrease in muscle fiber number and specific force. The strategy for strength preservation for the elderly should focus on improving firing rate. Graphical abstract Neuromuscular properties of Tibialis Anterior on force generated during ankle dorsiflexion.

  11. Differences in forage-acquisition and fungal enzyme activity contribute to niche segregation in Panamanian leaf-cutting ants.

    Directory of Open Access Journals (Sweden)

    Pepijn W Kooij

    Full Text Available The genera Atta and Acromyrmex are often grouped as leaf-cutting ants for pest management assessments and ecological surveys, although their mature colony sizes and foraging niches may differ substantially. Few studies have addressed such interspecific differences at the same site, which prompted us to conduct a comparative study across six sympatric leaf-cutting ant species in Central Panama. We show that foraging rates during the transition between dry and wet season differ about 60 fold between genera, but are relatively constant across species within genera. These differences appear to match overall differences in colony size, especially when Atta workers that return to their nests without leaves are assumed to carry liquid food. We confirm that Panamanian Atta specialize primarily on tree-leaves whereas Acromyrmex focus on collecting flowers and herbal leaves and that species within genera are similar in these overall foraging strategies. Species within genera tended to be spaced out over the three habitat categories that we distinguished (forest, forest edge, open grassland, but each of these habitats normally had only a single predominant Atta and Acromyrmex species. We measured activities of twelve fungus garden decomposition enzymes, belonging to the amylases, cellulases, hemicellulases, pectinases and proteinases, and show that average enzyme activity per unit of fungal mass in Atta gardens is lower than in Acromyrmex gardens. Expression profiles of fungal enzymes in Atta also appeared to be more specialized than in Acromyrmex, possibly reflecting variation in forage material. Our results suggest that species- and genus-level identities of leaf-cutting ants and habitat-specific foraging profiles may give predictable differences in the expression of fungal genes coding for decomposition enzymes.

  12. Cross-Cultural Differences in the Development of Behavior Problems: Contributions of Infant Temperament in Russia and U.S.

    Science.gov (United States)

    Maria A. Gartstein,; Slobodskaya, Helena R.; Kirchhoff, Cornelia; Putnam, Samuel P.

    2013-01-01

    The present study was designed to examine cross-cultural differences in longitudinal links between infant temperament toddler behavior problems in the U.S. (N= 250) and Russia (N= 129). Profiles of risk/protective temperament factors varied across the two countries, with fewer significant temperament effects observed for the Russian, relative to…

  13. Dental anomalies in different cleft groups related to neural crest developmental fields contributes to the understanding of cleft aetiology

    DEFF Research Database (Denmark)

    Riis, Louise Claudius; Kjær, Inger; Mølsted, Kirsten

    2014-01-01

    OBJECTIVE: To analyze dental deviations in three cleft groups and relate findings to embryological neural crest fields (frontonasal, maxillary, and palatal). The overall purpose was to evaluate how fields are involved in different cleft types. DESIGN: Retrospective audit of clinical photographs...

  14. The Contribution of Different Patterns of Teachers' Interactions to Young Children's Experiences of Democratic Values during Play

    Science.gov (United States)

    Zachrisen, Berit

    2016-01-01

    Developing a sense of belonging and experiences about the value of community are important democratic values that children may learn during play in preschool. Through the different ways that teachers' interact with children during play, children can learn about democratic values. This study is part of a Nordic project on values education in early…

  15. Rugby versus Soccer in South Africa: Content Familiarity Contributes to Cross-Cultural Differences in Cognitive Test Scores

    Science.gov (United States)

    Malda, Maike; van de Vijver, Fons J. R.; Temane, Q. Michael

    2010-01-01

    In this study, cross-cultural differences in cognitive test scores are hypothesized to depend on a test's cultural complexity (Cultural Complexity Hypothesis: CCH), here conceptualized as its content familiarity, rather than on its cognitive complexity (Spearman's Hypothesis: SH). The content familiarity of tests assessing short-term memory,…

  16. Re-Envisioned Contributions: Experiences of Faculty Employed at Institutional Types That Differ from Their Original Aspirations

    Science.gov (United States)

    Terosky, Aimee LaPointe; Gonzales, Leslie D.

    2016-01-01

    Guided by the theory of figured worlds, this qualitative study focuses on 18 faculty members employed at community colleges, broad access liberal arts, comprehensives, and regional research universities, who have constructed professionally and personally meaningful careers at institutions that differ from their original aspirations and/or their…

  17. Climate-model induced differences in the 21st century global and regional glacier contributions to sea-level rise

    NARCIS (Netherlands)

    Giesen, R.H.|info:eu-repo/dai/nl/304831603; Oerlemans, J.|info:eu-repo/dai/nl/06833656X

    2013-01-01

    The large uncertainty in future global glacier volume projections partly results from a substantial range in future climate conditions projected by global climate models. This study addresses the effect of global and regional differences in climate input data on the projected twenty-first century

  18. Influence of different contributions of scatter and attenuation on the threshold values in contrast-based algorithms for volume segmentation.

    Science.gov (United States)

    Matheoud, Roberta; Della Monica, Patrizia; Secco, Chiara; Loi, Gianfranco; Krengli, Marco; Inglese, Eugenio; Brambilla, Marco

    2011-01-01

    The aim of this work is to evaluate the role of different amount of attenuation and scatter on FDG-PET image volume segmentation using a contrast-oriented method based on the target-to-background (TB) ratio and target dimensions. A phantom study was designed employing 3 phantom sets, which provided a clinical range of attenuation and scatter conditions, equipped with 6 spheres of different volumes (0.5-26.5 ml). The phantoms were: (1) the Hoffman 3-dimensional brain phantom, (2) a modified International Electro technical Commission (IEC) phantom with an annular ring of water bags of 3 cm thickness fit over the IEC phantom, and (3) a modified IEC phantom with an annular ring of water bags of 9 cm. The phantoms cavities were filled with a solution of FDG at 5.4 kBq/ml activity concentration, and the spheres with activity concentration ratios of about 16, 8, and 4 times the background activity concentration. Images were acquired with a Biograph 16 HI-REZ PET/CT scanner. Thresholds (TS) were determined as a percentage of the maximum intensity in the cross section area of the spheres. To reduce statistical fluctuations a nominal maximum value is calculated as the mean from all voxel > 95%. To find the TS value that yielded an area A best matching the true value, the cross section were auto-contoured in the attenuation corrected slices varying TS in step of 1%, until the area so determined differed by less than 10 mm² versus its known physical value. Multiple regression methods were used to derive an adaptive thresholding algorithm and to test its dependence on different conditions of attenuation and scatter. The errors of scatter and attenuation correction increased with increasing amount of attenuation and scatter in the phantoms. Despite these increasing inaccuracies, PET threshold segmentation algorithms resulted not influenced by the different condition of attenuation and scatter. The test of the hypothesis of coincident regression lines for the three phantoms used

  19. A contribution to the methods of determining the optimal exploitation of hydraulically related hydroelectric power plants of different owners

    International Nuclear Information System (INIS)

    Gievski, Igor

    2013-01-01

    For the purpose of solving the water-supply and energy-related problems of the city of Skopje, the need has arisen to construct the 'Skopsko Pole' hydro system. The 'Skopsko Pole' hydro system consists of the power plants 'Kozjak', 'SvetaPetka' and 'Matka'. It is envisioned to use the watercourse of the Treska River and has been envisaged as a multipurpose system, that is, as an anti-flood system, system for irrigation of agricultural land and an electricity producer. Certainly, the meeting of the aforementioned needs will depend on the hydrological potential of the Treska River, which is why an exact and detailed review of the hydrological potential of the Treska River is of vital importance. It is a complex task to determine the optimal work of the hydroelectric power plants built along the same river, even if this is about the so-called run-of-the-water hydroelectric power plants, given the different interests of the water consumers of the same watercourse. This problem will become more complicated if one or more (that is, all) hydroelectric power plants have their own accumulative pools. In this case, the question arises of how the waters of each of the accumulations should be used. During this, we need to bear in mind the fact that every release of water from each of the accumulations alters the elevation points of all the hydroelectric power plants on the same watercourse and thus affects their production and eventually the benefit of their work. With the restructuring of the electric energy systems in different countries over the past 20 years, the vertically integrated power plants have been converted into horizontally integrated ones. In many cases, it is different companies that are the electricity producers, the high-voltage electricity transmitters, and the medium- and low-voltage electricity distributors. Some of these companies are private companies, whereas others are state-owned. Such diverse ownership of the power plants, which are by default

  20. Differences in gas exchange contribute to habitat differentiation in Iberian columbines from contrasting light and water environments.

    Science.gov (United States)

    Jaime, R; Serichol, C; Alcántara, J M; Rey, P J

    2014-03-01

    During photosynthesis, respiration and transpiration, gas exchange occurs via the stomata and so plants face a trade-off between maximising photosynthesis while minimising transpiration (expressed as water use efficiency, WUE). The ability to cope with this trade-off and regulate photosynthetic rate and stomatal conductance may be related to niche differentiation between closely related species. The present study explored this as a possible mechanism for habitat differentiation in Iberian columbines. The roles of irradiance and water stress were assessed to determine niche differentiation among Iberian columbines via distinct gas exchange processes. Photosynthesis-irradiance curves (P-I curves) were obtained for four taxa, and common garden experiments were conducted to examine plant responses to water and irradiance stress, by measuring instantaneous gas exchange and plant performance. Gas exchange was also measured in ten individuals using two to four field populations per taxon. The taxa had different P-I curves and gas exchange in the field. At the species level, water stress and irradiance explained habitat differentiation. Within each species, a combination of irradiance and water stress explained the between-subspecies habitat differentiation. Despite differences in stomatal conductance and CO2 assimilation, taxa did not have different WUE under field conditions, which suggests that the environment equally modifies photosynthesis and transpiration. The P-I curves, gas exchange in the field and plant responses to experimental water and irradiance stresses support the hypothesis that habitat differentiation is associated with differences among taxa in tolerance to abiotic stress mediated by distinct gas exchange responses. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

  1. Contribution to development of SPNDs for instantaneous and selective measurement of different radiation fields in nuclear reactors; Contribution au developpement de collectrons pour la mesure instantanee et selective des differents champs de rayonnements en reacteurs nucleaires

    Energy Technology Data Exchange (ETDEWEB)

    Blandin, Christophe [Institut National Polytechnique, 38 - Grenoble (France)

    1998-02-20

    The objective of this work was conceiving and experimentally optimizing the SPNDs (Self-Powdered Neutron Detector) able to control fast power transients in test reactors and also to cope with requirements of surveillanceand protection of EDF reactors. Thus, different SPND emitters of platinum, gadolinium, hafnium and cobalt were provided according to their nature with sheathing and stainless steel plugs as well as with zirconium over-sheathing in order to render them faster, more selective and adapted for wear checking. Special experimental devices were designed for measuring inside the Siloe reactor the promptness of the signals from SPND, on one hand, and their sensitivity to thermal and epithermal neutrons as well as to gamma rays, on the other hand. The follow-up of power transients in test reactors is ensured by the instantaneous measurement of thermal and epithermal neutron flux as well as of gamma field by means of three special SPND with gadolinium, hafnium and platinum. Also, we have defined the characteristics of a new SPND with cobalt, that delivers a current of unique neutronic origin, able to ensure the surveillance and protection of a power reactor over a period of at least six years.

  2. Different cellular response mechanisms contribute to the length-dependent cytotoxicity of multi-walled carbon nanotubes

    OpenAIRE

    Liu, Dun; Wang, Lijun; Wang, Zhigang; Cuschieri, Alfred

    2012-01-01

    To date, there has not been an agreement on the best methods for the characterisation of multi-walled carbon nanotube (MWCNT) toxicity. The length of MWCNTs has been identified as a factor in in vitro and in vivo studies, in addition to their purity and biocompatible coating. Another unresolved issue relates to the variable toxicity of MWCNTs on different cell types. The present study addressed the effects of MWCNTs' length on mammalian immune and epithelial cancer cells RAW264.7 and MCF-7, r...

  3. Individual differences in the development of early peer aggression: Integrating contributions of self-regulation, theory of mind, and parenting

    Science.gov (United States)

    OLSON, SHERYL L.; LOPEZ-DURAN, NESTOR; LUNKENHEIMER, ERIKA S.; CHANG, HYEIN; SAMEROFF, ARNOLD J.

    2014-01-01

    This prospective longitudinal study focused on self-regulatory, social–cognitive, and parenting precursors of individual differences in children’s peer-directed aggression at early school age. Participants were 1993-year-old boys and girls who were reassessed following the transition to kindergarten (5.5–6 years). Peer aggression was assessed in preschool and school settings using naturalistic observations and teacher reports. Children’s self-regulation abilities and theory of mind understanding were assessed during a laboratory visit, and parenting risk (corporal punishment and low warmth/responsiveness) was assessed using interview-based and questionnaire measures. Individual differences in children’s peer aggression were moderately stable across the preschool to school transition. Preschool-age children who manifested high levels of aggressive peer interactions also showed lower levels of self-regulation and theory of mind understanding, and experienced higher levels of adverse parenting than others. Our main finding was that early corporal punishment was associated with increased levels of peer aggression across the transition from preschool to school, as was the interaction between low maternal emotional support and children’s early delays in theory of mind understanding. These data highlight the need for family-directed preventive efforts during the early preschool years. PMID:21262052

  4. The Contribution of Cognitive Factors to Individual Differences in Understanding Noise-Vocoded Speech in Young and Older Adults

    Directory of Open Access Journals (Sweden)

    Stephanie Rosemann

    2017-06-01

    Full Text Available Noise-vocoded speech is commonly used to simulate the sensation after cochlear implantation as it consists of spectrally degraded speech. High individual variability exists in learning to understand both noise-vocoded speech and speech perceived through a cochlear implant (CI. This variability is partly ascribed to differing cognitive abilities like working memory, verbal skills or attention. Although clinically highly relevant, up to now, no consensus has been achieved about which cognitive factors exactly predict the intelligibility of speech in noise-vocoded situations in healthy subjects or in patients after cochlear implantation. We aimed to establish a test battery that can be used to predict speech understanding in patients prior to receiving a CI. Young and old healthy listeners completed a noise-vocoded speech test in addition to cognitive tests tapping on verbal memory, working memory, lexicon and retrieval skills as well as cognitive flexibility and attention. Partial-least-squares analysis revealed that six variables were important to significantly predict vocoded-speech performance. These were the ability to perceive visually degraded speech tested by the Text Reception Threshold, vocabulary size assessed with the Multiple Choice Word Test, working memory gauged with the Operation Span Test, verbal learning and recall of the Verbal Learning and Retention Test and task switching abilities tested by the Comprehensive Trail-Making Test. Thus, these cognitive abilities explain individual differences in noise-vocoded speech understanding and should be considered when aiming to predict hearing-aid outcome.

  5. Protective Effects of Testosterone on Presynaptic Terminals against Oligomeric β-Amyloid Peptide in Primary Culture of Hippocampal Neurons

    Directory of Open Access Journals (Sweden)

    Chi-Fai Lau

    2014-01-01

    Full Text Available Increasing lines of evidence support that testosterone may have neuroprotective effects. While observational studies reported an association between higher bioavailable testosterone or brain testosterone levels and reduced risk of Alzheimer’s disease (AD, there is limited understanding of the underlying neuroprotective mechanisms. Previous studies demonstrated that testosterone could alleviate neurotoxicity induced by β-amyloid (Aβ, but these findings mainly focused on neuronal apoptosis. Since synaptic dysfunction and degeneration are early events during the pathogenesis of AD, we aim to investigate the effects of testosterone on oligomeric Aβ-induced synaptic changes. Our data suggested that exposure of primary cultured hippocampal neurons to oligomeric Aβ could reduce the length of neurites and decrease the expression of presynaptic proteins including synaptophysin, synaptotagmin, and synapsin-1. Aβ also disrupted synaptic vesicle recycling and protein folding machinery. Testosterone preserved the integrity of neurites and the expression of presynaptic proteins. It also attenuated Aβ-induced impairment of synaptic exocytosis. By using letrozole as an aromatase antagonist, we further demonstrated that the effects of testosterone on exocytosis were unlikely to be mediated through the estrogen receptor pathway. Furthermore, we showed that testosterone could attenuate Aβ-induced reduction of HSP70, which suggests a novel mechanism that links testosterone and its protective function on Aβ-induced synaptic damage. Taken together, our data provide further evidence on the beneficial effects of testosterone, which may be useful for future drug development for AD.

  6. Release properties of individual presynaptic boutons expressed during homosynaptic depression and heterosynaptic facilitation of the Aplysia sensorimotor synapse

    Directory of Open Access Journals (Sweden)

    Guy eMalkinson

    2013-09-01

    Full Text Available Much of what we know about the mechanisms underlying Homosynaptic Depression (HSD and heterosynaptic facilitation is based on intracellular recordings of integrated postsynaptic potentials. This methodological approach views the presynaptic apparatus as a single compartment rather than taking a more realistic representation reflecting the fact that it is made up of tens to hundreds of individual and independent Presynaptic Release Boutons (PRBs. Using cultured Aplysia sensorimotor synapses, we reexamined HSD and its dishabituation by imaging the release properties of individual PRBs. We find that the PRB population is heterogeneous and can be clustered into three groups: approximately 25% of the PRBs consistently release neurotransmitter throughout the entire habituation paradigm (35 stimuli, 0.05Hz and have a relatively high quantal content, 36% of the PRBs display intermittent failures only after the tenth stimulation, and 39% are low quantal-content PRBs that exhibit intermittent release failures from the onset of the habituation paradigm. 5HT-induced synaptic dishabituation by a single 5HT application was generated by the enhanced recovery of the quantal content of the habituated PRBs and did not involve the recruitment of new release boutons. The characterization of the PRB population as heterogeneous in terms of its temporal pattern of release-probability and quantal content provides new insights into the mechanisms underlying HSD and its dishabituation.

  7. The contribution of intrapulmonary shunts to the alveolar-to-arterial oxygen difference during exercise is very small

    DEFF Research Database (Denmark)

    Vogiatzis, Ioannis; Zakynthinos, Spyros; Boushel, Robert

    2008-01-01

    Exercise is well known to cause arterial PO2 to fall and the alveolar-arterial PO2 difference(Aa PO2 ) to increase. Until recently, the physiological basis for this was considered to be mostly ventilation/perfusion ((.)VA/(.)Q) inequality and alveolar-capillary diffusion limitation. Recently......, arterio-venous shunting through dilated pulmonary blood vessels has been proposed to explain a significant part of the Aa PO2 during exercise. To test this hypothesis we determined venous admixture during 5 min of near-maximal, constant-load, exercise in hypoxia (in inspired O2 fraction, FIO2 , 0...... venous admixture, Aa PO2 and hypoxaemia during heavy exercise....

  8. [Evaluation of scientific production in different subareas of Public Health: limits of the current model and contributions to the debate].

    Science.gov (United States)

    Iriart, Jorge Alberto Bernstein; Deslandes, Suely Ferreira; Martin, Denise; Camargo, Kenneth Rochel de; Carvalho, Marilia Sá; Coeli, Cláudia Medina

    2015-10-01

    The aim of this study was to discuss the limits of the quantitative evaluation model for scientific production in Public Health. An analysis of the scientific production of professors from the various subareas of Public Health was performed for 2010-2012. Distributions of the mean annual score for professors were compared according to subareas. The study estimated the likelihood that 60% of the professors in the graduate studies programs scored P50 (Very Good) or higher in their area. Professors of Epidemiology showed a significantly higher median annual score. Graduate studies programs whose faculty included at least 60% of Epidemiology professors and fewer than 10% from the subarea Social and Human Sciences in Health were significantly more likely to achieve a "Very Good" classification. The observed inequalities in scientific production between different subareas of Public Health point to the need to rethink their evaluation in order to avoid reproducing iniquities that have harmful consequences for the field's diversity.

  9. Do Private Sustainability Standards Contribute to Income Growth and Poverty Alleviation? A Comparison of Different Coffee Certification Schemes in Ethiopia

    Directory of Open Access Journals (Sweden)

    Fikadu Mitiku

    2017-02-01

    Full Text Available Private sustainability standards are increasingly important in food trade with developing countries, but the implications for smallholder farmers are still poorly understood. We analyze the implications of different coffee certification schemes in Ethiopia using cross-sectional survey data, and regression and propensity-score-matching techniques. We find that: Rainforest Alliance (RA and double Fairtrade-Organic (FT-Org certifications are associated with higher incomes and reduced poverty, mainly because of higher prices; Fairtrade (FT certification hardly affects welfare; and Organic (Org certification reduces incomes, chiefly due to lower yields. Cooperative heterogeneity importantly shapes these results. Results imply that private standards may not always deliver what they promise to consumers.

  10. Abstinence environment contributes to age differences in reinstatement of cocaine seeking between adolescent and adult male rats.

    Science.gov (United States)

    Li, Chen; Frantz, Kyle J

    2017-07-01

    Extinction responding and cue-induced reinstatement of cocaine seeking after 60-days of forced abstinence are attenuated in male rats that self-administered cocaine during adolescence, compared with adults. Given that environmental enrichment during abstinence decreases reinstatement among adults, a possible explanation for attenuated reinstatement among adolescents is that standard pair-housing in prior studies creates a more stimulating environment for younger rats. Therefore, we tested whether standard pair-housing is necessary for the attenuated reinstatement among adolescents by determining whether an impoverished environment during abstinence would increase reinstatement among adolescents, up to adult levels. Conversely, we also tested whether environmental enrichment could further decrease reinstatement among adolescents, and whether we could replicate effects of environmental enrichment to decrease reinstatement among adults down to adolescent levels (positive controls). Adolescent and adult male Wistar rats self-administered cocaine intravenously for 12days (fixed ratio 1; 0.36mg/kg per infusion; 2h sessions). Rats were then moved into enriched (grouped, large cages, novel toys), standard (pair-housed, shoebox cages), or impoverished (isolated, hanging cages) housing conditions. After 60days, extinction and cue-induced reinstatement of cocaine seeking were tested, followed by drug-primed reinstatement (0, 5, 10mg/kg cocaine, i.p.). Consistent with previous results, extinction and cue-induced reinstatement were attenuated in adolescent-onset groups compared with adults; this age difference also extended to drug-primed reinstatement. In support of the present hypothesis, an impoverished environment during abstinence increased reinstatement among adolescents to levels that were not different from adult standard-housing levels. These data suggest that abstinence environment influences the enduring effects of cocaine among adolescents as well as adults

  11. The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism

    International Nuclear Information System (INIS)

    Booij, J.; Speelman, J.DE.; Horstink, M. W.I.M.; Wolters, E.C.

    2001-01-01

    [ 123 I]FP-CIT (N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane) has been developed successfully as a radioligand for single-photon emission tomography (SPET) imaging of dopamine transporters, which are situated in the membrane of dopaminergic neurons. Imaging of these transporters has shown promise as a clinical tool to detect degeneration of the dopaminergic nigrostriatal pathway. Several ''presynaptic parkinsonian'' syndromes, such as Parkinson's disease or multiple system atrophy, are characterised by degeneration of the nigrostriatal pathway. [ 123 I]FP-CIT SPET imaging studies have shown the ability to detect loss of striatal dopamine transporters in such syndromes. However, in clinical practice it is sometimes difficult, but important, to discriminate patients with ''presynaptic parkinsonism'' from those with other forms of parkinsonism not characterised by loss of presynaptic dopaminergic cells (e.g. psychogenic parkinsonism or drug-induced postsynaptic parkinsonism). In these inconclusive cases, it may be of value to confirm or exclude the existence of degeneration of nigrostriatal dopaminergic cells by using imaging techniques such as [ 123 I]FP-CIT SPET. Using [ 123 I]FP-CIT SPET, we have imaged the striatal dopamine transporters in a group of patients with inconclusive forms of parkinsonism, and, moreover, have been able to perform clinical follow-up of these patients 2-4 years after imaging. In 33 inconclusive cases, ratios of specific to non-specific binding were calculated for the caudate nucleus and putamen following [ 123 I]FP-CIT SPET imaging and compared with ratios obtained in healthy controls. In nine of the patients, degeneration of the nigrostriatal pathway was found scintigraphically and in all these cases, presynaptic parkinsonism was confirmed by clinical follow-up. In the other 24 subjects no degeneration was found scintigraphically. Forms of parkinsonism other than the presynaptic were confirmed at follow-up in 19 cases

  12. Comparison of two different dust emission mechanisms over the Horqin Sandy Land area: Aerosols contribution and size distributions

    Science.gov (United States)

    Ju, Tingting; Li, Xiaolan; Zhang, Hongsheng; Cai, Xuhui; Song, Yu

    2018-03-01

    Dust aerosols (PM10) emission fluxes due to convective turbulent dust emissions (CTDE) and saltation-bombardment and/or aggregation-disintegration dust emissions (SADE) events were comparatively studied using the data obtained from the Naiman station over the Horqin Sandy Land area in Inner Mongolia, China from 2011 to 2015. The annual cumulative dust fluxes released by CTDE events was about one third of that by SADE events, with the order of 103∼104 μg m-2 s-1. The particle size distributions (PSDs) with diameter between 0.1 and 20 μm during CTDE and SADE events over the Horqin Sandy Land area were simulated based on the fragmentation theory, respectively. The results indicated that an improved equation based on fragmentation theory could be applied to describe the PSDs over the Horqin site which may be because the scale-invariant fragmentation theory mainly explains the PSDs of free dust particles on the surface, which differ from the PSDs of suspend airborne dust and the improved equation was more applicable to the PSDs of SADE events because the dust emission mechanism of SADE are saltation bombardment and aggregation disintegration. The number-related mean aerosol diameters (DN) barely varied under different friction velocity (u*) for SADE events, while the volume-related mean aerosol diameters (DV) changed distinctly with the change of u*. For CTDE events, the DN and DV had no obvious relationship with the change of u* because the dominating influence factor during CTDE event was thermal convection rather than u*. The mass-related PSDs usually exhibited a peak between 0.45 and 0.70 μm during SADE events, while for CTDE events there was a wide peak in the range of 0.10 0.70 μm. The results suggest that DN should be not be recommended as an individual parameter to describe the PSDs. The mass-related PSDs can effectively distinguish the SADE and CTDE events.

