Time-dependent potential-functional embedding theory

International Nuclear Information System (INIS)

Huang, Chen; Libisch, Florian; Peng, Qing; Carter, Emily A.

2014-01-01

We introduce a time-dependent potential-functional embedding theory (TD-PFET), in which atoms are grouped into subsystems. In TD-PFET, subsystems can be propagated by different suitable time-dependent quantum mechanical methods and their interactions can be treated in a seamless, first-principles manner. TD-PFET is formulated based on the time-dependent quantum mechanics variational principle. The action of the total quantum system is written as a functional of the time-dependent embedding potential, i.e., a potential-functional formulation. By exploiting the Runge-Gross theorem, we prove the uniqueness of the time-dependent embedding potential under the constraint that all subsystems share a common embedding potential. We derive the integral equation that such an embedding potential needs to satisfy. As proof-of-principle, we demonstrate TD-PFET for a Na 4 cluster, in which each Na atom is treated as one subsystem and propagated by time-dependent Kohn-Sham density functional theory (TDDFT) using the adiabatic local density approximation (ALDA). Our results agree well with a direct TDDFT calculation on the whole Na 4 cluster using ALDA. We envision that TD-PFET will ultimately be useful for studying ultrafast quantum dynamics in condensed matter, where key regions are solved by highly accurate time-dependent quantum mechanics methods, and unimportant regions are solved by faster, less accurate methods

Forskolin suppresses delayed-rectifier K+ currents and enhances spike frequency-dependent adaptation of sympathetic neurons.

Science.gov (United States)

Angel-Chavez, Luis I; Acosta-Gómez, Eduardo I; Morales-Avalos, Mario; Castro, Elena; Cruzblanca, Humberto

2015-01-01

In signal transduction research natural or synthetic molecules are commonly used to target a great variety of signaling proteins. For instance, forskolin, a diterpene activator of adenylate cyclase, has been widely used in cellular preparations to increase the intracellular cAMP level. However, it has been shown that forskolin directly inhibits some cloned K+ channels, which in excitable cells set up the resting membrane potential, the shape of action potential and regulate repetitive firing. Despite the growing evidence indicating that K+ channels are blocked by forskolin, there are no studies yet assessing the impact of this mechanism of action on neuron excitability and firing patterns. In sympathetic neurons, we find that forskolin and its derivative 1,9-Dideoxyforskolin, reversibly suppress the delayed rectifier K+ current (IKV). Besides, forskolin reduced the spike afterhyperpolarization and enhanced the spike frequency-dependent adaptation. Given that IKV is mostly generated by Kv2.1 channels, HEK-293 cells were transfected with cDNA encoding for the Kv2.1 α subunit, to characterize the mechanism of forskolin action. Both drugs reversible suppressed the Kv2.1-mediated K+ currents. Forskolin inhibited Kv2.1 currents and IKV with an IC50 of ~32 μM and ~24 µM, respectively. Besides, the drug induced an apparent current inactivation and slowed-down current deactivation. We suggest that forskolin reduces the excitability of sympathetic neurons by enhancing the spike frequency-dependent adaptation, partially through a direct block of their native Kv2.1 channels.

Calcium-Induced calcium release during action potential firing in developing inner hair cells.

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Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J

2015-03-10

In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights

Ionic channels underlying the ventricular action potential in zebrafish embryo.

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Alday, Aintzane; Alonso, Hiart; Gallego, Monica; Urrutia, Janire; Letamendia, Ainhoa; Callol, Carles; Casis, Oscar

2014-06-01

Over the last years zebrafish has become a popular model in the study of cardiac physiology, pathology and pharmacology. Recently, the application of the 3Rs regulation and the characteristics of the embryo have reduced the use of adult zebrafish use in many studies. However, the zebrafish embryo cardiac physiology is poorly characterized since most works have used indirect techniques and direct recordings of cardiac action potential and ionic currents are scarce. In order to optimize the zebrafish embryo model, we used electrophysiological, pharmacological and immunofluorescence tools to identify the characteristics and the ionic channels involved in the ventricular action potentials of zebrafish embryos. The application of Na(+) or T-type Ca(+2) channel blockers eliminated the cardiac electrical activity, indicating that the action potential upstroke depends on Na(+) and T-type Ca(+2) currents. The plateau phase depends on L-type Ca(+2) channels since it is abolished by specific blockade. The direct channel blockade indicates that the action potential repolarization and diastolic potential depends on ERG K(+) channels. The presence in the embryonic heart of the Nav1.5, Cav1.2, Cav3.2 and ERG channels was also confirmed by immunofluorescence, while the absence of effect of specific blockers and immunostaining indicate that two K(+) repolarizing currents present in human heart, Ito and IKs, are absent in the embryonic zebrafish heart. Our results describe the ionic channels present and its role in the zebrafish embryo heart and support the use of zebrafish embryos to study human diseases and their use for drug testing. Copyright © 2014 Elsevier Ltd. All rights reserved.

MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro

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F Woodward Hopf

2013-04-01

Full Text Available The MCH and dopamine receptor systems have been shown to modulate a number of behaviors related to reward processing, addiction, and neuropsychiatric conditions such as schizophrenia and depression. In addition, MCH and dopamine receptors can interact in a positive manner, for example in the expression of cocaine self-administration. A recent report (Chung et al., 2011a showed that the DA1/DA2 dopamine receptor activator apomorphine suppresses pre-pulse inhibition, a preclinical model for some aspects of schizophrenia. Importantly, MCH can enhance the effects of lower doses of apomorphine, suggesting that co-modulation of dopamine and MCH receptors might alleviate some symptoms of schizophrenia with a lower dose of dopamine receptor modulator and thus fewer potential side effects. Here, we investigated whether MCH and apomorphine could enhance action potential firing in vitro in the nucleus accumbens shell (NAshell, a region which has previously been shown to mediate some behavioral effects of MCH. Using whole-cell patch-clamp electrophysiology, we found that MCH, which has no effect on firing on its own, was able to increase NAshell firing when combined with a subthreshold dose of apomorphine. Further, this MCH/apomorphine increase in firing was prevented by an antagonist of either a DA1 or a DA2 receptor, suggesting that apomorphine acts through both receptor types to enhance NAshell firing. The MCH/apomorphine-mediated firing increase was also prevented by an MCH receptor antagonist or a PKA inhibitor. Taken together, our results suggest that MCH can interact with lower doses of apomorphine to enhance NAshell firing, and thus that MCH and apomorphine might interact in vivo within the NAshell to suppress pre-pulse inhibition.

Forskolin suppresses delayed-rectifier K+ currents and enhances spike frequency-dependent adaptation of sympathetic neurons.

Directory of Open Access Journals (Sweden)

Luis I Angel-Chavez

Full Text Available In signal transduction research natural or synthetic molecules are commonly used to target a great variety of signaling proteins. For instance, forskolin, a diterpene activator of adenylate cyclase, has been widely used in cellular preparations to increase the intracellular cAMP level. However, it has been shown that forskolin directly inhibits some cloned K+ channels, which in excitable cells set up the resting membrane potential, the shape of action potential and regulate repetitive firing. Despite the growing evidence indicating that K+ channels are blocked by forskolin, there are no studies yet assessing the impact of this mechanism of action on neuron excitability and firing patterns. In sympathetic neurons, we find that forskolin and its derivative 1,9-Dideoxyforskolin, reversibly suppress the delayed rectifier K+ current (IKV. Besides, forskolin reduced the spike afterhyperpolarization and enhanced the spike frequency-dependent adaptation. Given that IKV is mostly generated by Kv2.1 channels, HEK-293 cells were transfected with cDNA encoding for the Kv2.1 α subunit, to characterize the mechanism of forskolin action. Both drugs reversible suppressed the Kv2.1-mediated K+ currents. Forskolin inhibited Kv2.1 currents and IKV with an IC50 of ~32 μM and ~24 µM, respectively. Besides, the drug induced an apparent current inactivation and slowed-down current deactivation. We suggest that forskolin reduces the excitability of sympathetic neurons by enhancing the spike frequency-dependent adaptation, partially through a direct block of their native Kv2.1 channels.

The DBI action, higher-derivative supergravity, and flattening inflaton potentials

International Nuclear Information System (INIS)

Bielleman, Sjoerd; Ibáñez, Luis E.; Pedro, Francisco G.; Valenzuela, Irene; Wieck, Clemens

2016-01-01

In string theory compactifications it is common to find an effective Lagrangian for the scalar fields with a non-canonical kinetic term. We study the effective action of the scalar position moduli of Type II Dp-branes. In many instances the kinetic terms are in fact modified by a term proportional to the scalar potential itself. This can be linked to the appearance of higher-dimensional supersymmetric operators correcting the Kähler potential. We identify the supersymmetric dimension-eight operators describing the α"′ corrections captured by the D-brane Dirac-Born-Infeld action. Our analysis then allows an embedding of the D-brane moduli effective action into an N=1 supergravity formulation. The effects of the potential-dependent kinetic terms may be very important if one of the scalars is the inflaton, since they lead to a flattening of the scalar potential. We analyze this flattening effect in detail and compute its impact on the CMB observables for single-field inflation with monomial potentials.

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

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Erum Malik

2016-11-01

Full Text Available Antimicrobial peptides (AMPs are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms, and here we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic, although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure/function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations

Triangulation of the monophasic action potential causes flattening of the electrocardiographic T-wave

DEFF Research Database (Denmark)

Bhuiyan, Tanveer Ahmed; Graff, Claus; Thomsen, Morten Bækgaard

2012-01-01

of the action potential under the effect of the IKr blocker sertindole and associated these changes to concurrent changes in the morphology of electrocardiographic T-waves in dogs. We show that, under the effect of sertindole, the peak changes in the morphology of action potentials occur at time points similar......It has been proposed that triangulation on the cardiac action potential manifests as a broadened, more flat and notched T-wave on the ECG but to what extent such morphology characteristics are indicative of triangulation is more unclear. In this paper, we have analyzed the morphological changes...... to those observed for the peak changes in T-wave morphology on the ECG. We further show that the association between action potential shape and ECG shape is dose-dependent and most prominent at the time corresponding to phase 3 of the action potential....

Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties.

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Casale, Amanda E; Foust, Amanda J; Bal, Thierry; McCormick, David A

2015-11-25

The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca(2+)-activated K(+) channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons contain three main

Compound sensory action potential in normal and pathological human nerves

DEFF Research Database (Denmark)

Krarup, Christian

2004-01-01

The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocitie...... effort and attention to theory and practical detail that may be time consuming....

Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons.

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Battefeld, Arne; Tran, Baouyen T; Gavrilis, Jason; Cooper, Edward C; Kole, Maarten H P

2014-03-05

Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na(v)) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these K(v)7 channels and the functional impact of colocalization with Na(v) channels remain poorly understood. Here, we quantitatively examined K(v)7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. K(v)7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ~12 (proximal) to 150 pS μm(-2) (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by K(v)7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (~15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic K(v)7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal K(v)7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains K(v)7.2/7.3 channels were found to increase Na(v) channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, K(v)7 clustering near axonal Na(v) channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential.

Voltage Gated Calcium Channel Activation by Backpropagating Action Potentials Downregulates NMDAR Function

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Anne-Kathrin Theis

2018-04-01

Full Text Available The majority of excitatory synapses are located on dendritic spines of cortical glutamatergic neurons. In spines, compartmentalized Ca2+ signals transduce electrical activity into specific long-term biochemical and structural changes. Action potentials (APs propagate back into the dendritic tree and activate voltage gated Ca2+ channels (VGCCs. For spines, this global mode of spine Ca2+ signaling is a direct biochemical feedback of suprathreshold neuronal activity. We previously demonstrated that backpropagating action potentials (bAPs result in long-term enhancement of spine VGCCs. This activity-dependent VGCC plasticity results in a large interspine variability of VGCC Ca2+ influx. Here, we investigate how spine VGCCs affect glutamatergic synaptic transmission. We combined electrophysiology, two-photon Ca2+ imaging and two-photon glutamate uncaging in acute brain slices from rats. T- and R-type VGCCs were the dominant depolarization-associated Ca2+conductances in dendritic spines of excitatory layer 2 neurons and do not affect synaptic excitatory postsynaptic potentials (EPSPs measured at the soma. Using two-photon glutamate uncaging, we compared the properties of glutamatergic synapses of single spines that express different levels of VGCCs. While VGCCs contributed to EPSP mediated Ca2+ influx, the amount of EPSP mediated Ca2+ influx is not determined by spine VGCC expression. On a longer timescale, the activation of VGCCs by bAP bursts results in downregulation of spine NMDAR function.

[Patterns of action potential firing in cortical neurons of neonatal mice and their electrophysiological property].

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Furong, Liu; Shengtian, L I

2016-05-25

To investigate patterns of action potential firing in cortical heurons of neonatal mice and their electrophysiological properties. The passive and active membrane properties of cortical neurons from 3-d neonatal mice were observed by whole-cell patch clamp with different voltage and current mode. Three patterns of action potential firing were identified in response to depolarized current injection. The effects of action potential firing patterns on voltage-dependent inward and outward current were found. Neurons with three different firing patterns had different thresholds of depolarized current. In the morphology analysis of action potential, the three type neurons were different in rise time, duration, amplitude and threshold of the first action potential evoked by 80 pA current injection. The passive properties were similar in three patterns of action potential firing. These results indicate that newborn cortical neurons exhibit different patterns of action potential firing with different action potential parameters such as shape and threshold.

Computer Simulations Support a Morphological Contribution to BDNF Enhancement of Action Potential Generation

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Domenico F Galati

2016-09-01

Full Text Available Abstract Brain-derived neurotrophic factor (BDNF regulates both action potential (AP generation and neuron morphology. However, whether BDNF-induced changes in neuron morphology directly impact AP generation is unclear. We quantified BDNF’s effect on cultured cortical neuron morphological parameters and found that BDNF stimulates dendrite growth and addition of dendrites while increasing both excitatory and inhibitory presynaptic inputs in a spatially restricted manner. To gain insight into how these combined changes in neuron structure and synaptic input impact AP generation, we used the morphological parameters we gathered to generate computational models. Simulations suggest that BDNF-induced neuron morphologies generate more APs under a wide variety of conditions. Synapse and dendrite addition have the greatest impact on AP generation. However, subtle alterations in excitatory/inhibitory synapse ratio and strength have a significant impact on AP generation when synaptic activity is low. Consistent with these simulations, BDNF rapidly enhances spontaneous activity in cortical cultures. We propose that BDNF promotes neuron morphologies that are intrinsically more efficient at translating barrages of synaptic activity into APs, which is a previously unexplored aspect of BDNF’s function.

Erythropoietin enhances hippocampal long-term potentiation and memory

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El-Kordi Ahmed

2008-09-01

Full Text Available Abstract Background Erythropoietin (EPO improves cognition of human subjects in the clinical setting by as yet unknown mechanisms. We developed a mouse model of robust cognitive improvement by EPO to obtain the first clues of how EPO influences cognition, and how it may act on hippocampal neurons to modulate plasticity. Results We show here that a 3-week treatment of young mice with EPO enhances long-term potentiation (LTP, a cellular correlate of learning processes in the CA1 region of the hippocampus. This treatment concomitantly alters short-term synaptic plasticity and synaptic transmission, shifting the balance of excitatory and inhibitory activity. These effects are accompanied by an improvement of hippocampus dependent memory, persisting for 3 weeks after termination of EPO injections, and are independent of changes in hematocrit. Networks of EPO-treated primary hippocampal neurons develop lower overall spiking activity but enhanced bursting in discrete neuronal assemblies. At the level of developing single neurons, EPO treatment reduces the typical increase in excitatory synaptic transmission without changing the number of synaptic boutons, consistent with prolonged functional silencing of synapses. Conclusion We conclude that EPO improves hippocampus dependent memory by modulating plasticity, synaptic connectivity and activity of memory-related neuronal networks. These mechanisms of action of EPO have to be further exploited for treating neuropsychiatric diseases.

Just do it: action-dependent learning allows sensory prediction.

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Itai Novick

Full Text Available Sensory-motor learning is commonly considered as a mapping process, whereby sensory information is transformed into the motor commands that drive actions. However, this directional mapping, from inputs to outputs, is part of a loop; sensory stimuli cause actions and vice versa. Here, we explore whether actions affect the understanding of the sensory input that they cause. Using a visuo-motor task in humans, we demonstrate two types of learning-related behavioral effects. Stimulus-dependent effects reflect stimulus-response learning, while action-dependent effects reflect a distinct learning component, allowing the brain to predict the forthcoming sensory outcome of actions. Together, the stimulus-dependent and the action-dependent learning components allow the brain to construct a complete internal representation of the sensory-motor loop.

Enhanced coal-dependent methanogenesis coupled with algal biofuels: Potential water recycle and carbon capture

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Barnhart, Elliott P.; Davis, Katherine J.; Varonka, Matthew; Orem, William H.; Cunningham, Alfred B.; Ramsay, Bradley D.; Fields, Matthew W.

2017-01-01

Many coal beds contain microbial communities that can convert coal to natural gas (coalbed methane). Native microorganisms were obtained from Powder River Basin (PRB) coal seams with a diffusive microbial sampler placed downhole and used as an inoculum for enrichments with different nutrients to investigate microbially-enhanced coalbed methane production (MECoM). Coal-dependent methanogenesis more than doubled when yeast extract (YE) and several less complex components (proteins and amino acids) were added to the laboratory microcosms. Stimulated coal-dependent methanogenesis with peptone was 86% of that with YE while glutamate-stimulated activity was 65% of that with YE, and a vitamin mix had only 33% of the YE stimulated activity. For field application of MECoM, there is interest in identifying cost-effective alternatives to YE and other expensive nutrients. In laboratory studies, adding algal extract (AE) with lipids removed stimulated coal-dependent methanogenesis and the activity was 60% of that with YE at 27 d and almost 90% of YE activity at 1406 d. Analysis of British Thermal Unit (BTU) content of coal (a measure of potential energy yield) from long-term incubations indicated > 99.5% of BTU content remained after coalbed methane (CBM) stimulation with either AE or YE. Thus, the coal resource remains largely unchanged following stimulated microbial methane production. Algal CBM stimulation could lead to technologies that utilize coupled biological systems (photosynthesis and methane production) that sustainably enhance CBM production and generate algal biofuels while also sequestering carbon dioxide (CO2).

Active action potential propagation but not initiation in thalamic interneuron dendrites

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Casale, Amanda E.; McCormick, David A.

2012-01-01

Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033

Inducing repetitive action potential firing in neurons via synthesized photoresponsive nanoscale cellular prostheses.

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Lu, Siyuan; Madhukar, Anupam

2013-02-01

Recently we reported an analysis that examined the potential of synthesized photovoltaic functional abiotic nanosystems (PVFANs) to modulate membrane potential and activate action potential firing in neurons. Here we extend the analysis to delineate the requirements on the electronic energy levels and the attendant photophysical properties of the PVFANs to induce repetitive action potential under continuous light, a capability essential for the proposed potential application of PVFANs as retinal cellular prostheses to compensate for loss of photoreceptors. We find that repetitive action potential firing demands two basic characteristics in the electronic response of the PVFANs: an exponential dependence of the PVFAN excited state decay rate on the membrane potential and a three-state system such that, following photon absorption, the electron decay from the excited state to the ground state is via intermediate state(s) whose lifetime is comparable to the refractory time following an action potential. In this study, the potential of synthetic photovoltaic functional abiotic nanosystems (PVFANs) is examined under continuous light to modulate membrane potential and activate action potential firing in neurons with the proposed potential application of PVFANs as retinal cellular prostheses. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of Acetylcholine and Noradrenalin on Action Potentials of Isolated Rabbit Sinoatrial and Atrial Myocytes

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Verkerk, Arie O.; Geuzebroek, Guillaume S. C.; Veldkamp, Marieke W.; Wilders, Ronald

2012-01-01

The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh) and noradrenalin (NA) as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signaling proteins (RGS proteins) suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 μM ACh and 1 μM NA on the intrinsic action potentials of sinoatrial (SA) nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA, or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1–1000 nM, while a clear-cut frequency dependence in the range of 1–4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA, or a combination of both and may thus guide further experiments with RGS proteins. PMID:22754533

Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells.

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Szabó, László; Szentandrássy, Norbert; Kistamás, Kornél; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Horváth, Balázs; Magyar, János; Bányász, Tamás; Pál, Balázs; Nánási, Péter P

2013-03-01

Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3-30 μM) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations ≥3 μM blocked a variety of ion currents, including I(Ca), I(to), I(K1), I(Kr), and I(Ks). Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations.

TRH regulates action potential shape in cerebral cortex pyramidal neurons.

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

2014-07-07

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

Prolonged action potential duration in cardiac ablation of PDK1 mice.

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Han, Zhonglin; Jiang, Yu; Yang, Zhongzhou; Cao, Kejiang; Wang, Dao W

2015-01-01

The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis.

A Parametric Computational Model of the Action Potential of Pacemaker Cells.

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Ai, Weiwei; Patel, Nitish D; Roop, Partha S; Malik, Avinash; Andalam, Sidharta; Yip, Eugene; Allen, Nathan; Trew, Mark L

2018-01-01

A flexible, efficient, and verifiable pacemaker cell model is essential to the design of real-time virtual hearts that can be used for closed-loop validation of cardiac devices. A new parametric model of pacemaker action potential is developed to address this need. The action potential phases are modeled using hybrid automaton with one piecewise-linear continuous variable. The model can capture rate-dependent dynamics, such as action potential duration restitution, conduction velocity restitution, and overdrive suppression by incorporating nonlinear update functions. Simulated dynamics of the model compared well with previous models and clinical data. The results show that the parametric model can reproduce the electrophysiological dynamics of a variety of pacemaker cells, such as sinoatrial node, atrioventricular node, and the His-Purkinje system, under varying cardiac conditions. This is an important contribution toward closed-loop validation of cardiac devices using real-time heart models.

Simulation of action potential propagation in plants.

Science.gov (United States)

Sukhov, Vladimir; Nerush, Vladimir; Orlova, Lyubov; Vodeneev, Vladimir

2011-12-21

Action potential is considered to be one of the primary responses of a plant to action of various environmental factors. Understanding plant action potential propagation mechanisms requires experimental investigation and simulation; however, a detailed mathematical model of plant electrical signal transmission is absent. Here, the mathematical model of action potential propagation in plants has been worked out. The model is a two-dimensional system of excitable cells; each of them is electrically coupled with four neighboring ones. Ion diffusion between excitable cell apoplast areas is also taken into account. The action potential generation in a single cell has been described on the basis of our previous model. The model simulates active and passive signal transmission well enough. It has been used to analyze theoretically the influence of cell to cell electrical conductivity and H(+)-ATPase activity on the signal transmission in plants. An increase in cell to cell electrical conductivity has been shown to stimulate an increase in the length constant, the action potential propagation velocity and the temperature threshold, while the membrane potential threshold being weakly changed. The growth of H(+)-ATPase activity has been found to induce the increase of temperature and membrane potential thresholds and the reduction of the length constant and the action potential propagation velocity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Action Potential Dynamics in Fine Axons Probed with an Axonally Targeted Optical Voltage Sensor.

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Ma, Yihe; Bayguinov, Peter O; Jackson, Meyer B

2017-01-01

The complex and malleable conduction properties of axons determine how action potentials propagate through extensive axonal arbors to reach synaptic terminals. The excitability of axonal membranes plays a major role in neural circuit function, but because most axons are too thin for conventional electrical recording, their properties remain largely unexplored. To overcome this obstacle, we used a genetically encoded hybrid voltage sensor (hVOS) harboring an axonal targeting motif. Expressing this probe in transgenic mice enabled us to monitor voltage changes optically in two populations of axons in hippocampal slices, the large axons of dentate granule cells (mossy fibers) in the stratum lucidum of the CA3 region and the much finer axons of hilar mossy cells in the inner molecular layer of the dentate gyrus. Action potentials propagated with distinct velocities in each type of axon. Repetitive firing broadened action potentials in both populations, but at an intermediate frequency the degree of broadening differed. Repetitive firing also attenuated action potential amplitudes in both mossy cell and granule cell axons. These results indicate that the features of use-dependent action potential broadening, and possible failure, observed previously in large nerve terminals also appear in much finer unmyelinated axons. Subtle differences in the frequency dependences could influence the propagation of activity through different pathways to excite different populations of neurons. The axonally targeted hVOS probe used here opens up the diverse repertoire of neuronal processes to detailed biophysical study.

Warm Body Temperature Facilitates Energy Efficient Cortical Action Potentials

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Yu, Yuguo; Hill, Adam P.; McCormick, David A.

2012-01-01

The energy efficiency of neural signal transmission is important not only as a limiting factor in brain architecture, but it also influences the interpretation of functional brain imaging signals. Action potential generation in mammalian, versus invertebrate, axons is remarkably energy efficient. Here we demonstrate that this increase in energy efficiency is due largely to a warmer body temperature. Increases in temperature result in an exponential increase in energy efficiency for single action potentials by increasing the rate of Na+ channel inactivation, resulting in a marked reduction in overlap of the inward Na+, and outward K+, currents and a shortening of action potential duration. This increase in single spike efficiency is, however, counterbalanced by a temperature-dependent decrease in the amplitude and duration of the spike afterhyperpolarization, resulting in a nonlinear increase in the spike firing rate, particularly at temperatures above approximately 35°C. Interestingly, the total energy cost, as measured by the multiplication of total Na+ entry per spike and average firing rate in response to a constant input, reaches a global minimum between 37–42°C. Our results indicate that increases in temperature result in an unexpected increase in energy efficiency, especially near normal body temperature, thus allowing the brain to utilize an energy efficient neural code. PMID:22511855

Warm body temperature facilitates energy efficient cortical action potentials.

Directory of Open Access Journals (Sweden)

Yuguo Yu

Full Text Available The energy efficiency of neural signal transmission is important not only as a limiting factor in brain architecture, but it also influences the interpretation of functional brain imaging signals. Action potential generation in mammalian, versus invertebrate, axons is remarkably energy efficient. Here we demonstrate that this increase in energy efficiency is due largely to a warmer body temperature. Increases in temperature result in an exponential increase in energy efficiency for single action potentials by increasing the rate of Na(+ channel inactivation, resulting in a marked reduction in overlap of the inward Na(+, and outward K(+, currents and a shortening of action potential duration. This increase in single spike efficiency is, however, counterbalanced by a temperature-dependent decrease in the amplitude and duration of the spike afterhyperpolarization, resulting in a nonlinear increase in the spike firing rate, particularly at temperatures above approximately 35°C. Interestingly, the total energy cost, as measured by the multiplication of total Na(+ entry per spike and average firing rate in response to a constant input, reaches a global minimum between 37-42°C. Our results indicate that increases in temperature result in an unexpected increase in energy efficiency, especially near normal body temperature, thus allowing the brain to utilize an energy efficient neural code.

Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

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Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

2012-10-25

Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in

Phytoestrogens Enhance the Vascular Actions of the Endocannabinoid Anandamide in Mesenteric Beds of Female Rats

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Roxana N. Peroni

2012-01-01

Full Text Available In rat isolated mesenteric beds that were contracted with NA as an in vitro model of the vascular adrenergic hyperactivity that usually precedes the onset of primary hypertension, the oral administration (3 daily doses of either 10 mg/kg genistein or 20 mg/kg daidzein potentiated the anandamide-induced reduction of contractility to NA in female but not in male rats. Oral treatment with phytoestrogens also restored the vascular effects of anandamide as well as the mesenteric content of calcitonin gene-related peptide (CGRP that were reduced after ovariectomy. The enhancement of anandamide effects caused by phytoestrogens was prevented by the concomitant administration of the estrogen receptor antagonist fulvestrant (2.5 mg/kg, s.c., 3 daily doses. It is concluded that, in the vasculature of female rats, phytoestrogens produced an estrogen-receptor-dependent enhancement of the anandamide-vascular actions that involves the modulation of CGRP levels and appears to be relevant whenever an adrenergic hyperactivity occurs.

Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location.

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Crago, Patrick E; Makowski, Nathaniel S

2014-10-01

Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic interventions involving motor or sensory stimulation.

Channel sialic acids limit hERG channel activity during the ventricular action potential.