  13. Do Interspecific Differences in Sapling Growth Traits Contribute to the Co-dominance of Acer saccharum and Fagus grandifolia?

    Science.gov (United States)

    Takahashi, Koichi; Lechowicz, Martin J.

    2008-01-01

    Background and Aims Acer saccharum and Fagus grandifolia are among the most dominant late-successional tree species in North America. The influence of sapling growth responses to canopy gaps on the co-dominance of the two species in an old-growth forest in southern Quebec, Canada was examined. Two predictions were evaluated: (a) F. grandifolia is more shade tolerant than A. saccharum due to greater sapling leaf area and net production per sapling in closed-canopy conditions; and (b) the height growth rate of A. saccharum in canopy gaps is greater than that of F. grandifolia due to increased net production per sapling. Methods Sapling crown allometry, net production and height growth rates were compared between and within the two species in closed canopy vs. canopy gaps. Standardized major axis regression was used to analyse differences in crown allometry. Key Results F. grandifolia had greater crown projection, sapling leaf area and net production rate per sapling than A. saccharum in closed-canopy conditions. In response to canopy gaps, net production per sapling increased to the same degree in both species. The net production per sapling of F. grandifolia thus was much greater than that of A. saccharum in both canopy gap and closed-canopy conditions. The height growth rate of both species increased in canopy gaps, but the degree of increase was greater in F. grandifolia than in A. saccharum. Conclusions F. grandifolia regenerated more successfully than A. saccharum in both closed-canopy conditions and canopy gaps, which indicates that the co-dominance of the two species cannot be maintained simply by interspecific differences in shade tolerance and growth in gaps. Previous research showed that although Fagus and Acer shared dominance at this site, their relative dominance shifted with edaphic conditions. This suggests that the widespread co-dominance of the two species in eastern North American forests is maintained by the joint influence of canopy disturbance

  14. Pharmacokinetic comparison of different flubendazole formulations in pigs: A further contribution to its development as a macrofilaricide molecule

    Directory of Open Access Journals (Sweden)

    L. Ceballos

    2015-12-01

    Full Text Available Despite the well established ivermectin activity against microfilaria, the success of human filariasis control programmes requires the use of a macrofilaricide compound. Different in vivo trials suggest that flubendazole (FLBZ, an anthelmintic benzimidazole compound, is a highly efficacious and potent macrofilaricide. However, since serious injection site reactions were reported in humans after the subcutaneous FLBZ administration, the search for alternative pharmaceutical strategies to improve the systemic availability of FLBZ has acquired special relevance both in human and veterinary medicine. The goal of the current experimental work was to compare the pharmacokinetic plasma behavior of FLBZ, and its metabolites, formulated as either an aqueous hydroxypropyl- β -cyclodextrin-solution (HPBCD, an aqueous carboxymethyl cellulose-suspension (CMC or a Tween 80-based formulation, in pigs. Animals were allocated into three groups and treated (2 mg/kg with FLBZ formulated as either a HPBCD-solution (oral, CMC-suspension (oral or Tween 80-based formulation (subcutaneous. Only trace amounts of FLBZ parent drug and its reduced metabolite were measured after administration of the different FLBZ formulations in pigs. The hydrolyzed FLBZ (H-FLBZ metabolite was the main analyte recovered in the bloodstream in pigs treated with the three experimental FLBZ formulations. The oral administration of the HPBCD-solution accounted for significantly higher (P < 0.05 Cmax and AUC (23.1 ± 4.4 μg h/mL values for the main metabolite (H-FLBZ, compared with those observed for the oral CMC-suspension (AUC = 3.5 ± 1.0 μg h/mL and injectable Tween 80-based formulation (AUC: 7.5 ± 1.7 μg h/mL. The oral administration of the HPBCD-solution significantly improved the poor absorption pattern (indirectly assessed as the H-FLBZ plasma concentrations observed after the oral administration of the FLBZ-CMC suspension or the subcutaneous injection of the

  15. Different sources of reduced carbon contribute to form three classes of terpenoid emitted by Quercus ilex L. leaves

    International Nuclear Information System (INIS)

    Loreto, F.; Ciccioli, P.; Brancaleoni, E.; Cecinato, A.; Frattoni, M.; Sharkey, T.D.

    1996-01-01

    Quercus ilex L. leaves emit terpenes but do not have specialized structures for terpene storage. We exploited this unique feature to investigate terpene biosynthesis in intact leaves of Q. ilex. Light induction allowed us to distinguish three classes of terpenes: (i) a rapidly induced class including alpha-pinene; (ii) a more slowly induced class, including cis-beta-ocimene; and (iii) the most slowly induced class, including 3-methyl-3-buten-1-ol. Using 13C, we found that alpha-pinene and cis-beta-ocimene were labeled quickly and almost completely while there was a delay before label appeared in linalool and 3-methyl-3-buten-1-ol. The acetyl group of 3-methyl-3-buten-1-yl acetate was labeled quickly but label was limited to 20% of the moiety. It is suggested that the ocimene class of monoterpenes is made from one or more terpenes of the alpha-pinene class and that both classes are made entirely from reduced carbon pools inside the chloroplasts. Linalool and 3-methyl-3-buten-1-ol are made from a different pool of reduced carbon, possibly in nonphotosynthetic plastids. The acetyl group of the 3-methyl-3-buten-1-yl acetate is derived mostly from carbon that does not participate in photosynthetic reactions. Low humidity and prolonged exposure to light favored ocimenes emission and induced linalool emission. This may indicate conversion between terpene classes

  16. Contribution to development of SPNDs for instantaneous and selective measurement of different radiation fields in nuclear reactors

    International Nuclear Information System (INIS)

    Blandin, Christophe

    1998-01-01

    The objective of this work was conceiving and experimentally optimizing the SPNDs (Self-Powdered Neutron Detector) able to control fast power transients in test reactors and also to cope with requirements of surveillance and protection of EDF reactors. Thus, different SPND emitters of platinum, gadolinium, hafnium and cobalt were provided according to their nature with sheathing and stainless steel plugs as well as with zirconium over-sheathing in order to render them faster, more selective and adapted for wear checking. Special experimental devices were designed for measuring inside the Siloe reactor the promptness of the signals from SPND, on one hand, and their sensitivity to thermal and epithermal neutrons as well as to gamma rays, on the other hand. The follow-up of power transients in test reactors is ensured by the instantaneous measurement of thermal and epithermal neutron flux as well as of gamma field by means of three special SPND with gadolinium, hafnium and platinum. Also, we have defined the characteristics of a new SPND with cobalt, that delivers a current of unique neutronic origin, able to ensure the surveillance and protection of a power reactor over a period of at least six years

  17. Different cellular response mechanisms contribute to the length-dependent cytotoxicity of multi-walled carbon nanotubes

    Science.gov (United States)

    Liu, Dun; Wang, Lijun; Wang, Zhigang; Cuschieri, Alfred

    2012-07-01

    To date, there has not been an agreement on the best methods for the characterisation of multi-walled carbon nanotube (MWCNT) toxicity. The length of MWCNTs has been identified as a factor in in vitro and in vivo studies, in addition to their purity and biocompatible coating. Another unresolved issue relates to the variable toxicity of MWCNTs on different cell types. The present study addressed the effects of MWCNTs' length on mammalian immune and epithelial cancer cells RAW264.7 and MCF-7, respectively. Our data confirm that MWCNTs induce cytotoxicity in a length- and cell type-dependent manner. Whereas, longer (3 to 14 μm) MWCNTs exert high toxicity, especially to RAW264.7 cells, shorter (1.5 μm) MWCNTs are significantly less cytotoxic. These findings confirm that the degree of biocompatibility of MWCNTs is closely related to their length and that immune cells appear to be more susceptible to damage by MWCNTs. Our study also indicates that MWCNT nanotoxicity should be analysed for various components of cellular response, and cytotoxicity data should be validated by the use of more than one assay system. Results from chromogenic-based assays should be confirmed by trypan blue exclusion.

  18. Do Gender Differences in Perceived Prototypical Computer Scientists and Engineers Contribute to Gender Gaps in Computer Science and Engineering?

    Science.gov (United States)

    Ehrlinger, Joyce; Plant, E Ashby; Hartwig, Marissa K; Vossen, Jordan J; Columb, Corey J; Brewer, Lauren E

    2018-01-01

    Women are vastly underrepresented in the fields of computer science and engineering (CS&E). We examined whether women might view the intellectual characteristics of prototypical individuals in CS&E in more stereotype-consistent ways than men might and, consequently, show less interest in CS&E. We asked 269 U.S. college students (187, 69.5% women) to describe the prototypical computer scientist (Study 1) or engineer (Study 2) through open-ended descriptions as well as through a set of trait ratings. Participants also rated themselves on the same set of traits and rated their similarity to the prototype. Finally, participants in both studies were asked to describe their likelihood of pursuing future college courses and careers in computer science (Study 1) or engineering (Study 2). Across both studies, we found that women offered more stereotype-consistent ratings than did men of the intellectual characteristics of prototypes in CS (Study 1) and engineering (Study 2). Women also perceived themselves as less similar to the prototype than men did. Further, the observed gender differences in prototype perceptions mediated the tendency for women to report lower interest in CS&E fields relative to men. Our work highlights the importance of prototype perceptions for understanding the gender gap in CS&E and suggests avenues for interventions that may increase women's representation in these vital fields.

  19. Contributed Review: Source-localization algorithms and applications using time of arrival and time difference of arrival measurements

    Science.gov (United States)

    Li, Xinya; Deng, Zhiqun Daniel; Rauchenstein, Lynn T.; Carlson, Thomas J.

    2016-04-01

    Locating the position of fixed or mobile sources (i.e., transmitters) based on measurements obtained from sensors (i.e., receivers) is an important research area that is attracting much interest. In this paper, we review several representative localization algorithms that use time of arrivals (TOAs) and time difference of arrivals (TDOAs) to achieve high signal source position estimation accuracy when a transmitter is in the line-of-sight of a receiver. Circular (TOA) and hyperbolic (TDOA) position estimation approaches both use nonlinear equations that relate the known locations of receivers and unknown locations of transmitters. Estimation of the location of transmitters using the standard nonlinear equations may not be very accurate because of receiver location errors, receiver measurement errors, and computational efficiency challenges that result in high computational burdens. Least squares and maximum likelihood based algorithms have become the most popular computational approaches to transmitter location estimation. In this paper, we summarize the computational characteristics and position estimation accuracies of various positioning algorithms. By improving methods for estimating the time-of-arrival of transmissions at receivers and transmitter location estimation algorithms, transmitter location estimation may be applied across a range of applications and technologies such as radar, sonar, the Global Positioning System, wireless sensor networks, underwater animal tracking, mobile communications, and multimedia.

  20. The contribution of different prion protein types and host polymorphisms to clinicopathological variations in Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Head, Mark W; Ironside, James W

    2012-07-01

    Creutzfeldt-Jakob disease is a fatal neurodegenerative disease that primarily affects the central nervous system. In this respect, it can be considered alongside the more frequently occurring neurodegenerative diseases, such as Alzheimer's disease. Creutzfeldt-Jakob disease is perhaps the paradigmatic protein misfolding disorder, so comparisons between the mechanisms involved in Creutzfeldt-Jakob disease and other neurodegenerative diseases associated with protein misfolding (such as the tauopathies and synucleinopathies) may also be informative. Like many of these diseases, Creutzfeldt-Jakob disease occurs sporadically or can, more rarely, be associated with mutations. However, Creutzfeldt-Jakob disease can also be acquired and is experimentally transmissible. These properties have had profound public health implications and made the disease of interest to virologists, in addition to those interested in protein misfolding disorders and neurodegeneration. The possible causes for the pronounced phenotypic variation among different forms of Creutzfeldt-Jakob disease are beginning to become understood, and these appear to depend in large measure on the genetics of the host (specifically the sequence of the prion protein gene, PRNP) and the epigenetic aspects of the agent (thought to be a misfolded and aggregated form of the PRNP gene product, termed a prion). This review will examine whether this model in its present form has sufficient complexity and subtlety to account for the clinicopathological variation evident in Creutzfeldt-Jakob disease and will outline the ways in which a more complete and informative molecular definition of human prions are currently being sought. Copyright © 2012 John Wiley & Sons, Ltd.

  1. Contributed Review: Source-localization algorithms and applications using time of arrival and time difference of arrival measurements

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xinya [Energy and Environment Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, USA; Deng, Zhiqun Daniel [Energy and Environment Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, USA; Rauchenstein, Lynn T. [Energy and Environment Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, USA; Carlson, Thomas J. [Energy and Environment Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, USA

    2016-04-01

    Locating the position of fixed or mobile sources (i.e., transmitters) based on received measurements from sensors is an important research area that is attracting much research interest. In this paper, we present localization algorithms using time of arrivals (TOA) and time difference of arrivals (TDOA) to achieve high accuracy under line-of-sight conditions. The circular (TOA) and hyperbolic (TDOA) location systems both use nonlinear equations that relate the locations of the sensors and tracked objects. These nonlinear equations can develop accuracy challenges because of the existence of measurement errors and efficiency challenges that lead to high computational burdens. Least squares-based and maximum likelihood-based algorithms have become the most popular categories of location estimators. We also summarize the advantages and disadvantages of various positioning algorithms. By improving measurement techniques and localization algorithms, localization applications can be extended into the signal-processing-related domains of radar, sonar, the Global Positioning System, wireless sensor networks, underwater animal tracking, mobile communications, and multimedia.

  2. Gender Differences in the Domain-Specific Contributions to Moderate-to-Vigorous Physical Activity, Accessed by GPS

    DEFF Research Database (Denmark)

    Pizarro, Andreia Nogueira; Schipperijn, Jasper; Ribeiro, José Carlos

    2017-01-01

    time in school (37.0%) and leisure (24.9%) than girls (24.7% and 18.1, respectively).Conclusions:Interventions to increase transport behavior may be relevant for children?s MVPA. School is an important domain for boys PA, while for girls increasing the supportiveness of the school environment for PA...... children (201 girls; X=11.7y) wore an accelerometer and a GPS for 7 days. PALMS software combined data, categorized non-sedentary time and bouts of moderate-to-vigorous physical activity (MVPA). Geographical information system allocated activity into 4 domains: school, leisure, transport and home.......Results:Overall, a higher proportion of time in MVPA was found in the transport domain (45.5%), school (30.5%), leisure (21.3%) and home (2.7%). Gender differences were found for the proportion of time spent across domains. Girls (54.5%) had more MVPA than boys (35.2%) in the transport domain, whereas boys spent more MVPA...

  3. Influence of craniofacial surgery on the social attitudes toward the malformed and their handling in different cultures and at different times: a contribution to social world history.

    Science.gov (United States)

    Sailer, H F; Kolb, E

    1995-07-01

    A historic overview including the European, American, Asian, and African continents is given on attitudes toward and the handling of humans with congenital malformations in ancient cultures and on pertinent customs in some prehistoric peoples. Figures of early works of art showing malformed individuals are presented testifying to this worldwide and timeless problem of humankind. In parallel, analogous patient photographs from our hospital before and after reconstructive surgery are shown. Philosophies of ancient Greece, rome, and China on the subject of malformed infants essentially did not differ from the known attitudes of the less developed tribes in Europe and pre-Columbian America, although the means of elimination of unwanted offspring were rather passive (exposure) than active (manual killing). A radical change in attitudes and practices occurred with the spread of the Christian religion and its political installment in Europe. The care for the underprivileged including the malformed ones was considered a Christian duty to be performed with compassion and love. In our century, the clocks have been and apparently are turned back again. Atheistic and Darwinian influences, political atheism, and the belief in "higher ethics" issued by "superman" have led to a relapse into barbarism, also within the medical system. We, as craniofacial surgeons, are privileged to have the means to turn the clocks forward again by rehabilitating the physically most underprivileged: those with conspicuous craniofacial malformations. The necessary techniques exist and are applied, as the figures of patients from our hospital demonstrate, but the will and the emotional strength for their consequent application require more than our hands.

  4. Estimation of different source contributions to sediment organic matter in an agricultural-forested watershed using end member mixing analyses based on stable isotope ratios and fluorescence spectroscopy.

    Science.gov (United States)

    Derrien, Morgane; Kim, Min-Seob; Ock, Giyoung; Hong, Seongjin; Cho, Jinwoo; Shin, Kyung-Hoon; Hur, Jin

    2018-03-15

    The two popular source tracing tools of stable isotope ratios (δ 13 C and δ 15 N) and fluorescence spectroscopy were used to estimate the relative source contributions to sediment organic matter (SeOM) at five different river sites in an agricultural-forested watershed (Soyang Lake watershed), and their capabilities for the source assignment were compared. Bulk sediments were used for the stable isotopes, while alkaline extractable organic matter (AEOM) from sediments was used to obtain fluorescent indices for SeOM. Several source discrimination indices were fully compiled for a range of the SeOM sources distributed in the catchments of the watershed, which included soils, forest leaves, crop (C3 and C4) and riparian plants, periphyton, and organic fertilizers. The relative source contributions to the river sediment samples were estimated via end member mixing analysis (EMMA) based on several selected discrimination indices. The EMMA based on the isotopes demonstrated that all sediments were characterized by a medium to a high contribution of periphyton ranging from ~30% to 70% except for one site heavily affected by forest and agricultural fields with relatively high contributions of terrestrial materials. The EMMA based on fluorescence parameters, however, did not show similar results with low contributions from forest leaf and periphyton. The characteristics of the studied watershed were more consistent with the source contributions determined by the isotope ratios. The discrepancy in the EMMA capability for source assignments between the two analytical tools can be explained by the limited analytical window of fluorescence spectroscopy for non-fluorescent dissolved organic matter (FDOM) and the inability of AEOM to represent original bulk particulate organic matter (POM). Copyright © 2017 Elsevier B.V. All rights reserved.

  5. [Nonuniform distribution and contribution of the P- and P/Q-type calcium channels to short-term inhibitory synaptic transmission in cultured hippocampal neurons].

    Science.gov (United States)

    Mizerna, O P; Fedulova, S A; Veselovs'kyĭ, M S

    2010-01-01

    In the present study, we investigated the sensitivity of GABAergic short-term plasticity to the selective P- and P/Q-type calcium channels blocker omega-agatoxin-IVA. To block the P-type channels we used 30 nM of this toxin and 200 nM of the toxin was used to block the P/Q channel types. The evoked inhibitory postsynaptic currents (eIPSC) were studied using patch-clamp technique in whole-cell configuration in postsynaptic neuron and local extracellular stimulation of single presynaptic axon by rectangular pulse. The present data show that the contribution of P- and P/Q-types channels to GABAergic synaptic transmission in cultured hippocampal neurons are 30% and 45%, respectively. It was shown that the mediate contribution of the P- and P/Q-types channels to the amplitudes of eIPSC is different to every discovered neuron. It means that distribution of these channels is non-uniform. To study the short-term plasticity of inhibitory synaptic transmission, axons of presynaptic neurons were paired-pulse stimulated with the interpulse interval of 150 ms. Neurons demonstrated both the depression and facilitation. The application of 30 nM and 200 nM of the blocker decreased the depression and increased facilitation to 8% and 11%, respectively. In addition, we found that the mediate contribution of the P- and P/Q-types channels to realization of synaptic transmission after the second stimuli is 4% less compared to that after the first one. Therefore, blocking of both P- and P/Q-types calcium channels can change the efficiency of synaptic transmission. In this instance it facilitates realization of the transmission via decreased depression or increased facilitation. These results confirm that the P- and P/Q-types calcium channels are involved in regulation of the short-term inhibitory synaptic plasticity in cultured hippocampal neurons.

  6. Modelling of the estimated contributions of different sub-watersheds and sources to phosphorous export and loading from the Dongting Lake watershed, China.

    Science.gov (United States)

    Hou, Ying; Chen, Weiping; Liao, Yuehua; Luo, Yueping

    2017-11-03

    Considerable growth in the economy and population of the Dongting Lake watershed in Southern China has increased phosphorus loading to the lake and resulted in a growing risk of lake eutrophication. This study aimed to reveal the spatial pattern and sources of phosphorus export and loading from the watershed. We applied an export coefficient model and the Dillon-Rigler model to quantify contributions of different sub-watersheds and sources to the total phosphorus (TP) export and loading in 2010. Together, the upper and lower reaches of the Xiang River watershed and the Dongting Lake Area contributed 60.9% of the TP exported from the entire watershed. Livestock husbandry appeared to be the largest anthropogenic source of TP, contributing more than 50% of the TP exported from each secondary sub-watersheds. The actual TP loading to the lake in 2010 was 62.9% more than the permissible annual TP loading for compliance with the Class III water quality standard for lakes. Three primary sub-watersheds-the Dongting Lake Area, the Xiang River, and the Yuan River watersheds-contributed 91.2% of the total TP loading. As the largest contributor among all sources, livestock husbandry contributed nearly 50% of the TP loading from the Dongting Lake Area and more than 60% from each of the other primary sub-watersheds. This study provides a methodology to identify the key sources and locations of TP export and loading in large lake watersheds. The study can provide a reference for the decision-making for controlling P pollution in the Dongting Lake watershed.

  7. Estimation of presynaptic calcium currents and endogenous calcium buffers at the frog neuromuscular junction with two different calcium fluorescent dyes.

    Science.gov (United States)

    Samigullin, Dmitry; Fatikhov, Nijaz; Khaziev, Eduard; Skorinkin, Andrey; Nikolsky, Eugeny; Bukharaeva, Ellya

    2014-01-01

    At the frog neuromuscular junction, under physiological conditions, the direct measurement of calcium currents and of the concentration of intracellular calcium buffers-which determine the kinetics of calcium concentration and neurotransmitter release from the nerve terminal-has hitherto been technically impossible. With the aim of quantifying both Ca(2+) currents and the intracellular calcium buffers, we measured fluorescence signals from nerve terminals loaded with the low-affinity calcium dye Magnesium Green or the high-affinity dye Oregon Green BAPTA-1, simultaneously with microelectrode recordings of nerve-action potentials and end-plate currents. The action-potential-induced fluorescence signals in the nerve terminals developed much more slowly than the postsynaptic response. To clarify the reasons for this observation and to define a spatiotemporal profile of intracellular calcium and of the concentration of mobile and fixed calcium buffers, mathematical modeling was employed. The best approximations of the experimental calcium transients for both calcium dyes were obtained when the calcium current had an amplitude of 1.6 ± 0.08 pA and a half-decay time of 1.2 ± 0.06 ms, and when the concentrations of mobile and fixed calcium buffers were 250 ± 13 μM and 8 ± 0.4 mM, respectively. High concentrations of endogenous buffers define the time course of calcium transients after an action potential in the axoplasm, and may modify synaptic plasticity.

  8. Estimation of presynaptic calcium currents and endogenous calcium buffers at the frog neuromuscular junction with two different calcium fluorescent dyes

    Directory of Open Access Journals (Sweden)

    Dmitry eSamigullin

    2015-01-01

    Full Text Available At the frog neuromuscular junction, under physiological conditions, the direct measurement of calcium currents and of the concentration of intracellular calcium buffers—which determine the kinetics of calcium concentration and neurotransmitter release from the nerve terminal—has hitherto been technically impossible. With the aim of quantifying both Ca2+ currents and the intracellular calcium buffers, we measured fluorescence signals from nerve terminals loaded with the low-affinity calcium dye Magnesium Green or the high-affinity dye Oregon Green BAPTA-1, simultaneously with microelectrode recordings of nerve-action potentials and end-plate currents. The action-potential-induced fluorescence signals in the nerve terminals developed much more slowly than the postsynaptic response. To clarify the reasons for this observation and to define a spatiotemporal profile of intracellular calcium and of the concentration of mobile and fixed calcium buffers, mathematical modeling was employed. The best approximations of the experimental calcium transients for both calcium dyes were obtained when the calcium current had an amplitude of 1.6 ± 0.08 рА and a half-decay time of 1.2 ± 0.06 ms, and when the concentrations of mobile and fixed calcium buffers were 250 ± 13 µM and 8 ± 0.4 mM, respectively. High concentrations of endogenous buffers define the time course of calcium transients after an action potential in the axoplasm, and may modify synaptic plasticity.

  9. Presynaptic learning and memory with a persistent firing neuron and a habituating synapse: a model of short term persistent habituation.

    Science.gov (United States)

    Ramanathan, Kiruthika; Ning, Ning; Dhanasekar, Dhiviya; Li, Guoqi; Shi, Luping; Vadakkepat, Prahlad

    2012-08-01

    Our paper explores the interaction of persistent firing axonal and presynaptic processes in the generation of short term memory for habituation. We first propose a model of a sensory neuron whose axon is able to switch between passive conduction and persistent firing states, thereby triggering short term retention to the stimulus. Then we propose a model of a habituating synapse and explore all nine of the behavioral characteristics of short term habituation in a two neuron circuit. We couple the persistent firing neuron to the habituation synapse and investigate the behavior of short term retention of habituating response. Simulations show that, depending on the amount of synaptic resources, persistent firing either results in continued habituation or maintains the response, both leading to longer recovery times. The effectiveness of the model as an element in a bio-inspired memory system is discussed.

  10. Regulation of presynaptic Ca2+, synaptic plasticity and contextual fear conditioning by a N-terminal β-amyloid fragment.

    Science.gov (United States)

    Lawrence, James L M; Tong, Mei; Alfulaij, Naghum; Sherrin, Tessi; Contarino, Mark; White, Michael M; Bellinger, Frederick P; Todorovic, Cedomir; Nichols, Robert A

    2014-10-22

    Soluble β-amyloid has been shown to regulate presynaptic Ca(2+) and synaptic plasticity. In particular, picomolar β-amyloid was found to have an agonist-like action on presynaptic nicotinic receptors and to augment long-term potentiation (LTP) in a manner dependent upon nicotinic receptors. Here, we report that a functional N-terminal domain exists within β-amyloid for its agonist-like activity. This sequence corresponds to a N-terminal fragment generated by the combined action of α- and β-secretases, and resident carboxypeptidase. The N-terminal β-amyloid fragment is present in the brains and CSF of healthy adults as well as in Alzheimer's patients. Unlike full-length β-amyloid, the N-terminal β-amyloid fragment is monomeric and nontoxic. In Ca(2+) imaging studies using a model reconstituted rodent neuroblastoma cell line and isolated mouse nerve terminals, the N-terminal β-amyloid fragment proved to be highly potent and more effective than full-length β-amyloid in its agonist-like action on nicotinic receptors. In addition, the N-terminal β-amyloid fragment augmented theta burst-induced post-tetanic potentiation and LTP in mouse hippocampal slices. The N-terminal fragment also rescued LTP inhibited by elevated levels of full-length β-amyloid. Contextual fear conditioning was also strongly augmented following bilateral injection of N-terminal β-amyloid fragment into the dorsal hippocampi of intact mice. The fragment-induced augmentation of fear conditioning was attenuated by coadministration of nicotinic antagonist. The activity of the N-terminal β-amyloid fragment appears to reside largely in a sequence surrounding a putative metal binding site, YEVHHQ. These findings suggest that the N-terminal β-amyloid fragment may serve as a potent and effective endogenous neuromodulator. Copyright © 2014 the authors 0270-6474/14/3414210-09$15.00/0.

  11. Bortezomib induces neuropathic pain through protein kinase C-mediated activation of presynaptic NMDA receptors in the spinal cord.

    Science.gov (United States)

    Xie, Jing-Dun; Chen, Shao-Rui; Chen, Hong; Pan, Hui-Lin

    2017-09-01

    Chemotherapeutic drugs, including bortezomib, often cause painful peripheral neuropathy, which is a severe dose-limiting adverse effect experienced by many cancer patients. The glutamate N-methyl-d-aspartate receptors (NMDARs) at the spinal cord level are critically involved in the synaptic plasticity associated with neuropathic pain. In this study, we determined whether treatment with bortezomib, a proteasome inhibitor, affects the NMDAR activity of spinal dorsal horn neurons. Systemic treatment with bortezomib in rats did not significantly affect postsynaptic NMDAR currents elicited by puff application of NMDA directly to dorsal horn neurons. Bortezomib treatment markedly increased the baseline frequency of miniature excitatory postsynaptic currents (EPSCs), which was completely normalized by the NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP5). AP5 also reduced the amplitude of monosynaptic EPSCs evoked by dorsal root stimulation in bortezomib-treated, but not vehicle-treated, rats. Furthermore, inhibition of protein kinase C (PKC) with chelerythrine fully reversed the increased frequency of miniature EPSCs and the amplitude of evoked EPSCs in bortezomib-treated rats. Intrathecal injection of AP5 and chelerythrine both profoundly attenuated mechanical allodynia and hyperalgesia induced by systemic treatment with bortezomib. In addition, treatment with bortezomib induced striking membrane translocation of PKC-βII, PKC-δ, and PKC-ε in the dorsal root ganglion. Our findings indicate that bortezomib treatment potentiates nociceptive input from primary afferent nerves via PKC-mediated tonic activation of presynaptic NMDARs. Targeting presynaptic NMDARs and PKC at the spinal cord level may be an effective strategy for treating chemotherapy-induced neuropathic pain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Rosiglitazone Suppresses In Vitro Seizures in Hippocampal Slice by Inhibiting Presynaptic Glutamate Release in a Model of Temporal Lobe Epilepsy.

    Directory of Open Access Journals (Sweden)

    Shi-Bing Wong

    Full Text Available Peroxisomal proliferator-activated receptor gamma (PPARγ is a nuclear hormone receptor whose agonist, rosiglitazone has a neuroprotective effect to hippocampal neurons in pilocarpine-induced seizures. Hippocampal slice preparations treated in Mg2+ free medium can induce ictal and interictal-like epileptiform discharges, which is regarded as an in vitro model of N-methyl-D-aspartate (NMDA receptor-mediated temporal lobe epilepsy (TLE. We applied rosiglitazone in hippocampal slices treated in Mg2+ free medium. The effects of rosiglitazone on hippocampal CA1-Schaffer collateral synaptic transmission were tested. We also examined the neuroprotective effect of rosiglitazone toward NMDA excitotoxicity on cultured hippocampal slices. Application of 10 μM rosiglitazone significantly suppressed amplitude and frequency of epileptiform discharges in CA1 neurons. Pretreatment with the PPARγ antagonist GW9662 did not block the effect of rosiglitazone on suppressing discharge frequency, but reverse the effect on suppressing discharge amplitude. Application of rosiglitazone suppressed synaptic transmission in the CA1-Schaffer collateral pathway. By miniature excitatory-potential synaptic current (mEPSC analysis, rosiglitazone significantly suppressed presynaptic neurotransmitter release. This phenomenon can be reversed by pretreating PPARγ antagonist GW9662. Also, rosiglitazone protected cultured hippocampal slices from NMDA-induced excitotoxicity. The protective effect of 10 μM rosiglitazone was partially antagonized by concomitant high dose GW9662 treatment, indicating that this effect is partially mediated by PPARγ receptors. In conclusion, rosiglitazone suppressed NMDA receptor-mediated epileptiform discharges by inhibition of presynaptic neurotransmitter release. Rosiglitazone protected hippocampal slice from NMDA excitotoxicity partially by PPARγ activation. We suggest that rosiglitazone could be a potential agent to treat patients with TLE.

  13. The contribution of psychological distress to socio-economic differences in cause-specific mortality: a population-based follow-up of 28 years

    Directory of Open Access Journals (Sweden)

    Ostamo Aini I

    2011-02-01

    Full Text Available Abstract Background Psychological factors associated with low social status have been proposed as one possible explanation for the socio-economic gradient in health. The aim of this study is to explore whether different indicators of psychological distress contribute to socio-economic differences in cause-specific mortality. Methods The data source is a nationally representative, repeated cross-sectional survey, "Health Behaviour and Health among the Finnish Adult Population" (AVTK. The survey results were linked with socio-economic register data from Statistics Finland (from the years 1979-2002 and mortality follow-up data up to 2006 from the Finnish National Cause of Death Register. The data included 32451 men and 35420 women (response rate 73.5%. Self-reported measures of depression, insomnia and stress were used as indicators of psychological distress. Socio-economic factors included education, employment status and household income. Mortality data consisted of unnatural causes of death (suicide, accidents and violence, and alcohol-related mortality and coronary heart disease (CHD mortality. Adjusted hazard ratios were calculated using the Cox regression model. Results In unnatural mortality, psychological distress accounted for some of the employment status (11-31% and income level (4-16% differences among both men and women, and for the differences related to the educational level (5-12% among men; the educational level was associated statistically significantly with unnatural mortality only among men. Psychological distress had minor or no contribution to socio-economic differences in CHD mortality. Conclusions Psychological distress partly accounted for socio-economic disparities in unnatural mortality. Further studies are needed to explore the role and mechanisms of psychological distress associated with socio-economic differences in cause-specific mortality.

  14. Effects of Levetiracetam, Carbamazepine, Phenytoin, Valproate, Lamotrigine, Oxcarbazepine, Topiramate, Vinpocetine and Sertraline on Presynaptic Hippocampal Na(+) and Ca(2+) Channels Permeability.

    Science.gov (United States)

    Sitges, María; Chiu, Luz María; Reed, Ronald C

    2016-04-01

    Ion channels are targets of various antiepileptic drugs. In cerebral presynaptic nerve endings Na(+) and Ca(2+) channels are particularly abundant, as they control neurotransmitter release, including the release of glutamate (Glu), the most concentrated excitatory amino acid neurotransmitter in the brain. Several pre-synaptic channels are implicated in the mechanism of action of the pro-convulsive agent, 4-aminopyridine (4-AP). In the present study the effects of levetiracetam and other established and newer (vinpocetine) anti-epileptic drugs, as well as of the anti-depressant, sertraline on the increase in Ca(2+) induced by 4-AP in hippocampal isolated nerve endings were investigated. Also the effects of some of the anti-seizure drugs on the selective increase in Ca(2+) induced by high K(+), or on the selective increase in Na(+) induced by veratridine were tested. Sertraline and vinpocetine effectively inhibited the rise in Ca(2+) induced by 4-AP, which was dependent on the out-in Na(+) gradient and tetrodotoxin sensitive. Carbamazepine, phenytoin, lamotrigine and oxcarbazepine inhibited the rise in Ca(2+) induced by 4-AP too, but at higher concentrations than sertraline and vinpocetine, whereas levetiracetam, valproic acid and topiramate did not. The three latter antiepileptic drugs also failed in modifying other responses mediated by the activation of brain presynaptic Na(+) or Ca(2+) channels, including Glu release. This indicates that levetiracetam, valproic acid and topiramate mechanisms of action are unrelated with a decrease in presynaptic Na(+) or Ca(2+) channels permeability. It is concluded that depolarized cerebral isolated nerve endings represent a useful tool to unmask potential antiepileptic drugs targeting presynaptic Na(+) and/or Ca(2+) channels in the brain; such as vinpocetine or the anti-depressant sertraline, which high effectiveness to control seizures in the animal in vivo has been demonstrated.

  15. Single cocaine exposure does not alter striatal pre-synaptic dopamine function in mice: an [18 F]-FDOPA PET study.

    Science.gov (United States)

    Bonsall, David R; Kokkinou, Michelle; Veronese, Mattia; Coello, Christopher; Wells, Lisa A; Howes, Oliver D

    2017-12-01

    Cocaine is a recreational drug of abuse that binds to the dopamine transporter, preventing reuptake of dopamine into pre-synaptic terminals. The increased presence of synaptic dopamine results in stimulation of both pre- and post-synaptic dopamine receptors, considered an important mechanism by which cocaine elicits its reinforcing properties. However, the effects of acute cocaine administration on pre-synaptic dopamine function remain unclear. Non-invasive imaging techniques such as positron emission tomography have revealed impaired pre-synaptic dopamine function in chronic cocaine users. Similar impairments have been seen in animal studies, with microdialysis experiments indicating decreased basal dopamine release. Here we use micro positron emission tomography imaging techniques in mice to measure dopamine synthesis capacity and determine the effect of acute cocaine administration of pre-synaptic dopamine function. We show that a dose of 20 mg/kg cocaine is sufficient to elicit hyperlocomotor activity, peaking 15-20 min post treatment (p dopamine synthesis capacity in the striatum was not significantly altered by acute cocaine treatment (KiCer: 0.0097 per min vs. 0.0112 per min in vehicle controls, p > 0.05). Furthermore, expression levels of two key enzymes related to dopamine synthesis, tyrosine hydroxylase and aromatic l-amino acid decarboxylase, within the striatum of scanned mice were not significantly affected by acute cocaine pre-treatment (p > 0.05). Our findings suggest that while the regulation of dopamine synthesis and release in the striatum have been shown to change with chronic cocaine use, leading to a reduced basal tone, these adaptations to pre-synaptic dopaminergic neurons are not initiated following a single exposure to the drug. © 2017 International Society for Neurochemistry.

  16. [The bioethics law revision: comparative analysis of contributions from different public and professional offices. Assisted Reproductive Technology, embryo and stem cells research, umbilical cord blood bank].

    Science.gov (United States)

    Merviel, P; Cabry, R; Lourdel, E; Brasseur, F; Devaux, A; Copin, H

    2009-09-01

    The revision of the bioethics law of 2004 must occur in a five year's time. For this revision, the authorities decided to organize general states of bioethics and requested the production of contributions by the companies, institutions or associations. These texts tackle various subjects, like the Assisted Reproductive Technologies, research on the embryo and the stem cells and the banks of umbilical cord blood. Certain opinions converge, others differ, but all take part in the great debate which will take place at the time of the general conference.

  17. Contribution of different regions of the prefrontal cortex and lesion laterality to deficit of decision-making on the Iowa Gambling Task.

    Science.gov (United States)

    Ouerchefani, Riadh; Ouerchefani, Naoufel; Allain, Philippe; Ben Rejeb, Mohamed Riadh; Le Gall, Didier

    2017-02-01

    Few studies have examined the contribution of different sub-regions of the prefrontal cortex and lesion laterality to decision-making abilities. In addition, there are inconsistent findings about the role of ventromedial and dorsolateral lesions in decision-making deficit. In this study, decision-making processes are investigated following different damaged areas of the prefrontal cortex. We paid particular attention to the contribution of laterality, lesion location and lesion volume in decision-making deficit. Twenty-seven patients with discrete ventromedial lesions, dorsolateral lesions or extended-frontal lesions were compared with normal subjects on the Iowa Gambling Task (IGT). Our results showed that all frontal subgroups were impaired on the IGT in comparison with normal subjects. We noted also that IGT performance did not vary systematically based on lesion laterality or location. More precisely, our lesion analysis revealed that decision-making processes depend on a large cerebral network, including both ventromedial and dorsolateral areas of the prefrontal cortex. Consistent with past findings, our results support the claim that IGT deficit is not solitarily associated with ventromedial prefrontal cortex lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Effect of different bulking agents on water variation and thermal balance and their respective contribution to bio-generated heat during long-term storage sludge biodrying process.

    Science.gov (United States)

    Liu, Tiantian; Cui, Chongwei; He, Junguo; Tang, Jian

    2018-04-17

    Biodrying was first used for the post-treatment of long-term storage sludge with vinasse as bulking agents. The effect of different bulking agents on water and heat variation and their respective contributions to bio-generated heat during storage sludge biodrying were investigated. Three different bulking agents (beer lees and distillers grains, with conventional straw used for comparison) were mixed with storage sludge for biodrying for an 18-day period. The results revealed the treatment with beer lees as bulking agent achieved the best performance with the highest water removal capacity (658 g kg -1 initial water). The extent of organic degradation in the mixture was related to the degradation ability of the bulking agents. The degradation of C- and H-containing materials (e.g., carboxylic acid) accounted for volatile solids (VS) loss. Water and thermal analyses showed that evaporation was the main way of water loss (accounting for 90%), while evaporation heat was the main component of heat consumption (accounting for 56.67-60.62%).The biodegradation of bulking agents contributed a high proportion of the bio-generated heat consumed by water evaporation (82.35-86.67%).

  19. Perinatal testosterone contributes to mid-to-post pubertal sex differences in risk for binge eating in male and female rats.

    Science.gov (United States)

    Culbert, Kristen M; Sinclair, Elaine B; Hildebrandt, Britny A; Klump, Kelly L; Sisk, Cheryl L

    2018-02-01

    Exposure to testosterone early in life may contribute to sex differences and pubertal changes in risk for eating pathology (i.e., females > males, after pubertal onset). Specifically, perinatal testosterone permanently alters brain structure/function and drives the masculinization of several sex-differentiated behaviors. However, the effects of perinatal testosterone are often not evident until puberty when increases in gonadal hormones activate the expression of sex typical behavior, including eating behaviors (e.g., chow intake; saccharin preference) in rodents. Despite perinatal testosterone's masculinizing effects on general feeding behavior, it remains unknown if perinatal testosterone exposure contributes to sex differences in pathological eating. The current study addressed this gap by examining whether perinatal testosterone exposure decreases risk for binge eating proneness after pubertal onset in male and female rats. Sprague-Dawley rats (n = 40 oil-treated control females; n = 39 testosterone-treated females; n = 40 oil-treated control males) were followed longitudinally across pre-to-early puberty, mid-to-late puberty, and adulthood. The binge eating prone (BEP)/binge eating resistant (BER) rodent model was used to identify individual differences in binge eating proneness across the dimensional spectrum. As expected, testosterone-treated females and control males showed masculinized (i.e., lower) risk for binge eating as compared to control females, but only after midpuberty. These animal data are significant in suggesting that perinatal testosterone exposure may protect against binge eating and underlie sex differences in binge eating prevalence during and after puberty. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  20. The Contribution of Different Components in QiShenYiQi Pills® to Its Potential to Modulate Energy Metabolism in Protection of Ischemic Myocardial Injury

    Directory of Open Access Journals (Sweden)

    Yuan-Chen Cui

    2018-04-01

    Full Text Available Ischemic heart diseases remain a challenge for clinicians. QiShenYiQi pills® (QSYQ has been reported to be curative during coronary heart diseases with modulation of energy metabolism as one of the underlying mechanisms. In this study, we detected the effect of QSYQ and its components on rat myocardial structure, mitochondrial respiratory chain complexes activity and energy metabolism, and heart function after 30 min of cardiac ischemia, with focusing on the contribution of each component to its potential to regulate energy metabolism. Results showed that treatment with QSYQ and all its five components protected myocardial structure from damage by ischemia. QSYQ also attenuated release of myocardial cTnI, and restored the production of ATP after cardiac ischemia. AS-IV and Rb1, but not Rg1, R1, and DLA, had similar effect as QSYQ in regulation of energy metabolism. These results indicate that QSYQ may prevent ischemia-induced cardiac injury via regulation of energy metabolism, to which each of its components contributes differently.

  1. An innovative expression model of human health risk based on the quantitative analysis of soil metals sources contribution in different spatial scales.

    Science.gov (United States)

    Zhang, Yimei; Li, Shuai; Wang, Fei; Chen, Zhuang; Chen, Jie; Wang, Liqun

    2018-09-01

    Toxicity of heavy metals from industrialization poses critical concern, and analysis of sources associated with potential human health risks is of unique significance. Assessing human health risk of pollution sources (factored health risk) concurrently in the whole and the sub region can provide more instructive information to protect specific potential victims. In this research, we establish a new expression model of human health risk based on quantitative analysis of sources contribution in different spatial scales. The larger scale grids and their spatial codes are used to initially identify the level of pollution risk, the type of pollution source and the sensitive population at high risk. The smaller scale grids and their spatial codes are used to identify the contribution of various sources of pollution to each sub region (larger grid) and to assess the health risks posed by each source for each sub region. The results of case study show that, for children (sensitive populations, taking school and residential area as major region of activity), the major pollution source is from the abandoned lead-acid battery plant (ALP), traffic emission and agricultural activity. The new models and results of this research present effective spatial information and useful model for quantifying the hazards of source categories and human health a t complex industrial system in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Presynaptic inhibition of spontaneous acetylcholine release mediated by P2Y receptors at the mouse neuromuscular junction.

    Science.gov (United States)

    De Lorenzo, S; Veggetti, M; Muchnik, S; Losavio, A

    2006-09-29

    At the neuromuscular junction, ATP is co-released with the neurotransmitter acetylcholine (ACh) and once in the synaptic space, it is degraded to the presynaptically active metabolite adenosine. Intracellular recordings were performed on diaphragm fibers of CF1 mice to determine the action of extracellular ATP (100 muM) and the slowly hydrolysable ATP analog 5'-adenylylimidodiphosphate lithium (betagamma-imido ATP) (30 muM) on miniature end-plate potential (MEPP) frequency. We found that application of ATP and betagamma-imido ATP decreased spontaneous secretion by 45.3% and 55.9% respectively. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A(1) adenosine receptor antagonist and alpha,beta-methylene ADP sodium salt (alphabeta-MeADP), which is an inhibitor of ecto-5'-nucleotidase, did not prevent the inhibitory effect of ATP, demonstrating that the nucleotide is able to modulate spontaneous ACh release through a mechanism independent of the action of adenosine. Blockade of Ca(2+) channels by both, Cd(2+) or the combined application of nitrendipine and omega-conotoxin GVIA (omega-CgTx) (L-type and N-type Ca(2+) channel antagonists, respectively) prevented the effect of betagamma-imido ATP, indicating that the nucleotide modulates Ca(2+) influx through the voltage-dependent Ca(2+) channels related to spontaneous secretion. betagamma-Imido ATP-induced modulation was antagonized by the non-specific P2 receptor antagonist suramin and the P2Y receptor antagonist 1-amino-4-[[4-[[4-chloro-6-[[3(or4)-sulfophenyl] amino]-1,3,5-triazin-2-yl]amino]-3-sulfophenyl] amino]-9,10-dihydro-9,10-dioxo-2-anthracenesulfonic acid (reactive blue-2), but not by pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt (PPADS), which has a preferential antagonist effect on P2X receptors. Pertussis toxin and N-ethylmaleimide (NEM), which are blockers of G(i/o) proteins, prevented the action of the nucleotide, suggesting that the effect is mediated by P2Y receptors

  3. Differential activity of Plasma and Vacuolar Membrane Transporters contributes to Genotypic Differences in Salinity Tolerance in a Halophyte Species, Chenopodium quinoa

    DEFF Research Database (Denmark)

    Bonales-Alatorre, Edgar; Pottosin, Igor; Shabala, Lana

    2013-01-01

    quinoa genotypes contrasting in their salinity tolerance. The work is complemented by studies of the kinetics of net ion fluxes across the plasma membrane of quinoa leaf mesophyll tissue. Our results suggest that multiple mechanisms contribute towards genotypic differences in salinity tolerance in quinoa....... These include: (i) a higher rate of Na+ exclusion from leaf mesophyll; (ii) maintenance of low cytosolic Na+ levels; (iii) better K+ retention in the leaf mesophyll; (iv) a high rate of H+ pumping, which increases the ability of mesophyll cells to restore their membrane potential; and (v) the ability to reduce......Halophytes species can be used as a highly convenient model system to reveal key ionic and molecular mechanisms that confer salinity tolerance in plants. Earlier, we reported that quinoa (Chenopodium quinoa Willd.), a facultative C3 halophyte species, can efficiently control the activity of slow...

  4. Climate, soil texture, and soil types affect the contributions of fine-fraction-stabilized carbon to total soil organic carbon in different land uses across China.

    Science.gov (United States)

    Cai, Andong; Feng, Wenting; Zhang, Wenju; Xu, Minggang

    2016-05-01

    Mineral-associated organic carbon (MOC), that is stabilized by fine soil particles (i.e., silt plus clay, organic carbon (SOC) persistence and sequestration, due to its large contribution to total SOC (TSOC) and long turnover time. Our objectives were to investigate how climate, soil type, soil texture, and agricultural managements affect MOC contributions to TSOC in China. We created a dataset from 103 published papers, including 1106 data points pairing MOC and TSOC across three major land use types: cropland, grassland, and forest. Overall, the MOC/TSOC ratio ranged from 0.27 to 0.80 and varied significantly among soil groups in cropland, grassland, and forest. Croplands and forest exhibited significantly higher median MOC/TSOC ratios than in grassland. Moreover, forest and grassland soils in temperate regions had higher MOC/TSOC ratios than in subtropical regions. Furthermore, the MOC/TSOC ratio was much higher in ultisol, compared with the other soil types. Both the MOC content and MOC/TSOC ratio were positively correlated with the amount of fine fraction (silt plus clay) in soil, highlighting the importance of soil texture in stabilizing organic carbon across various climate zones. In cropland, different fertilization practices and land uses (e.g., upland, paddy, and upland-paddy rotation) significantly altered MOC/TSOC ratios, but not in cropping systems (e.g., mono- and double-cropping) characterized by climatic differences. This study demonstrates that the MOC/TSOC ratio is mainly driven by soil texture, soil types, and related climate and land uses, and thus the variations in MOC/TSOC ratios should be taken into account when quantitatively estimating soil C sequestration potential of silt plus clay particles on a large scale. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. 2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size.

    Science.gov (United States)

    Otani, Tomoki; Marchetto, Maria C; Gage, Fred H; Simons, Benjamin D; Livesey, Frederick J

    2016-04-07

    Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Ciproxifan, a histamine H{sub 3} receptor antagonist and inverse agonist, presynaptically inhibits glutamate release in rat hippocampus

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Cheng-Wei; Lin, Tzu-Yu [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan (China); Department of Mechanical Engineering, Yuan Ze University, Taoyuan 320, Taiwan (China); Chang, Chia-Ying [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan (China); Department of Chemistry, Fu Jen Catholic University, No. 510, Chung-Cheng Road, Hsin-Chuang District, New Taipei City 24205, Taiwan (China); Huang, Shu-Kuei [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan (China); Wang, Su-Jane, E-mail: med0003@mail.fju.edu.tw [School of Medicine, Fu Jen Catholic University, No. 510, Chung-Cheng Rd., Hsin-Chuang, New Taipei 24205, Taiwan (China); Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City, Taiwan (China)

    2017-03-15

    Ciproxifan is an H{sub 3} receptor antagonist and inverse agonist with antipsychotic effects in several preclinical models; its effect on glutamate release has been investigated in the rat hippocampus. In a synaptosomal preparation, ciproxifan reduced 4-aminopyridine (4-AP)-evoked Ca{sup 2+}-dependent glutamate release and cytosolic Ca{sup 2+} concentration elevation but did not affect the membrane potential. The inhibitory effect of ciproxifan on 4-AP-evoked glutamate release was prevented by the Gi/Go-protein inhibitor pertussis toxin and Ca{sub v}2.2 (N-type) and Ca{sub v}2.1 (P/Q-type) channel blocker ω-conotoxin MVIIC, but was not affected by the intracellular Ca{sup 2+}-release inhibitors dantrolene and CGP37157. Furthermore, the phospholipase A{sub 2} (PLA{sub 2}) inhibitor OBAA, prostaglandin E{sub 2} (PGE{sub 2}), PGE2 subtype 2 (EP{sub 2}) receptor antagonist PF04418948, and extracellular signal-regulated kinase (ERK) inhibitor FR180204 eliminated the inhibitory effect of ciproxifan on glutamate release. Ciproxifan reduced the 4-AP-evoked phosphorylation of ERK and synapsin I, a presynaptic target of ERK. The ciproxifan-mediated inhibition of glutamate release was prevented in synaptosomes from synapsin I-deficient mice. Moreover, ciproxifan reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude in hippocampal slices. Our data suggest that ciproxifan, acting through the blockade of Gi/Go protein-coupled H{sub 3} receptors present on hippocampal nerve terminals, reduces voltage-dependent Ca{sup 2+} entry by diminishing PLA{sub 2}/PGE{sub 2}/EP{sub 2} receptor pathway, which subsequently suppresses the ERK/synapsin I cascade to decrease the evoked glutamate release. - Highlights: • Ciproxifan presynaptically reduces glutamate release in the hippocampus in vitro. • Decrease in voltage-dependent Ca{sup 2+} influx is involved. • A role for the PLA{sub 2}/PGE{sub 2}/EP{sub 2} pathway in the action of

  7. Differences of first-pass effect in the liver and intestine contribute to the stereoselective pharmacokinetics of rhynchophylline and isorhynchophylline epimers in rats.