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Norring, Sarah A; Ednie, Andrew R; Schwetz, Tara A; Du, Dongping; Yang, Hui; Bennett, Eric S

2013-02-01

Activity of human ether-a-go-go-related gene (hERG) 1 voltage-gated K(+) channels is responsible for portions of phase 2 and phase 3 repolarization of the human ventricular action potential. Here, we questioned whether and how physiologically and pathophysiologically relevant changes in surface N-glycosylation modified hERG channel function. Voltage-dependent hERG channel gating and activity were evaluated as expressed in a set of Chinese hamster ovary (CHO) cell lines under conditions of full glycosylation, no sialylation, no complex N-glycans, and following enzymatic deglycosylation of surface N-glycans. For each condition of reduced glycosylation, hERG channel steady-state activation and inactivation relationships were shifted linearly by significant depolarizing ∼9 and ∼18 mV, respectively. The hERG window current increased significantly by 50-150%, and the peak shifted by a depolarizing ∼10 mV. There was no significant change in maximum hERG current density. Deglycosylated channels were significantly more active (20-80%) than glycosylated controls during phases 2 and 3 of action potential clamp protocols. Simulations of hERG current and ventricular action potentials corroborated experimental data and predicted reduced sialylation leads to a 50-70-ms decrease in action potential duration. The data describe a novel mechanism by which hERG channel gating is modulated through physiologically and pathophysiologically relevant changes in N-glycosylation; reduced channel sialylation increases hERG channel activity during the action potential, thereby increasing the rate of action potential repolarization.

Cardiac action potential repolarization revisited: early repolarization shows all-or-none behaviour.

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Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Noble, Denis; Giles, Wayne

2017-11-01

In healthy mammalian hearts the action potential (AP) waveform initiates and modulates each contraction, or heartbeat. As a result, AP height and duration are key physiological variables. In addition, rate-dependent changes in ventricular AP duration (APD), and variations in APD at a fixed heart rate are both reliable biomarkers of electrophysiological stability. Present guidelines for the likelihood that candidate drugs will increase arrhythmias rely on small changes in APD and Q-T intervals as criteria for safety pharmacology decisions. However, both of these measurements correspond to the final repolarization of the AP. Emerging clinical evidence draws attention to the early repolarization phase of the action potential (and the J-wave of the ECG) as an additional important biomarker for arrhythmogenesis. Here we provide a mechanistic background to this early repolarization syndrome by summarizing the evidence that both the initial depolarization and repolarization phases of the cardiac action potential can exhibit distinct time- and voltage-dependent thresholds, and also demonstrating that both can show regenerative all-or-none behaviour. An important consequence of this is that not all of the dynamics of action potential repolarization in human ventricle can be captured by data from single myocytes when these results are expressed as 'repolarization reserve'. For example, the complex pattern of cell-to-cell current flow that is responsible for AP conduction (propagation) within the mammalian myocardium can change APD and the Q-T interval of the electrocardiogram alter APD stability, and modulate responsiveness to pharmacological agents (such as Class III anti-arrhythmic drugs). © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Modulatory action of acetylcholine on the Na+-dependent action potentials in Kenyon cells isolated from the mushroom body of the cricket brain.

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Terazima, E; Yoshino, M

2010-12-01

Kenyon cells, intrinsic neurons of the insect mushroom body, have been assumed to be a site of conditioning stimulus (CS) and unconditioned stimulus (US) association in olfactory learning and memory. Acetylcholine (ACh) has been implicated to be a neurotransmitter mediating CS reception in Kenyon cells, causing rapid membrane depolarization via nicotinic ACh receptors. However, the long-term effects of ACh on the membrane excitability of Kenyon cells are not fully understood. In this study, we examined the effects of ACh on Na(+) dependent action potentials (Na(+) spikes) elicited by depolarizing current injection and on net membrane currents under the voltage clamp condition in Kenyon cells isolated from the mushroom body of the cricket Gryllus bimaculatus. Current-clamp studies using amphotericin B perforated-patch recordings showed that freshly dispersed cricket Kenyon cells could produce repetitive Na(+) spikes in response to prolonged depolarizing current injection. Bath application of ACh increased both the instantaneous frequency and the amplitudes of Na(+) spikes. This excitatory action of ACh on Kenyon cells is attenuated by the pre-treatment of the cells with the muscarinic receptor antagonists, atropine and scopolamine, but not by the nicotinic receptor antagonist mecamylamine. Voltage-clamp studies further showed that bath application of ACh caused an increase in net inward currents that are sensitive to TTX, whereas outward currents were decreased by this treatment. These results indicate that in order to mediate CS, ACh may modulate the firing properties of Na(+) spikes of Kenyon cells through muscarinic receptor activation, thus increasing Na conductance and decreasing K conductance. Copyright © 2010 Elsevier Ltd. All rights reserved.

RXP-E: a connexin43-binding peptide that prevents action potential propagation block

DEFF Research Database (Denmark)

Lewandowski, Rebecca; Procida, Kristina; Vaidyanathan, Ravi

2008-01-01

. Separately, RXP-E was concatenated to a cytoplasmic transduction peptide (CTP) for cytoplasmic translocation (CTP-RXP-E). The effect of RXP-E on action potential propagation was assessed by high-resolution optical mapping in monolayers of neonatal rat ventricular myocytes, containing approximately 20......% of randomly distributed myofibroblasts. In contrast to control experiments, when heptanol (2 mmol/L) was added to the superfusate of monolayers loaded with CTP-RXP-E, action potential propagation was maintained, albeit at a slower velocity. Similarly, intracellular acidification (pH(i) 6.2) caused a loss...... of action potential propagation in control monolayers; however, propagation was maintained in CTP-RXP-E-treated cells, although at a slower rate. Patch-clamp experiments revealed that RXP-E did not prevent heptanol-induced block of sodium currents, nor did it alter voltage dependence or amplitude of Kir2...

Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo.

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Tallarida, Christopher S; Egan, Erin; Alejo, Gissel D; Raffa, Robert; Tallarida, Ronald J; Rawls, Scott M

2014-04-01

Levamisole is estimated by the Drug Enforcement Agency (DEA) to be present in about 80% of cocaine seized in the United States and linked to debilitating, and sometimes fatal, immunologic effects in cocaine abusers. One explanation for the addition of levamisole to cocaine is that it increases the amount of product and enhances profits. An alternative possibility, and one investigated here, is that levamisole alters cocaine's action in vivo. We specifically investigated effects of levamisole on cocaine's stereotypical and place-conditioning effects in an established invertebrate (planarian) assay. Acute exposure to levamisole or cocaine produced concentration-dependent increases in stereotyped movements. For combined administration of the two agents, isobolographic analysis revealed that the observed stereotypical response was enhanced relative to the predicted effect, indicating synergism for the interaction. In conditioned place preference (CPP) experiments, cocaine produced a significant preference shift; in contrast, levamisole was ineffective at all concentrations tested. For combination experiments, a submaximal concentration of cocaine produced CPP that was enhanced by inactive concentrations of levamisole, indicating synergism. The present results provide the first experimental evidence that levamisole enhances cocaine's action in vivo. Most important is the identification of synergism for the levamisole/cocaine interaction, which now requires further study in mammals. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Optimization and Prognosis of Cell Radiosensitivity Enhancement in vitro and in vivo after Sequential Thermoradiactive Action].

Science.gov (United States)

Belkina, S V; Petin, V G

2016-01-01

Previously developed mathematical model of simultaneous action of two inactivating agents has been adapted and tested to describe the results of sequential action. The possibility of applying the mathematical model to the interpretation and prognosis of the increase in radio-sensitivity of tumor cells as well as mammalian cells after sequential action of two high temperatures or hyperthermia and ionizing radiation is analyzed. The model predicts the value of the thermal enhancement ratio depending on the duration of thermal exposure, its greatest value, and the condition under which it is achieved.

Time-Dependent Risk Estimation and Cost-Benefit Analysis for Mitigation Actions

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van Stiphout, T.; Wiemer, S.; Marzocchi, W.

2009-04-01

Earthquakes strongly cluster in space and time. Consequently, the most dangerous time is right after a moderate earthquake has happened, because their is a ‘high' (i.e., 2-5 percent) probability that this event will be followed by a subsequent aftershock which happens to be as large or larger than the initiating event. The seismic hazard during this time-period exceeds the background probability significantly and by several orders of magnitude. Scientists have developed increasingly accurate forecast models that model this time-dependent hazard, and such models are currently being validated in prospective testing. However, this probabilistic information in the hazard space is difficult to digest for decision makers, the media and general public. Here, we introduce a possible bridge between seismology and decision makers (authorities, civil defense) by proposing a more objective way to estimate time-dependent risk assessment. Short Term Earthquake Risk assessment (STEER) combines aftershock hazard and loss assessments. We use site-specific information on site effects and building class distribution and combine this with existing loss models to compute site specific time-dependent risk curves (probability of exceedance for fatalities, injuries, damages etc). We show the effect of uncertainties in the different components using Monte Carlo Simulations of the input parameters. This time-dependent risk curves can act as a decision support. We extend the STEER approach by introducing a Cost-Benefit approach for certain mitigation actions after a medium-sized earthquake. Such Cost-Benefit approaches have been recently developed for volcanic risk assessment to rationalize precautionary evacuations in densely inhabitated areas threatened by volcanoes. Here we extend the concept to time-dependent probabilistic seismic risk assessment. For the Cost-Benefit analysis of mitigation actions we calculate the ratio between the cost for the mitigation actions and the cost of the

Compound sensory action potential in normal and pathological human nerves

DEFF Research Database (Denmark)

Krarup, Christian

2004-01-01

The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocities...... dispersion over increasing conduction distance is greater for the SNAP than CMAP, and demonstration of conduction block is therefore difficult. In addition, the effect of temporal dispersion on amplitude and shape is strongly dependent on the number of conducting fibers and their distribution, and......, with fiber loss or increased conduction velocity variability changes of the SNAP may be smaller than expected from normal nerve. The biophysical characteristics of sensory and motor fibers differ, and this may to some extent determine divergent pathophysiological changes in sensory and motor fibers...

Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

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Yang, Li-Zhen; Zhu, Yi-Chun

2015-07-05

We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation. Copyright © 2015 Elsevier B.V. All rights reserved.

Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells

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Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, PP

2012-01-01

BACKGROUND AND PURPOSE Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca2+ current (ICa), slow delayed rectifier K+ current (IKs) and fast delayed rectifier K+ current (IKr) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTAL APPROACH Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEY RESULTS In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the IKr blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the IKs blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the ICa blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating ICa followed by a rise in IKs, both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of IKs– but not IKr– may be responsible for the observed shortening of action potentials. PMID:22563726

Action potential bursts in central snail neurons elicited by paeonol: roles of ionic currents

Science.gov (United States)

Chen, Yi-hung; Lin, Pei-lin; Hsu, Hui-yu; Wu, Ya-ting; Yang, Han-yin; Lu, Dah-yuu; Huang, Shiang-suo; Hsieh, Ching-liang; Lin, Jaung-geng

2010-01-01

Aim: To investigate the effects of 2′-hydroxy-4′-methoxyacetophenone (paeonol) on the electrophysiological behavior of a central neuron (right parietal 4; RP4) of the giant African snail (Achatina fulica Ferussac). Methods: Intracellular recordings and the two-electrode voltage clamp method were used to study the effects of paeonol on the RP4 neuron. Results: The RP4 neuron generated spontaneous action potentials. Bath application of paeonol at a concentration of ≥500 μmol/L reversibly elicited action potential bursts in a concentration-dependent manner. Immersing the neurons in Co2+-substituted Ca2+-free solution did not block paeonol-elicited bursting. Pretreatment with the protein kinase A (PKA) inhibitor KT-5720 or the protein kinase C (PKC) inhibitor Ro 31-8220 did not affect the action potential bursts. Voltage-clamp studies revealed that paeonol at a concentration of 500 μmol/L had no remarkable effects on the total inward currents, whereas paeonol decreased the delayed rectifying K+ current (IKD) and the fast-inactivating K+ current (IA). Application of 4-aminopyridine (4-AP 5 mmol/L), an inhibitor of IA, or charybdotoxin 250 nmol/L, an inhibitor of the Ca2+-activated K+ current (IK(Ca)), failed to elicit action potential bursts, whereas tetraethylammonium chloride (TEA 50 mmol/L), an IKD blocker, successfully elicited action potential bursts. At a lower concentration of 5 mmol/L, TEA facilitated the induction of action potential bursts elicited by paeonol. Conclusion: Paeonol elicited a bursting firing pattern of action potentials in the RP4 neuron and this activity relates closely to the inhibitory effects of paeonol on the IKD. PMID:21042287

Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons.

Science.gov (United States)

Kimm, Tilia; Khaliq, Zayd M; Bean, Bruce P

2015-12-16

Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency-current (f-I) relationship, whereas BK channel inhibition had little effect on the f-I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f-I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra pars compacta. Although both

Screening action potentials: The power of light

Directory of Open Access Journals (Sweden)

Lars eKaestner

2011-07-01

Full Text Available Action potentials reflect the concerted activity of all electrogenic constituents in the plasma membrane during the excitation of a cell. Therefore, the action potential is an integrated readout and a promising parameter to detect electrophysiological failures or modifications thereof in diagnosis as well as in drug screens. Cellular action potentials can be recorded by optical approaches. To fulfill the pre-requirements to scale up for e.g. pharmacological screens the following preparatory work has to be provided: (i model cells under investigation need to represent target cells in the best possible manner; (ii optical sensors that can be either small molecule dyes or genetically encoded potential probes need to provide a reliable readout with minimal interaction with the naive behavior of the cells and (iii devices need to be capable to stimulate the cells, read out the signals with the appropriate speed as well as provide the capacity for a sufficient throughput. Here we discuss several scenarios for all three categories in the field of cardiac physiology and pharmacology and provide a perspective to use the power of light in screening cardiac action potentials.

Monophasic action potentials and activation recovery intervals as measures of ventricular action potential duration: experimental evidence to resolve some controversies

NARCIS (Netherlands)

Coronel, Ruben; de Bakker, Jacques M. T.; Wilms-Schopman, Francien J. G.; Opthof, Tobias; Linnenbank, André C.; Belterman, Charly N.; Janse, Michiel J.

2006-01-01

BACKGROUND: Activation recovery intervals (ARIs) and monophasic action potential (MAP) duration are used as measures of action potential duration in beating hearts. However, controversies exist concerning the correct way to record MAPs or calculate ARIs. We have addressed these issues

The monophasic action potential upstroke: a means of characterizing local conduction.

Science.gov (United States)

Levine, J H; Moore, E N; Kadish, A H; Guarnieri, T; Spear, J F

1986-11-01

The upstrokes of monophasic action potentials (MAPs) recorded with an extracellular pressure electrode were characterized in isolated canine tissue preparations in vitro. The characteristics of the MAP upstroke were compared with those of the local action potential foot as well as with the characteristics of approaching electrical activation during uniform and asynchronous conduction. The upstroke of the MAP was exponential during uniform conduction. The time constant of rise of the MAP upstroke (TMAP) correlated with that of the action potential foot (Tfoot): TMAP + 1.01 Tfoot + 0.50; r2 = .80. Furthermore, changes in Tfoot with alterations in cycle length were associated with similar changes in TMAP: Tfoot = 1.06 TMAP - 0.11; r2 = .78. In addition, TMAP and Tfoot both deviated from exponential during asynchronous activation; the inflections that developed in the MAP upstroke correlated in time with intracellular action potential upstrokes that were asynchronous in onset in these tissues. Finally, the field of view of the MAP was determined and was found to be dependent in part on tissue architecture and the space constant. Specifically, the field of view of the MAP was found to be greater parallel compared with transverse to fiber orientation (6.02 +/- 1.74 vs 3.03 +/- 1.10 mm; p less than .01). These data suggest that the MAP upstroke may be used to define and characterize local electrical activation. The relatively large field of view of the MAP suggests that this technique may be a sensitive means to record focal membrane phenomena in vivo.

Modelling in vivo action potential propagation along a giant axon.

Science.gov (United States)

George, Stuart; Foster, Jamie M; Richardson, Giles

2015-01-01

A partial differential equation model for the three-dimensional current flow in an excitable, unmyelinated axon is considered. Where the axon radius is significantly below a critical value R(crit) (that depends upon intra- and extra-cellular conductivity and ion channel conductance) the resistance of the intracellular space is significantly higher than that of the extracellular space, such that the potential outside the axon is uniformly small whilst the intracellular potential is approximated by the transmembrane potential. In turn, since the current flow is predominantly axial, it can be shown that the transmembrane potential is approximated by a solution to the one-dimensional cable equation. It is noted that the radius of the squid giant axon, investigated by (Hodgkin and Huxley 1952e), lies close to R(crit). This motivates us to apply the three-dimensional model to the squid giant axon and compare the results thus found to those obtained using the cable equation. In the context of the in vitro experiments conducted in (Hodgkin and Huxley 1952e) we find only a small difference between the wave profiles determined using these two different approaches and little difference between the speeds of action potential propagation predicted. This suggests that the cable equation approximation is accurate in this scenario. However when applied to the it in vivo setting, in which the conductivity of the surrounding tissue is considerably lower than that of the axoplasm, there are marked differences in both wave profile and speed of action potential propagation calculated using the two approaches. In particular, the cable equation significantly over predicts the increase in the velocity of propagation as axon radius increases. The consequences of these results are discussed in terms of the evolutionary costs associated with increasing the speed of action potential propagation by increasing axon radius.

ICRF enhanced potentials

International Nuclear Information System (INIS)

Nelson, B.A.

1987-01-01

Ion-confining potentials in the Phaedrus tandem mirror are shown to be enhanced over Boltzmann-relations predicted values by radio-frequency (rf) waves in the ion cyclotron range of frequencies (ICRF). The ICRF enhanced potential is larger in the end cell with a lower passing density. Peak potential values decrease with increasing ion endloss current (or central cell density) for a constant rf capacitor bank voltage, and increase with increasing rf-capacitor bank voltage, for a constant ion endloss value (or central cell density). In fully axisymmetric operation, a potential peak is produced in an end cell by the central-cell rf, (with-out end-cell rf) and is found only in the end cell nearer the central-cell antenna. ICRF enhanced potentials are explained as an equilibrium between the electron-collisional filling-in rate and the electron pumping out rate provided by axial time-varying electric fields. Thermal barrier-like potential structures were found in the transition regions between the central cell and end cells, in the fully axisymmetric Phaedrus. Central-cell ICRF trapping effects combined with end-cell μΔ B forces create and pump the barrier potential wells

Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats.

Science.gov (United States)

Hardy, Matthew E L; Pervolaraki, Eleftheria; Bernus, Olivier; White, Ed

2018-01-01

We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na + -channel blocker (5 μM) ranolazine or the intracellular Ca 2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus

Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory

Science.gov (United States)

Maher, Pamela; Akaishi, Tatsuhiro; Abe, Kazuho

2006-01-01

Small molecules that activate signaling pathways used by neurotrophic factors could be useful for treating CNS disorders. Here we show that the flavonoid fisetin activates ERK and induces cAMP response element-binding protein (CREB) phosphorylation in rat hippocampal slices, facilitates long-term potentiation in rat hippocampal slices, and enhances object recognition in mice. Together, these data demonstrate that the natural product fisetin can facilitate long-term memory, and therefore it may be useful for treating patients with memory disorders. PMID:17050681

Nerve growth factor enhances cough via a central mechanism of action.

Science.gov (United States)

El-Hashim, Ahmed Z; Jaffal, Sahar M; Al-Rashidi, Fatma T; Luqmani, Yunus A; Akhtar, Saghir

2013-08-01

The mechanisms involved in enhanced cough induced by central and inhaled NGF in guinea pigs were investigated. Cough and airway function were assessed by plethysmography following inhaled or intracerebroventricular (i.c.v.) NGF treatment. Expression of TrkA and/or TRPV1 was determined in bronchi and/or brainstem by real-time PCR and immunoblotting. I.c.v. and inhaled NGF enhanced citric acid induced-cough and airway obstruction. Pretreatment (i.c.v.) with antagonists of TrkA (K252a) or TRPV1 (IRTX) significantly reduced both the NGF (i.c.v.) enhanced cough and airway obstruction whereas the NK1 antagonist (FK888) inhibited only cough. The H1 antagonist (cetirizine) did not affect either. Inhaled NGF increased phosphorylation of TrkA receptors in the bronchi but not the brainstem at 0.5h post-treatment. TrkA mRNA was elevated at 0.5h in the bronchi and at 24h in the brainstem while TRPV1 mRNA was elevated from 0.5h to 24h in brainstem and at 24h in the bronchi. Pretreatment (i.c.v.) with IRTX, but not K252a, significantly inhibited the inhaled NGF-enhanced cough. Central NGF administration enhances cough and airway obstruction by mechanisms dependent on central activation of TrkA, TRPV1 and NK1 receptors while inhaled NGF enhances cough via a mechanism dependent on central TRPV1 and not TrkA receptors. These data show that NGF, in addition to its effects on the airways, has an important central mechanism of action in the enhancement of cough. Therefore, therapeutic strategies targeting NGF signaling in both the airways and CNS may be more effective in the management of cough. Copyright © 2013 Elsevier Ltd. All rights reserved.

Optical mapping of optogenetically shaped cardiac action potentials

Science.gov (United States)

Park, Sarah A.; Lee, Shin-Rong; Tung, Leslie; Yue, David T.

2014-01-01

Light-mediated silencing and stimulation of cardiac excitability, an important complement to electrical stimulation, promises important discoveries and therapies. To date, cardiac optogenetics has been studied with patch-clamp, multielectrode arrays, video microscopy, and an all-optical system measuring calcium transients. The future lies in achieving simultaneous optical acquisition of excitability signals and optogenetic control, both with high spatio-temporal resolution. Here, we make progress by combining optical mapping of action potentials with concurrent activation of channelrhodopsin-2 (ChR2) or halorhodopsin (eNpHR3.0), via an all-optical system applied to monolayers of neonatal rat ventricular myocytes (NRVM). Additionally, we explore the capability of ChR2 and eNpHR3.0 to shape action-potential waveforms, potentially aiding the study of short/long QT syndromes that result from abnormal changes in action potential duration (APD). These results show the promise of an all-optical system to acquire action potentials with precise temporal optogenetics control, achieving a long-sought flexibility beyond the means of conventional electrical stimulation. PMID:25135113

Is action potential threshold lowest in the axon?

NARCIS (Netherlands)

Kole, Maarten H. P.; Stuart, Greg J.

2008-01-01

Action potential threshold is thought to be lowest in the axon, but when measured using conventional techniques, we found that action potential voltage threshold of rat cortical pyramidal neurons was higher in the axon than at other neuronal locations. In contrast, both current threshold and voltage

The in vivo mechanism of action of CD20 monoclonal antibodies depends on local tumor burden

Science.gov (United States)

Boross, Peter; Jansen, J.H. Marco; de Haij, Simone; Beurskens, Frank J.; van der Poel, Cees E.; Bevaart, Lisette; Nederend, Maaike; Golay, Josée; van de Winkel, Jan G.J.; Parren, Paul W.H.I.; Leusen, Jeanette H.W.

2011-01-01

Background CD20 monoclonal antibodies are widely used in clinical practice. Antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and direct cell death have been suggested to be important effector functions for CD20 antibodies. However, their specific contributions to the in vivo mechanism of action of CD20 immunotherapy have not been well defined. Design and Methods Here we studied the in vivo mechanism of action of type I (rituximab and ofatumumab) and type II (HuMab-11B8) CD20 antibodies in a peritoneal, syngeneic, mouse model with EL4-CD20 cells using low and high tumor burden. Results Interestingly, we observed striking differences in the in vivo mechanism of action of CD20 antibodies dependent on tumor load. In conditions of low tumor burden, complement was sufficient for tumor killing both for type I and type II CD20 antibodies. In contrast, in conditions of high tumor burden, activating FcγR (specifically FcγRIII), active complement and complement receptor 3 were all essential for tumor killing. Our data suggest that complement-enhanced antibody-dependent cellular cytotoxicity may critically affect tumor killing by CD20 antibodies in vivo. The type II CD20 antibody 11B8, which is a poor inducer of complement activation, was ineffective against high tumor burden. Conclusions Tumor burden affects the in vivo mechanism of action of CD20 antibodies. Low tumor load can be eliminated by complement alone, whereas elimination of high tumor load requires multiple effector mechanisms. PMID:21880632

Action potential propagation: ion current or intramembrane electric field?

Science.gov (United States)

Martí, Albert; Pérez, Juan J; Madrenas, Jordi

2018-01-01

The established action potential propagation mechanisms do not satisfactorily explain propagation on myelinated axons given the current knowledge of biological channels and membranes. The flow across ion channels presents two possible effects: the electric potential variations across the lipid bilayers (action potential) and the propagation of an electric field through the membrane inner part. The proposed mechanism is based on intra-membrane electric field propagation, this propagation can explain the action potential saltatory propagation and its constant delay independent of distance between Ranvier nodes in myelinated axons.

Length dependence of staircase potentiation: interactions with caffeine and dantrolene sodium.

Science.gov (United States)

Rassier, D E; MacIntosh, B R

2000-04-01

In skeletal muscle, there is a length dependence of staircase potentiation for which the mechanism is unclear. In this study we tested the hypothesis that abolition of this length dependence by caffeine is effected by a mechanism independent of enhanced Ca2+ release. To test this hypothesis we have used caffeine, which abolishes length dependence of potentiation, and dantrolene sodium, which inhibits Ca2+ release. In situ isometric twitch contractions of rat gastrocnemius muscle before and after 20 s of repetitive stimulation at 5 Hz were analyzed at optimal length (Lo), Lo - 10%, and Lo + 10%. Potentiation was observed to be length dependent, with an increase in developed tension (DT) of 78 +/- 12, 51 +/- 5, and 34 +/- 9% (mean +/- SEM), at Lo - 10%, Lo, and Lo + 10%, respectively. Caffeine diminished the length dependence of activation and suppressed the length dependence of staircase potentiation, giving increases in DT of 65+/-13, 53 +/- 11, and 45 +/- 12% for Lo - 10%, Lo, and Lo + 10%, respectively. Dantrolene administered after caffeine did not reverse this effect. Dantrolene alone depressed the potentiation response, but did not affect the length dependence of staircase potentiation, with increases in DT of 58 +/- 17, 26 +/- 8, and 18 +/- 7%, respectively. This study confirms that there is a length dependence of staircase potentiation in mammalian skeletal muscle which is suppressed by caffeine. Since dantrolene did not alter this suppression of the length dependence of potentiation by caffeine, it is apparently not directly modulated by Ca2+ availability in the myoplasm.

ACTION-SPACE CLUSTERING OF TIDAL STREAMS TO INFER THE GALACTIC POTENTIAL

Energy Technology Data Exchange (ETDEWEB)

Sanderson, Robyn E.; Helmi, Amina [Kapteyn Astronomical Institute, P.O. Box 800, 9700 AV Groningen (Netherlands); Hogg, David W., E-mail: robyn@astro.columbia.edu [Center for Cosmology and Particle Physics, Department of Physics, New York University, 4 Washington Place, New York, NY 10003 (United States)

2015-03-10

We present a new method for constraining the Milky Way halo gravitational potential by simultaneously fitting multiple tidal streams. This method requires three-dimensional positions and velocities for all stars to be fit, but does not require identification of any specific stream or determination of stream membership for any star. We exploit the principle that the action distribution of stream stars is most clustered when the potential used to calculate the actions is closest to the true potential. Clustering is quantified with the Kullback-Leibler Divergence (KLD), which also provides conditional uncertainties for our parameter estimates. We show, for toy Gaia-like data in a spherical isochrone potential, that maximizing the KLD of the action distribution relative to a smoother distribution recovers the input potential. The precision depends on the observational errors and number of streams; using K III giants as tracers, we measure the enclosed mass at the average radius of the sample stars accurate to 3% and precise to 20%-40%. Recovery of the scale radius is precise to 25%, biased 50% high by the small galactocentric distance range of stars in our mock sample (1-25 kpc, or about three scale radii, with mean 6.5 kpc). 20-25 streams with at least 100 stars each are required for a stable confidence interval. With radial velocities (RVs) to 100 kpc, all parameters are determined with ∼10% accuracy and 20% precision (1.3% accuracy for the enclosed mass), underlining the need to complete the RV catalog for faint halo stars observed by Gaia.

Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.