    Science.gov (United States)

    Wang, Xin; Zheng, Mei; Liu, Jia; Huang, Zhifeng; Bai, Yidan; Ren, Zhuoying; Wang, Ziwen; Tian, Yangli; Qiao, Zhou; Liu, Wenyuan; Feng, Feng

    2017-09-14

    Uncaria rhynchophylla (Miq.) Miq. ex Havil., is a plant species used in traditional Chinese medicine to treat cardiovascular and central nervous system diseases. Rhynchophylline (RIN) and isorhynchophylline (IRN), a pair of epimers, are major alkaloids isolated from U. rhynchophylla and exhibit diverse pharmacological effects. Our previous study demonstrated that the pharmacokinetics of these epimers existed stereoselectivity after oral administration; however, the specific mechanism remains unknown and merits investigation. In the present study, the aim was to elucidate the mechanism underlying stereoselective pharmacokinetic characteristics of RIN and IRN in rats. The total (F), hepatic (F h ) and intestinal (F a ·F g ) bioavailabilities of each epimer were measured using portal vein cannulated rats following different dosing routes (intravenous, intraportal and intraduodenal) to assess individual contributions of the liver and intestine in stereoselective pharmacokinetics. Then the differences of first-pass metabolism in the liver and intestine between two epimers were evaluated by in vitro incubation with rat liver microsomes, intestinal S9 and gastrointestinal (GI) content solutions, respectively. Meanwhile, the membrane permeability and efflux by P-glycoprotein (P-gp) were examined by in situ single-pass intestinal perfusion with and without P-gp inhibitor verapamil. The configurational interconversion at different pH values and the excretions via feces and urine were also examined. Pharmacokinetic data showed that the total bioavailability of RIN was 5.9 folds higher than that of IRN (23.4% vs. 4.0%). The hepatic availability of RIN was 4.6 folds higher than that of IRN (46.9% vs. 10.3%), whereas the intestinal availability of RIN (48.1%) was comparable to that of IRN (42.7%). In addition, intestinal perfusion showed that IRN possessed higher intestinal permeability than RIN and co-perfusion with verapamil could affect absorption process of RIN but not IRN

  8. Variability in the contribution of different life stages to population growth as a key factor in the invasion success of Pinus strobus.

    Directory of Open Access Journals (Sweden)

    Zuzana Münzbergová

    Full Text Available Despite the increasing number of studies attempting to model population growth in various organisms, we still know relatively little about the population dynamics of long-lived species that reproduce only in the later stages of their life cycle, such as trees. Predictions of the dynamics of these species are, however, urgently needed for planning management actions when species are either endangered or invasive. In long-lived species, a single management intervention may have consequences for several decades, and detailed knowledge of long-term performance can therefore elucidate possible outcomes during the management planning phase.We studied the population dynamics of an invasive tree species, Pinus strobus, in three habitat types represented by their position along the elevation gradient occupied by the species. In agreement with previous studies on the population dynamics of long-lived perennials, our results show that the survival of the largest trees exhibits the highest elasticity in all of the studied habitats. In contrast, life table response experiments (LTRE analysis showed that different stages contribute the most to population growth rates in different habitats, with generative reproduction being more important in lower slopes and valley bottoms and survival being more important on rock tops and upper slopes.The results indicate that P. strobus exhibits different growth strategies in different habitats that result in similar population growth rates. We propose that this plasticity in growth strategies is a key factor in the invasion success of the white pine. In all of the investigated habitats, the population growth rates are above 1, indicating that the population of the species is still increasing and has the ability to spread and occupy a wide range of habitats.

  9. Distinct roles of presynaptic dopamine receptors in the differential modulation of the intrinsic synapses of medium-spiny neurons in the nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Schmauss Claudia

    2007-01-01

    Full Text Available Abstract Background In both schizophrenia and addiction, pathological changes in dopamine release appear to induce alterations in the circuitry of the nucleus accumbens that affect coordinated thought and motivation. Dopamine acts principally on medium-spiny GABA neurons, which comprise 95% of accumbens neurons and give rise to the majority of inhibitory synapses in the nucleus. To examine dopamine action at single medium-spiny neuron synapses, we imaged Ca2+ levels in their presynaptic varicosities in the acute brain slice using two-photon microscopy. Results Presynaptic Ca2+ rises were differentially modulated by dopamine. The D1/D5 selective agonist SKF81297 was exclusively facilitatory. The D2/D3 selective agonist quinpirole was predominantly inhibitory, but in some instances it was facilitatory. Studies using D2 and D3 receptor knockout mice revealed that quinpirole inhibition was either D2 or D3 receptor-mediated, while facilitation was mainly D3 receptor-mediated. Subsets of varicosities responded to both D1 and D2 agonists, showing that there was significant co-expression of these receptor families in single medium-spiny neurons. Neighboring presynaptic varicosities showed strikingly heterogeneous responses to DA agonists, suggesting that DA receptors may be differentially trafficked to individual varicosities on the same medium-spiny neuron axon. Conclusion Dopamine receptors are present on the presynaptic varicosities of medium-spiny neurons, where they potently control GABAergic synaptic transmission. While there is significant coexpression of D1 and D2 family dopamine receptors in individual neurons, at the subcellular level, these receptors appear to be heterogeneously distributed, potentially explaining the considerable controversy regarding dopamine action in the striatum, and in particular the degree of dopamine receptor segregation on these neurons. Assuming that post-receptor signaling is restricted to the microdomains of

  10. The contribution of qualitative research in designing a complex intervention for secondary prevention of coronary heart disease in two different healthcare systems.

    LENUS (Irish Health Repository)

    Corrrigan, Mairead

    2006-01-01

    BACKGROUND: Developing complex interventions for testing in randomised controlled trials is of increasing importance in healthcare planning. There is a need for careful design of interventions for secondary prevention of coronary heart disease (CHD). It has been suggested that integrating qualitative research in the development of a complex intervention may contribute to optimising its design but there is limited evidence of this in practice. This study aims to examine the contribution of qualitative research in developing a complex intervention to improve the provision and uptake of secondary prevention of CHD within primary care in two different healthcare systems. METHODS: In four general practices, one rural and one urban, in Northern Ireland and the Republic of Ireland, patients with CHD were purposively selected. Four focus groups with patients (N = 23) and four with staff (N = 29) informed the development of the intervention by exploring how it could be tailored and integrated with current secondary prevention activities for CHD in the two healthcare settings. Following an exploratory trial the acceptability and feasibility of the intervention were discussed in four focus groups (17 patients) and 10 interviews (staff). The data were analysed using thematic analysis. RESULTS: Integrating qualitative research into the development of the intervention provided depth of information about the varying impact, between the two healthcare systems, of different funding and administrative arrangements, on their provision of secondary prevention and identified similar barriers of time constraints, training needs and poor patient motivation. The findings also highlighted the importance to patients of stress management, the need for which had been underestimated by the researchers. The qualitative evaluation provided depth of detail not found in evaluation questionnaires. It highlighted how the intervention needed to be more practical by minimising administration

  11. The contribution of qualitative research in designing a complex intervention for secondary prevention of coronary heart disease in two different healthcare systems

    Directory of Open Access Journals (Sweden)

    Leathem Claire S

    2006-07-01

    Full Text Available Abstract Background Developing complex interventions for testing in randomised controlled trials is of increasing importance in healthcare planning. There is a need for careful design of interventions for secondary prevention of coronary heart disease (CHD. It has been suggested that integrating qualitative research in the development of a complex intervention may contribute to optimising its design but there is limited evidence of this in practice. This study aims to examine the contribution of qualitative research in developing a complex intervention to improve the provision and uptake of secondary prevention of CHD within primary care in two different healthcare systems. Methods In four general practices, one rural and one urban, in Northern Ireland and the Republic of Ireland, patients with CHD were purposively selected. Four focus groups with patients (N = 23 and four with staff (N = 29 informed the development of the intervention by exploring how it could be tailored and integrated with current secondary prevention activities for CHD in the two healthcare settings. Following an exploratory trial the acceptability and feasibility of the intervention were discussed in four focus groups (17 patients and 10 interviews (staff. The data were analysed using thematic analysis. Results Integrating qualitative research into the development of the intervention provided depth of information about the varying impact, between the two healthcare systems, of different funding and administrative arrangements, on their provision of secondary prevention and identified similar barriers of time constraints, training needs and poor patient motivation. The findings also highlighted the importance to patients of stress management, the need for which had been underestimated by the researchers. The qualitative evaluation provided depth of detail not found in evaluation questionnaires. It highlighted how the intervention needed to be more practical by minimising

  12. The contribution of qualitative research in designing a complex intervention for secondary prevention of coronary heart disease in two different healthcare systems.

    Science.gov (United States)

    Corrrigan, Mairead; Cupples, Margaret E; Smith, Susan M; Byrne, Molly; Leathem, Claire S; Clerkin, Pauline; Murphy, Andrew W

    2006-07-18

    Developing complex interventions for testing in randomised controlled trials is of increasing importance in healthcare planning. There is a need for careful design of interventions for secondary prevention of coronary heart disease (CHD). It has been suggested that integrating qualitative research in the development of a complex intervention may contribute to optimising its design but there is limited evidence of this in practice. This study aims to examine the contribution of qualitative research in developing a complex intervention to improve the provision and uptake of secondary prevention of CHD within primary care in two different healthcare systems. In four general practices, one rural and one urban, in Northern Ireland and the Republic of Ireland, patients with CHD were purposively selected. Four focus groups with patients (N = 23) and four with staff (N = 29) informed the development of the intervention by exploring how it could be tailored and integrated with current secondary prevention activities for CHD in the two healthcare settings. Following an exploratory trial the acceptability and feasibility of the intervention were discussed in four focus groups (17 patients) and 10 interviews (staff). The data were analysed using thematic analysis. Integrating qualitative research into the development of the intervention provided depth of information about the varying impact, between the two healthcare systems, of different funding and administrative arrangements, on their provision of secondary prevention and identified similar barriers of time constraints, training needs and poor patient motivation. The findings also highlighted the importance to patients of stress management, the need for which had been underestimated by the researchers. The qualitative evaluation provided depth of detail not found in evaluation questionnaires. It highlighted how the intervention needed to be more practical by minimising administration, integrating role plays into behaviour

  13. Characterization of Arabidopsis Transcriptional Responses to Different Aphid Species Reveals Genes that Contribute to Host Susceptibility and Non-host Resistance

    Science.gov (United States)

    Jaouannet, Maëlle; Morris, Jenny A.; Hedley, Peter E.; Bos, Jorunn I. B.

    2015-01-01

    Aphids are economically important pests that display exceptional variation in host range. The determinants of diverse aphid host ranges are not well understood, but it is likely that molecular interactions are involved. With significant progress being made towards understanding host responses upon aphid attack, the mechanisms underlying non-host resistance remain to be elucidated. Here, we investigated and compared Arabidopsis thaliana host and non-host responses to aphids at the transcriptional level using three different aphid species, Myzus persicae, Myzus cerasi and Rhopalosiphum pisum. Gene expression analyses revealed a high level of overlap in the overall gene expression changes during the host and non-host interactions with regards to the sets of genes differentially expressed and the direction of expression changes. Despite this overlap in transcriptional responses across interactions, there was a stronger repression of genes involved in metabolism and oxidative responses specifically during the host interaction with M. persicae. In addition, we identified a set of genes with opposite gene expression patterns during the host versus non-host interactions. Aphid performance assays on Arabidopsis mutants that were selected based on our transcriptome analyses identified novel genes contributing to host susceptibility, host defences during interactions with M. persicae as well to non-host resistance against R. padi. Understanding how plants respond to aphid species that differ in their ability to infest plant species, and identifying the genes and signaling pathways involved, is essential for the development of novel and durable aphid control in crop plants. PMID:25993686

  14. The role of arachidonic acid metabolites in signal transduction in an identified neural network mediating presynaptic inhibition in Aplysia

    International Nuclear Information System (INIS)

    Shapiro, E.; Piomelli, D.; Feinmark, S.; Vogel, S.; Chin, G.; Schwartz, J.H.

    1988-01-01

    Neuromodulation is a form of signal transduction that results in the biochemical control of neuronal excitability. Many neurotransmitters act through second messengers, and the examination of biochemical cascades initiated by neurotransmitter-receptor interaction has advanced the understanding of how information is acquired and stored in the nervous system. For example, 5-HT and other facilitory transmitters increase cAMP in sensory neurons of Aplysia, which enhances excitability and facilitates transmitter output. The authors have examined the role of arachidonic acid metabolites in a neuronal circuit mediating presynaptic inhibition. L32 cells are a cluster of putative histaminergic neurons that each make dual-action synaptic potentials onto two follower neurons, L10 and L14. The synaptic connections, biophysical properties, and roles in behavior of the L10 and L14 follower cells have been well studied. The types of ion channels causing each component of the L32-L10 and L32-L14 dual actions have been characterized and application of histamine mimics the effects of stimulating L32 in both L10 and L14

  15. Presynaptic type III neuregulin1-ErbB signaling targets {alpha}7 nicotinic acetylcholine receptors to axons.

    Science.gov (United States)

    Hancock, Melissa L; Canetta, Sarah E; Role, Lorna W; Talmage, David A

    2008-05-05

    Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of alpha7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface alpha7 nAChRs, which results from a redistribution of preexisting intracellular pools of alpha7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting alpha7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

  16. Presynaptic type III neuregulin1-ErbB signaling targets alpha7 nicotinic acetylcholine receptors to axons.

    Science.gov (United States)

    Hancock, Melissa L; Canetta, Sarah E; Role, Lorna W; Talmage, David A

    2008-06-01

    Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of alpha7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface alpha7 nAChRs, which results from a redistribution of preexisting intracellular pools of alpha7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting alpha7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

  17. Presynaptic Type III Neuregulin1-ErbB signaling targets α7 nicotinic acetylcholine receptors to axons

    Science.gov (United States)

    Hancock, Melissa L.; Canetta, Sarah E.; Role, Lorna W.; Talmage, David A.

    2008-01-01

    Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of α7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface α7 nAChRs, which results from a redistribution of preexisting intracellular pools of α7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting α7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function. PMID:18458158

  18. Inherent X-Linked Genetic Variability and Cellular Mosaicism Unique to Females Contribute to Sex-Related Differences in the Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Zoltan Spolarics

    2017-11-01

    Full Text Available Females have a longer lifespan and better general health than males. Considerable number of studies also demonstrated that, after trauma and sepsis, females present better outcomes as compared to males indicating sex-related differences in the innate immune response. The current notion is that differences in the immuno-modulatory effects of sex hormones are the underlying causative mechanism. However, the field remains controversial and the exclusive role of sex hormones has been challenged. Here, we propose that polymorphic X-linked immune competent genes, which are abundant in the population are important players in sex-based immuno-modulation and play a key role in causing sex-related outcome differences following trauma or sepsis. We describe the differences in X chromosome (ChrX regulation between males and females and its consequences in the context of common X-linked polymorphisms at the individual as well as population level. We also discuss the potential pathophysiological and immune-modulatory aspects of ChrX cellular mosaicism, which is unique to females and how this may contribute to sex-biased immune-modulation. The potential confounding effects of ChrX skewing of cell progenitors at the bone marrow is also presented together with aspects of acute trauma-induced de novo ChrX skewing at the periphery. In support of the hypothesis, novel observations indicating ChrX skewing in a female trauma cohort as well as case studies depicting the temporal relationship between trauma-induced cellular skewing and the clinical course are also described. Finally, we list and discuss a selected set of polymorphic X-linked genes, which are frequent in the population and have key regulatory or metabolic functions in the innate immune response and, therefore, are primary candidates for mediating sex-biased immune responses. We conclude that sex-related differences in a variety of disease processes including the innate inflammatory response to injury

  19. Presynaptic nicotinic α7 and non-α7 receptors stimulate endogenous GABA release from rat hippocampal synaptosomes through two mechanisms of action.

    Directory of Open Access Journals (Sweden)

    Stefania Zappettini

    Full Text Available BACKGROUND: Although converging evidence has suggested that nicotinic acetylcholine receptors (nAChR play a role in the modulation of GABA release in rat hippocampus, the specific involvement of different nAChR subtypes at presynaptic level is still a matter of debate. In the present work we investigated, using selective α7 and α4β2 nAChR agonists, the presence of different nAChR subtypes on hippocampal GABA nerve endings to assess to what extent and through which mechanisms they stimulate endogenous GABA release. METHODOLOGY/FINDINGS: All agonists elicited GABA overflow. Choline (Ch-evoked GABA overflow was dependent to external Ca(2+, but unaltered in the presence of Cd(2+, tetrodotoxin (TTX, dihydro-β-erythroidine (DHβE and 1-(4,4-Diphenyl-3-butenyl-3-piperidinecarboxylic acid hydrochloride SKF 89976A. The effect of Ch was blocked by methyllycaconitine (MLA, α-bungarotoxin (α-BTX, dantrolene, thapsigargin and xestospongin C, suggesting that GABA release might be triggered by Ca(2+ entry into synaptosomes through the α7 nAChR channel with the involvement of calcium from intracellular stores. Additionally, 5-Iodo-A-85380 dihydrochloride (5IA85380 elicited GABA overflow, which was Ca(2+ dependent, blocked by Cd(2+, and significantly inhibited by TTX and DHβE, but unaffected by MLA, SKF 89976A, thapsigargin and xestospongin C and dantrolene. These findings confirm the involvement of α4β2 nAChR in 5IA85380-induced GABA release that seems to occur following membrane depolarization and opening calcium channels. CONCLUSIONS/SIGNIFICANCE: Rat hippocampal synaptosomes possess both α7 and α4β2 nAChR subtypes, which can modulate GABA release via two distinct mechanisms of action. The finding that GABA release evoked by the mixture of sub-maximal concentration of 5IA85380 plus sub-threshold concentrations of Ch was significantly larger than that elicited by the sum of the effects of the two agonists is compatible with the possibility that

  20. Estimating the contribution from different ionospheric regions to the TEC response to the solar flares using data from the international GPS network

    Directory of Open Access Journals (Sweden)

    L. A. Leonovich

    Full Text Available This paper proposes a new method for estimating the contribution from different ionospheric regions to the response of total electron content variations to the solar flare, based on data from the international network of two-frequency multichannel receivers of the navigation GPS system. The method uses the effect of partial "shadowing" of the atmosphere by the terrestrial globe. The study of the solar flare influence on the atmosphere uses GPS stations located near the boundary of the shadow on the ground in the nightside hemisphere. The beams between the satellite-borne transmitter and the receiver on the ground for these stations pass partially through the atmosphere lying in the region of total shadow, and partially through the illuminated atmosphere. The analysis of the ionospheric effect of a powerful solar flare of class X5.7/3B that was recorded on 14 July 2000 (10:24 UT, N22 W07 in quiet geomagnetic conditions (Dst = -10 nT has shown that about 75% of the TEC increase corresponds to the ionospheric region lying below 300 km and about 25% to regions lying above 300 km.

    Key words. Ionosphere (solar radiation and cosmic ray effects; instruments and techniques – Solar physics, astrophysics and astronomy (ultraviolet emissions

  1. Differential Activity of Plasma and Vacuolar Membrane Transporters Contributes to Genotypic Differences in Salinity Tolerance in a Halophyte Species, Chenopodium quinoa

    Directory of Open Access Journals (Sweden)

    Edgar Bonales-Alatorre

    2013-04-01

    Full Text Available Halophytes species can be used as a highly convenient model system to reveal key ionic and molecular mechanisms that confer salinity tolerance in plants. Earlier, we reported that quinoa (Chenopodium quinoa Willd., a facultative C3 halophyte species, can efficiently control the activity of slow (SV and fast (FV tonoplast channels to match specific growth conditions by ensuring that most of accumulated Na+ is safely locked in the vacuole (Bonales-Alatorre et al. (2013 Plant Physiology. This work extends these finding by comparing the properties of tonoplast FV and SV channels in two quinoa genotypes contrasting in their salinity tolerance. The work is complemented by studies of the kinetics of net ion fluxes across the plasma membrane of quinoa leaf mesophyll tissue. Our results suggest that multiple mechanisms contribute towards genotypic differences in salinity tolerance in quinoa. These include: (i a higher rate of Na+ exclusion from leaf mesophyll; (ii maintenance of low cytosolic Na+ levels; (iii better K+ retention in the leaf mesophyll; (iv a high rate of H+ pumping, which increases the ability of mesophyll cells to restore their membrane potential; and (v the ability to reduce the activity of SV and FV channels under saline conditions. These mechanisms appear to be highly orchestrated, thus enabling the remarkable overall salinity tolerance of quinoa species.

  2. Differential activity of plasma and vacuolar membrane transporters contributes to genotypic differences in salinity tolerance in a Halophyte Species, Chenopodium quinoa.

    Science.gov (United States)

    Bonales-Alatorre, Edgar; Pottosin, Igor; Shabala, Lana; Chen, Zhong-Hua; Zeng, Fanrong; Jacobsen, Sven-Erik; Shabala, Sergey

    2013-04-29

    Halophytes species can be used as a highly convenient model system to reveal key ionic and molecular mechanisms that confer salinity tolerance in plants. Earlier, we reported that quinoa (Chenopodium quinoa Willd.), a facultative C3 halophyte species, can efficiently control the activity of slow (SV) and fast (FV) tonoplast channels to match specific growth conditions by ensuring that most of accumulated Na+ is safely locked in the vacuole (Bonales-Alatorre et al. (2013) Plant Physiology). This work extends these finding by comparing the properties of tonoplast FV and SV channels in two quinoa genotypes contrasting in their salinity tolerance. The work is complemented by studies of the kinetics of net ion fluxes across the plasma membrane of quinoa leaf mesophyll tissue. Our results suggest that multiple mechanisms contribute towards genotypic differences in salinity tolerance in quinoa. These include: (i) a higher rate of Na+ exclusion from leaf mesophyll; (ii) maintenance of low cytosolic Na+ levels; (iii) better K+ retention in the leaf mesophyll; (iv) a high rate of H+ pumping, which increases the ability of mesophyll cells to restore their membrane potential; and (v) the ability to reduce the activity of SV and FV channels under saline conditions. These mechanisms appear to be highly orchestrated, thus enabling the remarkable overall salinity tolerance of quinoa species.

  3. Evidence that the Na+-K+ leak/pump ratio contributes to the difference in endurance between fast- and slow-twitch muscles.

    Science.gov (United States)

    Clausen, T; Overgaard, K; Nielsen, O B

    2004-02-01

    Muscles containing predominantly fast-twitch (type II) fibres [ext. dig. longus (EDL)] show considerably lower contractile endurance than muscles containing mainly slow-twitch (type I) fibres (soleus). To assess whether differences in Na+-K+ fluxes and excitability might contribute to this phenomenon, we compared excitation-induced Na+-K+ leaks, Na+ channels, Na+-K+ pump capacity, force and compound action potentials (M-waves) in rat EDL and soleus muscles. Isolated muscles were mounted for isometric contractions in Krebs-Ringer bicarbonate buffer and exposed to direct or indirect continuous or intermittent electrical stimulation. The time-course of force decline and concomitant changes in Na+-K+ exchange and M-waves were recorded. During continuous stimulation at 60-120 Hz, EDL showed around fivefold faster rate of force decline than soleus. This was associated with a faster loss of excitability as estimated from the area and amplitude of the M-waves. The net uptake of Na+ and the release of K+ per action potential were respectively 6.5- and 6.6-fold larger in EDL than in soleus, which may in part be due to the larger content of Na+ channels in EDL. During intermittent stimulation with 1 s 60 Hz pulse trains, EDL showed eightfold faster rate of force decline than soleus. The considerably lower contractile endurance of fast-twitch compared with slow-twitch muscles reflects differences in the rate of excitation-induced loss of excitability. This is attributed to the much larger excitation-induced Na+ influx and K+ efflux, leading to a faster rise in [K+]o in fast-twitch muscles. This may only be partly compensated by the concomitant activation of the Na+-K+ pumps, in particular in fibres showing large passive Na+-K+ leaks or reduced content of Na+-K+ pumps. Thus, endurance depends on the leak/pump ratio for Na+ and K+.

  4. Contribution of Nitrogen Uptake and Retranslocation during Reproductive Growth to the Nitrogen Efficiency of Winter Oilseed-Rape Cultivars (Brassica napus L. Differing in Leaf Senescence

    Directory of Open Access Journals (Sweden)

    Fabian Koeslin-Findeklee

    2016-01-01

    Full Text Available Genotypic variation in N efficiency defined as high grain yield under limited nitrogen (N supply of winter oilseed-rape line-cultivars has been predominantly attributed to N uptake efficiency (NUPT through maintained N uptake during reproductive growth related to functional stay-green. For investigating the role of stay-green, N retranslocation and N uptake during the reproductive phase for grain yield formation, two line cultivars differing in N starvation-induced leaf senescence were grown in a field experiment without mineral N (N0 and with 160 kg N·ha−1 (N160. Through frequent harvests from full flowering until maturity N uptake, N utilization and apparent N remobilization from vegetative plant parts to the pods could be calculated. NUPT proved being more important than N utilization efficiency (NUE for grain yield formation under N-limiting (N0 conditions. For cultivar differences in N efficiency, particularly N uptake during flowering (NUPT and biomass allocation efficiency (HI to the grains, were decisive. Both crop traits were related to delayed senescence of the older leaves. Remobilization of N particularly from stems and leaves was more important for pod N accumulation than N uptake after full flowering. Pod walls (high N concentrations and stems (high biomass mainly contributed to the crop-residue N at maturity. Decreasing the crop-inherent high N budget surplus of winter oilseed-rape requires increasing the low N remobilization efficiency particularly of pod-wall N to the grains. Addressing this conclusion, multi-year and -location field experiments with an extended range of cultivars including hybrids are desirable.

  5. How Do Different Cognitive and Linguistic Variables Contribute to Reading in Arabic? A Cross-Sectional Study from First to Sixth Grade

    Science.gov (United States)

    Asadi, Ibrahim A.; Khateb, Asaid; Ibrahim, Raphiq; Taha, Haitham

    2017-01-01

    The contribution of linguistic and cognitive variables to reading processes might vary depending on the particularities of the languages studied. This view is thought to be particularly true for Arabic which is a diglossic language and has particular orthographic and morpho-syntactic systems. This cross-sectional study examined the contribution of…

  6. A New Group-Training Procedure for Habituation Demonstrates That Presynaptic Glutamate Release Contributes to Long-Term Memory in Caenorhabditis elegans

    OpenAIRE

    Rose, Jacqueline K.; Kaun, Karla R.; Rankin, Catharine H.

    2002-01-01

    In the experiments reported here we have developed a new group-training protocol for assessing long-term memory for habituation in Caenorhabditis elegans. We have replicated all of the major findings of the original single-worm protocol using the new protocol: (1) distributed training produced long-term retention of training, massed training did not; (2) distributed training at long interstimulus intervals (ISIs) produced long-term retention, short ISIs did not; and (3) long-term memory for d...

  7. Presynaptic muscarinic receptors: Change of sensitivity during long-term drug treatment

    International Nuclear Information System (INIS)

    Marchi, M.; Raiteri, M.

    1986-01-01

    The authors investigate some of the characteristics of auto- and heteroreceptors from different brain areas in male rats; their alteration in sensitivity following chronic drug treatment is monitored. The synaptosomes were prelabeled with tritium-choline or tritium-dopamine and the release of tritium-acetylcholine and tritium-DA was studied in superfusion. It is shown that the difference in susceptibility between auto- and heteroreceptors with respect to changes of sensitivity may represent a further criterion to discriminate between muscarinic receptor subtypes

  8. Changes in chemical components of aerosol particles in different haze regions in China from 2006 to 2013 and contribution of meteorological factors

    Science.gov (United States)

    Zhang, X. Y.; Wang, J. Z.; Wang, Y. Q.; Liu, H. L.; Sun, J. Y.; Zhang, Y. M.

    2015-11-01

    Since there have been individual reports of persistent haze-fog events in January 2013 in central-eastern China, questions on factors causing the drastic differences in changes in 2013 from changes in adjacent years have been raised. Changes in major chemical components of aerosol particles over the years also remain unclear. The extent of meteorological factors contributing to such changes is yet to be determined. The study intends to present the changes in daily based major water-soluble constituents, carbonaceous species, and mineral aerosol in PM10 at 13 stations within different haze regions in China from 2006 to 2013, which are associated with specific meteorological conditions that are highly related to aerosol pollution (parameterized as an index called Parameter Linking Aerosol Pollution and Meteorological Elements - PLAM). No obvious changes were found in annual mean concentrations of these various chemical components and PM10 in 2013, relative to 2012. By contrast, wintertime mass of these components was quite different. In Hua Bei Plain (HBP), sulfate, organic carbon (OC), nitrate, ammonium, element carbon (EC), and mineral dust concentrations in winter were approximately 43, 55, 28, 23, 21, and 130 μg m-3, respectively; these masses were approximately 2 to 4 times higher than those in background mass, which also exhibited a decline during 2006 to 2010 and then a rise till 2013. The mass of these concentrations and PM10, except minerals, respectively, increased by approximately 28 to 117 % and 25 % in January 2013 compared with that in January 2012. Thus, persistent haze-fog events occurred in January 2013, and approximately 60 % of this increase in component concentrations from 2012 to 2013 can be attributed to severe meteorological conditions in the winter of 2013. In the Yangtze River Delta (YRD) area, winter masses of these components, unlike HBP, have not significantly increase since 2010; PLAM were also maintained at a similar level without

  9. DC-Evoked Modulation of Excitability of Myelinated Nerve Fibers and Their Terminal Branches; Differences in Sustained Effects of DC.

    Science.gov (United States)

    Kaczmarek, Dominik; Jankowska, Elzbieta

    2018-03-15

    Direct current (DC) evokes long-lasting changes in neuronal networks both presynaptically and postsynaptically and different mechanisms were proposed to be involved in them. Different mechanisms were also suggested to account for the different dynamics of presynaptic DC actions on myelinated nerve fibers stimulated before they entered the spinal gray matter and on their terminal branches. The aim of the present study was to examine whether these different dynamics might be related to differences in the involvement of K + channels. To this end, we compared effects of the K + channel blocker 4-amino-pyridine (4-AP) on DC-evoked changes in the excitability of afferent fibers stimulated within the dorsal columns (epidurally) and within their projection areas in the dorsal horn and motor nuclei (intraspinally). 4-AP was applied systemically in deeply anesthetized rats. DC-evoked increases in the excitability of epidurally stimulated afferent nerve fibers, and increases in field potentials evoked by these fibers, were not affected by 4-AP. In contrast, sustained decreases rather than increases in the excitability of intraspinally stimulated terminal nerve branches were evoked by local application of DC in conjunction with 4-AP. The study leads to the conclusion that 4-AP-sensitive K + channels contribute to the sustained DC-evoked post-polarization increases in the excitability at the level of terminal branches of nerve fibers but not of the nodes of Ranvier nor within the juxta-paranodal regions where other mechanisms would be involved in inducing the sustained DC-evoked changes. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Long live the axon. Parallels between ageing and pathology from a presynaptic point of view.

    Science.gov (United States)

    Grillo, Federico W

    2016-10-01

    All animals have to find the right balance between investing resources into their reproductive cycle and protecting their tissues from age-related damage. In higher order organisms the brain is particularly vulnerable to ageing, as the great majority of post-mitotic neurons are there to stay for an entire life. While ageing is unavoidable, it may progress at different rates in different individuals of the same species depending on a variety of genetic and environmental factors. Inevitably though, ageing results in a cognitive and sensory-motor decline caused by changes in neuronal structure and function. Besides normal ageing, age-related pathological conditions can develop in a sizeable proportion of the population. While this wide array of diseases are considerably different compared to physiological ageing, the two processes share many similarities and are likely to interact. At the subcellular level, two key structures are involved in brain ageing: axons and their synapses. Here I highlight how the ageing process affects these structures in normal and neurodegenerative states in different brain areas. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. GABA-mediated synchronization in the human neocortex: elevations in extracellular potassium and presynaptic mechanisms.

    Science.gov (United States)

    Louvel, J; Papatheodoropoulos, C; Siniscalchi, A; Kurcewicz, I; Pumain, R; Devaux, B; Turak, B; Esposito, V; Villemeure, J G; Avoli, M

    2001-01-01

    contribute to interneuron synchronization in the absence of ionotropic excitatory synaptic transmission.

  12. Detection of marine neurotoxins and characterization of the presynaptic activity of iotrochotin from the sponge Iotrochota birotulata

    International Nuclear Information System (INIS)

    Martin, J.V.

    1987-01-01

    In order to detect novel presynaptic neurotoxins, a total of 766 extracts from marine organisms collected during expeditions of the research vessel Alpha Helix around the peninsula of Baja Mexico in 1974 and through the Caribbean in 1978 were tested for activity in a synaptosomal assay for the release of acetylcholine (ACh). To eliminate from consideration sample extracts which lysed the synaptosomal membrane, lactate dehydrogenase (LDH) activity was measured as a cytoplasmic marker. On the basis of the screening studies the extract of the sponge lotrochota birotulata was chosen for more detailed characterization. The active factor, iotrochotin (IOT), was sensitive to thermal inactivation, was partially activated by trypsin treatment and had a molecular weight of 12,000-13,000. The activity of IOT was found to be complete by one minute. The maximal release of radioactivity from synaptosomes preloaded with [ 3 H]choline was found to be dependent on the concentration of IOT irrespective of the time of further incubation. The concentration-response curve of IOT activity showed a sigmoid shape which did not fit the Hill equation. IOT caused release of both ACh and choline. Of the radioactivity released by IOT from synaptosomes preloaded with [ 3 H]choline, 50-60% was [ 3 H]ACh. IOT also released [ 3 H]GABA and [ 3 H]norepinephrine from synaptosomes preincubated with these labeled neurotransmitters. The activity of IOT was only minimally sensitive to reduction in Na + or Ca 2+ levels, and was not sensitive to tetrodotoxin. IOT did not dramatically change the fluorescence of synaptosomes incubated with a depolarization-indicating dye. However, depolarization of synaptosomes with high concentrations of K + was still detectable by this method in the presence of IOT

  13. Role of presynaptic receptors in the release and synthesis of /sup 3/H-dopamine by slices of rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Westfall, T C; Besson, M J; Giorguieff, M F; Glowinski, J [Institut National de la Sante et de la Recherche Medicale (INSERM), 75 - Paris (France). Groupe de Neuropharmacologie Biochimique

    1976-01-01

    Striatal slices were continuously superfused with L-3,5-/sup 3/H-Tyrosine(50..mu..Ci/ml) and /sup 3/H-H/sub 2/O (index of /sup 3/H-dopamine (/sup 3/H-DA) synthesis) and /sup 3/H-DA estimated in 0.5 ml (2.5min) superfusate fractions. Depolarization with 50 mM k/sup +/ for 7.5 min induced a marked increase in /sup 3/H-DA release and a biphasic effect on synthesis. The decrease in the rate of /sup 3/H-H/sub 2/O formation induced by K/sup +/ was not related to modifications of the specific activity of tyrosine in tissues. The possibility that the inhibition of synthesis was due to alterations in DA concentration in the synaptic cleft was examined. On the other hand, when the powerful neuroleptic fluphenazine was added to the superfusion medium in a concentration which only weakly blocked /sup 3/H-DA uptake (10/sup -6/M) it potentiated /sup 3/H-DA release and prevented the inhibition of synthesis both in the absence or presence of benztropine. The DA inhibitory effect on synthesis was still observed in the presence of benztropine (10/sup -6/M) while the NA effect was prevented. This concentration of benztropine blocked both DA and NA uptake. The administration of fluphenazine (10/sup -6/M) significantly prevented the decrease in /sup 3/H-DA synthesis induced by exogenous DA and partially prevented the effect of NA. The present results provide direct support for the concept that activation of presynaptic DA receptors located on DA terminals in the striatum of the rat results in an inhibition of synthesis and release of the transmitter.

  14. The role of presynaptic receptors in the release and synthesis of 3H-dopamine by slices of rat striatum

    International Nuclear Information System (INIS)

    Westfall, T.C.; Besson, M.J.; Giorguieff, M.F.; Glowinski, J.

    1976-01-01

    Striatal slices were continuously superfused with L-3,5- 3 H-Tyrosine(50μCi/ml) and 3 H-H 2 O [index of 3 H-dopamine ( 3 H-DA) synthesis] and 3 H-DA estimated in 0.5 ml (2.5min) superfusate fractions. Depolarization with 50 mM k + for 7.5 min induced a marked increase in 3 H-DA release and a biphasic effect on synthesis. The decrease in the rate of 3 H-H 2 O formation induced by K + was not related to modifications of the specific activity of tyrosine in tissues. The possibility that the inhibition of synthesis was due to alterations in DA concentration in the synaptic cleft was examined. On the other hand, when the powerful neuroleptic fluphenazine was added to the superfusion medium in a concentration which only weakly blocked 3 H-DA uptake (10 -6 M) it potentiated 3 H-DA release and prevented the inhibition of synthesis both in the absence or presence of benztropine. The DA inhibitory effect on synthesis was still observed in the presence of benztropine (10 -6 M) while the NA effect was prevented. This concentration of benztropine blocked both DA and NA uptake. The administration of fluphenazine (10 -6 M) significantly prevented the decrease in 3 H-DA synthesis induced by exogenous DA and partially prevented the effect of NA. The present results provide direct support for the concept that activation of presynaptic DA receptors located on DA terminals in the striatum of the rat results in an inhibition of synthesis and release of the transmitter. (orig.) [de

  15. Endomorphin-2 Inhibits the Activity of the Spinoparabrachial Projection Neuron through Presynaptic Mechanisms in the Spinal Dorsal Horn in Rats

    Directory of Open Access Journals (Sweden)

    Jun-Bin Yin

    2018-03-01

    Full Text Available Background/Aims: Spinal dorsal horn (SDH is one of the most important regions for analgesia produced by endomorphin-2 (EM2, which has a higher affinity and specificity for the µ-opioid receptor (MOR than morphine. Many studies have focused on substantia gelatinosa (SG, lamina II neurons to elucidate the cellular basis for its antinociceptive effects. However, the complicated types and local circuits of interneurons in the SG make it difficult to understand the real effects of EM2. Therefore, in the present study, we examined the effects of EM2 on projection neurons (PNs in lamina I. Methods: Tracing, immunofluoresence, and immunoelectron methods were used to examine the morphological connections between EM2-immunoreactive (-ir terminals and PNs. By using in vitro whole cell patch clamp recording technique, we investigated the functional effects of EM2 on PNs. Results: EM2-ir afferent terminals directly contacted PNs projecting to the parabrachial nucleus in lamina I. Their synaptic connections were further confirmed by immunoelectron microscopy, most of which were asymmetric synapses. It was found that EM2 had a strong inhibitory effect on the frequency, but not amplitude, of the spontaneous excitatory postsynaptic current (sEPSC of the spinoparabrachial PNs in lamina I, which could be reversed by MOR antagonist CTOP. However, their spontaneous inhibitory postsynaptic current (sIPSC and intrinsic properties were not changed after EM2 application. Conclusion: Applying EM2 to the SDH could produce analgesia through inhibiting the activities of the spinoparabrachial PNs in lamina I by reducing presynaptic neurotransmitters release from the primary afferent terminals.

  16. Serotonin, dopamine and noradrenaline adjust actions of myelinated afferents via modulation of presynaptic inhibition in the mouse spinal cord.

    Directory of Open Access Journals (Sweden)

    David L García-Ramírez

    Full Text Available Gain control of primary afferent neurotransmission at their intraspinal terminals occurs by several mechanisms including primary afferent depolarization (PAD. PAD produces presynaptic inhibition via a reduction in transmitter release. While it is known that descending monoaminergic pathways complexly regulate sensory processing, the extent these actions include modulation of afferent-evoked PAD remains uncertain. We investigated the effects of serotonin (5HT, dopamine (DA and noradrenaline (NA on afferent transmission and PAD. Responses were evoked by stimulation of myelinated hindlimb cutaneous and muscle afferents in the isolated neonatal mouse spinal cord. Monosynaptic responses were examined in the deep dorsal horn either as population excitatory synaptic responses (recorded as extracellular field potentials; EFPs or intracellular excitatory postsynaptic currents (EPSCs. The magnitude of PAD generated intraspinally was estimated from electrotonically back-propagating dorsal root potentials (DRPs recorded on lumbar dorsal roots. 5HT depressed the DRP by 76%. Monosynaptic actions were similarly depressed by 5HT (EFPs 54%; EPSCs 75% but with a slower time course. This suggests that depression of monosynaptic EFPs and DRPs occurs by independent mechanisms. DA and NA had similar depressant actions on DRPs but weaker effects on EFPs. IC50 values for DRP depression were 0.6, 0.8 and 1.0 µM for 5HT, DA and NA, respectively. Depression of DRPs by monoamines was nearly-identical in both muscle and cutaneous afferent-evoked responses, supporting a global modulation of the multimodal afferents stimulated. 5HT, DA and NA produced no change in the compound antidromic potentials evoked by intraspinal microstimulation indicating that depression of the DRP is unrelated to direct changes in the excitability of intraspinal afferent fibers, but due to metabotropic receptor activation. In summary, both myelinated afferent-evoked DRPs and monosynaptic

  17. Melatonin modulation of presynaptic nicotinic acetylcholine receptors located on short noradrenergic neurons of the rat vas deferens: a pharmacological characterization

    Directory of Open Access Journals (Sweden)

    Zago W.M.

    1999-01-01

    Full Text Available Melatonin, the pineal hormone produced during the dark phase of the light-dark cycle, modulates neuronal acetylcholine receptors located presynaptically on nerve terminals of the rat vas deferens. Recently we showed the presence of high affinity nicotine-binding sites during the light phase, and low and high affinity binding sites during the dark phase. The appearance of the low affinity binding sites was due to the nocturnal melatonin surge and could be mimicked by exposure to melatonin in vitro. The aim of the present research was to identify the receptor subtypes responsible for the functional response during the light and the dark phase. The rank order of potency of agonists was dimethylphenylpiperazinium (DMPP = cytisine > nicotine > carbachol and DMPP = nicotine = cytisine > carbachol, during the light and dark phase, respectively, due to an increase in apparent affinity for nicotine. Mecamylamine similarly blocked the DMPP response during the light and the dark phase, while the response to nicotine was more efficiently blocked during the light phase. In contrast, methyllycaconitine inhibited the nicotine-induced response only at 21:00 h. Since a7 nicotinic acetylcholine receptors (nAChRs have low affinity for nicotine in binding assays, we suggest that a mixed population composed of a3ß4 - plus a7-bearing nAChR subtypes is present at night. This plasticity in receptor subtypes is probably driven by melatonin since nicotine-induced contraction in organs from animals sacrificed at 15:00 h and incubated with melatonin (100 pg/ml, 4 h is not totally blocked by mecamylamine. Thus melatonin, by acting directly on the short adrenergic neurons that innervate the rat vas deferens, induces the appearance of the low affinity binding site, probably an a7 nAChR subtype.

  18. Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats.

    Science.gov (United States)

    Mairesse, Jérôme; Gatta, Eleonora; Reynaert, Marie-Line; Marrocco, Jordan; Morley-Fletcher, Sara; Soichot, Marion; Deruyter, Lucie; Camp, Gilles Van; Bouwalerh, Hammou; Fagioli, Francesca; Pittaluga, Anna; Allorge, Delphine; Nicoletti, Ferdinando; Maccari, Stefania

    2015-12-01

    Oxytocin receptors are known to modulate synaptic transmission and network activity in the hippocampus, but their precise function has been only partially elucidated. Here, we have found that activation of presynaptic oxytocin receptor with the potent agonist, carbetocin, enhanced depolarization-evoked glutamate release in the ventral hippocampus with no effect on GABA release. This evidence paved the way for examining the effect of carbetocin treatment in "prenatally restraint stressed" (PRS) rats, i.e., the offspring of dams exposed to repeated episodes of restraint stress during pregnancy. Adult PRS rats exhibit an anxious/depressive-like phenotype associated with an abnormal glucocorticoid feedback regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and, remarkably, with a reduced depolarization-evoked glutamate release in the ventral hippocampus. Chronic systemic treatment with carbetocin (1mg/kg, i.p., once a day for 2-3 weeks) in PRS rats corrected the defect in glutamate release, anxiety- and depressive-like behavior, and abnormalities in social behavior, in the HPA response to stress, and in the expression of stress-related genes in the hippocampus and amygdala. Of note, carbetocin treatment had no effect on these behavioral and neuroendocrine parameters in prenatally unstressed (control) rats, with the exception of a reduced expression of the oxytocin receptor gene in the amygdala. These findings disclose a novel function of oxytocin receptors in the hippocampus, and encourage the use of oxytocin receptor agonists in the treatment of stress-related psychiatric disorders in adult life. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Sex differences in stress responses: a critical role for corticotropin-releasing factor.

    Science.gov (United States)

    Bangasser, Debra A; Wiersielis, Kimberly R

    2018-03-01

    Rates of post-traumatic stress disorder, panic disorder, and major depression are higher in women than in men. Another shared feature of these disorders is that dysregulation of the stress neuropeptide, corticotropin-releasing factor (CRF), is thought to contribute to their pathophysiology. Therefore, sex differences in responses to CRF could contribute to this sex bias in disease prevalence. Here, we review emerging data from non-human animal models that reveal extensive sex differences in CRF functions ranging from its presynaptic regulation to its postsynaptic efficacy. Specifically, detailed are sex differences in the regulation of CRF-containing neurons and the amount of CRF that they produce. We also describe sex differences in CRF receptor expression, distribution, trafficking, and signaling. Finally, we highlight sex differences in the processes that mitigate the effects of CRF. In most cases, the identified sex differences can lead to increased stress sensitivity in females. Thus, the relevance of these differences for the increased risk of depression and anxiety disorders in women compared to men is also discussed.

  20. The contributions of unhealthy lifestyle factors to apparent resistant hypertension: findings from the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study.

    Science.gov (United States)

    Shimbo, Daichi; Levitan, Emily B; Booth, John N; Calhoun, David A; Judd, Suzanne E; Lackland, Daniel T; Safford, Monika M; Oparil, Suzanne; Muntner, Paul

    2013-02-01

    Unhealthy lifestyle factors may contribute to apparent treatment resistant hypertension (aTRH). We examined associations of unhealthy lifestyle factors with aTRH in individuals taking antihypertensive medications from three or more classes. Participants (n = 2602) taking three or more antihypertensive medication classes were identified from the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study. aTRH was defined as having SBP/DBP at least 140/90 mmHg despite the use of three or more antihypertensive medication classes or the use of four or more classes to achieve blood pressure control. Lifestyle factors included obesity, physical inactivity, current smoking, heavy alcohol consumption, a low Dietary Approaches to Stop Hypertension (DASH) diet score and high sodium-to-potassium (Na/K) intake. Among participants taking three or more antihypertensive medication classes, 1293 (49.7%) participants had aTRH. The prevalence of unhealthy lifestyle factors in participants with and without aTRH was 55.2 and 51.7%, respectively, for obesity, 42.2 and 40.5% for physical inactivity, 11.3 and 11.5% for current smoking, 3.1 and 4.0% for heavy alcohol consumption, 23.1 and 21.5% for low-DASH diet score, and 25.4 and 24.4% for high Na/K intake. After adjustment for age, sex, race, and geographic region of residence, none of the unhealthy lifestyle factors were associated with aTRH. The associations between each unhealthy lifestyle factor and aTRH remained nonsignificant after additional adjustment for education, income, depressive symptoms, total calorie intake, and comorbidities. Unhealthy lifestyle factors did not have independent associations with aTRH among individuals taking three or more antihypertensive medication classes.

  1. Mitochondrial oxidative stress contributes differently to rat pancreatic islet cell apoptosis and insulin secretory defects after prolonged culture in a low non-stimulating glucose concentration.

    Science.gov (United States)

    Roma, L P; Pascal, S M; Duprez, J; Jonas, J-C

    2012-08-01

    Pancreatic beta cells chronically exposed to low glucose concentrations show signs of oxidative stress, loss of glucose-stimulated insulin secretion (GSIS) and increased apoptosis. Our aim was to confirm the role of mitochondrial oxidative stress in rat islet cell apoptosis under these culture conditions and to evaluate whether its reduction similarly improves survival and GSIS. Apoptosis, oxidative stress-response gene mRNA expression and glucose-induced stimulation of mitochondrial metabolism, intracellular Ca(2+) concentration and insulin secretion were measured in male Wistar rat islets cultured for 1 week in RPMI medium containing 5-10 mmol/l glucose with or without manganese(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP) or N-acetyl-L-: cysteine (NAC). Oxidative stress was measured in islet cell clusters cultured under similar conditions using cytosolic and mitochondrial redox-sensitive green fluorescent protein (roGFP1/mt-roGFP1). Prolonged culture in 5 vs 10 mmol/l glucose increased mt-roGFP1 (but not roGFP1) oxidation followed by beta cell apoptosis and loss of GSIS resulting from reduced insulin content, mitochondrial metabolism, Ca(2+) influx and Ca(2+)-induced secretion. Tolbutamide-induced, but not high K(+)-induced, Ca(2+) influx was also suppressed. Under these conditions, MnTBAP, but not NAC, triggered parallel ~50-70% reductions in mt-roGFP1 oxidation and beta cell apoptosis, but failed to protect against the loss of GSIS despite significant improvement in glucose-induced and tolbutamide-induced Ca(2+) influx. Mitochondrial oxidative stress contributes differently to rat pancreatic islet cell apoptosis and insulin secretory defects during culture in a low glucose concentration. Thus, targeting beta cell survival may not be sufficient to restore insulin secretion when beta cells suffer from prolonged mitochondrial oxidative stress, e.g. in the context of reduced glucose metabolism.

  2. miRNA-135b Contributes to Triple Negative Breast Cancer Molecular Heterogeneity: Different Expression Profile in Basal-like Versus non-Basal-like Phenotypes.

    Science.gov (United States)

    Uva, Paolo; Cossu-Rocca, Paolo; Loi, Federica; Pira, Giovanna; Murgia, Luciano; Orrù, Sandra; Floris, Matteo; Muroni, Maria Rosaria; Sanges, Francesca; Carru, Ciriaco; Angius, Andrea; De Miglio, Maria Rosaria

    2018-01-01

    The clinical and genetic heterogeneity of Triple Negative Breast Cancer (TNBC) and the lack of unambiguous molecular targets contribute to the inadequacy of current therapeutic options for these variants. MicroRNAs (miRNA) are a class of small highly conserved regulatory endogenous non-coding RNA, which can alter the expression of genes encoding proteins and may play a role in the dysregulation of cellular pathways. Our goal was to improve the knowledge of the molecular pathogenesis of TNBC subgroups analyzing the miRNA expression profile, and to identify new prognostic and predictive biomarkers. We conducted a human miRNome analysis by TaqMan Low Density Array comparing different TNBC subtypes, defined by immunohistochemical basal markers EGFR and CK5/6. RT-qPCR confirmed differential expression of microRNAs. To inspect the function of the selected targets we perform Gene Ontology and KEGG enrichment analysis. We identified a single miRNA signature given by miR-135b expression level, which was strictly related to TNBC with basal-like phenotype. miR-135b target analysis revealed a role in the TGF-beta, WNT and ERBB pathways. A significant positive correlation was identified between neoplastic proliferative index and miR-135b expression. These findings confirm the oncogenic roles of miR-135b in the pathogenesis of TNBC expressing basal markers. A potential negative prognostic role of miR-135b overexpression might be related to the positive correlation with high proliferative index. Our study implies potential clinical applications: miR-135b could be a potential therapeutic target in basal-like TNBCs.

  3. Possible contributions of a novel form of synaptic plasticity in Aplysia to reward, memory, and their dysfunctions in mammalian brain.

    Science.gov (United States)

    Hawkins, Robert D

    2013-09-18

    Recent studies in Aplysia have identified a new variation of synaptic plasticity in which modulatory transmitters enhance spontaneous release of glutamate, which then acts on postsynaptic receptors to recruit mechanisms of intermediate- and long-term plasticity. In this review I suggest the hypothesis that similar plasticity occurs in mammals, where it may contribute to reward, memory, and their dysfunctions in several psychiatric disorders. In Aplysia, spontaneous release is enhanced by activation of presynaptic serotonin receptors, but presynaptic D1 dopamine receptors or nicotinic acetylcholine receptors could play a similar role in mammals. Those receptors enhance spontaneous release of glutamate in hippocampus, entorhinal cortex, prefrontal cortex, ventral tegmental area, and nucleus accumbens. In all of those brain areas, glutamate can activate postsynaptic receptors to elevate Ca(2+) and engage mechanisms of early-phase long-term potentiation (LTP), including AMPA receptor insertion, and of late-phase LTP, including protein synthesis and growth. Thus, presynaptic receptors and spontaneous release may contribute to postsynaptic mechanisms of plasticity in brain regions involved in reward and memory, and could play roles in disorders that affect plasticity in those regions, including addiction, Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD).