Science.gov (United States)

Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P

2012-10-01

Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Quadratic adaptive algorithm for solving cardiac action potential models.

Science.gov (United States)

Chen, Min-Hung; Chen, Po-Yuan; Luo, Ching-Hsing

2016-10-01

An adaptive integration method is proposed for computing cardiac action potential models accurately and efficiently. Time steps are adaptively chosen by solving a quadratic formula involving the first and second derivatives of the membrane action potential. To improve the numerical accuracy, we devise an extremum-locator (el) function to predict the local extremum when approaching the peak amplitude of the action potential. In addition, the time step restriction (tsr) technique is designed to limit the increase in time steps, and thus prevent the membrane potential from changing abruptly. The performance of the proposed method is tested using the Luo-Rudy phase 1 (LR1), dynamic (LR2), and human O'Hara-Rudy dynamic (ORd) ventricular action potential models, and the Courtemanche atrial model incorporating a Markov sodium channel model. Numerical experiments demonstrate that the action potential generated using the proposed method is more accurate than that using the traditional Hybrid method, especially near the peak region. The traditional Hybrid method may choose large time steps near to the peak region, and sometimes causes the action potential to become distorted. In contrast, the proposed new method chooses very fine time steps in the peak region, but large time steps in the smooth region, and the profiles are smoother and closer to the reference solution. In the test on the stiff Markov ionic channel model, the Hybrid blows up if the allowable time step is set to be greater than 0.1ms. In contrast, our method can adjust the time step size automatically, and is stable. Overall, the proposed method is more accurate than and as efficient as the traditional Hybrid method, especially for the human ORd model. The proposed method shows improvement for action potentials with a non-smooth morphology, and it needs further investigation to determine whether the method is helpful during propagation of the action potential. Copyright © 2016 Elsevier Ltd. All rights

Random paths with curvature dependent action

International Nuclear Information System (INIS)

Ambjoern, J.; Durhuus, B.

1986-11-01

We study discretized random paths with a curvature dependent action. The scaling limits of the corresponding statistical mechanical models can be constructed explicitly and are either usual Brownian motion or a theory where the correlations of tangents are nonzero and described by diffusion on the unit sphere. In the latter case the two point function has an anomalous dimension η = 1. (orig.)

Action video game training for cognitive enhancement

OpenAIRE

Green, C. Shawn; Bavelier, Daphné

2015-01-01

Here we review the literature examining the perceptual, attentional, and cognitive benefits of playing one sub-type of video games known as ‘action video games,’ as well as the mechanistic underpinnings of these behavioral effects. We then outline evidence indicating the potential usefulness of these commercial off-the-shelf games for practical, real-world applications such as rehabilitation or the training of job-related skills. Finally, we discuss potential core characteristics of action vi...

Exactly solvable energy-dependent potentials

International Nuclear Information System (INIS)

Garcia-Martinez, J.; Garcia-Ravelo, J.; Pena, J.J.; Schulze-Halberg, A.

2009-01-01

We introduce a method for constructing exactly-solvable Schroedinger equations with energy-dependent potentials. Our method is based on converting a general linear differential equation of second order into a Schroedinger equation with energy-dependent potential. Particular examples presented here include harmonic oscillator, Coulomb and Morse potentials with various types of energy dependence.

Re-construction of action awareness depends on an internal model of action-outcome timing.

Science.gov (United States)

Stenner, Max-Philipp; Bauer, Markus; Machts, Judith; Heinze, Hans-Jochen; Haggard, Patrick; Dolan, Raymond J

2014-04-01

The subjective time of an instrumental action is shifted towards its outcome. This temporal binding effect is partially retrospective, i.e., occurs upon outcome perception. Retrospective binding is thought to reflect post-hoc inference on agency based on sensory evidence of the action - outcome association. However, many previous binding paradigms cannot exclude the possibility that retrospective binding results from bottom-up interference of sensory outcome processing with action awareness and is functionally unrelated to the processing of the action - outcome association. Here, we keep bottom-up interference constant and use a contextual manipulation instead. We demonstrate a shift of subjective action time by its outcome in a context of variable outcome timing. Crucially, this shift is absent when there is no such variability. Thus, retrospective action binding reflects a context-dependent, model-based phenomenon. Such top-down re-construction of action awareness seems to bias agency attribution when outcome predictability is low. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Restitution slope is principally determined by steady-state action potential duration.

Science.gov (United States)

Shattock, Michael J; Park, Kyung Chan; Yang, Hsiang-Yu; Lee, Angela W C; Niederer, Steven; MacLeod, Kenneth T; Winter, James

2017-06-01

The steepness of the action potential duration (APD) restitution curve and local tissue refractoriness are both thought to play important roles in arrhythmogenesis. Despite this, there has been little recognition of the apparent association between steady-state APD and the slope of the restitution curve. The objective of this study was to test the hypothesis that restitution slope is determined by APD and to examine the relationship between restitution slope, refractoriness and susceptibility to VF. Experiments were conducted in isolated hearts and ventricular myocytes from adult guinea pigs and rabbits. Restitution curves were measured under control conditions and following intervention to prolong (clofilium, veratridine, bretylium, low [Ca]e, chronic transverse aortic constriction) or shorten (catecholamines, rapid pacing) ventricular APD. Despite markedly differing mechanisms of action, all interventions that prolonged the action potential led to a steepening of the restitution curve (and vice versa). Normalizing the restitution curve as a % of steady-state APD abolished the difference in restitution curves with all interventions. Effects on restitution were preserved when APD was modulated by current injection in myocytes pre-treated with the calcium chelator BAPTA-AM - to abolish the intracellular calcium transient. The non-linear relation between APD and the rate of repolarization of the action potential is shown to underpin the common influence of APD on the slope of the restitution curve. Susceptibility to VF was found to parallel changes in APD/refractoriness, rather than restitution slope. Steady-state APD is the principal determinant of the slope of the ventricular electrical restitution curve. In the absence of post-repolarization refractoriness, factors that prolong the action potential would be expected to steepen the restitution curve. However, concomitant changes in tissue refractoriness act to reduce susceptibility to sustained VF. Dependence on

Pheromones enhance somatosensory processing in newt brains through a vasotocin-dependent mechanism.

Science.gov (United States)

Thompson, R R; Dickinson, P S; Rose, J D; Dakin, K A; Civiello, G M; Segerdahl, A; Bartlett, R

2008-07-22

We tested whether the sex pheromones that stimulate courtship clasping in male roughskin newts do so, at least in part, by amplifying the somatosensory signals that directly trigger the motor pattern associated with clasping and, if so, whether that amplification is dependent on endogenous vasotocin (VT). Female olfactory stimuli increased the number of action potentials recorded in the medulla of males in response to tactile stimulation of the cloaca, which triggers the clasp motor reflex, as well as to tactile stimulation of the snout and hindlimb. That enhancement was blocked by exposing the medulla to a V1a receptor antagonist before pheromone exposure. However, the antagonist did not affect medullary responses to tactile stimuli in the absence of pheromone exposure, suggesting that pheromones amplify somatosensory signals by inducing endogenous VT release. The ability of VT to couple sensory systems together in response to social stimulation could allow this peptide to induce variable behavioural outcomes, depending on the immediate context of the social interaction and thus on the nature of the associated stimuli that are amplified. If widespread in vertebrates, this mechanism could account for some of the behavioural variability associated with this and related peptides both within and across species.

Enhanced visual short-term memory in action video game players.

Science.gov (United States)

Blacker, Kara J; Curby, Kim M

2013-08-01

Visual short-term memory (VSTM) is critical for acquiring visual knowledge and shows marked individual variability. Previous work has illustrated a VSTM advantage among action video game players (Boot et al. Acta Psychologica 129:387-398, 2008). A growing body of literature has suggested that action video game playing can bolster visual cognitive abilities in a domain-general manner, including abilities related to visual attention and the speed of processing, providing some potential bases for this VSTM advantage. In the present study, we investigated the VSTM advantage among video game players and assessed whether enhanced processing speed can account for this advantage. Experiment 1, using simple colored stimuli, revealed that action video game players demonstrate a similar VSTM advantage over nongamers, regardless of whether they are given limited or ample time to encode items into memory. Experiment 2, using complex shapes as the stimuli to increase the processing demands of the task, replicated this VSTM advantage, irrespective of encoding duration. These findings are inconsistent with a speed-of-processing account of this advantage. An alternative, attentional account, grounded in the existing literature on the visuo-cognitive consequences of video game play, is discussed.

The dependence level analysis between the human actions in NPP Operation

International Nuclear Information System (INIS)

Farcasiu, M.; Nitoi, M.; Apostol, M.; Florescu, G.; Prisecaru, Ilie

2009-01-01

The Human Reliability Analysis (HRA) is an important method in Probabilistic Safety Assessment (PSA) studies and offers desirability for concrete improvement of the man - machine - organization interfaces, reliability and safety. An important step in HRA is the dependence level analysis between the human actions performed by the same person or between the actions performed by different persons, step in quantitative analysis of the human errors probabilities. The purpose of this paper is to develop a model to analyze the dependence level between human actions for Nuclear Power Plant (NPP) operation. The model estimates the conditional human error probabilities (CHEP) and joint human error probabilities (JHEP). The achieved sensitivity analyses determine human performance sensibility to systematic variations for dependence level between human actions. The human error probabilities estimated in this paper are adequate values for integration both in HRA and in PSA realized for NPP. This type of analysis helps in finding and analyzing the ways of reducing the likelihood of human errors, so that the impact of human factor to systems availability, reliability and safety can be realistically estimated. In order to demonstrate the usability of this model an analysis is performed upon the dependences between the necessary human actions in mitigating the consequences of LOCA events, particularly for the case of Cernavoda NPP. (authors)

A physical action potential generator: design, implementation and evaluation.

Science.gov (United States)

Latorre, Malcolm A; Chan, Adrian D C; Wårdell, Karin

2015-01-01

The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon's action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1-40 in incremental steps of 1) and the node drive potential (0-2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxon's programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems.

Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes.

Science.gov (United States)

Kistamás, Kornél; Szentandrássy, Norbert; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Bárándi, László; Horváth, Balázs; Szebeni, Andrea; Magyar, János; Bányász, Tamás; Kecskeméti, Valéria; Nánási, Péter P

2013-06-15

Despite its widespread therapeutical use there is little information on the cellular cardiac effects of the antidiabetic drug pioglitazone in larger mammals. In the present study, therefore, the concentration-dependent effects of pioglitazone on ion currents and action potential configuration were studied in isolated canine ventricular myocytes using standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques. Pioglitazone decreased the maximum velocity of depolarization and the amplitude of phase-1 repolarization at concentrations ≥3 μM. Action potentials were shortened by pioglitazone at concentrations ≥10 μM, which effect was accompanied with significant reduction of beat-to-beat variability of action potential duration. Several transmembrane ion currents, including the transient outward K(+) current (Ito), the L-type Ca(2+) current (ICa), the rapid and slow components of the delayed rectifier K(+) current (IKr and IKs, respectively), and the inward rectifier K(+) current (IK1) were inhibited by pioglitazone under conventional voltage clamp conditions. Ito was blocked significantly at concentrations ≥3 μM, ICa, IKr, IKs at concentrations ≥10 μM, while IK1 at concentrations ≥30 μM. Suppression of Ito, ICa, IKr, and IK1 has been confirmed also under action potential voltage clamp conditions. ATP-sensitive K(+) current, when activated by lemakalim, was effectively blocked by pioglitazone. Accordingly, action potentials were prolonged by 10 μM pioglitazone when the drug was applied in the presence of lemakalim. All these effects developed rapidly and were readily reversible upon washout. In conclusion, pioglitazone seems to be a harmless agent at usual therapeutic concentrations. Copyright © 2013 Elsevier B.V. All rights reserved.

Enhanced change detection performance reveals improved strategy use in avid action video game players.

Science.gov (United States)

Clark, Kait; Fleck, Mathias S; Mitroff, Stephen R

2011-01-01

Recent research has shown that avid action video game players (VGPs) outperform non-video game players (NVGPs) on a variety of attentional and perceptual tasks. However, it remains unknown exactly why and how such differences arise; while some prior research has demonstrated that VGPs' improvements stem from enhanced basic perceptual processes, other work indicates that they can stem from enhanced attentional control. The current experiment used a change-detection task to explore whether top-down strategies can contribute to VGPs' improved abilities. Participants viewed alternating presentations of an image and a modified version of the image and were tasked with detecting and localizing the changed element. Consistent with prior claims of enhanced perceptual abilities, VGPs were able to detect the changes while requiring less exposure to the change than NVGPs. Further analyses revealed this improved change detection performance may result from altered strategy use; VGPs employed broader search patterns when scanning scenes for potential changes. These results complement prior demonstrations of VGPs' enhanced bottom-up perceptual benefits by providing new evidence of VGPs' potentially enhanced top-down strategic benefits. Copyright © 2010 Elsevier B.V. All rights reserved.

FKBP5/FKBP51 enhances autophagy to synergize with antidepressant action

Science.gov (United States)

Gassen, Nils C; Hartmann, Jakob; Schmidt, Mathias V; Rein, Theo

2015-01-01

Levels of autophagy markers rise upon treatment of cells with antidepressants. However, it was not known whether this phenomenon might be linked to other antidepressant pathways or to any physiological effect. In this punctum, we summarize and discuss our recent findings that provide evidence for a role of the cochaperone FKBP5/FKBP51 (FK506 binding protein 5) in autophagy as a prerequisite for antidepressant action in cells, mice, and humans. FKBP5 associates with BECN1, changes its phosphorylation and protein levels and enhances markers of autophagy and autophagic flux. The effects of antidepressants on autophagy as well as their physiological effects in mice and human depend on FKBP5. PMID:25714272

Backpropagating Action Potentials Enable Detection of Extrasynaptic Glutamate by NMDA Receptors

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Yu-Wei Wu

2012-05-01

Full Text Available Synaptic NMDA receptors (NMDARs are crucial for neural coding and plasticity. However, little is known about the adaptive function of extrasynaptic NMDARs occurring mainly on dendritic shafts. Here, we find that in CA1 pyramidal neurons, backpropagating action potentials (bAPs recruit shaft NMDARs exposed to ambient glutamate. In contrast, spine NMDARs are “protected,” under baseline conditions, from such glutamate influences by perisynaptic transporters: we detect bAP-evoked Ca2+ entry through these receptors upon local synaptic or photolytic glutamate release. During theta-burst firing, NMDAR-dependent Ca2+ entry either downregulates or upregulates an h-channel conductance (Gh of the cell depending on whether synaptic glutamate release is intact or blocked. Thus, the balance between activation of synaptic and extrasynaptic NMDARs can determine the sign of Gh plasticity. Gh plasticity in turn regulates dendritic input probed by local glutamate uncaging. These results uncover a metaplasticity mechanism potentially important for neural coding and memory formation.

Incorporated fish oil fatty acids prevent action potential shortening induced by circulating fish oil fatty acids

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Hester M Den Ruijter

2010-11-01

Full Text Available Increased consumption of fatty fish, rich in omega-3 polyunsaturated fatty acids (3-PUFAs reduces the severity and number of arrhythmias. Long term 3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating 3-PUFAs in the bloodstream and incorporated 3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating 3-PUFAs in the bloodstream enhance or diminish the effects of incorporated 3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (3 or sunflower oil (9, as control for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch clamp technique in the absence and presence of acutely administered 3-PUFAs. Plasma of 3 fed rabbits contained more free eicosapentaenoic acid (EPA and isolated myocytes of 3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA in their sarcolemma compared to control. In the absence of acutely administered fatty acids, 3 myocytes had a shorter action potential with a more negative plateau than 9 myocytes. In the 9 myocytes, but not in the 3 myocytes, acute administration of a mixture of EPA+DHA shortened the action potential significantly. From these data we conclude that incorporated 3-PUFAs into the sarcolemma and acutely administered 3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac 3-PUFA status will probably not benefit from short term 3 supplementation as an antiarrhythmic therapy.

State-dependent classical potentials

International Nuclear Information System (INIS)

D'Amico, M.

2001-01-01

As alternative treatment to the potential operators of standard quantum mechanics is presented. The method is derived from Bohm's mechanics. The operator scalar (V) and vector (A) potential functions are replaced by a quantum potential. It is argued that the classical potential is a special limiting case of a more general quantum potential. The theory is illustrated by deriving an equivalent single-particle equation for the i-th particle of an n-body Bohmian system. The resulting effective state-dependent potential holds the interaction between the single-particle self-wave ψ s and the environment wave ψ e of the n - 1 remaining particles. The effective state-dependent potential is offered as a resolution to the Aharonov-Bohm effect where the phase difference is shown to result from the presence of ψ e . Finally, the interaction between ψ s and ψ e is illustrated graphically

Components of action potential repolarization in cerebellar parallel fibres.

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Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna J; Raastad, Morten

2014-11-15

Repolarization of the presynaptic action potential is essential for transmitter release, excitability and energy expenditure. Little is known about repolarization in thin, unmyelinated axons forming en passant synapses, which represent the most common type of axons in the mammalian brain's grey matter.We used rat cerebellar parallel fibres, an example of typical grey matter axons, to investigate the effects of K(+) channel blockers on repolarization. We show that repolarization is composed of a fast tetraethylammonium (TEA)-sensitive component, determining the width and amplitude of the spike, and a slow margatoxin (MgTX)-sensitive depolarized after-potential (DAP). These two components could be recorded at the granule cell soma as antidromic action potentials and from the axons with a newly developed miniaturized grease-gap method. A considerable proportion of fast repolarization remained in the presence of TEA, MgTX, or both. This residual was abolished by the addition of quinine. The importance of proper control of fast repolarization was demonstrated by somatic recordings of antidromic action potentials. In these experiments, the relatively broad K(+) channel blocker 4-aminopyridine reduced the fast repolarization, resulting in bursts of action potentials forming on top of the DAP. We conclude that repolarization of the action potential in parallel fibres is supported by at least three groups of K(+) channels. Differences in their temporal profiles allow relatively independent control of the spike and the DAP, whereas overlap of their temporal profiles provides robust control of axonal bursting properties.

[Loudness optimized registration of compound action potential in cochlear implant recipients].

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Berger, Klaus; Hocke, Thomas; Hessel, Horst

2017-11-01

Background Postoperative measurements of compound action potentials are not always possible due to the insufficient acceptance of the CI-recipients. This study investigated the impact of different parameters on the acceptance of the measurements. Methods Compound action potentials of 16 CI recipients were measured with different pulse-widths. Recipients performed a loudness rating at the potential thresholds with the different sequences. Results Compound action potentials obtained with higher pulse-widths were rated softer than those obtained with smaller pulse-widths. Conclusions Compound action potentials measured with higher pulse-widths generate a gap between loudest acceptable presentation level and potential threshold. This gap contributes to a higher acceptance of postoperative measurements. Georg Thieme Verlag KG Stuttgart · New York.

Studies on the Action Potential From a Thermodynamic Perspective

DEFF Research Database (Denmark)

Wang, Tian

and nerves with ganglia. (2) Attempts have been made to measure the temperature change associated with an action potential as well as an oscillation reaction (Briggs-Rauscher reaction) that shares the adiabatic feature. It turns out that some practical issues need to be solved for the temperature measurement...... of the nerve impulses, while the measured temperature change during the oscillation reaction suggests that there are a reversible adiabatic process and a dissipative process. (3) Local anesthetic e↵ect on nerves is studied. Local anesthetic lidocaine causes a significant stimulus threshold shift of the action......Nerve impulse, also called action potential, has mostly been considered as a pure electrical phenomenon. However, changes in dimensions, e.g. thickness and length, and in temperature along with action potentials have been observed, which indicates that the nerve is a thermodynamic system. The work...

Potentiating action of propofol at GABAA receptors of retinal bipolar cells

DEFF Research Database (Denmark)

Yue, Lan; Xie, An; Bruzik, Karol S

2011-01-01

Purpose. Propofol (2,6-diisopropyl phenol), a widely used systemic anesthetic, is known to potentiate GABA(A) receptor activity in a number of CNS neurons and to produce changes in electroretinographically recorded responses of the retina. However, little is known about propofol's effects...... on specific retinal neurons. The authors investigated the action of propofol on GABA-elicited membrane current responses of retinal bipolar cells, which have both GABA(A) and GABA(C) receptors. Methods. Single, enzymatically dissociated bipolar cells obtained from rat retina were treated with propofol...... + propofol) led to a progressive increase in peak response amplitude and, at higher propofol concentrations, additional changes that included a prolonged time course of response recovery. Pre-exposure of the cell to perfusing propofol typically enhanced the rate of development of potentiation produced...

Wireless cardiac action potential transmission with ultrasonically inserted silicon microprobes

International Nuclear Information System (INIS)

Shen, C J; Ramkumar, A; Lal, A; Gilmour, R F Jr

2011-01-01

This paper reports on the integration of ultrasonically inserted horn-shaped cardiac probes with wireless transmission of 3D cardiac action potential measurement for applications in ex vivo preparations such as monitoring the onset of ventricular fibrillation. Ultrasonically inserted silicon horn probes permit reduced penetration force during insertion, allowing silicon, a brittle material, to penetrate cardiac tissue. The probes also allow recording from multiple sites that are lithographically defined. An application-specific integrated circuit has been designed with a 40 dB amplifying stage and a frequency modulating oscillator at 95 MHz to wirelessly transmit the recorded action potentials. This ultrasonically inserted microprobe wireless system demonstrates the initial results in wireless monitoring of 3D action potential propagation, and the extraction of parameters of interest including the action potential duration and diastolic interval

Potentiation of E-4031-induced torsade de pointes by HMR1556 or ATX-II is not predicted by action potential short-term variability or triangulation.

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Michael, G; Dempster, J; Kane, K A; Coker, S J

2007-12-01

Torsade de pointes (TdP) can be induced by a reduction in cardiac repolarizing capacity. The aim of this study was to assess whether IKs blockade or enhancement of INa could potentiate TdP induced by IKr blockade and to investigate whether short-term variability (STV) or triangulation of action potentials preceded TdP. Experiments were performed in open-chest, pentobarbital-anaesthetized, alpha 1-adrenoceptor-stimulated, male New Zealand White rabbits, which received three consecutive i.v. infusions of either the IKr blocker E-4031 (1, 3 and 10 nmol kg(-1) min(-1)), the IKs blocker HMR1556 (25, 75 and 250 nmol kg(-1) min(-1)) or E-4031 and HMR1556 combined. In a second study rabbits received either the same doses of E-4031, the INa enhancer, ATX-II (0.4, 1.2 and 4.0 nmol kg(-1)) or both of these drugs. ECGs and epicardial monophasic action potentials were recorded. HMR1556 alone did not cause TdP but increased E-4031-induced TdP from 25 to 80%. ATX-II alone caused TdP in 38% of rabbits, as did E-4031; 75% of rabbits receiving both drugs had TdP. QT intervals were prolonged by all drugs but the extent of QT prolongation was not related to the occurrence of TdP. No changes in STV were detected and triangulation was only increased after TdP occurred. Giving modulators of ion channels in combination substantially increased TdP but, in this model, neither STV nor triangulation of action potentials could predict TdP.

Traditional Japanese medicines inhibit compound action potentials in the frog sciatic nerve.

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Matsushita, Akitomo; Fujita, Tsugumi; Ohtsubo, Sena; Kumamoto, Eiichi

2016-02-03

Traditional Japanese (Kampo) medicines have a variety of clinical effects including pain alleviation, but evidence for a mechanism for their pain relief has not yet been elucidated fully. Considering that Kampo medicine contains many plant-derived chemicals having an ability to inhibit nerve action potential conduction, it is possible that this medicine inhibits nerve conduction. The purpose of the present study was to know how various Kampo medicines affect nerve conduction. We examined the effects of Kampo and crude medicines on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. Daikenchuto, rikkosan, kikyoto, rikkunshito, shakuyakukanzoto and kakkonto concentration-dependently reduced the peak amplitude of the CAP. Among the Kampo medicines, daikenchuto was the most effective in inhibiting CAPs. Daikenchuto is composed of three kinds of crude medicine, Japanese pepper, processed ginger and ginseng radix. When the crude medicines were tested, Japanese pepper and processed ginger reduced CAP peak amplitudes, while ginseng radix hardly affected CAPs. Moreover, there was an interaction between the Japanese pepper and processed ginger activities in such that one medicine at low but not high concentrations increased the extent of the inhibition by the other one that was co-applied. Kampo medicines have an ability to inhibit nerve conduction. This action of daikenchuto is due to Japanese pepper and processed ginger but not ginseng radix, probably through an interaction between Japanese pepper and processed ginger in a manner dependent on their concentrations. Nerve conduction inhibition could contribute to at least a part of Kampo medicine's clinical effects such as pain alleviation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cognitive Enhancement Through Action Video Game Training: Great Expectations Require Greater Evidence

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Joseph eBisoglio

2014-02-01

Full Text Available Action video game training may hold promise as a cognitive intervention with the potential to enhance daily functioning and remediate impairments, but this must be more thoroughly evaluated through evidence-based practices. We review current research on the effect of action video game training on visual attention and visuospatial processing, executive functions, and learning and memory. Focusing on studies that utilize strict experimental controls and synthesize behavioral and neurophysiological data, we examine whether there is sufficient evidence to support a causal relationship between action video game training and beneficial changes in cognition. Convergent lines of behavioral and neurophysiological evidence tentatively support the efficacy of training, but the magnitude and specificity of these effects remain obscure. Causal inference is thus far limited by a lack of standardized and well-controlled methodology. Considering future directions, we suggest stringent adherence to evidence based practices and collaboration modeled after clinical trial networks. Finally, we recommend the exploration of more complex causal models, such as indirect causal relationships and interactions that may be masking true effects.

Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications.

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Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs

2017-10-01

Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.

Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

Energy Technology Data Exchange (ETDEWEB)

Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi, E-mail: kumamote@cc.saga-u.ac.jp

2013-04-26

Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

Numerical investigation of action potential transmission in plants

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Mariusz Pietruszka

2014-01-01

Full Text Available In context of a fairly concise review of recent literature and well established experimental results we reconsider the problem of action potential propagating steadily down the plant cell(s. Having adopted slightly modified Hodgkin-Huxley set of differential equations for the action potential we carried out the numerical investigation of these equations in the course of time. We argue that the Hodgkin-Huxley-Katz model for the nerve impulse can be used to describe the phenomena which take place in plants - this point of view seems to be plausible since the mechanisms involving active ionic transport across membranes from the mathematical point of view are similar. Besides, we compare in a qualitative way our theoretical outcomes with typical experimental results for the action potentials which arise as the reaction of plants to electrical, mechanical and light stimuli. Moreover, we point out the relevance of the sequence of events during the pulse with the appropriate ionic fluxes.

Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

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Sung, Derrick; Mills, Robert W.; Schettler, Jan; Narayan, Sanjiv M.; Omens, Jeffrey H.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

2003-01-01

INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

Perturbation analysis of spontaneous action potential initiation by stochastic ion channels

KAUST Repository

Keener, James P.; Newby, Jay M.

2011-01-01

A stochastic interpretation of spontaneous action potential initiation is developed for the Morris-Lecar equations. Initiation of a spontaneous action potential can be interpreted as the escape from one of the wells of a double well potential

Effects of context on visuomotor interference depends on the perspective of observed actions.

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Marta Bortoletto

Full Text Available Visuomotor interference occurs when the execution of an action is facilitated by the concurrent observation of the same action and hindered by the concurrent observation of a different action. There is evidence that visuomotor interference can be modulated top-down by higher cognitive functions, depending on whether own performed actions or observed actions are selectively attended. Here, we studied whether these effects of cognitive context on visuomotor interference are also dependent on the point-of-view of the observed action. We employed a delayed go/no-go task known to induce visuomotor interference. Static images of hand gestures in either egocentric or allocentric perspective were presented as "go" stimuli after participants were pre-cued to prepare either a matching (congruent or non-matching (incongruent action. Participants performed this task in two different cognitive contexts: In one, they focused on the visual image of the hand gesture shown as the go stimulus (image context, whereas in the other they focused on the hand gesture they performed (action context. We analyzed reaction times to initiate the prepared action upon presentation of the gesture image and found evidence of visuomotor interference in both contexts and for both perspectives. Strikingly, results show that the effect of cognitive context on visuomotor interference also depends on the perspective of observed actions. When focusing on own-actions, visuomotor interference was significantly less for gesture images in allocentric perspective than in egocentric perspective; when focusing on observed actions, visuomotor interference was present regardless of the perspective of the gesture image. Overall these data suggest that visuomotor interference may be modulated by higher cognitive processes, so that when we are specifically attending to our own actions, images depicting others' actions (allocentric perspective have much less interference on our own actions.

Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice.

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Herde, Michel K; Herbison, Allan E

2015-11-01

GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ∼27 μm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 μm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G-positive axon-like structures. Almost all GnRH neurons (>90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body.

Glucocorticoid enhancement of dorsolateral striatum-dependent habit memory requires concurrent noradrenergic activity.

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Goodman, J; Leong, K-C; Packard, M G

2015-12-17

Previous findings indicate that post-training administration of glucocorticoid stress hormones can interact with the noradrenergic system to enhance consolidation of hippocampus- or amygdala-dependent cognitive/emotional memory. The present experiments were designed to extend these findings by examining the potential interaction of glucocorticoid and noradrenergic mechanisms in enhancement of dorsolateral striatum (DLS)-dependent habit memory. In experiment 1, different groups of adult male Long-Evans rats received training in two DLS-dependent memory tasks. In a cued water maze task, rats were released from various start points and were reinforced to approach a visibly cued escape platform. In a response-learning version of the water plus-maze task, animals were released from opposite starting positions and were reinforced to make a consistent egocentric body-turn to reach a hidden escape platform. Immediately post-training, rats received peripheral injections of the glucocorticoid corticosterone (1 or 3 mg/kg) or vehicle solution. In both tasks, corticosterone (3 mg/kg) enhanced DLS-dependent habit memory. In experiment 2, a separate group of animals received training in the response learning version of the water plus-maze task and were given peripheral post-training injections of corticosterone (3 mg/kg), the β-adrenoreceptor antagonist propranolol (3 mg/kg), corticosterone and propranolol concurrently, or control vehicle solution. Corticosterone injections again enhanced DLS-dependent memory, and this effect was blocked by concurrent administration of propranolol. Propranolol administration by itself (3 mg/kg) did not influence DLS-dependent memory. Taken together, the findings indicate an interaction between glucocorticoid and noradrenergic mechanisms in DLS-dependent habit memory. Propranolol administration may be useful in treating stress-related human psychopathologies associated with a dysfunctional DLS-dependent habit memory system. Copyright © 2015

Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction.

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Jabr, Rita I; Hatch, Fiona S; Salvage, Samantha C; Orlowski, Alejandro; Lampe, Paul D; Fry, Christopher H

2016-11-01

Cardiac arrhythmias are associated with raised intracellular [Ca 2+ ] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca 2+ -dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity. We investigated the role of the Ca 2+ -dependent phosphatase, calcineurin. Intracellular [Ca 2+ ] was raised in guinea-pig myocardium by a low-Na solution or increased stimulation. Conduction velocity and Gj were measured in multicellular strips. Phosphorylation of Cx43 serine residues (S365 and S368) and of the intermediary regulator I1 at threonine35 was measured by Western blot. Measurements were made in the presence and absence of inhibitors to calcineurin, I1 or protein phosphatase-1 and phosphatase-2.Raised [Ca 2 + ] i decreased Gj, reduced Cx43 phosphorylation at S365 and increased it at S368; these changes were reversed by calcineurin inhibitors. Cx43-S368 phosphorylation was reversed by the protein kinase C inhibitor chelerythrine. Raised [Ca 2+ ] i also decreased I1 phosphorylation, also prevented by calcineurin inhibitors, to increase activity of the Ca 2+ -independent phosphatase, PPI. The PP1 inhibitor, tautomycin, prevented Cx43-365 dephosphorylation, Cx43-S368 phosphorylation and Gj reduction in raised [Ca 2+ ] i . PP2A had no role. Conduction velocity was reduced by raised [Ca 2+ ] i and reversed by calcineurin inhibitors. Reduced action potential conduction and Gj in raised [Ca 2+ ] are regulated by calcineurin-dependent Cx43-S365 phosphorylation, leading to Cx43-S368 dephosphorylation. The calcineurin action is indirect, via I1 dephosphorylation and subsequent activation of PP1.

Enhancing perceptual and attentional skills requires common demands between the action video games and transfer tasks

Science.gov (United States)

Oei, Adam C.; Patterson, Michael D.

2015-01-01

Despite increasing evidence that shows action video game play improves perceptual and cognitive skills, the mechanisms of transfer are not well-understood. In line with previous work, we suggest that transfer is dependent upon common demands between the game and transfer task. In the current study, participants played one of four action games with varying speed, visual, and attentional demands for 20 h. We examined whether training enhanced performance for attentional blink, selective attention, attending to multiple items, visual search and auditory detection. Non-gamers who played the game (Modern Combat) with the highest demands showed transfer to tasks of attentional blink and attending to multiple items. The game (MGS Touch) with fewer attentional demands also decreased attentional blink, but to a lesser degree. Other games failed to show transfer, despite having many action game characteristics but at a reduced intensity. The results support the common demands hypothesis. PMID:25713551

Enhancing perceptual and attentional skills requires common demands between the action video games and transfer tasks.

Science.gov (United States)

Oei, Adam C; Patterson, Michael D

2015-01-01

Despite increasing evidence that shows action video game play improves perceptual and cognitive skills, the mechanisms of transfer are not well-understood. In line with previous work, we suggest that transfer is dependent upon common demands between the game and transfer task. In the current study, participants played one of four action games with varying speed, visual, and attentional demands for 20 h. We examined whether training enhanced performance for attentional blink, selective attention, attending to multiple items, visual search and auditory detection. Non-gamers who played the game (Modern Combat) with the highest demands showed transfer to tasks of attentional blink and attending to multiple items. The game (MGS Touch) with fewer attentional demands also decreased attentional blink, but to a lesser degree. Other games failed to show transfer, despite having many action game characteristics but at a reduced intensity. The results support the common demands hypothesis.

Enhancing perceptual and attentional skills requires common demands between the action video games and transfer tasks

Directory of Open Access Journals (Sweden)

Adam C Oei

2015-02-01

Full Text Available Despite increasing evidence that shows action video game play improves perceptual and cognitive skills, the mechanisms of transfer are not well understood. In line with previous work, we suggest that transfer is dependent upon common demands between the game and transfer task. In the current study, participants played one of four action games with varying speed, visual, and attentional demands for twenty hours. We examined whether training enhanced performance for attentional blink, selective attention, attending to multiple items, visual search and auditory detection. Non-gamers who played the game (Modern Combat with the highest demands showed transfer to tasks of attentional blink and attending to multiple items. The game (MGS Touch with fewer attentional demands also decreased attentional blink, but to a lesser degree. Other games failed to show transfer, despite having many action game characteristics but at a reduced intensity. The results support the common demands hypothesis

Reversed synaptic effects of hypocretin and NPY mediated by excitatory GABA-dependent synaptic activity in developing MCH neurons.

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Li, Ying; Xu, Youfen; van den Pol, Anthony N

2013-03-01

In mature neurons, GABA is the primary inhibitory neurotransmitter. In contrast, in developing neurons, GABA exerts excitatory actions, and in some neurons GABA-mediated excitatory synaptic activity is more prevalent than glutamate-mediated excitation. Hypothalamic neuropeptides that modulate cognitive arousal and energy homeostasis, hypocretin/orexin and neuropeptide Y (NPY), evoked reversed effects on synaptic actions that were dependent on presynaptic GABA release onto melanin-concentrating hormone (MCH) neurons. MCH neurons were identified by selective green fluorescent protein (GFP) expression in transgenic mice. In adults, hypocretin increased GABA release leading to reduced excitation. In contrast, in the developing brain as studied here with analysis of miniature excitatory postsynaptic currents, paired-pulse ratios, and evoked potentials, hypocretin acted presynaptically to enhance the excitatory actions of GABA. The ability of hypocretin to enhance GABA release increases inhibition in adult neurons but paradoxically enhances excitation in developing MCH neurons. In contrast, NPY attenuation of GABA release reduced inhibition in mature neurons but enhanced inhibition during development by attenuating GABA excitation. Both hypocretin and NPY also evoked direct actions on developing MCH neurons. Hypocretin excited MCH cells by activating a sodium-calcium exchanger and by reducing potassium currents; NPY reduced activity by increasing an inwardly rectifying potassium current. These data for the first time show that both hypocretin and NPY receptors are functional presynaptically during early postnatal hypothalamic development and that both neuropeptides modulate GABA actions during development with a valence of enhanced excitation or inhibition opposite to that of the adult state, potentially allowing neuropeptide modulation of use-dependent synapse stabilization.

[Effect of pulse magnetic field on distribution of neuronal action potential].

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Zheng, Yu; Cai, Di; Wang, Jin-Hai; Li, Gang; Lin, Ling

2014-08-25

The biological effect on the organism generated by magnetic field is widely studied. The present study was aimed to observe the change of sodium channel under magnetic field in neurons. Cortical neurons of Kunming mice were isolated, subjected to 15 Hz, 1 mT pulse magnetic stimulation, and then the currents of neurons were recorded by whole-cell patch clamp. The results showed that, under magnetic stimulation, the activation process of Na(+) channel was delayed, and the inactivation process was accelerated. Given the classic three-layer model, the polarization diagram of cell membrane potential distribution under pulse magnetic field was simulated, and it was found that the membrane potential induced was associated with the frequency and intensity of magnetic field. Also the effect of magnetic field-induced current on action potential was simulated by Hodgkin-Huxley (H-H) model. The result showed that the generation of action potential was delayed, and frequency and the amplitudes were decreased when working current was between -1.32 μA and 0 μA. When the working current was higher than 0 μA, the generation frequency of action potential was increased, and the change of amplitudes was not obvious, and when the working current was lower than -1.32 μA, the time of rising edge and amplitudes of action potential were decreased drastically, and the action potential was unable to generate. These results suggest that the magnetic field simulation can affect the distribution frequency and amplitude of action potential of neuron via sodium channel mediation.

Habitual action video game playing is associated with caudate nucleus-dependent navigational strategies.

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West, Greg L; Drisdelle, Brandi Lee; Konishi, Kyoko; Jackson, Jonathan; Jolicoeur, Pierre; Bohbot, Veronique D

2015-06-07

The habitual playing of video games is associated with increased grey matter and activity in the striatum. Studies in humans and rodents have shown an inverse relationship between grey matter in the striatum and hippocampus. We investigated whether action video game playing is also associated with increased use of response learning strategies during navigation, known to be dependent on the caudate nucleus of the striatum, when presented in a dual solution task. We tested 26 action video game players (actionVGPs) and 33 non-action video game players (nonVGPs) on the 4-on-8 virtual maze and a visual attention event-related potential (ERP) task, which elicits a robust N-2-posterior-controlateral (N2pc) component. We found that actionVGPs had a significantly higher likelihood of using a response learning strategy (80.76%) compared to nonVGPs (42.42%). Consistent with previous evidence, actionVGPs and nonVGPs differed in the way they deployed visual attention to central and peripheral targets as observed in the elicited N2pc component during an ERP visual attention task. Increased use of the response strategy in actionVGPs is consistent with previously observed increases in striatal volume in video game players (VGPs). Using response strategies is associated with decreased grey matter in the hippocampus. Previous studies have shown that decreased volume in the hippocampus precedes the onset of many neurological and psychiatric disorders. If actionVGPs have lower grey matter in the hippocampus, as response learners normally do, then these individuals could be at increased risk of developing neurological and psychiatric disorders during their lifetime. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Statistical mechanics of surfaces with curvature dependent action

International Nuclear Information System (INIS)

Jonsson, T.

1987-01-01

We review recent results about discretized random surfaces whose action (energy) depends on the extrinsic curvature. The surface tension scales to zero at an appropriate critical point if the coupling constant of the curvature term is taken to infinity. At this critical point one expects to be able to construct a continuum theory of smooth surfaces. (orig.)

Equivalence between deep energy-dependent and shallow angular momentum dependent potentials

International Nuclear Information System (INIS)

Fiedeldey, H.; Sofianos, S.A.; Papastylianos, A.; Amos, K.A.; Allen, L.J.

1989-01-01

Recently Baye showed that supersymmetry can be applied to determine a shallow l-dependent potential phase equivalent to a deep potential, assumed to be energy-independent and have Panli forbidden states (PFS), for α-α scattering. The PFS are eliminated by this procedure. Such deep potentials are generated as equivalent local potentials (ELP) to the Resonating Group Model (RGM) and are generally energy-dependent. To eliminate this E-dependence as required for the application of Baye's method, l-dependent, but E-independent, deep local potentials were generated by the exact inversion method of Marchenko. Subsequently, the supersymmetric method was used to eliminate the PFS, ensuring that the generalized Levinson theorem is satisfied. As an example, the method was applied to the simple model of two dineutrons scattering in the RGM, where the deep ELP of Horiuchi has a substantial energy-dependence and one PFS only for l=O. 16 refs., 5 figs

Activation of Mechanosensitive Transient Receptor Potential/Piezo Channels in Odontoblasts Generates Action Potentials in Cocultured Isolectin B4-negative Medium-sized Trigeminal Ganglion Neurons.

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Sato, Masaki; Ogura, Kazuhiro; Kimura, Maki; Nishi, Koichi; Ando, Masayuki; Tazaki, Masakazu; Shibukawa, Yoshiyuki

2018-04-27

Various stimuli to the dentin surface elicit dentinal pain by inducing dentinal fluid movement causing cellular deformation in odontoblasts. Although odontoblasts detect deformation by the activation of mechanosensitive ionic channels, it is still unclear whether odontoblasts are capable of establishing neurotransmission with myelinated A delta (Aδ) neurons. Additionally, it is still unclear whether these neurons evoke action potentials by neurotransmitters from odontoblasts to mediate sensory transduction in dentin. Thus, we investigated evoked inward currents and evoked action potentials form trigeminal ganglion (TG) neurons after odontoblast mechanical stimulation. We used patch clamp recordings to identify electrophysiological properties and record evoked responses in TG neurons. We classified TG cells into small-sized and medium-sized neurons. In both types of neurons, we observed voltage-dependent inward currents. The currents from medium-sized neurons showed fast inactivation kinetics. When mechanical stimuli were applied to odontoblasts, evoked inward currents were recorded from medium-sized neurons. Antagonists for the ionotropic adenosine triphosphate receptor (P2X 3 ), transient receptor potential channel subfamilies, and Piezo1 channel significantly inhibited these inward currents. Mechanical stimulation to odontoblasts also generated action potentials in the isolectin B 4 -negative medium-sized neurons. Action potentials in these isolectin B 4 -negative medium-sized neurons showed a short duration. Overall, electrophysiological properties of neurons indicate that the TG neurons with recorded evoked responses after odontoblast mechanical stimulation were myelinated Aδ neurons. Odontoblasts established neurotransmission with myelinated Aδ neurons via P2X 3 receptor activation. The results also indicated that mechanosensitive TRP/Piezo1 channels were functionally expressed in odontoblasts. The activation of P2X 3 receptors induced an action potential

Dynamics of action potential initiation in the GABAergic thalamic reticular nucleus in vivo.

Science.gov (United States)

Muñoz, Fabián; Fuentealba, Pablo

2012-01-01

Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold.

Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar disarray and pro-arrhythmic action potential changes in human iPSC cardiomyocytes.

Science.gov (United States)

Wang, Lili; Kim, Kyungsoo; Parikh, Shan; Cadar, Adrian Gabriel; Bersell, Kevin R; He, Huan; Pinto, Jose R; Kryshtal, Dmytro O; Knollmann, Bjorn C

2018-01-01

Mutations in cardiac troponin T (TnT) are linked to increased risk of ventricular arrhythmia and sudden death despite causing little to no cardiac hypertrophy. Studies in mice suggest that the hypertrophic cardiomyopathy (HCM)-associated TnT-I79N mutation increases myofilament Ca sensitivity and is arrhythmogenic, but whether findings from mice translate to human cardiomyocyte electrophysiology is not known. To study the effects of the TnT-I79N mutation in human cardiomyocytes. Using CRISPR/Cas9, the TnT-I79N mutation was introduced into human induced pluripotent stem cells (hiPSCs). We then used the matrigel mattress method to generate single rod-shaped cardiomyocytes (CMs) and studied contractility, Ca handling and electrophysiology. Compared to isogenic control hiPSC-CMs, TnT-I79N hiPSC-CMs exhibited sarcomere disorganization, increased systolic function and impaired relaxation. The Ca-dependence of contractility was leftward shifted in mutation containing cardiomyocytes, demonstrating increased myofilament Ca sensitivity. In voltage-clamped hiPSC-CMs, TnT-I79N reduced intracellular Ca transients by enhancing cytosolic Ca buffering. These changes in Ca handling resulted in beat-to-beat instability and triangulation of the cardiac action potential, which are predictors of arrhythmia risk. The myofilament Ca sensitizer EMD57033 produced similar action potential triangulation in control hiPSC-CMs. The TnT-I79N hiPSC-CM model not only reproduces key cellular features of TnT-linked HCM such as myofilament disarray, hypercontractility and diastolic dysfunction, but also suggests that this TnT mutation causes pro-arrhythmic changes of the human ventricular action potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessing farmer involvement in collective action for enhancing the ...

African Journals Online (AJOL)

Assessing farmer involvement in collective action for enhancing the sorghum value chain in Soroti, Uganda. ... in six sub-counties of Soroti, Uganda, where associations are established. A binomial logit regression model was employed to ascertain socio-economic factors that influenced membership to farmer associations.

Reconstruction of action potential of repolarization in patients with congenital long-QT syndrome

International Nuclear Information System (INIS)

Kandori, Akihiko; Shimizu, Wataru; Yokokawa, Miki; Kamakura, Shiro; Miyatake, Kunio; Murakami, Masahiro; Miyashita, Tsuyoshi; Ogata, Kuniomi; Tsukada, Keiji

2004-01-01

A method for reconstructing an action potential during the repolarization period was developed. This method uses a current distribution-plotted as a current-arrow map (CAM)-calculated using magnetocardiogram (MCG) signals. The current arrows are summarized during the QRS complex period and subtracted during the ST-T wave period in order to reconstruct the action-potential waveform. To ensure the similarity between a real action potential and the reconstructed action potential using CAM, a monophasic action potential (MAP) and an MCG of the same patient with type-I long-QT syndrome were measured. Although the MAP had one notch that was associated with early afterdepolarization (EAD), the reconstructed action potential had two large and small notches. The small notch timing agreed with the occurrence of the EAD in the MAP. On the other hand, the initiation time of an abnormal current distribution coincides with the appearance timing of the first large notch, and its end time coincides with that of the second small notch. These results suggest that a simple reconstruction method using a CAM based on MCG data can provide a similar action-potential waveform to a MAP waveform without having to introduce a catheter

A Randomized Trial of SMART Goal Enhanced Debriefing after Simulation to Promote Educational Actions

Directory of Open Access Journals (Sweden)

Amish Aghera

2017-12-01

Full Text Available Introduction Goal setting is used in education to promote learning and performance. Debriefing after clinical scenario-based simulation is a well-established practice that provides learners a defined structure to review and improve performance. Our objective was to integrate formal learning goal generation, using the SMART framework (Specific, Measurable, Attainable, Realistic, and Time-bound, into standard debriefing processes (i.e., “SMART Goal Enhanced Debriefing” and subsequently measure the impact on the development of learning goals and execution of educational actions. Methods This was a prospective multicenter randomized controlled study of 80 emergency medicine residents at three academic hospitals comparing the effectiveness of SMART Goal Enhanced Debriefing to a standard debriefing. Residents were block randomized on a rolling basis following a simulation case. SMART Goal Enhanced Debriefing included five minutes of formal instruction on the development of SMART learning goals during the summary/application phase of the debrief. Outcome measures included the number of recalled learning goals, self-reported executed educational actions, and quality of each learning goal and educational action after a two-week follow-up period. Results The mean number of reported learning goals was similar in the standard debriefing group (mean 2.05 goals, SD 1.13, n=37 residents, and in the SMART Goal Enhanced Debriefing group (mean 1.93, SD 0.96, n=43, with no difference in learning goal quality. Residents receiving SMART Goal Enhanced Debriefing completed more educational actions on average (Control group actions completed 0.97 (SD 0.87, SMART debrief group 1.44 (SD 1.03 p=0.03. Conclusion The number and quality of learning goals reported by residents was not improved as a result of SMART Goal Enhanced Debriefing. Residents did, however, execute more educational actions, which is consistent with the overarching intent of any educational

Effect of an educational game on university students' learning about action potentials.

Science.gov (United States)

Luchi, Kelly Cristina Gaviao; Montrezor, Luís Henrique; Marcondes, Fernanda K

2017-06-01

The aim of this study was to evaluate the effect of an educational game that is used for teaching the mechanisms of the action potentials in cell membranes. The game was composed of pieces representing the intracellular and extracellular environments, ions, ion channels, and the Na + -K + -ATPase pump. During the game activity, the students arranged the pieces to demonstrate how the ions move through the membrane in a resting state and during an action potential, linking the ion movement with a graph of the action potential. To test the effect of the game activity on student understanding, first-year dental students were given the game to play at different times in a series of classes teaching resting membrane potential and action potentials. In all experiments, students who played the game performed better in assessments. According to 98% of the students, the game supported the learning process. The data confirm the students' perception, indicating that the educational game improved their understanding about action potentials. Copyright © 2017 the American Physiological Society.

Oxidative shift in tissue redox potential increases beat-to-beat variability of action potential duration.

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Kistamás, Kornél; Hegyi, Bence; Váczi, Krisztina; Horváth, Balázs; Bányász, Tamás; Magyar, János; Szentandrássy, Norbert; Nánási, Péter P

2015-07-01

Profound changes in tissue redox potential occur in the heart under conditions of oxidative stress frequently associated with cardiac arrhythmias. Since beat-to-beat variability (short term variability, SV) of action potential duration (APD) is a good indicator of arrhythmia incidence, the aim of this work was to study the influence of redox changes on SV in isolated canine ventricular cardiomyocytes using a conventional microelectrode technique. The redox potential was shifted toward a reduced state using a reductive cocktail (containing dithiothreitol, glutathione, and ascorbic acid) while oxidative changes were initiated by superfusion with H2O2. Redox effects were evaluated as changes in "relative SV" determined by comparing SV changes with the concomitant APD changes. Exposure of myocytes to the reductive cocktail decreased SV significantly without any detectable effect on APD. Application of H2O2 increased both SV and APD, but the enhancement of SV was the greater, so relative SV increased. Longer exposure to H2O2 resulted in the development of early afterdepolarizations accompanied by tremendously increased SV. Pretreatment with the reductive cocktail prevented both elevation in relative SV and the development of afterdepolarizations. The results suggest that the increased beat-to-beat variability during an oxidative stress contributes to the generation of cardiac arrhythmias.

The human ether-a-go-go-related gene (hERG) current inhibition selectively prolongs action potential of midmyocardial cells to augment transmural dispersion.

Science.gov (United States)

Yasuda, C; Yasuda, S; Yamashita, H; Okada, J; Hisada, T; Sugiura, S

2015-08-01

The majority of drug induced arrhythmias are related to the prolongation of action potential duration following inhibition of rapidly activating delayed rectifier potassium current (I(Kr)) mediated by the hERG channel. However, for arrhythmias to develop and be sustained, not only the prolongation of action potential duration but also its transmural dispersion are required. Herein, we evaluated the effect of hERG inhibition on transmural dispersion of action potential duration using the action potential clamp technique that combined an in silico myocyte model with the actual I(Kr) measurement. Whole cell I(Kr) current was measured in Chinese hamster ovary cells stably expressing the hERG channel. The measured current was coupled with models of ventricular endocardial, M-, and epicardial cells to calculate the action potentials. Action potentials were evaluated under control condition and in the presence of 1, 10, or 100 μM disopyramide, an hERG inhibitor. Disopyramide dose-dependently increased the action potential durations of the three cell types. However, action potential duration of M-cells increased disproportionately at higher doses, and was significantly different from that of epicardial and endocardial cells (dispersion of repolarization). By contrast, the effects of disopyramide on peak I(Kr) and instantaneous current-voltage relation were similar in all cell types. Simulation study suggested that the reduced repolarization reserve of M-cell with smaller amount of slowly activating delayed rectifier potassium current levels off at longer action potential duration to make such differences. The action potential clamp technique is useful for studying the mechanism of arrhythmogenesis by hERG inhibition through the transmural dispersion of repolarization.

A phantom axon setup for validating models of action potential recordings.

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Rossel, Olivier; Soulier, Fabien; Bernard, Serge; Guiraud, David; Cathébras, Guy

2016-08-01

Electrode designs and strategies for electroneurogram recordings are often tested first by computer simulations and then by animal models, but they are rarely implanted for long-term evaluation in humans. The models show that the amplitude of the potential at the surface of an axon is higher in front of the nodes of Ranvier than at the internodes; however, this has not been investigated through in vivo measurements. An original experimental method is presented to emulate a single fiber action potential in an infinite conductive volume, allowing the potential of an axon to be recorded at both the nodes of Ranvier and the internodes, for a wide range of electrode-to-fiber radial distances. The paper particularly investigates the differences in the action potential amplitude along the longitudinal axis of an axon. At a short radial distance, the action potential amplitude measured in front of a node of Ranvier is two times larger than in the middle of two nodes. Moreover, farther from the phantom axon, the measured action potential amplitude is almost constant along the longitudinal axis. The results of this new method confirm the computer simulations, with a correlation of 97.6 %.

Mutations in ash1 and trx enhance P-element-dependent silencing in Drosophila melanogaster.

Science.gov (United States)

McCracken, Allen; Locke, John

2016-08-01

In Drosophila melanogaster, the mini-w(+) transgene in Pci is normally expressed throughout the adult eye; however, when other P or KP elements are present, a variegated-eye phenotype results, indicating random w(+) silencing during development called P-element-dependent silencing (PDS). Mutant Su(var)205 and Su(var)3-7 alleles act as haplo-suppressors/triplo-enhancers of this variegated phenotype, indicating that these heterochromatic modifiers act dose dependently in PDS. Previously, we recovered a spontaneous mutation of P{lacW}ci(Dplac) called P{lacW}ci(DplacE1) (E1) that variegated in the absence of P elements, presumably due to the insertion of an adjacent gypsy element. From a screen for genetic modifiers of E1 variegation, we describe here the isolation of five mutations in ash1 and three in trx that enhance the E1 variegated phenotype in a dose-dependent and cumulative manner. These mutant alleles enhance PDS at E1, and in E1/P{lacW}ci(Dplac), but suppress position effect variegation (PEV) at In(1)w(m)(4). This opposite action is consistent with a model where ASH1 and TRX mark transcriptionally active chromatin domains. If ASH1 or TRX function is lost or reduced, heterochromatin can spread into these domains creating a sink that diverts heterochromatic proteins from other variegating locations, which then may express a suppressed phenotype.

Refractive index dependent local electric field enhancement in cylindrical gold nanohole

International Nuclear Information System (INIS)

Zhu Jian

2011-01-01

We report on the local electric field characters in a long cylindrical gold nanohole. Theoretical calculation results based on quasi-static model show that the local environmental dielectric constant dependent electric field intensity and field distribution in the gold nanohole show quite unique properties, different from those in the thin gold nanotube. Because of the thick gold wall, no plasmon hybridization exists. So there is only one resonance frequency taking place, and the intense local field has been focused into the gold nanohole. Our main finding is that, the local field in the nanohole is largely dependent on the inner hole refractive index and outer environmental refractive index. The competition between inner hole and outer polarization leads to a non-monotonic change of the local field intensity with increasing the dielectric constant of the nanohole. This refractive index controlled local field enhancement in cylindrical gold nanohole presents a potential for tunable surface-enhanced fluorescence and novel nano-optical biosensing applications.