  4. Effects of spinal transection on presynaptic markers for glutamatergic neurons in the rat

    International Nuclear Information System (INIS)

    Singer, H.S.; Coyle, J.T.; Frangia, J.; Price, D.L.

    1981-01-01

    To evaluate the hypothesis that glutamic acid may be the neurotransmitter of descending, excitatory supraspinal pathways, the uptake and release of L-[3H] glutamate and the levels of endogenous glutamate were measured in preparations from rat lumbar spinal cord following complete mid-thoracic transection. Following transection, the activity of the synaptosomal high-affinity glutamate uptake process was increased in both dorsal and ventral halves of lumbar cord between 1 and 14 days after transection and returned to control levels by 21 days posttransection. At 7 days, the increased activity of the uptake process for L-[3H]glutamate resulted in elevation of Vmax with no significant alteration in KT as compared to age-matched controls. Depolarization-induced release of L-[3H]glutamate from prelabeled slices did not differ significantly from control in the lesioned rat except at 21 days after lesion when the amount of tritium release was significantly greater in the transected preparations than in control. Amino acid analysis of the lumbar cord from control and transected rats indicated only a 10% decrease in the level of endogenous glutamate and no alterations in the concentration of GABA and glycine 7 days after lesion. These findings do not support the hypothesis that glutamate serves as a major excitatory neurotransmitter in supraspinal pathways innervating the lumbar cord of the rat

  5. Metaplasticity at CA1 Synapses by Homeostatic Control of Presynaptic Release Dynamics

    Directory of Open Access Journals (Sweden)

    Cary Soares

    2017-10-01

    Full Text Available Summary: Hebbian and homeostatic forms of plasticity operate on different timescales to regulate synaptic strength. The degree of mechanistic overlap between these processes and their mutual influence are still incompletely understood. Here, we report that homeostatic synaptic strengthening induced by prolonged network inactivity compromised the ability of CA1 synapses to exhibit LTP. This effect could not be accounted for by an obvious deficit in the postsynaptic capacity for LTP expression, since neither the fraction of silent synapses nor the ability to induce LTP by two-photon glutamate uncaging were reduced by the homeostatic process. Rather, optical quantal analysis reveals that homeostatically strengthened synapses display a reduced capacity to maintain glutamate release fidelity during repetitive stimulation, ultimately impeding the induction, and thus expression, of LTP. By regulating the short-term dynamics of glutamate release, the homeostatic process thus influences key aspects of dynamic network function and exhibits features of metaplasticity. : Several forms of synaptic plasticity operating over distinct spatiotemporal scales have been described at hippocampal synapses. Whether these distinct plasticity mechanisms interact and influence one another remains incompletely understood. Here, Soares et al. show that homeostatic plasticity induced by network silencing influences short-term release dynamics and Hebbian plasticity rules at hippocampal synapses. Keywords: synapse, LTP, homeostatic plasticity, metaplasticity, iGluSNFR

  6. Depression of presynaptic excitation by the activation of vanilloid receptor 1 in the rat spinal dorsal horn revealed by optical imaging

    Directory of Open Access Journals (Sweden)

    Ikeda Hiroshi

    2006-02-01

    Full Text Available Abstract In this study, we show that capsaicin (CAP depresses primary afferent fiber terminal excitability by acting on vanilloid receptor 1 (TRPV1 channels of primary afferent fibers in adenosine 5'-triphosphate (ATP- and temperature-dependent manner using two optical imaging methods. First, transverse slices of spinal cord were stained with a voltage-sensitive dye and the net excitation in the spinal dorsal horn was recorded. Prolonged treatment (>20 min with the TRPV1 channel agonist, CAP, resulted in a long-lasting inhibition of the net excitation evoked by single-pulse stimulation of C fiber-activating strength. A shorter application of CAP inhibited the excitation in a concentration-dependent manner and the inhibition was reversed within several minutes. This inhibition was Ca++-dependent, was antagonized by the TRPV1 channel antagonist, capsazepine (CPZ, and the P2X and P2Y antagonist, suramin, and was facilitated by the P2Y agonist, uridine 5'-triphosphate (UTP. The inhibition of excitation was unaffected by bicuculline and strychnine, antagonists of GABAA and glycine receptors, respectively. Raising the perfusate temperature to 39°C from 27°C inhibited the excitation (-3%/°C. This depressant effect was antagonized by CPZ and suramin, but not by the P2X antagonist, 2', 3'-O-(2,4,6-trinitrophenyl adenosine 5'-triphosphate (TNP-ATP. Second, in order to record the presynaptic excitation exclusively, we stained the primary afferent fibers anterogradely from the dorsal root. CAP application and a temperature increase from 27°C to 33°C depressed the presynaptic excitation, and CPZ antagonized these effects. Thus, this study showed that presynaptic excitability is modulated by CAP, temperature, and ATP under physiological conditions, and explains the reported central actions of CAP. These results may have clinical importance, especially for the control of pain.

  7. Muscle Contraction Regulates BDNF/TrkB Signaling to Modulate Synaptic Function through Presynaptic cPKCα and cPKCβI.

    Science.gov (United States)

    Hurtado, Erica; Cilleros, Víctor; Nadal, Laura; Simó, Anna; Obis, Teresa; Garcia, Neus; Santafé, Manel M; Tomàs, Marta; Halievski, Katherine; Jordan, Cynthia L; Lanuza, Maria A; Tomàs, Josep

    2017-01-01

    The neurotrophin brain-derived neurotrophic factor (BDNF) acts via tropomyosin-related kinase B receptor (TrkB) to regulate synapse maintenance and function in the neuromuscular system. The potentiation of acetylcholine (ACh) release by BDNF requires TrkB phosphorylation and Protein Kinase C (PKC) activation. BDNF is secreted in an activity-dependent manner but it is not known if pre- and/or postsynaptic activities enhance BDNF expression in vivo at the neuromuscular junction (NMJ). Here, we investigated whether nerve and muscle cell activities regulate presynaptic conventional PKC (cPKCα and βI) via BDNF/TrkB signaling to modulate synaptic strength at the NMJ. To differentiate the effects of presynaptic activity from that of muscle contraction, we stimulated the phrenic nerve of rat diaphragms (1 Hz, 30 min) with or without contraction (abolished by μ-conotoxin GIIIB). Then, we performed ELISA, Western blotting, qRT-PCR, immunofluorescence and electrophysiological techniques. We found that nerve-induced muscle contraction: (1) increases the levels of mature BDNF protein without affecting pro-BDNF protein or BDNF mRNA levels; (2) downregulates TrkB.T1 without affecting TrkB.FL or p75 neurotrophin receptor (p75) levels; (3) increases presynaptic cPKCα and cPKCβI protein level through TrkB signaling; and (4) enhances phosphorylation of cPKCα and cPKCβI. Furthermore, we demonstrate that cPKCβI, which is exclusively located in the motor nerve terminals, increases activity-induced acetylcholine release. Together, these results show that nerve-induced muscle contraction is a key regulator of BDNF/TrkB signaling pathway, retrogradely activating presynaptic cPKC isoforms (in particular cPKCβI) to modulate synaptic function. These results indicate that a decrease in neuromuscular activity, as occurs in several neuromuscular disorders, could affect the BDNF/TrkB/PKC pathway that links pre- and postsynaptic activity to maintain neuromuscular function.

  8. Muscle Contraction Regulates BDNF/TrkB Signaling to Modulate Synaptic Function through Presynaptic cPKCα and cPKCβI

    Directory of Open Access Journals (Sweden)

    Erica Hurtado

    2017-05-01

    Full Text Available The neurotrophin brain-derived neurotrophic factor (BDNF acts via tropomyosin-related kinase B receptor (TrkB to regulate synapse maintenance and function in the neuromuscular system. The potentiation of acetylcholine (ACh release by BDNF requires TrkB phosphorylation and Protein Kinase C (PKC activation. BDNF is secreted in an activity-dependent manner but it is not known if pre- and/or postsynaptic activities enhance BDNF expression in vivo at the neuromuscular junction (NMJ. Here, we investigated whether nerve and muscle cell activities regulate presynaptic conventional PKC (cPKCα and βI via BDNF/TrkB signaling to modulate synaptic strength at the NMJ. To differentiate the effects of presynaptic activity from that of muscle contraction, we stimulated the phrenic nerve of rat diaphragms (1 Hz, 30 min with or without contraction (abolished by μ-conotoxin GIIIB. Then, we performed ELISA, Western blotting, qRT-PCR, immunofluorescence and electrophysiological techniques. We found that nerve-induced muscle contraction: (1 increases the levels of mature BDNF protein without affecting pro-BDNF protein or BDNF mRNA levels; (2 downregulates TrkB.T1 without affecting TrkB.FL or p75 neurotrophin receptor (p75 levels; (3 increases presynaptic cPKCα and cPKCβI protein level through TrkB signaling; and (4 enhances phosphorylation of cPKCα and cPKCβI. Furthermore, we demonstrate that cPKCβI, which is exclusively located in the motor nerve terminals, increases activity-induced acetylcholine release. Together, these results show that nerve-induced muscle contraction is a key regulator of BDNF/TrkB signaling pathway, retrogradely activating presynaptic cPKC isoforms (in particular cPKCβI to modulate synaptic function. These results indicate that a decrease in neuromuscular activity, as occurs in several neuromuscular disorders, could affect the BDNF/TrkB/PKC pathway that links pre- and postsynaptic activity to maintain neuromuscular function.

  9. Contributions: SAGE

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Contributions: SAGE. Space Alternating Generalized Expectation (SAGE) Maximization algorithm provides an iterative approach to parameter estimation when direct maximization of the likelihood function may be infeasible. Complexity is less in those applications ...

  10. Various Contributions

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Various Contributions. Developed an Off –Diagonal MIMO Canceller to mitigate Upstream Crosstalk in VDSL. Developed a low complexity, Expectation Maximization based iterative Crosstalk cancellation. Developed an optimal way of computational complexity ...

  11. Original contributions

    African Journals Online (AJOL)

    hefere

    Original contributions ... Results suggest that there is a significant positive ... psychological abuse, including economic abuse, intimidation, harassment, stalking, damage ... or maintaining the structure and function of the African home (Alio et al., 2011; Jewkes,. Levin ... Revictimisation occurs due to emotional violence and.

  12. Presynaptic Regulation of Leptin in a Defined Lateral Hypothalamus-Ventral Tegmental Area Neurocircuitry Depends on Energy State.

    Science.gov (United States)

    Liu, Jing-Jing; Bello, Nicholas T; Pang, Zhiping P

    2017-12-06

    Synaptic transmission controls brain activity and behaviors, including food intake. Leptin, an adipocyte-derived hormone, acts on neurons located in the lateral hypothalamic area (LHA) to maintain energy homeostasis and regulate food intake behavior. The specific synaptic mechanisms, cell types, and neural projections mediating this effect remain unclear. In male mice, using pathway-specific retrograde tracing, whole-cell patch-clamp recordings and post hoc cell type identification, we found that leptin reduces excitatory synaptic strength onto both melanin-concentrating hormone- and orexin-expressing neurons projecting from the LHA to the ventral tegmental area (VTA), which may affect dopamine signaling and motivation for feeding. A presynaptic mechanism mediated by distinct intracellular signaling mechanisms may account for this regulation by leptin. The regulatory effects of leptin depend on intact leptin receptor signaling. Interestingly, the synaptic regulatory function of leptin in the LHA-to-VTA neuronal pathway is highly sensitive to energy states: both energy deficiency (acute fasting) and excessive energy storage (high-fat diet-induced obesity) blunt the effect of leptin. These data revealed that leptin may regulate synaptic transmission in the LHA-to-VTA neurocircuitry in an inverted "U-shape" fashion dependent on plasma glucose levels and related to metabolic states. SIGNIFICANCE STATEMENT The lateral hypothalamic area (LHA) to ventral tegmental area (VTA) projection is an important neural pathway involved in balancing whole-body energy states and reward. We found that the excitatory synaptic inputs to both orexin- and melanin-concentrating hormone expressing LHA neurons projecting to the VTA were suppressed by leptin, a peptide hormone derived from adipocytes that signals peripheral energy status to the brain. Interestingly, energy states seem to affect how leptin regulates synaptic transmission since both the depletion of energy induced by acute food

  13. Presynaptic mGlu1 and mGlu5 autoreceptors facilitate glutamate exocytosis from mouse cortical nerve endings.

    Science.gov (United States)

    Musante, Veronica; Neri, Elisa; Feligioni, Marco; Puliti, Aldamaria; Pedrazzi, Marco; Conti, Valerio; Usai, Cesare; Diaspro, Alberto; Ravazzolo, Roberto; Henley, Jeremy M; Battaglia, Giuseppe; Pittaluga, Anna

    2008-09-01

    The effects of mGlu1 and mGlu5 receptor activation on the depolarization-evoked release of [3H]d-aspartate ([3H]D-ASP) from mouse cortical synaptosomes were investigated. The mGlu1/5 receptor agonist 3,5-DHPG (0.1-100microM) potentiated the K+(12mM)-evoked [3H]D-ASP overflow. The potentiation occurred in a concentration-dependent manner showing a biphasic pattern. The agonist potentiated [3H]D-ASP exocytosis when applied at 0.3microM; the efficacy of 3,5-DHPG then rapidly declined and reappeared at 30-100microM. The fall of efficacy of agonist at intermediate concentration may be consistent with 3,5-DHPG-induced receptor desensitization. Facilitation of [3H]D-ASP exocytosis caused by 0.3microM 3,5-DHPG was prevented by the selective mGlu5 receptor antagonist MPEP, but was insensitive to the selective mGlu1 receptor antagonist CPCCOEt. In contrast, CPCCOEt prevented the potentiation by 50microM 3,5-DHPG, while MPEP had minimal effect. Unexpectedly, LY 367385 antagonized both the 3,5-DHPG-induced effects. A total of 0.3microM 3,5-DHPG failed to facilitate the K+-evoked [3H]D-ASP overflow from mGlu5 receptor knockout (mGlu5-/-) cortical synaptosomes, but not from nerve terminals prepared from the cortex of animals lacking the mGlu1 receptors, the crv4/crv4 mice. On the contrary, 50microM 3,5-DHPG failed to affect the [3H]D-ASP exocytosis from cortical synaptosomes obtained from crv4/crv4 and mGlu5-/-mice. Western blot analyses in subsynaptic fractions support the existence of both mGlu1 and mGlu5 autoreceptors located presynaptically, while immunocytochemistry revealed their presence at glutamatergic terminals. We propose that mGlu1 and mGlu5 autoreceptors exist on mouse glutamatergic cortical terminals; mGlu5 receptors may represent the "high affinity" binding sites for 3,5-DHPG, while mGlu1 autoreceptors represent the "low affinity" binding sites.

  14. Nef does not contribute to replication differences between R5 pre-AIDS and AIDS HIV-1 clones from patient ACH142

    Directory of Open Access Journals (Sweden)

    Rekosh David

    2008-05-01

    Full Text Available Abstract AIDS-associated, CCR5-tropic (R5 HIV-1 clones, isolated from a patient that never developed CXCR4-tropic HIV-1, replicate to a greater extent and cause greater cytopathic effects than R5 HIV-1 clones isolated before the onset of AIDS. Previously, we showed that HIV-1 Env substantially contributed to the enhanced replication of an AIDS clone. In order to determine if Nef makes a similar contribution, we cloned and phenotypically analyzed nef genes from a series of patient ACH142 derived R5 HIV-1 clones. The AIDS-associated Nef contains a series of residues found in Nef proteins from progressors 1. In contrast to other reports 123, this AIDS-associated Nef downmodulated MHC-I to a greater extent and CD4 less than pre-AIDS Nef proteins. Additionally, all Nef proteins enhanced infectivity similarly in a single round of replication. Combined with our previous study, these data show that evolution of the HIV-1 env gene, but not the nef gene, within patient ACH142 significantly contributed to the enhanced replication and cytopathic effects of the AIDS-associated R5 HIV-1 clone.

  15. The contribution of health selection to occupational status inequality in Germany - differences by gender and between the public and private sectors.

    Science.gov (United States)

    Kröger, H

    2016-04-01

    Estimating the size of health inequalities between hierarchical levels of job status and the contribution of direct health selection to these inequalities for men and women in the private and public sector in Germany. The study uses prospective data from the Socio-Economic Panel study on 11,788 women and 11,494 men working in the public and private sector in Germany. Direct selection effects of self-rated health on job status are estimated using fixed-effects linear probability models. The contribution of health selection to overall health-related inequalities between high and low status jobs is calculated. Women in the private sector who report very good health have a 1.9 [95% CI: 0.275; 3.507] percentage point higher probability of securing a high status job than women in poor self-rated health. This direct selection effect constitutes 20.12% of total health inequalities between women in high and low status jobs. For men in the private and men and women in the public sector no relevant health selection effects were identified. The contribution of health selection to total health inequalities between high and low status jobs varies with gender and public versus private sector. Women in the private sector in Germany experience the strongest health selection. Possible explanations are general occupational disadvantages that women have to overcome to secure high status jobs. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  16. Development of a modular streamflow model to quantify runoff contributions from different land uses in tropical urban environments using Genetic Programming

    Science.gov (United States)

    Meshgi, Ali; Schmitter, Petra; Chui, Ting Fong May; Babovic, Vladan

    2015-06-01

    The decrease of pervious areas during urbanization has severely altered the hydrological cycle, diminishing infiltration and therefore sub-surface flows during rainfall events, and further increasing peak discharges in urban drainage infrastructure. Designing appropriate waster sensitive infrastructure that reduces peak discharges requires a better understanding of land use specific contributions towards surface and sub-surface processes. However, to date, such understanding in tropical urban environments is still limited. On the other hand, the rainfall-runoff process in tropical urban systems experiences a high degree of non-linearity and heterogeneity. Therefore, this study used Genetic Programming to establish a physically interpretable modular model consisting of two sub-models: (i) a baseflow module and (ii) a quick flow module to simulate the two hydrograph flow components. The relationship between the input variables in the model (i.e. meteorological data and catchment initial conditions) and its overall structure can be explained in terms of catchment hydrological processes. Therefore, the model is a partial greying of what is often a black-box approach in catchment modelling. The model was further generalized to the sub-catchments of the main catchment, extending the potential for more widespread applications. Subsequently, this study used the modular model to predict both flow components of events as well as time series, and applied optimization techniques to estimate the contributions of various land uses (i.e. impervious, steep grassland, grassland on mild slope, mixed grasses and trees and relatively natural vegetation) towards baseflow and quickflow in tropical urban systems. The sub-catchment containing the highest portion of impervious surfaces (40% of the area) contributed the least towards the baseflow (6.3%) while the sub-catchment covered with 87% of relatively natural vegetation contributed the most (34.9%). The results from the quickflow

  17. Short term memory may be the depletion of the readily releasable pool of presynaptic neurotransmitter vesicles of a metastable long term memory trace pattern.

    Science.gov (United States)

    Tarnow, Eugen

    2009-09-01

    The Tagging/Retagging model of short term memory was introduced earlier (Tarnow in Cogn Neurodyn 2(4):347-353, 2008) to explain the linear relationship between response time and correct response probability for word recall and recognition: At the initial stimulus presentation the words displayed tag the corresponding long term memory locations. The tagging process is linear in time and takes about one second to reach a tagging level of 100%. After stimulus presentation the tagging level decays logarithmically with time to 50% after 14 s and to 20% after 220 s. If a probe word is reintroduced the tagging level has to return to 100% for the word to be properly identified, which leads to a delay in response time. This delay is proportional to the tagging loss. The tagging level is directly related to the probability of correct word recall and recognition. Evidence presented suggests that the tagging level is the level of depletion of the Readily Releasable Pool (RRP) of neurotransmitter vesicles at presynaptic terminals. The evidence includes the initial linear relationship between tagging level and time as well as the subsequent logarithmic decay of the tagging level. The activation of a short term memory may thus be the depletion of RRP (exocytosis) and short term memory decay may be the ensuing recycling of the neurotransmitter vesicles (endocytosis). The pattern of depleted presynaptic terminals corresponds to the long term memory trace.

  18. [Development of the Human Olfactory Bulbs in the Prenatal Ontogenesis: an Immunochistochemical Study with Markers of Presynaptic Terminals (anti-SNAP-25, -Synapsin-I, -Synaptophysin)].

    Science.gov (United States)

    Kharlamova, A S; Barabanov, V M; Saveliev, S V

    2015-01-01

    We provide the data of the olfactory bulbs (OB) development in the human fetuses on the stages from 8 week to birth. Immunochistochemical markers of presynaptic terminals (anti-SNAP-25, -synapsin-I, -synaptophysin) were used to evaluate the maturation of the OB. Differentiation of the OB layers begins from periphery, which implicitly evidences that growth of the olfactory nerves fibers induses not only anatomical differentiation of the OB, but also differentiation of its functional layers. The sites of the developing glomerulus are revealed using the immunochistochemical prosedure on the stage before distinct glomerulus can be identified with common histological procedure. OB conductive system demonstrates immunoreactivity with the antibodies to the presynaptic proteins on the all stages from 10-11 weeks of fetus development. Four stages of the OB development are described. All functional layers of the OB are mature at the 22-weeks stage. Further differentiation of the OB neuroblasts, including lamina formation of the internal granular leyer, glomerular layer development, OB growth continue after 20-22 weeks stage until 38-40 weeks of the fetus develoment. Patterns of the immunoreactivity with antibodies to SNAP-25, synapsin-I and synaptophysin are completely appropriate to those of adult's OB on the 38-40 weeks of the prenatal development. Complete maturity of the human OB is achived at 38-40 weeks of the prenatal development.

  19. LRRK2 phosphorylates pre-synaptic N-ethylmaleimide sensitive fusion (NSF) protein enhancing its ATPase activity and SNARE complex disassembling rate.

    Science.gov (United States)

    Belluzzi, Elisa; Gonnelli, Adriano; Cirnaru, Maria-Daniela; Marte, Antonella; Plotegher, Nicoletta; Russo, Isabella; Civiero, Laura; Cogo, Susanna; Carrion, Maria Perèz; Franchin, Cinzia; Arrigoni, Giorgio; Beltramini, Mariano; Bubacco, Luigi; Onofri, Franco; Piccoli, Giovanni; Greggio, Elisa

    2016-01-13

    Lrrk2, a gene linked to Parkinson's disease, encodes a large scaffolding protein with kinase and GTPase activities implicated in vesicle and cytoskeletal-related processes. At the presynaptic site, LRRK2 associates with synaptic vesicles through interaction with a panel of presynaptic proteins. Here, we show that LRRK2 kinase activity influences the dynamics of synaptic vesicle fusion. We therefore investigated whether LRRK2 phosphorylates component(s) of the exo/endocytosis machinery. We have previously observed that LRRK2 interacts with NSF, a hexameric AAA+ ATPase that couples ATP hydrolysis to the disassembling of SNARE proteins allowing them to enter another fusion cycle during synaptic exocytosis. Here, we demonstrate that NSF is a substrate of LRRK2 kinase activity. LRRK2 phosphorylates full-length NSF at threonine 645 in the ATP binding pocket of D2 domain. Functionally, NSF phosphorylated by LRRK2 displays enhanced ATPase activity and increased rate of SNARE complex disassembling. Substitution of threonine 645 with alanine abrogates LRRK2-mediated increased ATPase activity. Given that the most common Parkinson's disease LRRK2 G2019S mutation displays increased kinase activity, our results suggest that mutant LRRK2 may impair synaptic vesicle dynamics via aberrant phosphorylation of NSF.

  20. Surface antigens contribute differently to the pathophysiological features in serotype K1 and K2 Klebsiella pneumoniae strains isolated from liver abscesses.

    Science.gov (United States)

    Yeh, Kuo-Ming; Chiu, Sheng-Kung; Lin, Chii-Lan; Huang, Li-Yueh; Tsai, Yu-Kuo; Chang, Jen-Chang; Lin, Jung-Chung; Chang, Feng-Yee; Siu, Leung-Kei

    2016-01-01

    The virulence role of surface antigens in a single serotype of Klebsiella pneumoniae strain have been studied, but little is known about whether their contribution will vary with serotype. To investigate the role of K and O antigen in hyper-virulent strains, we constructed O and K antigen deficient mutants from serotype K1 STL43 and K2 TSGH strains from patients with liver abscess, and characterized their virulence in according to the abscess formation and resistance to neutrophil phagocytosis, serum, and bacterial clearance in liver. Both of K1 and K2-antigen mutants lost their wildtype resistance to neutrophil phagocytosis and hepatic clearance, and failed to cause abscess formation. K2-antigen mutant became serum susceptible while K1-antigen mutant maintained its resistance to serum killing. The amount of glucuronic acid, indicating the amount of capsular polysaccharide (CPS, K antigen), was inversed proportional to the rate of phagocytosis. O-antigen mutant of serotype K1 strains had significantly more amount of CPS, and more resistant to neutrophil phagocytosis than its wildtype counterpart. O-antigen mutants of serotype K1 and K2 strains lost their wildtype serum resistance, and kept resistant to neutrophil phagocytosis. While both mutants lacked the same O1 antigen, O-antigen mutant of serotype K1 became susceptible to liver clearance and cause mild abscess formation, but its serotype K2 counterpart maintained these wildtype virulence. We conclude that the contribution of surface antigens to virulence of K. pneumoniae strains varies with serotypes.