Enhancing local action planning through quantitative flood risk analysis: a case study in Spain

Science.gov (United States)

Castillo-Rodríguez, Jesica Tamara; Escuder-Bueno, Ignacio; Perales-Momparler, Sara; Ramón Porta-Sancho, Juan

2016-07-01

This article presents a method to incorporate and promote quantitative risk analysis to support local action planning against flooding. The proposed approach aims to provide a framework for local flood risk analysis, combining hazard mapping with vulnerability data to quantify risk in terms of expected annual affected population, potential injuries, number of fatalities, and economic damages. Flood risk is estimated combining GIS data of loads, system response, and consequences and using event tree modelling for risk calculation. The study area is the city of Oliva, located on the eastern coast of Spain. Results from risk modelling have been used to inform local action planning and to assess the benefits of structural and non-structural risk reduction measures. Results show the potential impact on risk reduction of flood defences and improved warning communication schemes through local action planning: societal flood risk (in terms of annual expected affected population) would be reduced up to 51 % by combining both structural and non-structural measures. In addition, the effect of seasonal population variability is analysed (annual expected affected population ranges from 82 to 107 %, compared with the current situation, depending on occupancy rates in hotels and campsites). Results highlight the need for robust and standardized methods for urban flood risk analysis replicability at regional and national scale.

Sarcomere length-dependence of activity-dependent twitch potentiation in mouse skeletal muscle

Directory of Open Access Journals (Sweden)

MacIntosh Brian R

2002-12-01

Full Text Available Abstract Background It has been reported that potentiation of a skeletal muscle twitch response is proportional to muscle length with a negative slope during staircase, and a positive slope during posttetanic potentiation. This study was done to directly compare staircase and posttetanic responses with measurement of sarcomere length to compare their length-dependence. Methods Mouse extensor digitorum longus (EDL muscles were dissected to small bundles of fibers, which permit measurement of sarcomere length (SL, by laser diffraction. In vitro fixed-end contractions of EDL fiber bundles were elicited at 22°C and 35°C at sarcomere lengths ranging from 2.35 μm to 3.85 μm. Twitch contractions were assessed before and after 1.5 s of 75 Hz stimulation at 22°C or during 10 s of 10 Hz stimulation at 22°C or 35°C. Results Staircase potentiation was greater at 35°C than 22°C, and the relative magnitude of the twitch contraction (Pt*/Pt was proportional to sarcomere length with a negative slope, over the range 2.3 μm – 3.7 μm. Linear regression yielded the following: Pt*/Pt = -0.59·SL+3.27 (r2 = 0.74; Pt*/Pt = -0.39·SL+2.34 (r2 = 0.48; and Pt*/Pt = -0.50·SL+2.45 (r2 = 0.80 for staircase at 35°C, and 22°C and posttetanic response respectively. Posttetanic depression rather than potentiation was present at long SL. This indicates that there may be two processes operating in these muscles to modulate the force: one that enhances and a second that depresses the force. Either or both of these processes may have a length-dependence of its mechanism. Conclusion There is no evidence that posttetanic potentiation is fundamentally different from staircase in these muscles.

Single K ATP channel opening in response to action potential firing in mouse dentate granule neurons.

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Tanner, Geoffrey R; Lutas, Andrew; Martínez-François, Juan Ramón; Yellen, Gary

2011-06-08

ATP-sensitive potassium channels (K(ATP) channels) are important sensors of cellular metabolic state that link metabolism and excitability in neuroendocrine cells, but their role in nonglucosensing central neurons is less well understood. To examine a possible role for K(ATP) channels in modulating excitability in hippocampal circuits, we recorded the activity of single K(ATP) channels in cell-attached patches of granule cells in the mouse dentate gyrus during bursts of action potentials generated by antidromic stimulation of the mossy fibers. Ensemble averages of the open probability (p(open)) of single K(ATP) channels over repeated trials of stimulated spike activity showed a transient increase in p(open) in response to action potential firing. Channel currents were identified as K(ATP) channels through blockade with glibenclamide and by comparison with recordings from Kir6.2 knock-out mice. The transient elevation in K(ATP) p(open) may arise from submembrane ATP depletion by the Na(+)-K(+) ATPase, as the pump blocker strophanthidin reduced the magnitude of the elevation. Both the steady-state and stimulus-elevated p(open) of the recorded channels were higher in the presence of the ketone body R-β-hydroxybutyrate, consistent with earlier findings that ketone bodies can affect K(ATP) activity. Using perforated-patch recording, we also found that K(ATP) channels contribute to the slow afterhyperpolarization following an evoked burst of action potentials. We propose that activity-dependent opening of K(ATP) channels may help granule cells act as a seizure gate in the hippocampus and that ketone-body-mediated augmentation of the activity-dependent opening could in part explain the effect of the ketogenic diet in reducing epileptic seizures.

Fiber Optic Detection of Action Potentials in Axons

National Research Council Canada - National Science Library

Smela, Elisabeth

2006-01-01

In prior exploratory research, we had designed a fiber optic sensor utilizing a long period Bragg grating for the purpose of detecting action potentials in axons optically, through a change in index...

Statistical mechanics of paths with curvature dependent action

International Nuclear Information System (INIS)

Ambjoern, J.; Durhuus, B.; Jonsson, T.

1987-01-01

We analyze the scaling limit of discretized random paths with curvature dependent action. For finite values of the curvature coupling constant the theory belongs to the universality class of simple random walk. It is possible to define a non-trivial scaling limit if the curvature coupling tends to infinity. We compute exactly the two point function in this limit and discuss the relevance of our results for random surfaces and string theories. (orig.)

Membrane, action, and oscillatory potentials in simulated protocells

Science.gov (United States)

Syren, R. M.; Fox, S. W.; Przybylski, A. T.; Stratten, W. P.

1982-01-01

Electrical membrane potentials, oscillations, and action potentials are observed in proteinoid microspheres impaled with (3 M KCl) microelectrodes. Although effects are of greater magnitude when the vesicles contain glycerol and natural or synthetic lecithin, the results in the purely synthetic thermal protein structures are substantial, attaining 20 mV amplitude in some cases. The results add the property of electrical potential to the other known properties of proteinoid microspheres, in their role as models for protocells.

Introducing the Action Potential to Psychology Students

Science.gov (United States)

Simon-Dack, Stephanie L.

2014-01-01

For this simple active learning technique for teaching, students are assigned "roles" and act out the process of the action potential (AP), including the firing threshold, ion-specific channels for ions to enter and leave the cell, diffusion, and the refractory period. Pre-post test results indicated that students demonstrated increased…

Enhanced diffusion with abnormal temperature dependence in underdamped space-periodic systems subject to time-periodic driving

Science.gov (United States)

Marchenko, I. G.; Marchenko, I. I.; Zhiglo, A. V.

2018-01-01

We present a study of the diffusion enhancement of underdamped Brownian particles in a one-dimensional symmetric space-periodic potential due to external symmetric time-periodic driving with zero mean. We show that the diffusivity can be enhanced by many orders of magnitude at an appropriate choice of the driving amplitude and frequency. The diffusivity demonstrates abnormal (decreasing) temperature dependence at the driving amplitudes exceeding a certain value. At any fixed driving frequency Ω normal temperature dependence of the diffusivity is restored at low enough temperatures, T oscillation frequency at the potential minimum, the diffusivity is shown to decrease with Ω according to a power law, with the exponent related to the transient superdiffusion exponent. This behavior is found similar for the cases of sinusoidal in time and piecewise constant periodic ("square") driving.

Perturbation analysis of spontaneous action potential initiation by stochastic ion channels

KAUST Repository

Keener, James P.

2011-07-01

A stochastic interpretation of spontaneous action potential initiation is developed for the Morris-Lecar equations. Initiation of a spontaneous action potential can be interpreted as the escape from one of the wells of a double well potential, and we develop an asymptotic approximation of the mean exit time using a recently developed quasistationary perturbation method. Using the fact that the activating ionic channel\\'s random openings and closings are fast relative to other processes, we derive an accurate estimate for the mean time to fire an action potential (MFT), which is valid for a below-threshold applied current. Previous studies have found that for above-threshold applied current, where there is only a single stable fixed point, a diffusion approximation can be used. We also explore why different diffusion approximation techniques fail to estimate the MFT. © 2011 American Physical Society.

Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential.

Science.gov (United States)

Eickenscheidt, Max; Zeck, Günther

2014-06-01

The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

Enhanced intensity dependence and aggression history indicate previous regular ecstasy use in abstinent polydrug users.

Science.gov (United States)

Wan, Li; Baldridge, Robyn M; Colby, Amanda M; Stanford, Matthew S

2009-11-13

Intensity dependence is an electrophysiological measure of intra-individual stability of the augmenting/reducing characteristic of N1/ P2 event-related potential amplitudes in response to stimuli of varying intensities. Abstinent ecstasy users typically show enhanced intensity dependence and higher levels of impulsivity and aggression. Enhanced intensity dependence and high impulsivity and aggression levels may be due to damage in the brain's serotonergic neurons as a result of ecstasy use. The present study investigated whether intensity dependence, impulsivity and aggression history can be used as indicators of previous chronic ecstasy usage. Forty-four abstinent polydrug users (8 women; age 19 to 61 years old) were recruited. All participants were currently residents at a local substance abuse facility receiving treatment and had been free of all drugs for a minimum of 21 days. The study found significantly enhanced intensity dependence of tangential dipole source activity and a history of more aggressive behavior in those who had previously been involved in chronic ecstasy use. Intensity dependence of the tangential dipole source and aggressive behavior history correctly identified 73.3% of those who had been regular ecstasy users and 78.3% of those who had not. Overall, 76.3% of the participants were correctly classified.

Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials

Science.gov (United States)

Riisager, Anders; Duehmke, Rudy; Nielsen, Ole Bækgaard; Huang, Christopher L; Pedersen, Thomas Holm

2014-01-01

Recent studies in rat muscle fibres show that repetitive firing of action potentials causes changes in fibre resting membrane conductance (Gm) that reflect regulation of ClC-1 Cl− and KATP K+ ion channels. Methodologically, these findings were obtained by inserting two microelectrodes at close proximity in the same fibres enabling measurements of fibre input resistance (Rin) in between action potential trains. Since the fibre length constant (λ) could not be determined, however, the calculation of Gm relied on the assumptions that the specific cytosolic resistivity (Ri) and muscle fibre volume remained constant during the repeated action potential firing. Here we present a three-microelectrode technique that enables determinations of multiple cable parameters in action potential-firing fibres including Rin and λ as well as waveform and conduction velocities of fully propagating action potentials. It is shown that in both rat and mouse extensor digitorum longus (EDL) fibres, action potential firing leads to substantial changes in both muscle fibre volume and Ri. The analysis also showed, however, that regardless of these changes, rat and mouse EDL fibres both exhibited initial decreases in Gm that were eventually followed by a ∼3-fold, fully reversible increase in Gm after the firing of 1450–1800 action potentials. Using this three-electrode method we further show that the latter rise in Gm was closely associated with excitation failures and loss of action potential signal above −20 mV. PMID:25128573

NR2B subunit-dependent long-term potentiation enhancement in the rat cortical auditory system in vivo following masking of patterned auditory input by white noise exposure during early postnatal life.

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Hogsden, Jennifer L; Dringenberg, Hans C

2009-08-01

The composition of N-methyl-D-aspartate (NMDA) receptor subunits influences the degree of synaptic plasticity expressed during development and into adulthood. Here, we show that theta-burst stimulation of the medial geniculate nucleus reliably induced NMDA receptor-dependent long-term potentiation (LTP) of field postsynaptic potentials recorded in the primary auditory cortex (A1) of urethane-anesthetized rats. Furthermore, substantially greater levels of LTP were elicited in juvenile animals (30-37 days old; approximately 55% maximal potentiation) than in adult animals (approximately 30% potentiation). Masking patterned sound via continuous white noise exposure during early postnatal life (from postnatal day 5 to postnatal day 50-60) resulted in enhanced, juvenile-like levels of LTP (approximately 70% maximal potentiation) relative to age-matched controls reared in unaltered acoustic environments (approximately 30%). Rats reared in white noise and then placed in unaltered acoustic environments for 40-50 days showed levels of LTP comparable to those of adult controls, indicating that white noise rearing results in a form of developmental arrest that can be overcome by subsequent patterned sound exposure. We explored the mechanisms mediating white noise-induced plasticity enhancements by local NR2B subunit antagonist application in A1. NR2B subunit antagonists (Ro 25-6981 or ifenprodil) completely reversed white noise-induced LTP enhancement at concentrations that did not affect LTP in adult or age-matched controls. We conclude that white noise exposure during early postnatal life results in the maintenance of juvenile-like, higher levels of plasticity in A1, an effect that appears to be critically dependent on NR2B subunit activation.

Feature-Specific Event-Related Potential Effects to Action- and Sound-Related Verbs during Visual Word Recognition.

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Popp, Margot; Trumpp, Natalie M; Kiefer, Markus

2016-01-01

Grounded cognition theories suggest that conceptual representations essentially depend on modality-specific sensory and motor systems. Feature-specific brain activation across different feature types such as action or audition has been intensively investigated in nouns, while feature-specific conceptual category differences in verbs mainly focused on body part specific effects. The present work aimed at assessing whether feature-specific event-related potential (ERP) differences between action and sound concepts, as previously observed in nouns, can also be found within the word class of verbs. In Experiment 1, participants were visually presented with carefully matched sound and action verbs within a lexical decision task, which provides implicit access to word meaning and minimizes strategic access to semantic word features. Experiment 2 tested whether pre-activating the verb concept in a context phase, in which the verb is presented with a related context noun, modulates subsequent feature-specific action vs. sound verb processing within the lexical decision task. In Experiment 1, ERP analyses revealed a differential ERP polarity pattern for action and sound verbs at parietal and central electrodes similar to previous results in nouns. Pre-activation of the meaning of verbs in the preceding context phase in Experiment 2 resulted in a polarity-reversal of feature-specific ERP effects in the lexical decision task compared with Experiment 1. This parallels analogous earlier findings for primed action and sound related nouns. In line with grounded cognitions theories, our ERP study provides evidence for a differential processing of action and sound verbs similar to earlier observation for concrete nouns. Although the localizational value of ERPs must be viewed with caution, our results indicate that the meaning of verbs is linked to different neural circuits depending on conceptual feature relevance.

Compensatory plasticity in the action observation network: virtual lesions of STS enhance anticipatory simulation of seen actions.

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Avenanti, Alessio; Annella, Laura; Candidi, Matteo; Urgesi, Cosimo; Aglioti, Salvatore M

2013-03-01

Observation of snapshots depicting ongoing motor acts increases corticospinal motor excitability. Such motor facilitation indexes the anticipatory simulation of observed (implied) actions and likely reflects computations occurring in the parietofrontal nodes of a cortical network subserving action perception (action observation network, AON). However, direct evidence for the active role of AON in simulating the future of seen actions is lacking. Using a perturb-and-measure transcranial magnetic stimulation (TMS) approach, we show that off-line TMS disruption of regions within (inferior frontal cortex, IFC) and upstream (superior temporal sulcus, STS) the parietofrontal AON transiently abolishes and enhances the motor facilitation to observed implied actions, respectively. Our findings highlight the critical role of IFC in anticipatory motor simulation. More importantly, they show that disruption of STS calls into play compensatory motor simulation activity, fundamental for counteracting the noisy visual processing induced by TMS. Thus, short-term plastic changes in the AON allow motor simulation to deal with any gap or ambiguity of ever-changing perceptual worlds. These findings support the active, compensatory, and predictive role of frontoparietal nodes of the AON in the perception and anticipatory simulation of implied actions.

Rosewood oil induces sedation and inhibits compound action potential in rodents.

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de Almeida, Reinaldo Nóbrega; Araújo, Demétrius Antonio Machado; Gonçalves, Juan Carlos Ramos; Montenegro, Fabrícia Costa; de Sousa, Damião Pergentino; Leite, José Roberto; Mattei, Rita; Benedito, Marco Antonio Campana; de Carvalho, José Gilberto Barbosa; Cruz, Jader Santos; Maia, José Guilherme Soares

2009-07-30

Aniba rosaeodora is an aromatic plant which has been used in Brazil folk medicine due to its sedative effect. Therefore, the purpose of the present study was to evaluate the sedative effect of linalool-rich rosewood oil in mice. In addition we sought to investigate the linalool-rich oil effects on the isolated nerve using the single sucrose-gap technique. Sedative effect was determined by measuring the potentiation of the pentobarbital-induced sleeping time. The compound action potential amplitude was evaluated as a way to detect changes in excitability of the isolated nerve. The results showed that administration of rosewood oil at the doses of 200 and 300 mg/kg significantly decreased latency and increased the duration of sleeping time. On the other hand, the dose of 100 mg/kg potentiated significantly the pentobarbital action decreasing pentobarbital latency time and increasing pentobarbital sleeping time. In addition, the effect of linalool-rich rosewood oil on the isolated nerve of the rat was also investigated through the single sucrose-gap technique. The amplitude of the action potential decreased almost 100% when it was incubated for 30 min at 100 microg/ml. From this study, it is suggested a sedative effect of linalool-rich rosewood oil that could, at least in part, be explained by the reduction in action potential amplitude that provokes a decrease in neuronal excitability.

Improving Cardiac Action Potential Measurements: 2D and 3D Cell Culture.

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Daily, Neil J; Yin, Yue; Kemanli, Pinar; Ip, Brian; Wakatsuki, Tetsuro

2015-11-01

Progress in the development of assays for measuring cardiac action potential is crucial for the discovery of drugs for treating cardiac disease and assessing cardiotoxicity. Recently, high-throughput methods for assessing action potential using induced pluripotent stem cell (iPSC) derived cardiomyocytes in both two-dimensional monolayer cultures and three-dimensional tissues have been developed. We describe an improved method for assessing cardiac action potential using an ultra-fast cost-effective plate reader with commercially available dyes. Our methods improve dramatically the detection of the fluorescence signal from these dyes and make way for the development of more high-throughput methods for cardiac drug discovery and cardiotoxicity.

Multiple modes of action potential initiation and propagation in mitral cell primary dendrite

DEFF Research Database (Denmark)

Chen, Wei R; Shen, Gongyu Y; Shepherd, Gordon M

2002-01-01

recordings with computational modeling to analyze action-potential initiation and propagation in the primary dendrite. In response to depolarizing current injection or distal olfactory nerve input, fast Na(+) action potentials were recorded along the entire length of the primary dendritic trunk. With weak......-to-moderate olfactory nerve input, an action potential was initiated near the soma and then back-propagated into the primary dendrite. As olfactory nerve input increased, the initiation site suddenly shifted to the distal primary dendrite. Multi-compartmental modeling indicated that this abrupt shift of the spike......-initiation site reflected an independent thresholding mechanism in the distal dendrite. When strong olfactory nerve excitation was paired with strong inhibition to the mitral cell basal secondary dendrites, a small fast prepotential was recorded at the soma, which indicated that an action potential was initiated...

Decoupling Action Potential Bias from Cortical Local Field Potentials

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Stephen V. David

2010-01-01

Full Text Available Neurophysiologists have recently become interested in studying neuronal population activity through local field potential (LFP recordings during experiments that also record the activity of single neurons. This experimental approach differs from early LFP studies because it uses high impendence electrodes that can also isolate single neuron activity. A possible complication for such studies is that the synaptic potentials and action potentials of the small subset of isolated neurons may contribute disproportionately to the LFP signal, biasing activity in the larger nearby neuronal population to appear synchronous and cotuned with these neurons. To address this problem, we used linear filtering techniques to remove features correlated with spike events from LFP recordings. This filtering procedure can be applied for well-isolated single units or multiunit activity. We illustrate the effects of this correction in simulation and on spike data recorded from primary auditory cortex. We find that local spiking activity can explain a significant portion of LFP power at most recording sites and demonstrate that removing the spike-correlated component can affect measurements of auditory tuning of the LFP.

Social interaction enhances motor resonance for observed human actions.

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Hogeveen, Jeremy; Obhi, Sukhvinder S

2012-04-25

Understanding the neural basis of social behavior has become an important goal for cognitive neuroscience and a key aim is to link neural processes observed in the laboratory to more naturalistic social behaviors in real-world contexts. Although it is accepted that mirror mechanisms contribute to the occurrence of motor resonance (MR) and are common to action execution, observation, and imitation, questions remain about mirror (and MR) involvement in real social behavior and in processing nonhuman actions. To determine whether social interaction primes the MR system, groups of participants engaged or did not engage in a social interaction before observing human or robotic actions. During observation, MR was assessed via motor-evoked potentials elicited with transcranial magnetic stimulation. Compared with participants who did not engage in a prior social interaction, participants who engaged in the social interaction showed a significant increase in MR for human actions. In contrast, social interaction did not increase MR for robot actions. Thus, naturalistic social interaction and laboratory action observation tasks appear to involve common MR mechanisms, and recent experience tunes the system to particular agent types.

Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity.

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Christian Albers

Full Text Available Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP. Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious and strong (teacher spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns.

Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity.

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Albers, Christian; Westkott, Maren; Pawelzik, Klaus

2016-01-01

Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP). Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious) and strong (teacher) spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns.

Direct detection of a single evoked action potential with MRS in Lumbricus terrestris.

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Poplawsky, Alexander J; Dingledine, Raymond; Hu, Xiaoping P

2012-01-01

Functional MRI (fMRI) measures neural activity indirectly by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In this study, we used MR to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation, and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background-subtracted FID exhibited a systematic change, with a peak phase difference of (-1.2 ± 0.3) × 10(-5) radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase caused by a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using MR. Copyright © 2011 John Wiley & Sons, Ltd.

Role of cyclophilins in somatolactogenic action.

Science.gov (United States)

Rycyzyn, M A; Clevenger, C V

2000-01-01

Prolactin (PRL) and growth hormone (GH) are members of the somatolactogenic hormone family, the pleiotropic actions of which are necessary for vertebrate growth and mammary differentiation. The basis for the specific function of these hormones has remained uncertain; however, their action is associated with internalization and translocation into the nucleus. A yeast two-hybrid screen identified an interaction between PRL and cyclophilin B (CypB), a peptidyl prolyl isomerase (PPI) found in the endoplasmic reticulum (ER), extracellular space, and nucleus. The interaction between CypB and PRL/GH was confirmed in vitro and in vivo through the use of recombinant proteins and coimmunoprecipitation studies. The exogenous addition of CypB potentiated the proliferation of PRL- and GH-dependent cell lines 18- and 40-fold, respectively. The potentiation of PRL action by CypB was accompanied by a dramatic increase in the nuclear retrotranslocation of PRL. Immunogold electron microscopy has revealed this retrotransport to occur via a vesicular pathway. A CypB mutant, termed CypB-NT, was generated that lacked the putative wild-type N-terminal nuclear localization sequence. Although CypB-NT demonstrated levels of PRL binding and PPI activity equivalent to wild-type CypB, it was incapable of mediating the nuclear retrotranslocation of PRL or enhancing PRL-driven proliferation. These studies reveal CypB as an important chaperone facilitating the nuclear retrotransport and action of the somatolactogenic hormone family.

A fast Na+/Ca2+-based action potential in a marine diatom.

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Alison R Taylor

Full Text Available BACKGROUND: Electrical impulses in animals play essential roles in co-ordinating an array of physiological functions including movement, secretion, environmental sensing and development. Underpinning many of these electrical signals is a fast Na+-based action potential that has been fully characterised only in cells associated with the neuromuscular systems of multicellular animals. Such rapid action potentials are thought to have evolved with the first metazoans, with cnidarians being the earliest representatives. The present study demonstrates that a unicellular protist, the marine diatom Odontella sinensis, can also generate a fast Na+/Ca2+ based action potential that has remarkably similar biophysical and pharmacological properties to invertebrates and vertebrate cardiac and skeletal muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: The kinetic, ionic and pharmacological properties of the rapid diatom action potential were examined using single electrode current and voltage clamp techniques. Overall, the characteristics of the fast diatom currents most closely resemble those of vertebrate and invertebrate muscle Na+/Ca2+ currents. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration of voltage-activated Na+ channels and the capacity to generate fast Na+-based action potentials in a unicellular photosynthetic organism. The biophysical and pharmacological characteristics together with the presence of a voltage activated Na+/Ca2+ channel homologue in the recently sequenced genome of the diatom Thalassiosira pseudonana, provides direct evidence supporting the hypothesis that this rapid signalling mechanism arose in ancestral unicellular eukaryotes and has been retained in at least two phylogenetically distant lineages of eukaryotes; opisthokonts and the stramenopiles. The functional role of the fast animal-like action potential in diatoms remains to be elucidated but is likely involved in rapid environmental sensing of these widespread and

Geodiversity action plans for the enhancement of geoheritage in the Piemonte region (north-western Italy

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Elena Ferrero

2012-07-01

Full Text Available A geoethical approach to geodiversity allows better understanding of the value of abiotic nature and enhances its conservation and development. Our basic assumption is that even during an economical crisis, geoheritage sites can serve both public and private interests. A set of nine strategic geothematic areas were chosen to represent the geodiversity of the Piemonte region, north-western Italy, each of which is characterized by great potential for scientific studies, enhancement of public understanding of science, recreational activities, and economic support to the local communities. Specialized research teams individuated critical aspects to advance our knowledge of the geological history of the Piemonte region, through climate and environmental changes, natural hazards, soil processes, and georesources. The scientific concepts and techniques were coupled with geodiffusion actions and products: not only geosites, but also museum collections, evidence of mining and quarrying activities, science exhibitions, and nature trails. The preliminary results have allowed action plans to be developed with local partners, to assess the geoheritage management requirements. A series of investigations were carried out to improve the visual representation of the geological processes and the evolutionary scenarios. Further outcomes of the project will include didactic tools for educators, schools, and the public in general.

Energy dependence of nonlocal optical potentials

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Lovell, A. E.; Bacq, P.-L.; Capel, P.; Nunes, F. M.; Titus, L. J.

2017-11-01

Recently, a variety of studies have shown the importance of including nonlocality in the description of reactions. The goal of this work is to revisit the phenomenological approach to determining nonlocal optical potentials from elastic scattering. We perform a χ2 analysis of neutron elastic scattering data off 40Ca, 90Zr, and 208Pb at energies E ≈5 -40 MeV, assuming a Perey and Buck [Nucl. Phys. 32, 353 (1962), 10.1016/0029-5582(62)90345-0] or Tian et al. [Int. J. Mod. Phys. E 24, 1550006 (2015), 10.1142/S0218301315500068] nonlocal form for the optical potential. We introduce energy and asymmetry dependencies in the imaginary part of the potential and refit the data to obtain a global parametrization. Independently of the starting point in the minimization procedure, an energy dependence in the imaginary depth is required for a good description of the data across the included energy range. We present two parametrizations, both of which represent an improvement over the original potentials for the fitted nuclei as well as for other nuclei not included in our fit. Our results show that, even when including the standard Gaussian nonlocality in optical potentials, a significant energy dependence is required to describe elastic-scattering data.

Solitary wave dynamics in time-dependent potentials

International Nuclear Information System (INIS)

Abou Salem, Walid K.

2008-01-01

The long time dynamics of solitary wave solutions of the nonlinear Schroedinger equation in time-dependent external potentials is rigorously studied. To set the stage, the well-posedness of the Cauchy problem for a generalized nonautonomous nonlinear Schroedinger equation with time-dependent nonlinearities and potential is established. Afterward, the dynamics of NLS solitary waves in time-dependent potentials is studied. It is shown that in the space-adiabatic regime where the external potential varies slowly in space compared to the size of the soliton, the dynamics of the center of the soliton is described by Hamilton's equations, plus terms due to radiation damping. Finally, two physical applications are discussed: the first is adiabatic transportation of solitons and the second is the Mathieu instability of trapped solitons due to time-periodic perturbations

Neuroprotective and Cognitive Enhancement Potentials of Baicalin: A Review

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Kandhasamy Sowndhararajan

2018-06-01

Full Text Available Neurodegenerative diseases are a heterogeneous group of disorders that are characterized by the gradual loss of neurons. The development of effective neuroprotective agents to prevent and control neurodegenerative diseases is specifically important. Recently, there has been an increasing interest in selecting flavonoid compounds as potential neuroprotective agents, owing to their high effectiveness with low side effects. Baicalin is one of the important flavonoid compounds, which is mainly isolated from the root of Scutellaria baicalensis Georgi (an important Chinese medicinal herb. In recent years, a number of studies have shown that baicalin has a potent neuroprotective effect in various in vitro and in vivo models of neuronal injury. In particular, baicalin effectively prevents neurodegenerative diseases through various pharmacological mechanisms, including antioxidative stress, anti-excitotoxicity, anti-apoptotic, anti-inflammatory, stimulating neurogenesis, promoting the expression of neuronal protective factors, etc. This review mainly focuses on the neuroprotective and cognitive enhancement effects of baicalin. The aim of the present review is to compile all information in relation to the neuroprotective and cognitive enhancement effects of baicalin and its molecular mechanisms of action in various in vitro and in vivo experimental models.