  1. Combining Automatic Item Generation and Experimental Designs to Investigate the Contribution of Cognitive Components to the Gender Difference in Mental Rotation

    Science.gov (United States)

    Arendasy, Martin E.; Sommer, Markus; Gittler, Georg

    2010-01-01

    Marked gender differences in three-dimensional mental rotation have been broadly reported in the literature in the last few decades. Various theoretical models and accounts were used to explain the observed differences. Within the framework of linking item design features of mental rotation tasks to cognitive component processes associated with…

  2. Contribution of on-site Coulomb repulsion energy to structural, electronic and magnetic properties of SrCoO3 for different space groups: first-principles study

    Directory of Open Access Journals (Sweden)

    Muhammady Shibghatullah

    2018-03-01

    Full Text Available We report structural, electronic, and magnetic properties of SrCoO3 in Pm3̅m and P4/mbm space groups, which are calculated by using generalized gradient approximation corrected with on-site Coulomb repulsion U and exchange energies J. The cubic lattice parameter a and local magnetic moments of Co (μCo are optimized by varying U at Co 3d site. Employing ultrasoft pseudopotential, the values of U = 8 eV and J = 0.75 eV are the best choice for Pm3̅m space group. We found the value of μCo = 2.56 μB, which is consistent with the previous results. It was also found that Co 3d, hybridized with O 2p, is the main contributor to ferromagnetic metallic properties. Besides, norm-conserving pseudopotential promotes a, which is in good agreement with experimental result. However, it is not suitable for P4/mbm space group. By using ultrasoft pseudopotential, the value of U = 3 eV (J = 0.75 is the most suitable for P4/mbm group. Ferromagnetic metallic properties, Jahn-Teller distortion, and reasonable lattice parameters have been obtained. This study shows that U has significant contribution to the calculated properties and also points out that P4/mbm space group with US-PP is suitable to describe experimental results.

  3. Different flavonoids present in the micronized purified flavonoid fraction (Daflon 500 mg) contribute to its anti-hyperpermeability effect in the hamster cheek pouch microcirculation.

    Science.gov (United States)

    Paysant, J; Sansilvestri-Morel, P; Bouskela, E; Verbeuren, T J

    2008-02-01

    This study evaluated microcirculatory effects of the flavonoid substances that constitute the micronized purified flavonoid fraction (MPFF) (Daflon 500 mg) in comparison to diosmin. In groups of 3 male hamsters, oral treatment with MPFF or diosmin (15 min before anesthesia) did not alter blood pressure. At 10 or 30 mg/kg, both MPFF and diosmin significantly decreased the leaky sites caused by ischemia/reperfusion (I/R) (30 min) in the hamster cheek pouch; the effect was significantly higher with MPFF (39+/-1% and 52+/-1%, respectively) than diosmin (18+/-1% and 37+/-3%, respectively). Eight groups of 3 hamsters each were treated with the components of MPFF. Diosmetin only decreased the number leaky sites at 30 mg/kg (decrease: 15+/-2%). The decrement at 10 and 30 mg/kg averaged at: 17+/-3% and 44+/-1%, respectively, for hesperidin; 19+/-1% and 46+/-2%, respectively, for linarin; and 30+/-1% and 44+/-1%, respectively, for isorhoifolin. Hesperidin, linarin, and isorhoifolin each displayed an anti-leakage effect comparable to or greater than diosmin. MPFF decreases permeability more than any of its single constituents, suggesting that the flavonoids present in its formulation have a synergistic action. These results illustrate that MPFF is more potent than single diosmin in this model of hyperpermeability and that each of the flavonoid substances present in MPFF contribute to its action.

  4. 2010-2015 methane trends over Canada, the United States, and Mexico observed by the GOSAT satellite: contributions from different source sectors

    Science.gov (United States)

    Sheng, J. X.; Jacob, D.; Turner, A. J.; Maasakkers, J. D.; Benmergui, J. S.; Bloom, A. A.; Arndt, C.; Gautam, R.; Zavala Araiza, D.; Hamburg, S.; Boesch, H.; Parker, R.

    2017-12-01

    We use six years (2010-2015) of methane column data from the GOSAT satellite to examine trends in atmospheric methane over North America and infer trends in emissions. Local methane enhancements above background are diagnosed in the GOSAT data on a 0.5°x0.5° grid by estimating the local background as the low (10th-25th) quantile of the deseasonalized frequency distributions of the data for individual years. Trends in methane enhancements on the 0.5°x0.5° grid are then aggregated nationally and for individual source sectors, using information from state-of-science bottom-up inventories, to increase statistical power. We infer that US methane emissions increased by 1.9% a-1 over the six-year period, with contributions from both oil/gas systems (possibly unconventional gas production) and from livestock in the Midwest (possibly swine production). Mexican emissions show a decrease that can be attributed to a decreasing cattle population. Canadian emissions show interannual variability driven by wetlands emissions and correlated with wetland areal extent. The US emission trends inferred from the GOSAT data are within the constraint provided by surface observations from the North American Carbon Program network.

  5. Conductive Hearing Loss Has Long-Lasting Structural and Molecular Effects on Presynaptic and Postsynaptic Structures of Auditory Nerve Synapses in the Cochlear Nucleus.

    Science.gov (United States)

    Clarkson, Cheryl; Antunes, Flora M; Rubio, Maria E

    2016-09-28

    Sound deprivation by conductive hearing loss increases hearing thresholds, but little is known about the response of the auditory brainstem during and after conductive hearing loss. Here, we show in young adult rats that 10 d of monaural conductive hearing loss (i.e., earplugging) leads to hearing deficits that persist after sound levels are restored. Hearing thresholds in response to clicks and frequencies higher than 8 kHz remain increased after a 10 d recovery period. Neural output from the cochlear nucleus measured at 10 dB above threshold is reduced and followed by an overcompensation at the level of the lateral lemniscus. We assessed whether structural and molecular substrates at auditory nerve (endbulb of Held) synapses in the cochlear nucleus could explain these long-lasting changes in hearing processing. During earplugging, vGluT1 expression in the presynaptic terminal decreased and synaptic vesicles were smaller. Together, there was an increase in postsynaptic density (PSD) thickness and an upregulation of GluA3 AMPA receptor subunits on bushy cells. After earplug removal and a 10 d recovery period, the density of synaptic vesicles increased, vesicles were also larger, and the PSD of endbulb synapses was larger and thicker. The upregulation of the GluA3 AMPAR subunit observed during earplugging was maintained after the recovery period. This suggests that GluA3 plays a role in plasticity in the cochlear nucleus. Our study demonstrates that sound deprivation has long-lasting alterations on structural and molecular presynaptic and postsynaptic components at the level of the first auditory nerve synapse in the auditory brainstem. Despite being the second most prevalent form of hearing loss, conductive hearing loss and its effects on central synapses have received relatively little attention. Here, we show that 10 d of monaural conductive hearing loss leads to an increase in hearing thresholds, to an increased central gain upstream of the cochlear nucleus at

  6. Sex differences in general knowledge: meta-analysis and new data on the contribution of school-related moderators among high-school students.

    Science.gov (United States)

    Tran, Ulrich S; Hofer, Agnes A; Voracek, Martin

    2014-01-01

    Research from various countries consistently reported an advantage of boys over girls in general knowledge and was also suggestive of some overall trends regarding specific domains of general knowledge that were speculated to stem from biologically differentiated interests. However, results were heterogeneous and, as of yet, had not been evaluated meta-analytically. Moreover, previous research drew on overly homogeneous high-school or undergraduate samples whose representativeness appears problematic; mostly, likely moderators, such as school type, student age or parental education, were also not directly investigated or controlled for. We provide a meta-analytical aggregation of available results regarding sex differences in general knowledge and present new data, investigating the psychometric properties of the General Knowledge Test (GKT), on which previous research primarily relied, and explored sex differences in a large and heterogeneous Austrian high-school student sample (N = 1088). The aggregated sex effect in general knowledge was of medium size in previous research, but differences in specific domains were heterogeneous across countries and only modest at best. Large sex differences in our data could be explained to a large part by school-related moderators (school type, school, student age, parental education) and selection processes. Boys had a remaining advantage over girls that was only small in size and that was consistent with the magnitude of sex differences in general intelligence. Analysis of the GKT yielded no evidence of biologically differentiated interests, but of a specific interest in the humanities among girls. In conclusion, previous research likely overestimated sex differences in general knowledge.

  7. South Korean University Students' Perceptions of Different English Varieties and Their Contribution to the Learning of English as a Foreign Language

    Science.gov (United States)

    Ahn, So-Yeon; Kang, Hyun-Sook

    2017-01-01

    This study explored South Korean university students' perceptions of different English varieties and their speakers, student attitudes towards the learning of English and its varieties, and the role of these attitudinal variables in the learning of English as a foreign language. One-hundred-one students who were enrolled in four sections of a…

  8. Age Differences in the Contribution of Recollection and Familiarity to False-Memory Formation: A New Paradigm to Examine Developmental Reversals

    Science.gov (United States)

    Lyons, Kristen E.; Ghetti, Simona; Cornoldi, Cesare

    2010-01-01

    Using a new method for studying the development of false-memory formation, we examined developmental differences in the rates at which 6-, 7-, 9-, 10-, and 18-year-olds made two types of memory errors: backward causal-inference errors (i.e. falsely remembering having viewed the non-viewed cause of a previously viewed effect), and gap-filling…

  9. Quantitative and Qualitative Analysis of Bone Marrow CD8(+) T Cells from Different Bones Uncovers a Major Contribution of the Bone Marrow in the Vertebrae.

    Science.gov (United States)

    Geerman, Sulima; Hickson, Sarah; Brasser, Giso; Pascutti, Maria Fernanda; Nolte, Martijn A

    2015-01-01

    Bone marrow (BM) plays an important role in the long-term maintenance of memory T cells. Yet, BM is found in numerous bones throughout the body, which are not equal in structure, as they differ in their ratio of cortical and trabecular bone. This implies that BM cells within different bones are subjected to different microenvironments, possibly leading to differences in their frequencies and function. To address this, we examined BM from murine tibia, femur, pelvis, sternum, radius, humerus, calvarium, and the vertebrae and analyzed the presence of effector memory (TEM), central memory (TCM), and naïve (TNV) CD8(+) T cells. During steady-state conditions, the frequency of the total CD8(+) T cell population was comparable between all bones. Interestingly, most CD8(+) T cells were located in the vertebrae, as it contained the highest amount of BM cells. Furthermore, the frequencies of TEM, TCM, and TNV cells were similar between all bones, with a majority of TNV cells. Additionally, CD8(+) T cells collected from different bones similarly expressed the key survival receptors IL-7Rα and IL-15Rβ. We also examined BM for memory CD8(+) T cells with a tissue-resident memory phenotype and observed that approximately half of all TEM cells expressed the retention marker CD69. Remarkably, in the memory phase of acute infection with the lymphocytic choriomeningitis virus (LCMV), we found a massive compositional change in the BM CD8(+) T cell population, as the TEM cells became the dominant subset at the cost of TNV cells. Analysis of Ki-67 expression established that these TEM cells were in a quiescent state. Finally, we detected higher frequencies of LCMV-specific CD8(+) T cells in BM compared to spleen and found that BM in its entirety contained fivefold more LCMV-specific CD8(+) T cells. In conclusion, although infection with LCMV caused a dramatic change in the BM CD8(+) T cell population, this did not result in noticeable differences between BM collected from different

  10. Comments on the Brazilian Proposal and contributions to global temperature increase with different climate responses - CO2 emissions due to fossil fuels, CO2 emissions due to land use change

    International Nuclear Information System (INIS)

    Rosa, L.P.; Ribeiro, S.K.; Muylaert, M.S.; Campos, C.P.

    2004-01-01

    This paper addresses the question of how to take into account the anthropogenic contribution to the increase of global temperature, instead of being restricted to the carbon emissions adopted in the Kyoto Protocol on responsibility sharing. It is shown the sensibility of the results to the variation of the parameters from different authors used for simulating the climate response based in the so-called Brazilian Proposal (BP). It is also discussed the methodological and scientific aspects of the BP being discussed by an expert group coordinated by SBSTA/UNFCCC and results of energy sector and land use change contributions by groups of countries. (author)

  11. Comments on the Brazilian Proposal and contributions to global temperature increase with different climate responses--CO2 emissions due to fossil fuels, CO2 emissions due to land use change

    International Nuclear Information System (INIS)

    Rosa, L.P.; Ribeiro, S.K.; Muylaert, M.S.; Pires de Campos, Christiano

    2004-01-01

    This paper addresses the question of how to take into account the anthropogenic contribution to the increase of global temperature, instead of being restricted to the Carbon emissions adopted in the Kyoto Protocol on responsibility sharing. It is shown the sensibility of the results to the variation of the parameters from different authors used for simulating the climate response based in the so-called Brazilian Proposal (BP). It is also discussed the methodological and scientific aspects of the BP being discussed by an expert group coordinated by SBSTA/UNFCCC and results of energy sector and land use change contributions by groups of countries

  12. Structural encoding processes contribute to individual differences in face and object cognition: Inferences from psychometric test performance and event-related brain potentials.

    Science.gov (United States)

    Nowparast Rostami, Hadiseh; Sommer, Werner; Zhou, Changsong; Wilhelm, Oliver; Hildebrandt, Andrea

    2017-10-01

    The enhanced N1 component in event-related potentials (ERP) to face stimuli, termed N170, is considered to indicate the structural encoding of faces. Previously, individual differences in the latency of the N170 have been related to face and object cognition abilities. By orthogonally manipulating content domain (faces vs objects) and task demands (easy/speed vs difficult/accuracy) in both psychometric and EEG tasks, we investigated the uniqueness of the processes underlying face cognition as compared with object cognition and the extent to which the N1/N170 component can explain individual differences in face and object cognition abilities. Data were recorded from N = 198 healthy young adults. Structural equation modeling (SEM) confirmed that the accuracies of face perception (FP) and memory are specific abilities above general object cognition; in contrast, the speed of face processing was not differentiable from the speed of object cognition. Although there was considerable domain-general variance in the N170 shared with the N1, there was significant face-specific variance in the N170. The brain-behavior relationship showed that faster face-specific processes for structural encoding of faces are associated with higher accuracy in both perceiving and memorizing faces. Moreover, in difficult task conditions, qualitatively different processes are additionally needed for recognizing face and object stimuli as compared with easy tasks. The difficulty-dependent variance components in the N170 amplitude were related with both face and object memory (OM) performance. We discuss implications for understanding individual differences in face cognition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. microRNA-4516 Contributes to Different Functions of Epithelial Permeability Barrier by Targeting Poliovirus Receptor Related Protein 1 in Enterovirus 71 and Coxsackievirus A16 Infections

    Directory of Open Access Journals (Sweden)

    Yajie Hu

    2018-04-01

    Full Text Available Enterovirus 71 (EV-A71 and coxsackievirus A16 (CV-A16 remain the predominant etiological agents of hand, foot, and mouth disease (HFMD. The clinical manifestations caused by the two viruses are obviously different. CV-A16 usually triggers a repeated infection, and airway epithelial integrity is often the potential causative factor of respiratory repeated infections. Our previous studies have demonstrated that there were some differentially expressed miRNAs involved in the regulation of adhesion function of epithelial barrier in EV-A71 and CV-A16 infections. In this study, we compared the differences between EV-A71 and CV-A16 infections on the airway epithelial barrier function in human bronchial epithelial (16HBE cells and further screened the key miRNA which leaded to the formation of these differences. Our results showed that more rapid proliferation, more serious destruction of 16HBE cells permeability, more apoptosis and disruption of intercellular adhesion-associated molecules were found in CV-A16 infection as compared to EV-A71 infection. Furthermore, we also identified that microRNA-4516 (miR-4516, which presented down-regulation in EV-A71 infection and up-regulation in CV-A16 infection was an important regulator of intercellular junctions by targeting Poliovirus receptor related protein 1(PVRL1. The expressions of PVRL1, claudin4, ZO-1 and E-cadherin in CV-A16-infected cells were significantly less than those in EV-A71-infected cells, while the expressions of these proteins were subverted when pre-treated with miR-4516-overexpression plasmid in EV-A71 infected and miR-4516-knockdown plasmid in CV-A16 infected 16HBE cells. Thus, these data suggested that the opposite expression of miR-4516 in EV-A71 and CV-A16 infections might be the initial steps leading to different epithelial impairments of 16HBE cells by destroying intercellular adhesion, which finally resulted in different outcomes of EV-A71 and CV-A16 infections.

  14. T-helper 17 and interleukin-17-producing lymphoid tissue inducer-like cells make different contributions to colitis in mice.

    Science.gov (United States)

    Ono, Yuichi; Kanai, Takanori; Sujino, Tomohisa; Nemoto, Yasuhiro; Kanai, Yasumasa; Mikami, Yohei; Hayashi, Atsushi; Matsumoto, Atsuhiro; Takaishi, Hiromasa; Ogata, Haruhiko; Matsuoka, Katsuyoshi; Hisamatsu, Tadakazu; Watanabe, Mamoru; Hibi, Toshifumi

    2012-11-01

    T helper (Th) 17 cells that express the retinoid-related orphan receptor (ROR) γt contribute to the development of colitis in mice, yet are found in normal and inflamed intestine. We investigated their development and functions in intestines of mice. We analyzed intestinal Th17 cells in healthy and inflamed intestinal tissues of mice. We analyzed expression of lymphotoxin (LT)α by Th17 cells and lymphoid tissue inducer-like cells. LTα(-/-) and RORγt(-/-) mice had significantly lower percentages of naturally occurring Th17 cells in the small intestine than wild-type mice. Numbers of CD3(-)CD4(+/-)interleukin-7Rα(+)c-kit(+)CCR6(+)NKp46(-) lymphoid tissue inducer-like cells that produce interleukin-17A were increased in LTα(-/-) and LTα(-/-) × recombination activating gene (RAG)-2(-/-) mice, compared with wild-type mice, but were absent from RORγt(-/-) mice. Parabiosis of wild-type and LTα(-/-) mice and bone marrow transplant experiments revealed that LTα-dependent gut-associated lymphoid tissue structures are required for generation of naturally occurring Th17 cells. However, when wild-type or LTα(-/-) CD4(+)CD45RB(high) T cells were transferred to RAG-2(-/-) or LTα(-/-)×RAG-2(-/-) mice, all groups, irrespective of the presence or absence of LTα on the donor or recipient cells, developed colitis and generated Th1, Th17, and Th17/Th1 cells. RAG-2(-/-) mice that received a second round of transplantation, with colitogenic but not naturally occurring Th17 cells, developed intestinal inflammation. The presence of naturally occurring Th17 cells in the colons of mice inhibited development of colitis after transfer of CD4(+)CD45RB(high) T cells and increased the numbers of Foxp3(+) cells derived from CD4(+)CD45RB(high) T cells. Gut-associated lymphoid tissue structures are required to generate naturally occurring Th17 cells that have regulatory activities in normal intestines of mice, but not for colitogenic Th17 and Th17/Th1 cells during inflammation

  15. Examination of the presynaptic dopaminergic system using positron emission tomography in a family with autosomal dominant parkinsonism and dementia due to pallido-ponto-nigral degeneration (PPNO)

    International Nuclear Information System (INIS)

    Cordes, M.; Wszolek, Z.K.; Pfeiffer, R.F.; Calne, D.B.

    1993-01-01

    We report positron emission tomography (PET) examinations of presynaptic nigrostriatal dopaminergic function in a large family with an autosomal dominant neuro-degenerative disorder characterized pathologically by pallido-ponto-nigral degeneration, and clinically by parkinsonism, dystonia, paresis of conjugate gaze, apraxia of eyelid opening and closing, pyramidal tract dysfunction, and urinary incontinence. Dopaminergic function was studied and quantified with [ 18 F[-L-6-fluorodopa (6 FD) and PET in five affected patients, 13 individuals at-risk, and 15 similarly aged controls. The rate constant K i (mL/striatum/min) for 6 FD was decreased in all patients. None of the individuals at risk had reduced 6 FD uptake. In fact, three of them had increased values. Repeat scans have revealed a fall in 6 FD uptake in two out of the three with initially high constants. This may reflect a preclinical stage of involvement, but longer observation is necessary. (orig.) [de

  16. Contributions of the CEA-Valduc Centre control to the understanding of the transfers of atmospheric tritiated water into the different parts of the environment

    International Nuclear Information System (INIS)

    Guetat, P.; Vichot, L.; Tognelli, A.

    2009-01-01

    After a description of the geological environment of the Valduc Centre dedicated to tritium purification and tritiated waste processing and storage, this document presents the assessment of quantities of tritiated water released by the Valduc Centre and of their evolution in the hydro-geological environment. It provides in situ macroscopically observed data on the transfer mechanisms of water into the different parts of the environment and into the food chain by means. This is made possible by the exceptional traceability of tritiated water. Finally, a comparison between computational models and experimental measurements is given

  17. Analysis of the Contribution of the Road Traffic Industry to the PM2.5 Emission for Different Land-Use Types

    Directory of Open Access Journals (Sweden)

    Peng Xu

    2014-01-01

    Full Text Available Road dust and vehicle exhaust are the main sources of air pollution in cities, especially in recent years with the quantity of vehicles and transportation construction continuously soaring; the hazy weather has been a dominant urban pollution form which is widely concerned by the Chinese society. By establishing a relationship model between traffic and land use, then applying analytic hierarchy process on the data from air quality monitoring station, this paper concludes the influence of different traffic behavior on air pollution which provides support to abate urban air pollution caused by traffic reasons through taking measures to control traffic.

  18. Contribution of water hyacinth (Eichhornia crassipes (Mart.) Solms) grown under different nutrient conditions to Fe-removal mechanisms in constructed wetlands.

    Science.gov (United States)

    Jayaweera, Mahesh W; Kasturiarachchi, Jagath C; Kularatne, Ranil K A; Wijeyekoon, Suren L J

    2008-05-01

    Severe contamination of water resources including groundwater with iron (Fe) due to various anthropogenic activities has been a major environmental problem in industrial areas of Sri Lanka. Hence, the use of the obnoxious weed, water hyacinth (Eichhornia crassipes (Mart.) Solms) in constructed wetlands (floating aquatic macrophyte-based plant treatment systems) to phytoremediate Fe-rich wastewaters seems to be an appealing option. Although several studies have documented that hyacinths are good metal-accumulating plants none of these studies have documented the ability of this plant grown under different nutrient conditions to remove heavy metals from wastewaters. This paper, therefore, reports the phytoremediation efficiencies of water hyacinth grown under different nutrient conditions for Fe-rich wastewaters in batch-type constructed wetlands. This study was conducted for 15 weeks after 1-week acclimatization by culturing young water hyacinth plants (average height of 20+/-2cm) in 590L capacity fiberglass tanks under different nutrient concentrations of 1-fold [28 and 7.7mg/L of total nitrogen (TN) and total phosphorous (TP), respectively], 2-fold, 1/2-fold, 1/4-fold and 1/8-fold with synthetic wastewaters containing 9.27Femg/L. Another set-up of hyacinths containing only Fe as a heavy metal but without any nutrients (i.e., 0-fold) was also studied. A mass balance was carried out to investigate the phytoremediation efficiencies and to determine the different mechanisms governing Fe removal from the wastewaters. Fe removal was largely due to phytoremediation mainly through the process of rhizofiltration and chemical precipitation of Fe2O3 and FeOH3 followed by flocculation and sedimentation. However, chemical precipitation was more significant especially during the first 3 weeks of the study. Plants grown in the 0-fold set-up showed the highest phytoremediation efficiency of 47% during optimum growth at the 6th week with a highest accumulation of 6707Femg/kg dry

  19. Active zone protein Bassoon co-localizes with presynaptic calcium channel, modifies channel function, and recovers from aging related loss by exercise.

    Science.gov (United States)

    Nishimune, Hiroshi; Numata, Tomohiro; Chen, Jie; Aoki, Yudai; Wang, Yonghong; Starr, Miranda P; Mori, Yasuo; Stanford, John A

    2012-01-01

    The P/Q-type voltage-dependent calcium channels (VDCCs) are essential for synaptic transmission at adult mammalian neuromuscular junctions (NMJs); however, the subsynaptic location of VDCCs relative to active zones in rodent NMJs, and the functional modification of VDCCs by the interaction with active zone protein Bassoon remain unknown. Here, we show that P/Q-type VDCCs distribute in a punctate pattern within the NMJ presynaptic terminals and align in three dimensions with Bassoon. This distribution pattern of P/Q-type VDCCs and Bassoon in NMJs is consistent with our previous study demonstrating the binding of VDCCs and Bassoon. In addition, we now show that the interaction between P/Q-type VDCCs and Bassoon significantly suppressed the inactivation property of P/Q-type VDCCs, suggesting that the Ca(2+) influx may be augmented by Bassoon for efficient synaptic transmission at NMJs. However, presynaptic Bassoon level was significantly attenuated in aged rat NMJs, which suggests an attenuation of VDCC function due to a lack of this interaction between VDCC and Bassoon. Importantly, the decreased Bassoon level in aged NMJs was ameliorated by isometric strength training of muscles for two months. The training increased Bassoon immunoreactivity in NMJs without affecting synapse size. These results demonstrated that the P/Q-type VDCCs preferentially accumulate at NMJ active zones and play essential role in synaptic transmission in conjunction with the active zone protein Bassoon. This molecular mechanism becomes impaired by aging, which suggests altered synaptic function in aged NMJs. However, Bassoon level in aged NMJs can be improved by muscle exercise.

  20. Pre-synaptic glycine GlyT1 transporter--NMDA receptor interaction: relevance to NMDA autoreceptor activation in the presence of Mg2+ ions.

    Science.gov (United States)

    Musante, Veronica; Summa, Maria; Cunha, Rodrigo A; Raiteri, Maurizio; Pittaluga, Anna

    2011-05-01

    Rat hippocampal glutamatergic terminals possess NMDA autoreceptors whose activation by low micromolar NMDA elicits glutamate exocytosis in the presence of physiological Mg(2+) (1.2 mM), the release of glutamate being significantly reduced when compared to that in Mg(2+)-free condition. Both glutamate and glycine were required to evoke glutamate exocytosis in 1.2 mM Mg(2+), while dizocilpine, cis-4-[phosphomethyl]-piperidine-2-carboxylic acid and 7-Cl-kynurenic acid prevented it, indicating that occupation of both agonist sites is needed for receptor activation. D-serine mimicked glycine but also inhibited the NMDA/glycine-induced release of [(3H]D-aspartate, thus behaving as a partial agonist. The NMDA/glycine-induced release in 1.2 mM Mg(2+) strictly depended on glycine uptake through the glycine transporter type 1 (GlyT1), because the GlyT1 blocker N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl])sarcosine hydrochloride, but not the GlyT2 blocker Org 25534, prevented it. Accordingly, [(3)H]glycine was taken up during superfusion, while lowering the external concentration of Na(+), the monovalent cation co-transported with glycine by GlyT1, abrogated the NMDA-induced effect. Western blot analysis of subsynaptic fractions confirms that GlyT1 and NMDA autoreceptors co-localize at the pre-synaptic level, where GluN3A subunits immunoreactivity was also recovered. It is proposed that GlyT1s coexist with NMDA autoreceptors on rat hippocampal glutamatergic terminals and that glycine taken up by GlyT1 may permit physiological activation of NMDA pre-synaptic autoreceptors. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

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

    Science.gov (United States)

    Petri, Doris; Schlicker, Eberhard

    2016-07-01

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

  2. Polymorphisms in the dopamine D4 receptor gene (DRD4) contribute to individual differences in human sexual behavior: desire, arousal and sexual function.