Nuclear three-body problem and energy-dependent potentials

International Nuclear Information System (INIS)

Abdurakhmanov, A.; Akhmadkhodzhaev, B.; Zubarev, A.L.; Irgaziev, B.F.

1985-01-01

Energy-dependent potentials in the three-body problem are being considered. Three-particle equations for the case of pairing energy-dependent potentials are generalized and the problems related to this ambiguous generalization are investigated. In terms of the equations obtained the tritium binding energy and vertex coupling constants (Tdn) and (Tdν) are evaluated. The binding energy and, especially, coupling constants are shown to be sensitive to a shape of the energy-dependent potential

Imaging Action Potential in Single Mammalian Neurons by Tracking the Accompanying Sub-Nanometer Mechanical Motion.

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Yang, Yunze; Liu, Xian-Wei; Wang, Hui; Yu, Hui; Guan, Yan; Wang, Shaopeng; Tao, Nongjian

2018-03-28

Action potentials in neurons have been studied traditionally by intracellular electrophysiological recordings and more recently by the fluorescence detection methods. Here we describe a label-free optical imaging method that can measure mechanical motion in single cells with a sub-nanometer detection limit. Using the method, we have observed sub-nanometer mechanical motion accompanying the action potential in single mammalian neurons by averaging the repeated action potential spikes. The shape and width of the transient displacement are similar to those of the electrically recorded action potential, but the amplitude varies from neuron to neuron, and from one region of a neuron to another, ranging from 0.2-0.4 nm. The work indicates that action potentials may be studied noninvasively in single mammalian neurons by label-free imaging of the accompanying sub-nanometer mechanical motion.

Enhancing excitability of dopamine neurons promotes motivational behaviour through increased action initiation.

Science.gov (United States)

Boekhoudt, Linde; Wijbrans, Ellen C; Man, Jodie H K; Luijendijk, Mieneke C M; de Jong, Johannes W; van der Plasse, Geoffrey; Vanderschuren, Louk J M J; Adan, Roger A H

2018-01-01

Motivational deficits are a key symptom in multiple psychiatric disorders, including major depressive disorder, schizophrenia and addiction. A likely neural substrate for these motivational deficits is the brain dopamine (DA) system. In particular, DA signalling in the nucleus accumbens, which originates from DA neurons in the ventral tegmental area (VTA), has been identified as a crucial substrate for effort-related and activational aspects of motivation. Unravelling how VTA DA neuronal activity relates to motivational behaviours is required to understand how motivational deficits in psychiatry can be specifically targeted. In this study, we therefore used designer receptors exclusively activated by designer drugs (DREADD) in TH:Cre rats, in order to determine the effects of chemogenetic DA neuron activation on different aspects of motivational behaviour. We found that chemogenetic activation of DA neurons in the VTA, but not substantia nigra, significantly increased responding for sucrose under a progressive ratio schedule of reinforcement. More specifically, high effort exertion was characterized by increased initiations of reward-seeking actions. This effect was dependent on effort requirements and instrumental contingencies, but was not affected by sucrose pre-feeding. Together, these findings indicate that VTA DA neuronal activation drives motivational behaviour by facilitating action initiation. With this study, we show that enhancing excitability of VTA DA neurons is a viable strategy to improve motivational behaviour. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Rapidity dependence of strangeness enhancement factor at FAIR energies

International Nuclear Information System (INIS)

Dey, Kalyan; Bhattacharjee, B.

2014-01-01

Strange particles are produced only at the time of collisions and thus expected to carry important information of collision dynamics. Strangeness enhancement is considered to be one of the traditional signatures of formation of Quark Gluon Plasma (QGP). Due to the limitation of the detector acceptance, the past and ongoing heavy ion experiments could measure the strangeness enhancement at midrapidity only. But the future heavy ion experiment CBM at FAIR will have the access to the entire forward rapidity hemisphere and thus the experimental determination of rapidity dependent strangeness enhancement is a possibility. In this work, an attempt has therefore been made to study the rapidity dependent strangeness enhancement at FAIR energies with the help of a string based hadronic model (UrQMD). A sum of 93 million minimum biased UrQMD events have been used for the present analysis

Re-modeling Chara action potential: II. The action potential form under salinity stress

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Mary Jane Beilby

2017-04-01

Full Text Available In part I we established Thiel-Beilby model of the Chara action potential (AP. In part II the AP is investigated in detail at the time of saline stress. Even very short exposure of salt-sensitive Chara cells to artificial pond water with 50 mM NaCl (Saline APW modified the AP threshold and drastically altered the AP form. Detailed modeling of 14 saline APs from 3 cells established that both the Ca2+ pump and the Ca2+ channels on internal stores seem to be affected, with the changes sometimes cancelling and sometimes re-enforcing each other, leading to APs with long durations and very complex forms. The exposure to salinity offers further insights into AP mechanism and suggests future experiments. The prolonged APs lead to greater loss of chloride and potassium ions, compounding the effects of saline stress.

Attention-dependent sound offset-related brain potentials.

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Horváth, János

2016-05-01

When performing sensory tasks, knowing the potentially occurring goal-relevant and irrelevant stimulus events allows the establishment of selective attention sets, which result in enhanced sensory processing of goal-relevant events. In the auditory modality, such enhancements are reflected in the increased amplitude of the N1 ERP elicited by the onsets of task-relevant sounds. It has been recently suggested that ERPs to task-relevant sound offsets are similarly enhanced in a tone-focused state in comparison to a distracted one. The goal of the present study was to explore the influence of attention on ERPs elicited by sound offsets. ERPs elicited by tones in a duration-discrimination task were compared to ERPs elicited by the same tones in not-tone-focused attentional setting. Tone offsets elicited a consistent, attention-dependent biphasic (positive-negative--P1-N1) ERP waveform for tone durations ranging from 150 to 450 ms. The evidence, however, did not support the notion that the offset-related ERPs reflected an offset-specific attention set: The offset-related ERPs elicited in a duration-discrimination condition (in which offsets were task relevant) did not significantly differ from those elicited in a pitch-discrimination condition (in which the offsets were task irrelevant). Although an N2 reflecting the processing of offsets in task-related terms contributed to the observed waveform, this contribution was separable from the offset-related P1 and N1. The results demonstrate that when tones are attended, offset-related ERPs may substantially overlap endogenous ERP activity in the postoffset interval irrespective of tone duration, and attention differences may cause ERP differences in such postoffset intervals. © 2016 Society for Psychophysiological Research.

Insulin secretion and insulin action in non-insulin-dependent diabetes mellitus: which defect is primary?

Science.gov (United States)

Reaven, G M

1984-01-01

Defects in both insulin secretion and insulin action exist in patients with non-insulin-dependent diabetes mellitus (NIDDM). The loss of the acute plasma insulin response to intravenous glucose is seen in patients with relatively mild degrees of fasting hyperglycemia, but patients with severe fasting hyperglycemia also demonstrate absolute hypoinsulinemia in response to an oral glucose challenge. In contrast, day-long circulating insulin levels are within normal limits even in severely hyperglycemic patients with NIDDM. The relationship between NIDDM and insulin action in NIDDM is less complex, and is a characteristic feature of the syndrome. This metabolic defect is independent of obesity, and the severity of the resistance to insulin-stimulated glucose uptake increases with magnitude of hyperglycemia. Control of hyperglycemia with exogenous insulin ameliorates the degree of insulin resistance, and reduction of insulin resistance with weight loss in obese patients with NIDDM leads to an enhanced insulin response. Since neither therapeutic intervention is capable of restoring all metabolic abnormalities to normal, these observations do not tell us which of these two defects is primarily responsible for the development of NIDDM. Similarly, the observation that most patients with impaired glucose tolerance are hyperinsulinemic and insulin resistant does not prove that insulin resistance is the primary defect in NIDDM. In conclusion, reduction in both insulin secretion and action is seen in patients with NIDDM, and the relationship between these two metabolic abnormalities is very complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

Science.gov (United States)

Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

2015-05-01

Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Potential impact of enhanced fracture-toughness data on pressurized-thermal-shock analysis

International Nuclear Information System (INIS)

Dickson, T.L.; Theiss, T.J.

1990-01-01

The Heavy Section Steel Technology (HSST) Program is involved with the generation of ''enhanced'' fracture-initiation toughness and fracture-arrest toughness data of prototypic nuclear reactor vessel steels. These two sets of data are enhanced because they have distinguishing characteristics that could potentially impact PWR pressure vessel integrity assessments for the pressurized-thermal shock (PTS) loading condition which is a major plant-life extension issue to be confronted in the 1990's. Currently, the HSST Program is planning experiments to verify and quantify, for A533B steel, the distinguishing characteristic of elevated initiation-fracture toughness for shallow flaws which has been observed for other steels. Deterministic and probabilistic fracture-mechanics analyses were performed to examine the influence of the enhanced initiation and arrest fracture-toughness data on the cleavage fracture response of a nuclear reactor pressure vessel subjected to PTS loading. The results of the analyses indicated that application of the enhanced K Ia data does reduce the conditional probability of failure P(F|E); however, it does not appear to have the potential to significantly impact the results of PTS analyses. The application of enhanced fracture-initiation-toughness data for shallow flaws also reduces P(F|E), but it does appear to have a potential for significantly affecting the results of PTS analyses. The effect of including Type I warm prestress in probabilistic fracture-mechanics analyses is beneficial. The benefit is transient dependent and, in some cases, can be quite significant. 19 refs., 12 figs., 1 tab

7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

Science.gov (United States)

2010-01-01

... 7 Agriculture 13 2010-01-01 2009-01-01 true Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid reporting...

Enhanced activation of motor execution networks using action observation combined with imagination of lower limb movements.

Directory of Open Access Journals (Sweden)

Michael Villiger

Full Text Available The combination of first-person observation and motor imagery, i.e. first-person observation of limbs with online motor imagination, is commonly used in interactive 3D computer gaming and in some movie scenes. These scenarios are designed to induce a cognitive process in which a subject imagines himself/herself acting as the agent in the displayed movement situation. Despite the ubiquity of this type of interaction and its therapeutic potential, its relationship to passive observation and imitation during observation has not been directly studied using an interactive paradigm. In the present study we show activation resulting from observation, coupled with online imagination and with online imitation of a goal-directed lower limb movement using functional MRI (fMRI in a mixed block/event-related design. Healthy volunteers viewed a video (first-person perspective of a foot kicking a ball. They were instructed to observe-only the action (O, observe and simultaneously imagine performing the action (O-MI, or imitate the action (O-IMIT. We found that when O-MI was compared to O, activation was enhanced in the ventralpremotor cortex bilaterally, left inferior parietal lobule and left insula. The O-MI and O-IMIT conditions shared many activation foci in motor relevant areas as confirmed by conjunction analysis. These results show that (i combining observation with motor imagery (O-MI enhances activation compared to observation-only (O in the relevant foot motor network and in regions responsible for attention, for control of goal-directed movements and for the awareness of causing an action, and (ii it is possible to extensively activate the motor execution network using O-MI, even in the absence of overt movement. Our results may have implications for the development of novel virtual reality interactions for neurorehabilitation interventions and other applications involving training of motor tasks.

Understanding the Electrical Behavior of the Action Potential in Terms of Elementary Electrical Sources

Science.gov (United States)

Rodriguez-Falces, Javier

2015-01-01

A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However,…

Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites

Science.gov (United States)

Colgan, Lesley A.; Cavolo, Samantha L.; Commons, Kathryn G.; Levitan, Edwin S.

2012-01-01

Serotonin released within the dorsal raphe nucleus (DR) induces feedback inhibition of serotonin neuron activity and consequently regulates mood-controlling serotonin release throughout the forebrain. Serotonin packaged in vesicles is released in response to action potentials by the serotonin neuron soma and terminals, but the potential for release by dendrites is unknown. Here three-photon (3P) microscopy imaging of endogenous serotonin in living rat brain slice, immunofluorescence and immuno-gold electron microscopy detection of VMAT2 (vesicular monoamine transporter 2) establish the presence of vesicular serotonin within DR dendrites. Furthermore, activation of glutamate receptors is shown to induce vesicular serotonin release from dendrites. However, unlike release from the soma and terminals, dendritic serotonin release is independent of action potentials, relies on L-type Ca2+ channels, is induced preferentially by NMDA, and displays distinct sensitivity to the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine. The unique control of dendritic serotonin release has important implications for DR physiology and the antidepressant action of SSRIs, dihydropyridines and NMDA receptor antagonists. PMID:23136413

Nitric oxide donors enhance the frequency dependence of dopamine release in nucleus accumbens.

Science.gov (United States)

Hartung, Henrike; Threlfell, Sarah; Cragg, Stephanie J

2011-08-01

Dopamine (DA) neurotransmission in the nucleus accumbens (NAc) is critically involved in normal as well as maladaptive motivated behaviors including drug addiction. Whether the striatal neuromodulator nitric oxide (NO) influences DA release in NAc is unknown. We investigated whether exogenous NO modulates DA transmission in NAc core and how this interaction varies depending on the frequency of presynaptic activation. We detected DA with cyclic voltammetry at carbon-fiber microelectrodes in mouse NAc in slices following stimuli spanning a full range of DA neuron firing frequencies (1-100 Hz). NO donors 3-morpholinosydnonimine hydrochloride (SIN-1) or z-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate (PAPA/NONOate) enhanced DA release with increasing stimulus frequency. This NO-mediated enhancement of frequency sensitivity of DA release was not prevented by inhibition of soluble guanylyl cyclase (sGC), DA transporters, or large conductance Ca(2+)-activated K(+) channels, and did not require glutamatergic or GABAergic input. However, experiments to identify whether frequency-dependent NO effects were mediated via changes in powerful acetylcholine-DA interactions revealed multiple components to NO modulation of DA release. In the presence of a nicotinic receptor antagonist (dihydro-β-erythroidine), NO donors increased DA release in a frequency-independent manner. These data suggest that NO in the NAc can modulate DA release through multiple GC-independent neuronal mechanisms whose net outcome varies depending on the activity in DA neurons and accumbal cholinergic interneurons. In the presence of accumbal acetylcholine, NO promotes the sensitivity of DA release to presynaptic activation, but with reduced acetylcholine input, NO will promote DA release in an activity-independent manner through a direct action on dopaminergic terminals.

Consequences of Converting Graded to Action Potentials upon Neural Information Coding and Energy Efficiency

Science.gov (United States)

Sengupta, Biswa; Laughlin, Simon Barry; Niven, Jeremy Edward

2014-01-01

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation. PMID:24465197

Selective effects of potassium elevations on glutamate signaling and action potential conduction in hippocampus.

Science.gov (United States)

Meeks, Julian P; Mennerick, Steven

2004-01-07

High-frequency synaptic transmission is depressed by moderate rises in the extracellular potassium concentration ([K+]o). Previous reports have indicated that depression of action potential signaling may underlie the synaptic depression. Here, we investigated the specific contribution of K+-induced action potential changes to synaptic depression. We found that glutamatergic transmission in the hippocampal area CA1 was significantly depressed by 8-10 mM [K+]o, but that GABAergic transmission remained intact. Riluzole, a drug that slows recovery from inactivation of voltage-gated sodium channels (NaChs), interacts with subthreshold [K+]o to depress afferent volleys and EPSCs strongly. Thus, elevated [K+]o likely depresses synapses by slowing NaCh recovery from inactivation. It is unclear from previous studies whether [K+]o-induced action potential depression is caused by changes in initiation, reliability, or waveform. We investigated these possibilities explicitly. [K+]o-induced afferent volley depression was independent of stimulus strength, suggesting that changes in action potential initiation do not explain [K+]o-induced depression. Measurements of action potentials from single axons revealed that 8 mM [K+]o increased conduction failures in a subpopulation of fibers and depressed action potential amplitude in all fibers. Together, these changes quantitatively account for the afferent volley depression. We estimate that conduction failure explains more than half of the synaptic depression observed at 8 mM [K+]o, with the remaining depression likely explained by waveform changes. These mechanisms of selective sensitivity of glutamate release to [K+]o accumulation represent a unique neuromodulatory mechanism and a brake on runaway excitation.

Threshold-dependent variability of coronary artery calcification measurements - implications for contrast-enhanced multi-detector row-computed tomography

International Nuclear Information System (INIS)

Moselewski, Fabian; Ferencik, Maros; Achenbach, Stephan; Abbara, Suhny; Cury, Ricardo C.; Booth, Sarah L.; Jang, Ik-Kyung; Brady, Thomas J.; Hoffmann, Udo

2006-01-01

Introduction: The present study investigated the threshold-dependent variability of coronary artery calcification (CAC) measurements and the potential to quantify CAC in contrast-enhanced multi-detector row-computed tomography (MDCT). Methods: We compared the mean CT attenuation of CAC to luminal contrast enhancement of the coronary arteries in 30 patients (n = 30) undergoing standard coronary contrast-enhanced spiral MDCT. The modified Agatston score [AS], calcified plaque volume [CV], and mineral mass [MM]) at four different thresholds (130, 200, 300, and 400 HU) were measured in 50 patients who underwent non-contrast-enhanced MDCT. Results: Mean CT attenuation of CAC was similar to the attenuation of the contrast-enhanced coronary lumen (CAC 297.1 ± 68.7 HU versus 295 ± 65 HU (p < 0.0001), respectively). Above a threshold of 300 HU CAC measurements significantly varied to standard measurements obtained at a threshold of 130 HU (p < 0.0001). The threshold-dependent variation of MM measurements was significantly smaller than for AS and CV (130 HU versus 400 HU: 63, 75, and 81, respectively; p < 0.001). These differences resulted in a change of age and gender based percentile category for AS in 78% of subjects. Discussion: We demonstrated that CAC measurements are threshold dependent with MM measurements having significantly less variation than AS or CV. Due to the similarity of mean CT attenuation of CAC and the contrast-enhanced coronary lumen accurate quantification of CAC may be difficult in standard coronary contrast-enhanced spiral MDCT

Threshold-dependent variability of coronary artery calcification measurements - implications for contrast-enhanced multi-detector row-computed tomography

Energy Technology Data Exchange (ETDEWEB)

Moselewski, Fabian [Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Ferencik, Maros [Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Achenbach, Stephan [Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Department of Internal Medicine II (Cardiology), University of Erlangen (Germany); Abbara, Suhny [Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Cury, Ricardo C. [Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Booth, Sarah L. [Jean Mayer USDA Human Nutrition Research Center on Aging, 711 Washington St., Boston, MA 02114 (United States); Jang, Ik-Kyung [Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Brady, Thomas J. [Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Hoffmann, Udo [Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)]. E-mail: uhoffman@partners.org

2006-03-15

Introduction: The present study investigated the threshold-dependent variability of coronary artery calcification (CAC) measurements and the potential to quantify CAC in contrast-enhanced multi-detector row-computed tomography (MDCT). Methods: We compared the mean CT attenuation of CAC to luminal contrast enhancement of the coronary arteries in 30 patients (n = 30) undergoing standard coronary contrast-enhanced spiral MDCT. The modified Agatston score [AS], calcified plaque volume [CV], and mineral mass [MM] at four different thresholds (130, 200, 300, and 400 HU) were measured in 50 patients who underwent non-contrast-enhanced MDCT. Results: Mean CT attenuation of CAC was similar to the attenuation of the contrast-enhanced coronary lumen (CAC 297.1 {+-} 68.7 HU versus 295 {+-} 65 HU (p < 0.0001), respectively). Above a threshold of 300 HU CAC measurements significantly varied to standard measurements obtained at a threshold of 130 HU (p < 0.0001). The threshold-dependent variation of MM measurements was significantly smaller than for AS and CV (130 HU versus 400 HU: 63, 75, and 81, respectively; p < 0.001). These differences resulted in a change of age and gender based percentile category for AS in 78% of subjects. Discussion: We demonstrated that CAC measurements are threshold dependent with MM measurements having significantly less variation than AS or CV. Due to the similarity of mean CT attenuation of CAC and the contrast-enhanced coronary lumen accurate quantification of CAC may be difficult in standard coronary contrast-enhanced spiral MDCT.

Blahut-Arimoto algorithm and code design for action-dependent source coding problems

DEFF Research Database (Denmark)

Trillingsgaard, Kasper Fløe; Simeone, Osvaldo; Popovski, Petar

2013-01-01

The source coding problem with action-dependent side information at the decoder has recently been introduced to model data acquisition in resource-constrained systems. In this paper, an efficient Blahut-Arimoto-type algorithm for the numerical computation of the rate-distortion-cost function...... for this problem is proposed. Moreover, a simplified two-stage code structure based on multiplexing is put forth, whereby the first stage encodes the actions and the second stage is composed of an array of classical Wyner-Ziv codes, one for each action. Leveraging this structure, specific coding/decoding...... strategies are designed based on LDGM codes and message passing. Through numerical examples, the proposed code design is shown to achieve performance close to the rate-distortion-cost function....

Permeability dependence of streaming potential coefficient in porous media

NARCIS (Netherlands)

Thanh, L.D.; Sprik, R.

2015-01-01

In theory, the streaming potential coefficient depends not only on the zeta potential but also on the permeability of the rocks that partially determines the surface conductivity of the rocks. However, in practice, it is hard to show the permeability dependence of streaming potential coefficients

Different role of TTX-sensitive voltage-gated sodium channel (NaV 1) subtypes in action potential initiation and conduction in vagal airway nociceptors.

Science.gov (United States)

Kollarik, M; Sun, H; Herbstsomer, R A; Ru, F; Kocmalova, M; Meeker, S N; Undem, B J

2018-04-15

The action potential initiation in the nerve terminals and its subsequent conduction along the axons of afferent nerves are not necessarily dependent on the same voltage-gated sodium channel (Na V 1) subunits. The action potential initiation in jugular C-fibres within airway tissues is not blocked by TTX; nonetheless, conduction of action potentials along the vagal axons of these nerves is often dependent on TTX-sensitive channels. This is not the case for nodose airway Aδ-fibres and C-fibres, where both action potential initiation and conduction is abolished by TTX or selective Na V 1.7 blockers. The difference between the initiation of action potentials within the airways vs. conduction along the axons should be considered when developing Na V 1 blocking drugs for topical application to the respiratory tract. The action potential (AP) initiation in the nerve terminals and its subsequent AP conduction along the axons do not necessarily depend on the same subtypes of voltage-gated sodium channels (Na V 1s). We evaluated the role of TTX-sensitive and TTX-resistant Na V 1s in vagal afferent nociceptor nerves derived from jugular and nodose ganglia innervating the respiratory system. Single cell RT-PCR was performed on vagal afferent neurons retrogradely labelled from the guinea pig trachea. Almost all of the jugular neurons expressed the TTX-sensitive channel Na V 1.7 along with TTX-resistant Na V 1.8 and Na V 1.9. Tracheal nodose neurons also expressed Na V 1.7 but, less frequently, Na V 1.8 and Na V 1.9. Na V 1.6 were expressed in ∼40% of the jugular and 25% of nodose tracheal neurons. Other Na V 1 α subunits were only rarely expressed. Single fibre recordings were made from the vagal nodose and jugular nerve fibres innervating the trachea or lung in the isolated perfused vagally-innervated preparations that allowed for selective drug delivery to the nerve terminal compartment (AP initiation) or to the desheathed vagus nerve (AP conduction). AP initiation in

Dynamics of the inward rectifier K+ current during the action potential of guinea pig ventricular myocytes

OpenAIRE

Ibarra, J.; Morley, G.E.; Delmar, M.

1991-01-01

The potassium selective, inward rectifier current (IK1) is known to be responsible for maintaining the resting membrane potential of quiescent ventricular myocytes. However, the contribution of this current to the different phases of the cardiac action potential has not been adequately established. In the present study, we have used the action potential clamp (APC) technique to characterize the dynamic changes of a cesium-sensitive (i.e., Ik1) current which occur during the action potential. ...

[Effects of dauricine on action potentials and slow inward currents of guinea pig ventricular papillary muscles].

Science.gov (United States)

Li, S N; Zhang, K Y

1992-11-01

Effects of dauricine (Dau) on the action potentials (AP), the slow action potentials (SAP), and the slow inward currents (Isi) of guinea pig ventricular papillary muscles were observed by means of intracellular microelectrode and single sucrose gap voltage clamp technique. In the early stage, Dau shortened action potential duration 100 (APD100) and effective refractory period (ERP) (ERP/APD ERP, and APD20, significantly decreased action potential amplitude (APA), maximum velocity (Vmax), and overshot (OS) (ERP/APD > 1; P SAP induced by isoprenaline (P < 0.01), and remarkably inhibited Isi (P < 0.01). The results suggested that Dau exerted an inhibitory effect on Na+, Ca2+, and K+ channels.

Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers

Science.gov (United States)

Sérandour, Aurélien A.; Avner, Stéphane; Percevault, Frédéric; Demay, Florence; Bizot, Maud; Lucchetti-Miganeh, Céline; Barloy-Hubler, Frédérique; Brown, Myles; Lupien, Mathieu; Métivier, Raphaël; Salbert, Gilles; Eeckhoute, Jérôme

2011-01-01

Transcription factors (TFs) bind specifically to discrete regions of mammalian genomes called cis-regulatory elements. Among those are enhancers, which play key roles in regulation of gene expression during development and differentiation. Despite the recognized central regulatory role exerted by chromatin in control of TF functions, much remains to be learned regarding the chromatin structure of enhancers and how it is established. Here, we have analyzed on a genomic-scale enhancers that recruit FOXA1, a pioneer transcription factor that triggers transcriptional competency of these cis-regulatory sites. Importantly, we found that FOXA1 binds to genomic regions showing local DNA hypomethylation and that its cell-type-specific recruitment to chromatin is linked to differential DNA methylation levels of its binding sites. Using neural differentiation as a model, we showed that induction of FOXA1 expression and its subsequent recruitment to enhancers is associated with DNA demethylation. Concomitantly, histone H3 lysine 4 methylation is induced at these enhancers. These epigenetic changes may both stabilize FOXA1 binding and allow for subsequent recruitment of transcriptional regulatory effectors. Interestingly, when cloned into reporter constructs, FOXA1-dependent enhancers were able to recapitulate their cell type specificity. However, their activities were inhibited by DNA methylation. Hence, these enhancers are intrinsic cell-type-specific regulatory regions of which activities have to be potentiated by FOXA1 through induction of an epigenetic switch that includes notably DNA demethylation. PMID:21233399

[Potentiation of anti-ischemic and anti-anginal action of nitrates by hydrogen sulfide balneotherapy in patients with angina of effort].

Science.gov (United States)

Zunnunov, Z R

2010-01-01

The objective of this comparative study was to evaluate effects of nitrosorbid (NS) and hydrogen sulfide-based balneotherapy (HSB) applied alone or in combination for the treatment of patients presenting with angina of effort. It was shown that long-term HSB therapy enhances the anti-anginal and anti-ischemic action of NS in such patients. The authors argue that prolonged HSB-based maintenance therapy in combination with nitrates prevents habituation to these preparations and potentiates their beneficial therapeutic effect.

Implementing participatory action research in Lithuania: potential and challenges

Directory of Open Access Journals (Sweden)

Gabija Jarašiūnaitė

2015-12-01

Full Text Available Participatory action research is a quite new approach to research in Lithuania. The aim of an article was to disscuss the potential and challenges of participatory action research while implementing it in Lithuanian organizations. The qualitative approach was chosen for the study using the method of Focus groups. 20 researchers from social and biomedicine sciences from six institutions of High education in Lithuania participated in the study. The results of the study showed that participatory action reasearch is seen as an approach with many possibilities because of a wide range of used methods, constant interactions with research participants and the lenght of the research process. Researchers value the possibility to access organization at the begining, during research process and evaluate the effectiveness of the changes after the process. The research challenges are associated with the competence of a researcher including his/her sensitivity during process, ability to involve active participation of organization members in the ongoing process by creating safe and trusting environment. Some specific challenges associated with Lithuanian organizations are organizations‘ tiredness of researches and lack of faith of the benefits of researches because of some previous experiences. Keywords: Participatory Action Research, Organization, Lithuania.

Caffeine and length dependence of staircase potentiation in skeletal muscle.

Science.gov (United States)

Rassier, D E; Tubman, L A; MacIntosh, B R

1998-01-01

Skeletal muscle sensitivity to Ca2+ is greater at long lengths, and this results in an optimal length for twitch contractions that is longer than optimal length for tetanic contractions. Caffeine abolishes this length dependence of Ca2+ sensitivity. Muscle length (ML) also affects the degree of staircase potentiation. Since staircase potentiation is apparently caused by an increased Ca2+ sensitivity of the myofilaments, we tested the hypothesis that caffeine depresses the length dependence of staircase potentiation. In situ isometric twitch contractions of rat gastrocnemius muscle before and after 10 s of 10-Hz stimulation were analyzed at seven different lengths to evaluate the length dependence of staircase potentiation. In the absence of caffeine, length dependence of Ca2+ sensitivity was observed, and the degree of potentiation after 10-Hz stimulation showed a linear decrease with increased length (DT = 1.47 - 0.05 ML, r2 = 0.95, where DT is developed tension). Length dependence of Ca2+ sensitivity was decreased by caffeine when caffeine was administered in amounts estimated to result in 0.5 and 0.75 mM concentrations. Furthermore, the negative slope of the relationship between staircase potentiation and muscle length was diminished at the lower caffeine dose, and the slope was not different from zero after the higher dose (DT = 1.53 - 0.009 ML, r2 = 0.43). Our study shows that length dependence of Ca2+ sensitivity in intact skeletal muscle is diminished by caffeine. Caffeine also suppressed the length dependence of staircase potentiation, suggesting that the mechanism of this length dependence may be closely related to the mechanism for length dependence of Ca2+ sensitivity.

Further studies on the H-2 linked dependence of the adjuvant action of Brucella abortus

International Nuclear Information System (INIS)

Oth, D.; Sabolovic, D.

1978-01-01

The B 19S strain of Brucella abortus has been found to act as an adjuvant to the anti-sheep red blood cell (SRBC) reaction in some congenic strains of mice but not in others. If the recipient was H-2sup(b), there was no adjuvant effect (B 19S); neither was there (thymus-dependent) anti-B 19S reaction as measured by thymocyte activation and change of electrophoretic mobility. In contrast, there was a thymus-independent anti-B 19S reaction (production of haemagglutinins) as good in the H-2sup(b) mice as in the others. Experiments with T cell deprived mice showed that the adjuvant action of B 19S was thymus-dependent. As the anti-SRBC reaction without adjuvant was also thymus-dependent, it was difficult to distinguish anti-SRBC and anti-B reactions from the adjuvant action of B 19S on the anti-SRBC reaction. Several explanations are possible, all involving H-2 (Isup(r)) controlled thymus dependent mechanisms. (author)

Arsenic Trioxide Modulates the Central Snail Neuron Action Potential

Directory of Open Access Journals (Sweden)

Guan-Ling Lu

2009-09-01

Conclusion: As2O3 at 10 mM elicits BoPs in central snail neurons and this effect may relate to the PLC activity of the neuron, rather than protein kinase A activity, or calcium influxes of the neuron. As2O3 at higher concentration irreversibly abolishes the spontaneous action potentials of the neuron.

Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells

Science.gov (United States)

Saung, Wint Thu; Foskett, J. Kevin

2017-01-01

Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na+ currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na+ and K+ channels but contributed modestly to the kinetics of action potentials. PMID:28202574

Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

Directory of Open Access Journals (Sweden)

Philip Gemmell

Full Text Available Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+, inward rectifying K(+, L-type Ca(2+, and Na(+/K(+ pump currents in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al. at multiple cycle lengths (400, 600, 1,000 ms was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in

Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

Science.gov (United States)

Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T Alexander

2014-01-01

Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+), inward rectifying K(+), L-type Ca(2+), and Na(+)/K(+) pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally

Fluoxetine increases insulin action in obese type II (non-insulin dependent) diabetic patients

NARCIS (Netherlands)

Potter van Loon, B. J.; Radder, J. K.; Froelich, M.; Krans, H. Michiel J.; Zwinderman, A. H.; Meinders, A. E.

1992-01-01

Insulin resistance contributes to the metabolic defects in non-insulin dependent diabetes mellitus (NIDDM). Anorectic agents have been shown to improve insulin action in NIDDM, irrespective of weight reduction. In a double-blind placebo-controlled cross-over study, we examined hepatic and peripheral

Blocking the eIF2α kinase (PKR) enhances positive and negative forms of cortex-dependent taste memory.

Science.gov (United States)

Stern, Elad; Chinnakkaruppan, Adaikkan; David, Orit; Sonenberg, Nahum; Rosenblum, Kobi

2013-02-06

Age-associated memory deterioration (and the decline in ability to acquire new information) is one of the major diseases of our era. Cognitive enhancement can be achieved by using psycho-stimulants, such as caffeine or nicotine, but very little is known about drugs that can enhance the consolidation phase of memories in the cortex, the brain structure considered to store, at least partially, long-term memories. We used cortex-dependent taste-learning paradigms to test the hypothesis that pharmacological manipulation of the translation initiation eIF2α, which plays a role in hippocampus-dependent memory, can enhance positive or negative forms of taste memories. We found that dephosphorylation (Ser51) of eIF2α, specifically in the cortex, is both correlated with and necessary for normal memory consolidation. To reduce eIF2α phosphorylation and improve memory consolidation, we pharmacologically inhibited one of the eIF2α kinases, PKR, which is known to be involved in brain aging and Alzheimer's disease. Systemic or local microinjection of PKR inhibitor to the gustatory cortex enhanced both positive and negative forms of taste memory in rats and mice. Our results provide clear evidence that PKR plays a major role in cortex-dependent memory consolidation and, therefore, that pharmacological inhibition of PKR is a potential target for drugs to enhance cognition.

An intact action-perception coupling depends on the integrity of the cerebellum.

Science.gov (United States)

Christensen, Andrea; Giese, Martin A; Sultan, Fahad; Mueller, Oliver M; Goericke, Sophia L; Ilg, Winfried; Timmann, Dagmar

2014-05-07

It is widely accepted that action and perception in humans functionally interact on multiple levels. Moreover, areas originally suggested to be predominantly motor-related, as the cerebellum, are also involved in action observation. However, as yet, few studies provided unequivocal evidence that the cerebellum is involved in the action perception coupling (APC), specifically in the integration of motor and multisensory information for perception. We addressed this question studying patients with focal cerebellar lesions in a virtual-reality paradigm measuring the effect of action execution on action perception presenting self-generated movements as point lights. We measured the visual sensitivity to the point light stimuli based on signal detection theory. Compared with healthy controls cerebellar patients showed no beneficial influence of action execution on perception indicating deficits in APC. Applying lesion symptom mapping, we identified distinct areas in the dentate nucleus and the lateral cerebellum of both hemispheres that are causally involved in APC. Lesions of the right ventral dentate, the ipsilateral motor representations (lobules V/VI), and most interestingly the contralateral posterior cerebellum (lobule VII) impede the benefits of motor execution on perception. We conclude that the cerebellum establishes time-dependent multisensory representations on different levels, relevant for motor control as well as supporting action perception. Ipsilateral cerebellar motor representations are thought to support the somatosensory state estimate of ongoing movements, whereas the ventral dentate and the contralateral posterior cerebellum likely support sensorimotor integration in the cerebellar-parietal loops. Both the correct somatosensory as well as the multisensory state representations are vital for an intact APC.

Conduction velocity of action potentials measured from unidimensional latency-topography in human and frog skeletal muscle fibers.

Science.gov (United States)

Homma, S; Nakajima, Y; Hayashi, K; Toma, S

1986-01-01

Conduction of an action potential along skeletal muscle fibers was graphically displayed by unidimensional latency-topography, UDLT. Since the slopes of the equipotential line were linear and the width of the line was constant, it was possible to calculate conduction velocity from the slope. To determine conduction direction of the muscle action potential elicited by electric stimulation applied directly to the muscle, surface recording electrodes were placed on a two-dimensional plane over a human muscle. Thus a bi-dimensional topography was obtained. Then, twelve or sixteen surface electrodes were placed linearly along the longitudinal direction of the action potential conduction which was disclosed by the bi-dimensional topography. Thus conduction velocity of muscle action potential in man, calculated from the slope, was for m. brachioradialis, 3.9 +/- 0.4 m/s; for m. biceps brachii, 3.6 +/- 0.2 m/s; for m. sternocleidomastoideus, 3.6 +/- 0.4 m/s. By using a tungsten microelectrode to stimulate the motor axons, a convex-like equipotential line of an action potential in UDLT was obtained from human muscle fibers. Since a similar pattern of UDLT was obtained from experiments on isolated frog muscles, in which the muscle action potential was elicited by stimulating the motor axon, it was assumed that the maximum of the curve corresponds to the end-plate region, and that the slopes on both sides indicate bi-directional conduction of the action potential.

Fish oil curtails the human action potential dome in a heterogeneous manner: Implication for arrhythmogenesis

NARCIS (Netherlands)

Verkerk, Arie O.; den Ruijter, Hester M.; de Jonge, Nicolaas; Coronel, Ruben

2009-01-01

Omega-3 polyunsaturated fatty acids (omega3-PUFAs) from fish oil modulate various ion channels, including the L-type calcium current (I(Ca,L)). As a result, fish oil shortens the cardiac action potential and may cause a loss of the dome of the action potential (AP). Under conditions of increased

Inhibiting ROS-TFEB-Dependent Autophagy Enhances Salidroside-Induced Apoptosis in Human Chondrosarcoma Cells.

Science.gov (United States)

Zeng, Wei; Xiao, Tao; Cai, Anlie; Cai, Weiliang; Liu, Huanhuan; Liu, Jingling; Li, Jie; Tan, Miduo; Xie, Li; Liu, Ying; Yang, Xiangcheng; Long, Yi

2017-01-01

Autophagy modulation has been considered a potential therapeutic strategy for human chondrosarcoma, and a previous study indicated that salidroside exhibits significant anti-carcinogenic activity. However, the ability of salidroside to induce autophagy and its role in human chondrosarcoma cell death remains unclear. We exposed SW1353 cells to different concentrations of salidroside (0.5, 1 and 2 mM) for 24 h. RT-PCR, Western-blotting, Immunocytofluorescence, and Luciferase Reporter Assays were used to evaluate whether salidroside activated the TFEB-dependent autophagy. We show that salidroside induced significant apoptosis in the human chondrosarcoma cell line SW1353. In addition, we demonstrate that salidroside-induced an autophagic response in SW1353 cells, as evidenced by the upregulation of LC3-II and downregulation of P62. Moreover, pharmacological or genetic blocking of autophagy enhanced salidroside -induced apoptosis, indicating the cytoprotective role of autophagy in salidroside-treated SW1353 cells. Salidroside also induced TFEB (Ser142) dephosphorylation, subsequently to activated TFEB nuclear translocation and increase of TFEB reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes. Importantly, we found that salidroside triggered the generation of ROS in SW1353 cells. Furthermore, NAC, a ROS scavenger, abrogated the effects of salidroside on TFEB-dependent autophagy. These data demonstrate that salidroside increased TFEB-dependent autophagy by activating ROS signaling pathways in human chondrosarcoma cells. These data also suggest that blocking ROS-TFEB-dependent autophagy to enhance the activity of salidroside warrants further attention in treatment of human chondrosarcoma cells. © 2017 The Author(s). Published by S. Karger AG, Basel.

Frequency-Dependent Enhancement of Fluid Intelligence Induced by Transcranial Oscillatory Potentials

Energy Technology Data Exchange (ETDEWEB)

Santarnecchi, Emiliano [Univ. of Siena (Italy). Dept. of Medicine, Surgery and Neuroscience; Polizzotto, Nicola Riccardo [Univ. of Pittsburgh, PA (United States). Dept. of Psychiatry; Godone, Marco [Univ. of Siena (Italy). Dept. of Medicine, Surgery and Neuroscience; Giovannelli, Fabio [San Giovanni di Dio Hospital, Florence (Italy). Complex Unit of Neurology; Feurra, Matteo [Univ. of Siena (Italy). Dept. of Medicine, Surgery and Neuroscience; Matzen, Laura [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Rossi, Alessandro [Univ. of Siena (Italy). Dept. of Medicine, Surgery and Neuroscience; Rossi, Simone [Univ. of Siena (Italy). Dept. of Medicine, Surgery and Neuroscience

2013-08-05

Everyday problem solving requires the ability to go beyond experience by efficiently encoding and manipulating new information, i.e., fluid intelligence (Gf) [1]. Performance in tasks involving Gf, such as logical and abstract reasoning, has been shown to rely on distributed neural networks, with a crucial role played by prefrontal regions [2]. Synchronization of neuronal activity in the gamma band is a ubiquitous phenomenon within the brain; however, no evidence of its causal involvement in cognition exists to date [3]. Here, we show an enhancement of Gf ability in a cognitive task induced by exogenous rhythmic stimulation within the gamma band. Imperceptible alternating current [4] delivered through the scalp over the left middle frontal gyrus resulted in a frequency-specific shortening of the time required to find the correct solution in a visuospatial abstract reasoning task classically employed to measure Gf abilities (i.e., Raven’s matrices) [5]. Crucially, gamma-band stimulation (γ-tACS) selectively enhanced performance only on more complex trials involving conditional/logical reasoning. The finding presented here supports a direct involvement of gamma oscillatory activity in the mechanisms underlying higher-order human cognition.

Differential effects of thioridazine enantiomers on action potential duration in rabbit papillary muscle

DEFF Research Database (Denmark)

Jensen, Ask Schou; Pennisi, Cristian Pablo; Sevcencu, Cristian

2015-01-01

with (+)-thioridazine. In this study we for the first time investigate the cardiotoxicity of the isolated thioridazine enantiomers and show their effects on ventricular repolarization. The effects of (+)-thioridazine, (-)-thioridazine, and racemate on the rabbit ventricular action potential duration (APD) were...... investigated in a randomized controlled blinded experiment. Action potentials were measured in papillary muscles isolated from 21 female rabbits, and the drug effect on 90% APD in comparison with control (DeltaDelta-APD90) was evaluated. Increasing concentrations of (+)-thioridazine and the racemate caused...

Information and Communication Technologies (ICT) as keys to the enhancement of public awareness about potential earth impacts

Science.gov (United States)

Usikov, Denis A.

2013-09-01

The 2007 Planetary Defense Conference recommends "to provide or enhance Internet sites to show how threats evolve and to illustrate possible action scenarios". Thereby, establishment of informational and communicational AsteroidAware web-site with the exact, authentic data about the past and the present of Earth's impact events will assist in achievement of positive results and progress in different directions on political, international, social and scientific levels. Expanded ICT's capabilities for popularization of planetary defense can help in resolving the problem of low public interest. The project's primary intent lies in popularizing the concept of planetary defenses and attracting attention to the potential dangers that threaten the Earth from outer space. The result of the efforts falling into the boundaries of this project would be an increased amount of social participation in the process of developing solutions for and increasing awareness of potential collisions between various astral bodies and the Earth. The project is also aimed at creating a foundation for the interaction between scientists and executives from around the world to facilitate international efforts of searching for fitting measures towards lowering threat levels and developing strategies revolving around united actions against potential threats.

Environmentally dependent bond-order potentials: New ...

Indian Academy of Sciences (India)

Environmentally dependent bond-order potentials: New developments and applications ... for modelling amorphous structure we found that the and bond integrals are not only transferable between graphite and diamond structures but they are also strongly anisotropic due to inter-plan bonding between graphite sheets.

Recovery of Action Potentials and Twitches after K-contractures in Frog Skeletal Muscle(Physiology)

OpenAIRE

Atsuko, Suzuki; Ibuki, Shirakawa; Kazunari, Noguchi; Hirohiko, Kishi; Haruo, Sugi; Department of Physiology, School of Medicine, Teikyo University:(Present office)Department of Physical Therapy, Health Science University; Department of Physiology, School of Medicine, Teikyo University; Department of Physiology, School of Medicine, Teikyo University; Department of Physiology, School of Medicine, Teikyo University; Department of Physiology, School of Medicine, Teikyo University

2004-01-01

To give information about intracellular Ca^ translocation during and after K-contractures in vertebrate skeletal muscle fibers, we examined recovery of action potentials and twitches after interruption and spontaneous relaxation of K-contractures at low temperature (3℃) that greatly reduced the rate of Ca^ reuptake by the sarcoplasmic reticulum. On membrane repolarization interrupting K-contractures, the amplitude of both action potentials and twitches recovered quickly, while the falling pha...

Surface deformation during an action potential in pearled cells

Science.gov (United States)

Mussel, Matan; Fillafer, Christian; Ben-Porath, Gal; Schneider, Matthias F.

2017-11-01

Electric pulses in biological cells (action potentials) have been reported to be accompanied by a propagating cell-surface deformation with a nanoscale amplitude. Typically, this cell surface is covered by external layers of polymer material (extracellular matrix, cell wall material, etc.). It was recently demonstrated in excitable plant cells (Chara braunii) that the rigid external layer (cell wall) hinders the underlying deformation. When the cell membrane was separated from the cell wall by osmosis, a mechanical deformation, in the micrometer range, was observed upon excitation of the cell. The underlying mechanism of this mechanical pulse has, to date, remained elusive. Herein we report that Chara cells can undergo a pearling instability, and when the pearled fragments were excited even larger and more regular cell shape changes were observed (˜10 -100 μ m in amplitude). These transient cellular deformations were captured by a curvature model that is based on three parameters: surface tension, bending rigidity, and pressure difference across the surface. In this paper these parameters are extracted by curve-fitting to the experimental cellular shapes at rest and during excitation. This is a necessary step to identify the mechanical parameters that change during an action potential.

Davydov–Chaban Hamiltonian in presence of time-dependent potential

Energy Technology Data Exchange (ETDEWEB)

Sobhani, Hadi; Hassanabadi, Hassan, E-mail: h.hassanabadi@shahroodut.ac.ir

2016-09-10

In this article, we have investigated collective effects of atomic nuclei in presence of a time-dependent potential in Davydov–Chaban Hamiltonian. Since such potential has an explicit time-dependency, in order to obtain the wave function of considered system, we should face with time-dependent Schrödinger equation. Obtaining the wave function could be possible using Lewis–Riesenfeld dynamical invariant method. Appropriate dynamical invariant has been constructed after determining the wave functions and values, the wave function will obtain.

Onset Dynamics of Action Potentials in Rat Neocortical Neurons and Identified Snail Neurons: Quantification of the Difference

OpenAIRE

Volgushev, Maxim; Malyshev, Aleksey; Balaban, Pavel; Chistiakova, Marina; Volgushev, Stanislav; Wolf, Fred

2008-01-01

The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the...

Rapid corticosteroid actions on synaptic plasticity in the mouse basolateral amygdala: relevance of recent stress history and β-adrenergic signaling.

Science.gov (United States)

Sarabdjitsingh, R A; Joëls, M

2014-07-01

The rodent stress hormone corticosterone rapidly enhances long-term potentiation in the CA1 hippocampal area, but leads to a suppression when acting in a more delayed fashion. Both actions are thought to contribute to stress effects on emotional memory. Emotional memory formation also involves the basolateral amygdala, an important target area for corticosteroid actions. We here (1) investigated the rapid effects of corticosterone on amygdalar synaptic potentiation, (2) determined to what extent these effects depend on the mouse's recent stress history or (3) on prior β-adrenoceptor activation; earlier studies at the single cell level showed that especially a recent history of stress changes the responsiveness of basolateral amygdala neurons to corticosterone. We report that, unlike the hippocampus, stress enhances amygdalar synaptic potentiation in a slow manner. In vitro exposure to 100 nM corticosterone quickly decreases synaptic potentiation, and causes only transient potentiation in tissue from stressed mice. This transient type of potentiation is also seen when β-adrenoceptors are blocked during stress and this is further exacerbated by subsequent in vitro administered corticosterone. We conclude that stress and corticosterone change synaptic potentiation in the basolateral amygdala in a manner opposite to that seen in the hippocampus and that renewed exposure to corticosterone only allows induction of non-persistent forms of synaptic potentiation. Copyright © 2013 Elsevier Inc. All rights reserved.

Glucose enhancement of memory depends on initial thirst.

Science.gov (United States)

Scholey, Andrew B; Sünram-Lea, Sandra I; Greer, Joanna; Elliott, Jade; Kennedy, David O

2009-12-01

This double-blind, placebo-controlled study examined the influence of appetitive state on glucose enhancement of memory. Participants rated their mood, hunger and thirst, then consumed a 25 g glucose drink or a matched placebo 20 min prior to a verbal memory task. There was a double dissociation when the effects of thirst ratings and drink on subsequent memory performance were considered. Those who were initially less thirsty recalled significantly more words following glucose than placebo; those who were more thirsty recalled significantly fewer words after glucose than placebo. Glucose enhancement of memory may therefore critically depend on participants' initial thirst.

Hearing, listening, action: Enhancing nursing practice through aural awareness education.

Science.gov (United States)

Collins, Anita; Vanderheide, Rebecca; McKenna, Lisa

2014-01-01

Abstract Noise overload within the clinical environment has been found to interfere with the healing process for patients, as well as nurses' ability to assess patients effectively. Awareness and responsibility for noise production begins during initial nursing training and consequently a program to enhance aural awareness skills was designed for graduate entry nursing students in an Australian university. The program utilized an innovative combination of music education activities to develop the students' ability to distinguishing individual sounds (hearing), appreciate patients' experience of sounds (listening) and improve their auscultation skills and reduce the negative effects of noise on patients (action). Using a mixed methods approach, students reported heightened auscultation skills and greater recognition of both patients' and clinicians' aural overload. Results of this pilot suggest that music education activities can assist nursing students to develop their aural awareness and to action changes within the clinical environment to improve the patient's experience of noise.

Scaling of the quark-antiquark potential and improved actions in SU(2) lattice gauge theory

International Nuclear Information System (INIS)

Montvay, I.; Gutbrod, F.

1983-11-01

The scaling behaviour of the quark-antiquark potential is investigated by a high statistics Monte Carlo calculation in SU(2) lattice gauge theory. Besides the standard one-plaquette action we also use Symanzik's tree-level improved action and Wilson's block-spin improved action. No significant differences between Symanzik's action and the standard action have been observed. For small β Wilson's action scales differently. The string tension value chi extracted from the data corresponds to Λsub(latt) = (0.018 +- 0.001) √chi for the one-plaquette action. (orig.)

ICT Enhanced Buildings Potentials

DEFF Research Database (Denmark)

Christiansson, Per

2007-01-01

component systems that are accessed and integrated in the real world of building use in different contexts. The ICT systems may be physically or virtually embedded in the building. Already in 1982 AT&T established the 'intelligent buildings', IB, concept due to marketing reasons and the Informart building...... with focus on virtual building models support, new services and user environment definitions and development, virtual spaces and augmented reality, intelligent building components, application ontologies, and ICT systems integration to illustrate ICT enhanced buildings potentials and R&D needs.  ...

Labor potential: enhancing its development

Directory of Open Access Journals (Sweden)

O.P. Melnichuk

2016-06-01

Full Text Available This publication presents the views of the author about the need to expand research of labor potential, estimation of quantitative indicators and qualitative characteristics at the individual, regional levels and the state as a whole to develop the mechanisms of its development. The existing methods of labour potential assessment are mainly based on the probable approach taking into account external and internal factors. In the case of assessment of labour potential of a single enterprise for the most suitable for this production method the mechanisms of its development can be worked out. However, for the state under a certain depreciation of the resource, property, financial and other potentials, aggressive manifestations of the crisis phenomena, processes etc. to resolve urgent is the problem of enhancing the development of qualitative characteristics of labor potential at all its levels. In this context it is important to exploit the potential of domestic education and science which now continue to be reformed for the sake of achieving European standards, using the advanced experience of other countries. Every means of legal, financial, managerial, and organizational impact should be used for this.

Automated grouping of action potentials of human embryonic stem cell-derived cardiomyocytes.

Science.gov (United States)

Gorospe, Giann; Zhu, Renjun; Millrod, Michal A; Zambidis, Elias T; Tung, Leslie; Vidal, Rene

2014-09-01

Methods for obtaining cardiomyocytes from human embryonic stem cells (hESCs) are improving at a significant rate. However, the characterization of these cardiomyocytes (CMs) is evolving at a relatively slower rate. In particular, there is still uncertainty in classifying the phenotype (ventricular-like, atrial-like, nodal-like, etc.) of an hESC-derived cardiomyocyte (hESC-CM). While previous studies identified the phenotype of a CM based on electrophysiological features of its action potential, the criteria for classification were typically subjective and differed across studies. In this paper, we use techniques from signal processing and machine learning to develop an automated approach to discriminate the electrophysiological differences between hESC-CMs. Specifically, we propose a spectral grouping-based algorithm to separate a population of CMs into distinct groups based on the similarity of their action potential shapes. We applied this method to a dataset of optical maps of cardiac cell clusters dissected from human embryoid bodies. While some of the nine cell clusters in the dataset are presented with just one phenotype, the majority of the cell clusters are presented with multiple phenotypes. The proposed algorithm is generally applicable to other action potential datasets and could prove useful in investigating the purification of specific types of CMs from an electrophysiological perspective.

GSK3β-dependent inhibition of AMPK potentiates activation of neutrophils and macrophages and enhances severity of acute lung injury

Science.gov (United States)

Park, Dae Won; Jiang, Shaoning; Liu, Yanping; Siegal, Gene P.; Inoki, Ken; Abraham, Edward

2014-01-01

Although AMP-activated protein kinase (AMPK) is involved in regulating carbohydrate and lipid metabolism, activated AMPK also plays an anti-inflammatory role in many cell populations. However, despite the ability of AMPK activation to diminish the severity of inflammatory responses, previous studies have found that AMPK activity is diminished in LPS-treated neutrophils and also in lungs of mice with LPS-induced acute lung injury (ALI). Since GSK3β participates in regulating AMPK activity, we examined potential roles for GSK3β in modulating LPS-induced activation of neutrophils and macrophages and in influencing severity of ALI. We found that GSK3β-dependent phosphorylation of T479-AMPK was associated with pT172 dephosphorylation and inactivation of AMPK following TLR4 engagement. GSK3β inhibitors BIO (6-bromoindirubin-3′-oxime), SB216763, or siRNA knockdown of GSK3β, but not the PI3K/AKT inhibitor LY294002, prevented Thr172-AMPK dephosphorylation. Exposure to LPS resulted in rapid binding between IKKβ and AMPKα, and phosphorylation of S485-AMPK by IKKβ. These results suggest that IKKβ-dependent phosphorylation of S485-AMPK was an essential step in subsequent phosphorylation and inactivation AMPK by GSK3β. Inhibition of GSK3β activity delayed IκBα degradation and diminished expression of the proinflammatory TNF-α in LPS-stimulated neutrophils and macrophages. In vivo, inhibition of GSK3β decreased the severity of LPS-induced lung injury as assessed by development of pulmonary edema, production of TNF-α and MIP-2, and release of the alarmins HMGB1 and histone 3 in the lungs. These results show that inhibition of AMPK by GSK3β plays an important contributory role in enhancing LPS-induced inflammatory responses, including worsening the severity of ALI. PMID:25239914

The different intracellular action potentials of fast and slow muscle fibres = Différences entre les potentiels d'action intracellulaires de fibres musculaires rapides et lentes

NARCIS (Netherlands)

Wallinga, W.; Gielen, Frans L.H.; Wirtz, Peter; de Jong, Paul; Broenink, Johannes F.

1985-01-01

The time course of the intracellular action potential was studied quantitatively, because it is an important factor in the generation of electromyographic signals. In in vivo preparations of the m. EDL and m. soleus of the rat single motor units were stimulated and intracellular action potentials

The Potential of Deweyan-Inspired Action Research

Science.gov (United States)

Stark, Jody L.