    Science.gov (United States)

    Ben Zion, I Z; Tessler, R; Cohen, L; Lerer, E; Raz, Y; Bachner-Melman, R; Gritsenko, I; Nemanov, L; Zohar, A H; Belmaker, R H; Benjamin, J; Ebstein, R P

    2006-08-01

    Although there is some evidence from twin studies that individual differences in sexual behavior are heritable, little is known about the specific molecular genetic design of human sexuality. Recently, a specific dopamine D4 receptor (DRD4) agonist was shown in rats to induce penile erection through a central mechanism. These findings prompted us to examine possible association between the well-characterized DRD4 gene and core phenotypes of human sexual behavior that included desire, arousal and function in a group of 148 nonclinical university students. We observed association between the exon 3 repeat region, and the C-521T and C-616G promoter region SNPs, with scores on scales that measure human sexual behavior. The single most common DRD4 5-locus haplotype (19%) was significantly associated with Desire, Function and Arousal scores. The current results are consistent with animal studies that show a role for dopamine and specifically the DRD4 receptor in sexual behavior and suggest that one pathway by which individual variation in human desire, arousal and function are mediated is based on allelic variants coding for differences in DRD4 receptor gene expression and protein concentrations in key brain areas.

  3. Contribution of Chromosomes 1HchS and 6HchS to Fertility Restoration in the Wheat msH1 CMS System under Different Environmental Conditions.

    Science.gov (United States)

    Castillo, Almudena; Rodríguez-Suárez, Cristina; Martín, Azahara C; Pistón, Fernando

    2015-01-01

    Exploiting hybrid wheat heterosis has been long pursued to increase crop yield, stability and uniformity. Cytoplasmic male sterility (CMS) systems based in the nuclear-cytoplasmic incompatible interactions are a classic way for hybrid seed production, but to date, no definitive system is available in wheat. The msH1 CMS system results from the incompatibility between the nuclear genome of wheat and the cytoplasmic genome of the wild barley Hordeum chilense. Fertility restoration of the CMS phenotype was first associated with the disomic addition of the short arm of chromosome 6H from H. chilense. In further studies it was observed that chromosome arm 1HchS was also implicated, and the combination of genes in both chromosome arms restored fertility more efficiently. In this work we aim to dissect the effect of each chromosome in fertility restoration when combined in different genomic backgrounds and under different environmental conditions. We propose a model to explain how restoration behaves in the msH1 system and generate valuable information necessary to develop an efficient system for hybrid wheat production.

  4. Contributions to the history of psychology: XC. Evolutionary biology and heritable traits (with reference to oriental-white-black differences): the 1989 AAAS paper.

    Science.gov (United States)

    Rushton, J P

    1992-12-01

    Genetic distance estimates calculated from DNA sequencing indicate that in years since emergence from the ancestral hominid line, Mongoloids = 41,000, Caucasoids = 110,000, and Negroids = 200,000. Data also show that this succession is matched by numerous other differences such that Mongoloids > Caucasoids > Negroids in brain size and intelligence (cranial capacity = 1448, 1408, 1334 cm3; brain weight = 1351, 1336, 1286 gm.; millions of excess neurons = 8900, 8650, 8550; IQ = 107, 100, 85); maturational delay (age to walk alone, age of first intercourse, age of death); sexual restraint (ovulation rate, intercourse frequencies, sexually transmitted diseases including AIDS); quiescent temperament (aggressiveness, anxiety, sociability); and social organization (law abidingness, marital stability, mental health). This pattern is ordered by a theory of r/K reproductive strategies in which Mongoloids are posited to be more K-selected than Caucasoids and especially more than Negroids. (K-selected reproductive strategies emphasize parental care and are to be contrasted with r-selected strategies which emphasize fecundity, the bioenergetic trade-off between which is postulated to underlie cross-species differences in brain size, speed of maturation, reproductive effort, and longevity.) It is suggested that this pattern came about because the ice ages exerted greater selection pressures on the later emerging populations to produce larger brains, longer lives, and more K-like behavior. One theoretical possibility is that evolution is progressive and that some populations are more "advanced" than others. Predictions are made concerning economic projections and the spread of AIDS.

  5. Understanding differences in conception and abortion rates among under-20 year olds in Britain and France: Examining the contribution of social disadvantage.

    Science.gov (United States)

    Scott, Rachel H; Bajos, Nathalie; Slaymaker, Emma; Wellings, Kaye; Mercer, Catherine H

    2017-01-01

    Socioeconomic status has been shown to be associated with sexual activity, contraceptive-use, pregnancy and abortion among young people. Less is known about whether the strength of the association differs for each outcome, between men and women, or cross-nationally. We investigate this using contemporaneous national probability survey data from Britain and France. Data were analysed for 17-29 year-olds in Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3, n = 5959) undertaken 2010-2012, and the 2010 French Fertility, Contraception and Sexual Dysfunction survey (FECOND, n = 3027). For each country, we estimated the gender-specific prevalence of sex before-16, contraceptive-use, conception before-20, and abortion in the event of conception, and used logistic regression to examine associations between two measures of socioeconomic status-educational-level and parental socioeconomic-group-and each outcome. We tested for interactions between socioeconomic characteristics and country, and socioeconomic characteristics and gender, for each outcome. For each outcome, Britain and France differed with regard to prevalence but associations with socioeconomic characteristics were similar. Respondents of higher educational level, and, less consistently, with parents from higher socioeconomic-groups, were less likely to report sex before-16 (Britain, men: adjusted OR (aOR) 0.5, women: aOR 0.5; France, men: aOR 0.5, women: aOR 0.5), no contraception at first sex (Britain, men: aOR 0.4, women: aOR 0.6; France, men: aOR 0.4, women: aOR 0.4), pregnancy before-20 (Britain: aOR 0.3; France: aOR 0.1), and in Britain, a birth rather than an abortion in the event of conception (Britain: aOR 3.1). We found no strong evidence of variation in the magnitude of the associations with socioeconomic characteristics by country or gender. Population level differences in conception and abortion rates between the two countries may partly be driven by the larger proportion

  6. Understanding differences in conception and abortion rates among under-20 year olds in Britain and France: Examining the contribution of social disadvantage.

    Directory of Open Access Journals (Sweden)

    Rachel H Scott

    Full Text Available Socioeconomic status has been shown to be associated with sexual activity, contraceptive-use, pregnancy and abortion among young people. Less is known about whether the strength of the association differs for each outcome, between men and women, or cross-nationally. We investigate this using contemporaneous national probability survey data from Britain and France.Data were analysed for 17-29 year-olds in Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3, n = 5959 undertaken 2010-2012, and the 2010 French Fertility, Contraception and Sexual Dysfunction survey (FECOND, n = 3027. For each country, we estimated the gender-specific prevalence of sex before-16, contraceptive-use, conception before-20, and abortion in the event of conception, and used logistic regression to examine associations between two measures of socioeconomic status-educational-level and parental socioeconomic-group-and each outcome. We tested for interactions between socioeconomic characteristics and country, and socioeconomic characteristics and gender, for each outcome.For each outcome, Britain and France differed with regard to prevalence but associations with socioeconomic characteristics were similar. Respondents of higher educational level, and, less consistently, with parents from higher socioeconomic-groups, were less likely to report sex before-16 (Britain, men: adjusted OR (aOR 0.5, women: aOR 0.5; France, men: aOR 0.5, women: aOR 0.5, no contraception at first sex (Britain, men: aOR 0.4, women: aOR 0.6; France, men: aOR 0.4, women: aOR 0.4, pregnancy before-20 (Britain: aOR 0.3; France: aOR 0.1, and in Britain, a birth rather than an abortion in the event of conception (Britain: aOR 3.1. We found no strong evidence of variation in the magnitude of the associations with socioeconomic characteristics by country or gender.Population level differences in conception and abortion rates between the two countries may partly be driven by the larger

  7. Two different motor learning mechanisms contribute to learning reaching movements in a rotated visual environment [version 2; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Virginia Way Tong Chu

    2014-12-01

    Full Text Available Practice of movement in virtual-reality and other artificially altered environments has been proposed as a method for rehabilitation following neurological injury and for training new skills in healthy humans.  For such training to be useful, there must be transfer of learning from the artificial environment to the performance of desired skills in the natural environment.  Therefore an important assumption of such methods is that practice in the altered environment engages the same learning and plasticity mechanisms that are required for skill performance in the natural environment.  We test the hypothesis that transfer of learning may fail because the learning and plasticity mechanism that adapts to the altered environment is different from the learning mechanism required for improvement of motor skill.  In this paper, we propose that a model that separates skill learning and environmental adaptation is necessary to explain the learning and aftereffects that are observed in virtual reality experiments.  In particular, we studied the condition where practice in the altered environment should lead to correct skill performance in the original environment. Our 2-mechanism model predicts that aftereffects will still be observed when returning to the original environment, indicating a lack of skill transfer from the artificial environment to the original environment. To illustrate the model prediction, we tested 10 healthy participants on the interaction between a simple overlearned motor skill (straight hand movements to targets in different directions and an artificially altered visuomotor environment (rotation of visual feedback of the results of movement.  As predicted by the models, participants show adaptation to the altered environment and after-effects on return to the baseline environment even when practice in the altered environment should have led to correct skill performance.  The presence of aftereffect under all conditions that

  8. Contribution to the study of degradation products of spent fuel reprocessing solvents using mass spectroscopy, its different linkages and by the use of stable isotopes

    International Nuclear Information System (INIS)

    Lesage, Denis

    1995-01-01

    Tributylphosphate (TBP) is used as an extraction solvent in nuclear fuel reprocessing. The presence of uranium fission products leads to the formation of a large variety of organic compounds resulting from radiolytic degradation of TBP. Some of these compounds can complex metallic cations, and as a result, to decrease nuclear fuel extraction yields. In this work we have studied by tandem mass spectrometry the fragmentation mechanisms of different TBP and their dimers. These molecules are interesting because of the similarity of their structures to other more complex molecules formed by irradiation (functionalized TBP and TBP dimers). This work allowed to identify mixtures of degradation products and relate their structures to radiolytic mechanisms. Ail these results, including structure determination and formation mechanisms, have been validated by using specifically labeled compounds (deuterium, oxygen 18, nitrogen 15). (author) [fr

  9. The plasma membrane H+ -ATPase AHA2 contributes to the root architecture in response to different nitrogen supply

    DEFF Research Database (Denmark)

    Młodzińska, Ewa; Kłobus, Grażyna; Christensen, Monica Daugbjerg

    2015-01-01

    of lateral root primordia, root elongation and increase the root biomass. However, the signal transduction mechanisms, which enable roots to sense changes in different mineral environments and match their growth and development patterns to actual conditions in the soil, are still unknown. Most recent...... comments have focused on one of the essential macroelements, namely nitrogen, and its role in the modification of the root architecture of Arabidopsis thaliana. As yet, not all elements of the signal transduction pathway leading to the perception of the nitrate stimulus, and hence to anatomical changes...... of the root, which allow for adaptation to variable ion concentrations in the soil, are known. Our data demonstrate that primary and lateral root length were shorter lower in aha2 mutant lines compared to wild-type plants in response to a variable nitrogen source. This suggests that the plasma membrane proton...

  10. Can combining different risk interventions into a single formulation contribute to improved cardiovascular disease risk reduction? The single pill of amlodipine/atorvastatin

    Directory of Open Access Journals (Sweden)

    FD Richard Hobbs

    2007-11-01

    Full Text Available FD Richard HobbsUniversity of Birmingham, Edgbaston, Birmingham B15 2TT, UK.Abstract: In order to prevent cardiovascular events, it is essential to effectively manage overall risk of cardiovascular disease. However, despite guideline recommendations to this effect, current management of the major, modifiable cardiovascular risk factors such as hypertension and dyslipidemia is disconnected and patient adherence to therapy is poor. This is particularly important for patients with multiple cardiovascular risk factors, who are often prescribed multiple medications. The JEWEL study program investigated the use of single-pill amlodipine/atorvastatin as a strategy to improve management of these patients. The JEWEL program consisted of two 16-week, international, openlabel, multicenter, titration-to-goal studies in patients with hypertension and dyslipidemia. The two studies differed based on country of enrollment and certain tertiary endpoints, but the overall designs were very similar. Patients were enrolled from 255 centers across Canada and 13 European countries. The study was designed to assess the efficacy, safety, and utility of amlodipine/atorvastatin single pill therapy in a real-world setting. Patients were initiated at a dose of amlodipine 5 mg/atorvastatin 10 mg, unless previously treated, and were uptitrated as necessary. The primary efficacy parameter was the percentage of patients, at different levels of cardiovascular risk, achieving country-specific guideline-recommended target levels for blood pressure and lipids. A secondary analysis of efficacy measured attainment of the same single goal for blood pressure across all study participants (JEWEL I and II and the same single goal for LDL-C across all study participants (JEWEL I and II. The program utilized a newly developed questionnaire to gain better understanding of participants’ beliefs and behaviors towards medical treatment of their multiple risk factors. Approximately 2850

  11. Toxicity screening of soils from different mine areas—A contribution to track the sensitivity and variability of Arthrobacter globiformis assay

    Energy Technology Data Exchange (ETDEWEB)

    Marques, Catarina R., E-mail: crmarques@ua.pt [Departamento de Biologia and CESAM (Centro de Estudos do Ambiente e do Mar), Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro (Portugal); Caetano, Ana L. [Departamento de Biologia and CESAM (Centro de Estudos do Ambiente e do Mar), Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro (Portugal); Haller, Andreas [ECT Oekotoxikologie GmbH, Böttgerstraße 2–14, D-65439 Flörsheim a. M. (Germany); Gonçalves, Fernando [Departamento de Biologia and CESAM (Centro de Estudos do Ambiente e do Mar), Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro (Portugal); Pereira, Ruth [Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007 Porto (Portugal); Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), Universidade do Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Römbke, Jörg [ECT Oekotoxikologie GmbH, Böttgerstraße 2–14, D-65439 Flörsheim a. M. (Germany)

    2014-06-01

    Highlights: • The assay gave rapid and feasible discrimination of toxic soils to A. globiformis. • Sensitive and low variability response to soils from different regions. • Soil properties may interfere with metal toxicity and fluorescence measurements. • Proposal of a toxicity threshold for the contact assay regarding soils. • A. globiformis assay should be included in the Tier I of risk assessment frameworks. - Abstract: This study used the Arthrobacter globiformis solid-contact test for assessing the quality of soils collected in areas subjected to past and present mine activities in Europe (uranium mine, Portugal) and North Africa (phosphogypsum pile, Tunisia; iron mine, Morocco). As to discriminate the influence of soils natural variability from the effect of contaminants, toxicity thresholds were derived for this test, based on the dataset of each study area. Furthermore, the test sensitivity and variability was also evaluated. As a result, soils that inhibited A. globiformis dehydrogenase activity above 45% or 50% relatively to the control, were considered to be toxic. Despite the soil metal content determined, the properties of soils seemed to influence dehydrogenase activity. Overall, the contact test provided a coherent outcome comparing to other more time-consuming and effort-demanding ecotoxicological assays. Our results strengthened the feasibility and ecological relevance of this assay, which variability was quite reduced hence suggesting its potential integration within the test battery of tier 1 of soil risk assessment schemes.

  12. Toxicity screening of soils from different mine areas—A contribution to track the sensitivity and variability of Arthrobacter globiformis assay

    International Nuclear Information System (INIS)

    Marques, Catarina R.; Caetano, Ana L.; Haller, Andreas; Gonçalves, Fernando; Pereira, Ruth; Römbke, Jörg

    2014-01-01

    Highlights: • The assay gave rapid and feasible discrimination of toxic soils to A. globiformis. • Sensitive and low variability response to soils from different regions. • Soil properties may interfere with metal toxicity and fluorescence measurements. • Proposal of a toxicity threshold for the contact assay regarding soils. • A. globiformis assay should be included in the Tier I of risk assessment frameworks. - Abstract: This study used the Arthrobacter globiformis solid-contact test for assessing the quality of soils collected in areas subjected to past and present mine activities in Europe (uranium mine, Portugal) and North Africa (phosphogypsum pile, Tunisia; iron mine, Morocco). As to discriminate the influence of soils natural variability from the effect of contaminants, toxicity thresholds were derived for this test, based on the dataset of each study area. Furthermore, the test sensitivity and variability was also evaluated. As a result, soils that inhibited A. globiformis dehydrogenase activity above 45% or 50% relatively to the control, were considered to be toxic. Despite the soil metal content determined, the properties of soils seemed to influence dehydrogenase activity. Overall, the contact test provided a coherent outcome comparing to other more time-consuming and effort-demanding ecotoxicological assays. Our results strengthened the feasibility and ecological relevance of this assay, which variability was quite reduced hence suggesting its potential integration within the test battery of tier 1 of soil risk assessment schemes

  13. 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.

  14. The contribution of epidemiology

    NARCIS (Netherlands)

    Brandt, P. van den; Voorrips, L.; Hertz-Picciotto, I.; Shuker, D.; Boeing, H.; Speijers, G.; Guittard, C.; Kleiner, J.; Knowles, M.; Wolk, A.; Goldbohm, A.

    2002-01-01

    Epidemiologic studies directly contribute data on risk (or benefit) in humans as the investigated species, and in the full food intake range normally encountered by humans. This paper starts with introducing the epidemiologic approach, followed by a discussion of perceived differences between

  15. Swi5-Sfr1 protein stimulates Rad51-mediated DNA strand exchange reaction through organization of DNA bases in the presynaptic filament.

    KAUST Repository

    Fornander, Louise H

    2013-12-03

    The Swi5-Sfr1 heterodimer protein stimulates the Rad51-promoted DNA strand exchange reaction, a crucial step in homologous recombination. To clarify how this accessory protein acts on the strand exchange reaction, we have analyzed how the structure of the primary reaction intermediate, the Rad51/single-stranded DNA (ssDNA) complex filament formed in the presence of ATP, is affected by Swi5-Sfr1. Using flow linear dichroism spectroscopy, we observe that the nucleobases of the ssDNA are more perpendicularly aligned to the filament axis in the presence of Swi5-Sfr1, whereas the bases are more randomly oriented in the absence of Swi5-Sfr1. When using a modified version of the natural protein where the N-terminal part of Sfr1 is deleted, which has no affinity for DNA but maintained ability to stimulate the strand exchange reaction, we still observe the improved perpendicular DNA base orientation. This indicates that Swi5-Sfr1 exerts its activating effect through interaction with the Rad51 filament mainly and not with the DNA. We propose that the role of a coplanar alignment of nucleobases induced by Swi5-Sfr1 in the presynaptic Rad51/ssDNA complex is to facilitate the critical matching with an invading double-stranded DNA, hence stimulating the strand exchange reaction.

  16. Effect of rocuronium on the level and mode of pre-synaptic acetylcholine release by facial and somatic nerves, and changes following facial nerve injury in rabbits.

    Science.gov (United States)

    Tan, Jinghua; Xu, Jing; Xing, Yian; Chen, Lianhua; Li, Shitong

    2015-01-01

    Muscles innervated by the facial nerve show differential sensitivities to muscle relaxants than muscles innervated by somatic nerves. The evoked electromyography (EEMG) response is also proportionally reduced after facial nerve injury. This forms the theoretical basis for proper utilization of muscle relaxants to balance EEMG monitoring and immobility under general anesthesia. (1) To observe the relationships between the level and mode of acetylcholine (ACh) release and the duration of facial nerve injury, and the influence of rocuronium in an in vitro rabbit model. (2) To explore the pre-synaptic mechanisms of discrepant responses to a muscle relaxant. Quantal and non-quantal ACh release were measured by using intracellular microelectrode recording in the orbicularis oris 1 to 42 days after graded facial nerve injury and in the gastrocnemius with/without rocuronium. Quantal ACh release was significantly decreased by rocuronium in the orbicularis oris and gastrocnemius, but significantly more so in gastrocnemius. Quantal release was reduced after facial nerve injury, which was significantly correlated with the severity of nerve injury in the absence but not in the presence of rocuronium. Non-quantal ACh release was reduced after facial nerve injury, with many relationships observed depending on the extent of the injury. The extent of inhibition of non-quantal release by rocuronium correlated with the grade of facial nerve injury. These findings may explain why EEMG amplitude might be diminished after acute facial nerve injury but relatively preserved after chronic injury and differential responses in sensitivity to rocuronium.

  17. Presynaptic muscarinic receptors, calcium channels, and protein kinase C modulate the functional disconnection of weak inputs at polyinnervated neonatal neuromuscular synapses.

    Science.gov (United States)

    Santafe, M M; Garcia, N; Lanuza, M A; Tomàs, M; Besalduch, N; Tomàs, J

    2009-04-01

    We studied the relation among calcium inflows, voltage-dependent calcium channels (VDCC), presynaptic muscarinic acetylcholine receptors (mAChRs), and protein kinase C (PKC) activity in the modulation of synapse elimination. We used intracellular recording to determine the synaptic efficacy in dually innervated endplates of the levator auris longus muscle of newborn rats during axonal competition in the postnatal synaptic elimination period. In these dual junctions, the weak nerve terminal was potentiated by partially reducing calcium entry (P/Q-, N-, or L-type VDCC-specific block or 500 muM magnesium ions), M1- or M4-type selective mAChR block, or PKC block. Moreover, reducing calcium entry or blocking PKC or mAChRs results in unmasking functionally silent nerve endings that now recover neurotransmitter release. Our results show interactions between these molecules and indicate that there is a release inhibition mechanism based on an mAChR-PKC-VDCC intracellular cascade. When it is fully active in certain weak motor axons, it can depress ACh release and even disconnect synapses. We suggest that this mechanism plays a central role in the elimination of redundant neonatal synapses, because functional axonal withdrawal can indeed be reversed by mAChRs, VDCCs, or PKC block.

  18. 7-[3-(4-[2,3-dimethylphenyl]piperazinyl)propoxy]-2 (1H)-quinolinone (OPC-4392), a presynaptic dopamine autoreceptor agonist and postsynaptic D2 receptor antagonist

    International Nuclear Information System (INIS)

    Yasuda, Y.; Kikuchi, T.; Suzuki, S.; Tsutsui, M.; Yamada, K.; Hiyama, T.

    1988-01-01

    The assertion that OPC-4392 acts as an agonist at presynaptic dopamine autoreceptors is supported by the following behavioral and biochemical observations: OPC-4392, 3-PPP and apomorphine inhibited the reserpine-induced increase in DOPA accumulation in the forebrain of mice and in the frontal cortex, limbic forebrain and striatum of rats. In addition, the gamma-butyrolactone (GBL)-induced increase in DOPA accumulation in the mouse forebrain was also inhibited by OPC-4392, 3-PPP and apomorphine. The inhibitory effect of OPC-4392 on GBL-induced DOPA accumulation lasted for at least 8 hours after oral administration to mice, while that of 3-PPP and apomorphine disappeared in 4 hours after subcutaneous injection. OPC-4392 failed to increase spontaneous motor activity in reserpinized mice, enhance spontaneous ipsilateral rotation in rats with unilateral striatal kainic acid (KA) lesions, induce contralateral rotation in rats with unilateral striatal 6-hydroxydopamine (6-OHDA) lesions and inhibit 14 C-acetylcholine (Ach) release stimulated by 20 mM KCl in rat striatal slices

  19. Monte Carlo simulation of laser beam propagation in a plane layer of the erythrocyte suspension: comparison of contributions from different scattering orders to the angular distribution of light intensity

    International Nuclear Information System (INIS)

    Kirillin, M Yu; Priezzhev, A V

    2002-01-01

    The scattering phase functions of light are obtained for a layer of the erythrocyte suspension by the Monte Carlo method. At the erythrocyte concentration corresponding to a whole blood, these functions substantially differ from the phase function of a single erythrocyte. Contributions from the low-order and multiple scattering to the light intensity measured at different angles are compared. It is shown that scattering of light from a suspension layer of thickness of about 100 μm to the forward half-plane is mainly determined by the low-order scattering (by snake photons), whereas scattering to the back half-plane is mainly determined by multiple scattering. The possibility of using the diffuse approximation for the theoretical description of scattering is analysed.

  20. The N- and C-terminal carbohydrate recognition domains of Haemonchus contortus galectin bind to distinct receptors of goat PBMC and contribute differently to its immunomodulatory functions in host-parasite interactions.

    Science.gov (United States)

    Lu, MingMin; Tian, XiaoWei; Yang, XinChao; Yuan, Cheng; Ehsan, Muhammad; Liu, XinChao; Yan, RuoFeng; Xu, LiXin; Song, XiaoKai; Li, XiangRui

    2017-09-05

    Hco-gal-m is a tandem-repeat galectin isolated from the adult worm of Haemonchus contortus. A growing body of studies have demonstrated that Hco-gal-m could exert its immunomodulatory effects on host peripheral blood mononuclear cells (PBMC) to facilitate the immune evasion. Our previous work revealed that C-terminal and N-terminal carbohydrate recognition domains (CRD) of Hco-gal-m had different sugar binding abilities. However, whether different domains of Hco-gal-m account differently for its multiple immunomodulatory functions in the host-parasite interaction remains to be elucidated. We found that the N-terminal CRD of Hco-gal-m (MNh) and the C-terminal CRD (MCh) could bind to goat peripheral blood mononuclear cells by distinct receptors: transmembrane protein 63A (TMEM63A) was a binding receptor of MNh, while transmembrane protein 147 (TMEM147) was a binding receptor of MCh. In addition, MCh was much more potent than MNh in inhibiting cell proliferation and inducing apoptosis, while MNh was much more effective in inhibiting NO production. Moreover, MNh could suppress the transcription of interferon-γ (IFN-γ), but MCh not. Our data suggested that these two CRDs of Hco-gal-m bind to distinct receptors and contributed differently<