2014-01-01

In its broadest sense, pragmatism could be said to be the philosophical orientation of all action research. Action research is characterized by research, action, and participation grounded in democratic principles and guided by the aim of social improvement. Furthermore, action research is an active process of inquiry that does not admit…

Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

Science.gov (United States)

Meredith, Rhiannon M.; van Ooyen, Arjen

2012-01-01

CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy. PMID:22719238

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

Directory of Open Access Journals (Sweden)

Zexuan eLi

2012-05-01

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

Ficus deltoidea: A Potential Alternative Medicine for Diabetes Mellitus

Directory of Open Access Journals (Sweden)

Zainah Adam

2012-01-01

Full Text Available Ficus deltoidea from the Moraceae family has been scientifically proven to reduce hyperglycemia at different prandial states. In this study, we evaluate the mechanisms that underlie antihyperglycemic action of Ficus deltoidea. The results had shown that hot aqueous extract of Ficus deltoidea stimulated insulin secretion significantly with the highest magnitude of stimulation was 7.31-fold (P<0.001. The insulin secretory actions of the hot aqueous extract involved K+ ATP channel-dependent and K+ ATP-channel-independent pathway. The extract also has the ability to induce the usage of intracellular Ca2+ to trigger insulin release. The ethanolic and methanolic extracts enhanced basal and insulin-mediated glucose uptake into adipocytes cells. The extracts possess either insulin-mimetic or insulin-sensitizing property or combination of both properties during enhancing glucose uptake into such cells. Meanwhile, the hot aqueous and methanolic extracts augmented basal and insulin-stimulated adiponectin secretion from adipocytes cells. From this study, it is suggested that Ficus deltoidea has the potential to be developed as future oral antidiabetic agent.

ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players.

Science.gov (United States)

Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

2016-09-15

The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca(2+)) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca(2+) regulates cell death both at the early and late stages of apoptosis. Severe Ca(2+) dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca(2+) (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca(2+) and action potential in ER stress-mediated apoptosis.

Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential.

Science.gov (United States)

Desbois, Andrew P; Smith, Valerie J

2010-02-01

Amongst the diverse and potent biological activities of free fatty acids (FFAs) is the ability to kill or inhibit the growth of bacteria. The antibacterial properties of FFAs are used by many organisms to defend against parasitic or pathogenic bacteria. Whilst their antibacterial mode of action is still poorly understood, the prime target of FFA action is the cell membrane, where FFAs disrupt the electron transport chain and oxidative phosphorylation. Besides interfering with cellular energy production, FFA action may also result from the inhibition of enzyme activity, impairment of nutrient uptake, generation of peroxidation and auto-oxidation degradation products or direct lysis of bacterial cells. Their broad spectrum of activity, non-specific mode of action and safety makes them attractive as antibacterial agents for various applications in medicine, agriculture and food preservation, especially where the use of conventional antibiotics is undesirable or prohibited. Moreover, the evolution of inducible FFA-resistant phenotypes is less problematic than with conventional antibiotics. The potential for commercial or biomedical exploitation of antibacterial FFAs, especially for those from natural sources, is discussed.

Fokker-action principle for a system of particles interacting through a linear potential

International Nuclear Information System (INIS)

Rivacoba, A.

1984-01-01

A Fokker-action principle for a system of scalar particles interacting through their time-symmetric relativistic generalization of linear potential is obtained. From this action, motion equations and conservation laws for the total energy and angular momentum of the system, in which field contributions are included, are derived. These equations are exactly applied to the problem suggested by Schild of two particles moving in circular concentric orbits

Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy

NARCIS (Netherlands)

Kole, Maarten H. P.; Letzkus, Johannes J.; Stuart, Greg J.

2007-01-01

Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action

Enhanced basal late sodium current appears to underlie the age-related prolongation of action potential duration in guinea pig ventricular myocytes.

Science.gov (United States)

Song, Yejia; Belardinelli, Luiz

2017-12-14

Aging hearts have prolonged QT interval and are vulnerable to oxidative stress. Because the QT interval indirectly reflects the action potential duration (APD), we examined the hypotheses that 1) the APD of ventricular myocytes increases with age; 2) the age-related prolongation of APD is due to an enhancement of basal late Na + current (I NaL ); 3) inhibition of I NaL may protect aging hearts from arrhythmogenic effects of hydrogen peroxide (H 2 O 2 ). Experiments were performed on ventricular myocytes isolated from one-month (young) and one-year (old) guinea pigs (GPs). The APD of myocytes from old GPs was significantly longer than that from young GPs and was shortened by the I NaL inhibitors GS967 and tetrodotoxin. The magnitude of I NaL was significantly larger in myocytes from old than from young GPs. The CaMKII inhibitors KN-93 and AIP and the Na V 1.5-channel blocker MTSEA blocked the I NaL . There were no significant differences between myocytes from young and old GPs in L-type Ca 2+ current and the rapidly- and slowly-activating delayed rectifier K + currents, although the inward rectifier K + current was slightly decreased in myocytes from old GPs. H 2 O 2 induced more early afterdepolarizations in myocytes from old than from young GPs. The effect of H 2 O 2 was attenuated by GS967. The results suggest that 1) the APD of myocytes from old GPs is prolonged, 2) a CaMKII-mediated increase in Na V 1.5-channel I NaL is responsible for the prolongation of APD, and 3) Inhibition of I NaL may be beneficial for maintaining electrical stability under oxidative stress in myocytes of old GPs.

Application of Emergency Action Levels from Potential Release at Research Reactor HANARO

International Nuclear Information System (INIS)

Kim, Jongsoo; Lee, Goan Yub; Lee, Hae Choi; Kim, Bong Suk

2014-01-01

Execution of the protective action promptly is possible that Emergency Action Levels (EALs) must be established for a radiological release from nuclear facility. The EALs for electric power reactor are already developed and applied to recognize an emergency situation rapidly. Recently the IAEA published the safety report including the EALs for research reactor. This paper describes the EALs to apply for a potential release pathway at the research reactor HANARO. The results of table 1 and 2 will be higher than actual because the weather condition in real situation is difference. However, the EALs applying the potential stack release, ground release and site can be useful for research reactor HANARO making the emergency declaration. The EALs at the site boundary of the table 3 can be applied to protect the off-site public

Comparative investigations of manual action representations: evidence that chimpanzees represent the costs of potential future actions involving tools.

Science.gov (United States)

Frey, Scott H; Povinelli, Daniel J

2012-01-12

The ability to adjust one's ongoing actions in the anticipation of forthcoming task demands is considered as strong evidence for the existence of internal action representations. Studies of action selection in tool use reveal that the behaviours that we choose in the present moment differ depending on what we intend to do next. Further, they point to a specialized role for mechanisms within the human cerebellum and dominant left cerebral hemisphere in representing the likely sensory costs of intended future actions. Recently, the question of whether similar mechanisms exist in other primates has received growing, but still limited, attention. Here, we present data that bear on this issue from a species that is a natural user of tools, our nearest living relative, the chimpanzee. In experiment 1, a subset of chimpanzees showed a non-significant tendency for their grip preferences to be affected by anticipation of the demands associated with bringing a tool's baited end to their mouths. In experiment 2, chimpanzees' initial grip preferences were consistently affected by anticipation of the forthcoming movements in a task that involves using a tool to extract a food reward. The partial discrepancy between the results of these two studies is attributed to the ability to accurately represent differences between the motor costs associated with executing the two response alternatives available within each task. These findings suggest that chimpanzees are capable of accurately representing the costs of intended future actions, and using those predictions to select movements in the present even in the context of externally directed tool use.

Enhanced clathrin-dependent endocytosis in the absence of calnexin.

Directory of Open Access Journals (Sweden)

Hao-Dong Li

Full Text Available Calnexin, together with calreticulin, constitute the calnexin/calreticulin cycle. Calnexin is a type I endoplasmic reticulum integral membrane protein and molecular chaperone responsible for the folding and quality control of newly-synthesized (glycoproteins. The endoplasmic reticulum luminal domain of calnexin is responsible for lectin-like activity and interaction with nascent polypeptide chains. The role of the C-terminal, cytoplasmic portion of calnexin is not clear.Using yeast two hybrid screen and immunoprecipitation techniques, we showed that the Src homology 3-domain growth factor receptor-bound 2-like (Endophilin interacting protein 1 (SGIP1, a neuronal specific regulator of endocytosis, forms complexes with the C-terminal cytoplasmic domain of calnexin. The calnexin cytoplasmic C-tail interacts with SGIP1 C-terminal domains containing the adaptor complexes medium subunit (Adap-Comp-Sub region. Calnexin-deficient cells have enhanced clathrin-dependent endocytosis in neuronal cells and mouse neuronal system. This is reversed by expression of full length calnexin or calnexin C-tail.We show that the effects of SGIP1 and calnexin C-tail on clathrin-dependent endocytosis are due to modulation of the internalization of the receptor-ligand complexes. Enhanced clathrin-dependent endocytosis in the absence of calnexin may contribute to the neurological phenotype of calnexin-deficient mice.

Characterizing the effects of intermittent faults on a processor for dependability enhancement strategy.

Science.gov (United States)

Wang, Chao Saul; Fu, Zhong-Chuan; Chen, Hong-Song; Wang, Dong-Sheng

2014-01-01

As semiconductor technology scales into the nanometer regime, intermittent faults have become an increasing threat. This paper focuses on the effects of intermittent faults on NET versus REG on one hand and the implications for dependability strategy on the other. First, the vulnerability characteristics of representative units in OpenSPARC T2 are revealed, and in particular, the highly sensitive modules are identified. Second, an arch-level dependability enhancement strategy is proposed, showing that events such as core/strand running status and core-memory interface events can be candidates of detectable symptoms. A simple watchdog can be deployed to detect application running status (IEXE event). Then SDC (silent data corruption) rate is evaluated demonstrating its potential. Third and last, the effects of traditional protection schemes in the target CMT to intermittent faults are quantitatively studied on behalf of the contribution of each trap type, demonstrating the necessity of taking this factor into account for the strategy.

Characterizing the Effects of Intermittent Faults on a Processor for Dependability Enhancement Strategy

Directory of Open Access Journals (Sweden)

Chao(Saul Wang

2014-01-01

Full Text Available As semiconductor technology scales into the nanometer regime, intermittent faults have become an increasing threat. This paper focuses on the effects of intermittent faults on NET versus REG on one hand and the implications for dependability strategy on the other. First, the vulnerability characteristics of representative units in OpenSPARC T2 are revealed, and in particular, the highly sensitive modules are identified. Second, an arch-level dependability enhancement strategy is proposed, showing that events such as core/strand running status and core-memory interface events can be candidates of detectable symptoms. A simple watchdog can be deployed to detect application running status (IEXE event. Then SDC (silent data corruption rate is evaluated demonstrating its potential. Third and last, the effects of traditional protection schemes in the target CMT to intermittent faults are quantitatively studied on behalf of the contribution of each trap type, demonstrating the necessity of taking this factor into account for the strategy.

Actions for Professional Development to Enhance Competence in Communicating Scientific Results

Directory of Open Access Journals (Sweden)

Alexeis Ruíz-Díaz

2017-04-01

Full Text Available The main goal of this research is to propose an action plan for professional development to enhance competence in communicating scientific results in teachers of municipal secondary schools. The research is part of a complementary methodological approach that combines different quantitative and qualitative methods based on specific objectives. The diagnosis was made at the Municipal University Center of Sagua La Grande, with a sample of 25 teachers who are members of the Industrial Engineering career staff at the institution, attached to the Central University “Marta Abreu” of Las Villas, Cuba. Regularities were found from the stage of the initial diagnosis of professional development needs and the level in which the “competence in communicating scientific results” variable was. With this information justifying the purposes of this research, a process was designed following a systemic approach, and the practical result was the proposal of the organization and design of an action plan for development through postgraduate education forms during the implementation phase.

Power effects on cognitive control: Turning conflict into action.

Science.gov (United States)

Schmid, Petra C; Kleiman, Tali; Amodio, David M

2015-06-01

Power is known to promote effective goal pursuit, especially when it requires one to overcome distractions or bias. We proposed that this effect involves the ability to engage and implement cognitive control. In Study 1, we demonstrated that power enhances behavioral performance on a response conflict task and that it does so by enhancing controlled processing rather than by reducing automatic processing. In Study 2, we used an event-related potential index of anterior cingulate activity to test whether power effects on control were due to enhanced conflict sensitivity or action implementation. Power did not significantly affect neural sensitivity to conflict; rather, high power was associated with a stronger link between conflict processing and intended action, relative to low power. These findings suggest a new perspective on how social factors can affect controlled processing and offer new evidence regarding the transition between conflict detection and the implementation of action control. (c) 2015 APA, all rights reserved).

A study on the dependency evaluation for multiple human actions in human reliability analysis of probabilistic safety assessment

International Nuclear Information System (INIS)

Kang, D. I.; Yang, J. E.; Jung, W. D.; Sung, T. Y.; Park, J. H.; Lee, Y. H.; Hwang, M. J.; Kim, K. Y.; Jin, Y. H.; Kim, S. C.

1997-02-01

This report describes the study results on the method of the dependency evaluation and the modeling, and the limited value of human error probability (HEP) for multiple human actions in accident sequences of probabilistic safety assessment (PSA). THERP and Parry's method, which have been generally used in dependency evaluation of human reliability analysis (HRA), are introduced and their limitations are discussed. New dependency evaluation method in HRA is established to make up for the weak points of THERP and Parry's methods. The limited value of HEP is also established based on the review of several HRA related documents. This report describes the definition, the type, the evaluation method, and the evaluation example of dependency to help the reader's understanding. It is expected that this study results will give a guidance to HRA analysts in dependency evaluation of multiple human actions and enable PSA analysts to understand HRA in detail. (author). 23 refs., 3 tabs., 2 figs

Sensitivity to structure in action sequences: An infant event-related potential study.

Science.gov (United States)

Monroy, Claire D; Gerson, Sarah A; Domínguez-Martínez, Estefanía; Kaduk, Katharina; Hunnius, Sabine; Reid, Vincent

2017-05-06

Infants are sensitive to structure and patterns within continuous streams of sensory input. This sensitivity relies on statistical learning, the ability to detect predictable regularities in spatial and temporal sequences. Recent evidence has shown that infants can detect statistical regularities in action sequences they observe, but little is known about the neural process that give rise to this ability. In the current experiment, we combined electroencephalography (EEG) with eye-tracking to identify electrophysiological markers that indicate whether 8-11-month-old infants detect violations to learned regularities in action sequences, and to relate these markers to behavioral measures of anticipation during learning. In a learning phase, infants observed an actor performing a sequence featuring two deterministic pairs embedded within an otherwise random sequence. Thus, the first action of each pair was predictive of what would occur next. One of the pairs caused an action-effect, whereas the second did not. In a subsequent test phase, infants observed another sequence that included deviant pairs, violating the previously observed action pairs. Event-related potential (ERP) responses were analyzed and compared between the deviant and the original action pairs. Findings reveal that infants demonstrated a greater Negative central (Nc) ERP response to the deviant actions for the pair that caused the action-effect, which was consistent with their visual anticipations during the learning phase. Findings are discussed in terms of the neural and behavioral processes underlying perception and learning of structured action sequences. Copyright © 2017 Elsevier Ltd. All rights reserved.

An in vitro study of enhanced H+ diffusion by urease action on urea. Implications for Helicobacter pylori-associated peptic ulceration.

Science.gov (United States)

Desai, M A; Vadgama, P M

1993-10-01

The in vitro effect of urea and hydrolysis of urea by urease on mucus H+ permeability is reported here. The effective DHCl values indicate a strong pH dependence for H+ diffusion in both water and mucus layers, with no apparent trend at concentrations between 1 and 50 mM urea. However, the estimated DHCl at near-neutral and alkaline pH are 4- to 10-fold lower through mucus than through aqueous films. Moreover, the pKa values of HCO3- and NH3 (generated by urease action on urea) had a profound effect on measured DHCl. These in vitro studies suggest that a high local concentration of NH3 and HCO3- within the mucus layer, generated by the action of Helicobacter pylori urease on endogenous intragastric urea, could greatly accelerate proton flux to the surface epithelium by operation of a buffer shuttle. This results in enhanced H+ permeability, particularly at pKa values of HCO3- and NH3, and in extreme circumstances it may result in gastric ulcer formation.

FLUOXETINE INCREASES INSULIN ACTION IN OBESE NONDIABETIC AND IN OBESE NON-INSULIN-DEPENDENT DIABETIC INDIVIDUALS

NARCIS (Netherlands)

Potter van Loon, B. J.; Radder, J. K.; Froelich, M.; Krans, H. M.; Zwinderman, A. H.; Meinders, A. E.

1992-01-01

Insulin resistance contributes to the metabolic defects in non-insulin-dependent diabetes mellitus (NIDDM). Anorectic agents have been shown to improve insulin action in NIDDM, irrespective of weight reduction. The serotonin-reuptake inhibiting agent fluoxetine has recently been recognized as an

A distance-dependent metal-enhanced fluorescence sensing platform based on molecular beacon design.

Science.gov (United States)

Zhou, Zhenpeng; Huang, Hongduan; Chen, Yang; Liu, Feng; Huang, Cheng Zhi; Li, Na

2014-02-15

A new metal-enhanced fluorescence (MEF) based platform was developed on the basis of distance-dependent fluorescence quenching-enhancement effect, which combined the easiness of Ag-thiol chemistry with the MEF property of noble-metal structures as well as the molecular beacon design. For the given sized AgNPs, the fluorescence enhancement factor was found to increase with a d(6) dependency in agreement with fluorescence resonance energy transfer mechanism at shorter distance and decrease with a d(-3) dependency in agreement with plasmonic enhancement mechanism at longer distance between the fluorophore and the AgNP surface. As a proof of concept, the platform was demonstrated by a sensitive detection of mercuric ions, using thymine-containing molecular beacon to tune silver nanoparticle (AgNP)-enhanced fluorescence. Mercuric ions were detected via formation of a thymine-mercuric-thymine structure to open the hairpin, facilitating fluorescence recovery and AgNP enhancement to yield a limit of detection of 1 nM, which is well below the U.S. Environmental Protection Agency regulation of the Maximum Contaminant Level Goal (10nM) in drinking water. Since the AgNP functioned as not only a quencher to reduce the reagent blank signal but also an enhancement substrate to increase fluorescence of the open hairpin when target mercuric ions were present, the quenching-enhancement strategy can greatly improve the detection sensitivity and can in principle be a universal approach for various targets when combined with molecular beacon design. © 2013 Elsevier B.V. All rights reserved.

Exact time-dependent exchange-correlation potentials for strong-field electron dynamics

International Nuclear Information System (INIS)

Lein, Manfred; Kuemmel, Stephan

2005-01-01

By solving the time-dependent Schroedinger equation and inverting the time-dependent Kohn-Sham scheme we obtain the exact time-dependent exchange-correlation potential of density-functional theory for the strong-field dynamics of a correlated system. We demonstrate that essential features of the exact exchange-correlation potential can be related to derivative discontinuities in stationary density-functional theory. Incorporating the discontinuity in a time-dependent density-functional calculation greatly improves the description of the ionization process

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

International Nuclear Information System (INIS)

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

1990-01-01

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

Isospin-dependent term in the relativistic microscopic optical potential

International Nuclear Information System (INIS)

Rong Jian; Ma Zhongyu; National Laboratory of Heavy Ion Accelerator of Lanzhou, Lanzhou; Chinese Academy of Sciences, Beijing

2005-01-01

The isospin-dependence of the relativistic microscopic optical potential is investigated in the Dirac Brueckner-Hartree-Fock approach. The isospin part of the microscopic optical potential is emphasized. A local density approximation is adopted for finite nuclei. Taking 208 Pb as example, the difference between proton and neutron optical potentials is studied and compared with the phenomenological Lane Model potential. (authors)

Glycoengineering of therapeutic antibodies enhances monocyte/macrophage-mediated phagocytosis and cytotoxicity.

Science.gov (United States)

Herter, Sylvia; Birk, Martina C; Klein, Christian; Gerdes, Christian; Umana, Pablo; Bacac, Marina

2014-03-01

Therapeutic Abs possess several clinically relevant mechanisms of action including perturbation of tumor cell signaling, activation of complement-dependent cytotoxicity, Ab-dependent cellular cytotoxicity (ADCC), Ab-dependent cellular phagocytosis (ADCP), and induction of adaptive immunity. In view of the important role of phagocytic lineage cells in the mechanism of action of therapeutic Abs, we analyzed FcγR receptor-dependent effector functions of monocytes and macrophages triggered by glycoengineered (GE) Abs (having enhanced FcγRIIIa [CD16a] binding affinity) versus their wild-type (WT) counterparts under different experimental conditions. We first defined the precise FcγR repertoire on classical and nonclassical intermediate monocytes--M1 and M2c macrophage populations. We further show that WT and GE Abs display comparable binding and induce similar effector functions (ADCC and ADCP) in the absence of nonspecific, endogenous IgGs. However, in the presence of these IgGs (i.e., in a situation that more closely mimics physiologic conditions), GE Abs display significantly superior binding and promote stronger monocyte and macrophage activity. These data show that in addition to enhancing CD16a-dependent NK cell cytotoxicity, glycoengineering also enhances monocyte and macrophage phagocytic and cytotoxic activities through enhanced binding to CD16a under conditions that more closely resemble the physiologic setting.

Do enhanced states exist? Boosting cognitive capacities through an action video-game.

Science.gov (United States)

Kozhevnikov, Maria; Li, Yahui; Wong, Sabrina; Obana, Takashi; Amihai, Ido

2018-04-01

This research reports the existence of enhanced cognitive states in which dramatic temporary improvements in temporal and spatial aspects of attention were exhibited by participants who played (but not by those who merely observed) action video-games meeting certain criteria. Specifically, Experiments 1 and 2 demonstrate that the attentional improvements were exhibited only by participants whose skills matched the difficulty level of the video game. Experiment 2 showed that arousal (as reflected by the reduction in parasympathetic activity and increase in sympathetic activity) is a critical physiological condition for enhanced cognitive states and corresponding attentional enhancements. Experiment 3 showed that the cognitive enhancements were transient, and were no longer observed after 30 min of rest following video-gaming. Moreover, the results suggest that the enhancements were specific to tasks requiring visual-spatial focused attention, but not distribution of spatial attention as has been reported to improve significantly and durably as a result of long-term video-game playing. Overall, the results suggest that the observed enhancements cannot be simply due to the activity of video-gaming per se, but might rather represent an enhanced cognitive state resulting from specific conditions (heightened arousal in combination with active engagement and optimal challenge), resonant with what has been described in previous phenomenological literature as "flow" (Csikszentmihalyi, 1975) or "peak experiences" (Maslov, 1962). The findings provide empirical evidence for the existence of the enhanced cognitive states and suggest possibilities for consciously accessing latent resources of our brain to temporarily boost our cognitive capacities upon demand. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

Liu, Pin W.

2014-01-01

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

Ketamine produces antidepressant-like effects through phosphorylation-dependent nuclear export of histone deacetylase 5 (HDAC5) in rats

Science.gov (United States)

Choi, Miyeon; Lee, Seung Hoon; Wang, Sung Eun; Ko, Seung Yeon; Song, Mihee; Choi, June-Seek; Duman, Ronald S.; Son, Hyeon

2015-01-01

Ketamine produces rapid antidepressant-like effects in animal assays for depression, although the molecular mechanisms underlying these behavioral actions remain incomplete. Here, we demonstrate that ketamine rapidly stimulates histone deacetylase 5 (HDAC5) phosphorylation and nuclear export in rat hippocampal neurons through calcium/calmodulin kinase II- and protein kinase D-dependent pathways. Consequently, ketamine enhanced the transcriptional activity of myocyte enhancer factor 2 (MEF2), which leads to regulation of MEF2 target genes. Transfection of a HDAC5 phosphorylation-defective mutant (Ser259/Ser498 replaced by Ala259/Ala498, HDAC5-S/A), resulted in resistance to ketamine-induced nuclear export, suppression of ketamine-mediated MEF2 transcriptional activity, and decreased expression of MEF2 target genes. Behaviorally, viral-mediated hippocampal knockdown of HDAC5 blocked or occluded the antidepressant effects of ketamine both in unstressed and stressed animals. Taken together, our results reveal a novel role of HDAC5 in the actions of ketamine and suggest that HDAC5 could be a potential mechanism contributing to the therapeutic actions of ketamine. PMID:26647181

Action of caffeine on x-irradiated HeLa cells. III. enhancement of x-ray-induced killing during G2 arrest

International Nuclear Information System (INIS)

Busse, P.M.; Bose, S.K.; Jones, R.W.; Tolmach, L.J.

1978-01-01

The ability of caffeine to enhance the expression of potentially lethal x-ray damage in HeLa S3 cells was examined as a function of the age of the cells in the generation cycle. Synchronous populations were irradiated at different times after mitotic collection and treated for various intervals with 1 mM caffeiene, which causes negligible killing of unirradiated cells. The response was thereby determined as a function of cell age at both the time of irradiation and the time of exposure to caffeine. The amount of cell killing depends strongly on when in the cycle caffeine is present and only weakly on when the cells are irradiated. If cells are irradiated in early G 1 , caffeine treatment enhances killing for 2 to 3 hr. No additional enhancement is observed until 16 to 17 hr postcollection, corresponding to G 2 ; here they enter a second period of much greater sensitivity. Similarly, fluorodeoxyuridine resynchronized cells irradiated during S and treated with caffeine suffer no enhanced killing until they pass into this sensitive phase in G 2 , approximately 7 hr after release from the fluorodeoxyuridine block. The sensitive period appears to coincide with G 2 arrest. The rate and extent of killing during this period are dependent upon the x-ray dose and the caffeine concentration. In the absence of caffeine, cells irradiated in G 1 lose sensitivity to caffeine in about 9 hr; they do so faster in G 2 . It is concluded that the potentially lethal x-ray damage expressed on treatment with caffeine is retained for many hours in the presence of caffeine and is maximally manifested by G 2 -arrested cells

Action Research as an Agent for Enhancing Teaching and Learning in Physical Education: A Physical Education Teacher's Perspective

Science.gov (United States)

Keegan, Rosemary

2016-01-01

Introduction: Action research is a useful method for implementing change through its spiral of plan, act, observe, and reflect, but little research has been published on it in the area of physical education. The purpose of this intervention was to assess the effectiveness of action research as an agent of change and its impact on enhancing my…

Enhancing the potential of e-savings to boost women's investment ...

International Development Research Centre (IDRC) Digital Library (Canada)

The project seeks to promote the transformative potential of financial ... best increase women's financial inclusion and labour market and economic choices ... Institution. Innovations for Poverty Action, a non-profit corporation. Institution Country.

The mode of inotropic action of ciguatoxin on guinea-pig cardiac muscle.

Science.gov (United States)

Seino, A.; Kobayashi, M.; Momose, K.; Yasumoto, T.; Ohizumi, Y.

1988-01-01

1. Ciguatoxin (CTX) caused a dose-dependent increase in the contractile force of the guinea-pig isolated left atria at concentrations ranging from 0.1 to 10 ng ml-1 with the ED50 value of 0.5 ng ml-1. 2. In the atria, tetrodotoxin (5 x 10(-7) M) inhibited markedly the inotropic action of CTX. The inotropic effect of CTX at low concentrations was abolished by practolol (10(-5) M) and reserpine (2 mg kg-1 daily, for 3 days), whereas that of CTX at high concentrations was partially inhibited by both drugs. 3. In single atrial cells, CTX (3 ng ml-1) produced a marked increase in the amplitude of longitudinal contractions. 4. CTX (3 ng ml-1) caused marked prolongation in the falling phase of action potentials of atrial strips without affecting the maximum rate of rise of action potentials and membrane resting potentials. The effect of CTX on action potentials was abolished by tetrodotoxin (10(-6) M). 5. The whole-cell patch-clamp experiments on myocytes revealed that CTX (20 ng ml-1) shifted the current-voltage curve of Na inward currents by 40 mV in the negative direction. CTX caused a small sustained Na inward current even at resting membrane potentials. 6. These results suggest that the inotropic action of lower concentrations of CTX is primarily due to an indirect action via noradrenaline release, whereas that of higher concentrations is caused not only by an indirect action but also by a direct action on voltage-dependent Na channels of cardiac muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3207997

Defining the action spectrum of potential PGC-1α activators on a mitochondrial and cellular level in vivo.

Science.gov (United States)

Hofer, Annette; Noe, Natalie; Tischner, Christin; Kladt, Nikolay; Lellek, Veronika; Schauß, Astrid; Wenz, Tina

2014-05-01

Previous studies have demonstrated a therapeutic benefit of pharmaceutical PGC-1α activation in cellular and murine model of disorders linked to mitochondrial dysfunction. While in some cases, this effect seems to be clearly associated with boosting of mitochondrial function, additional alterations as well as tissue- and cell-type-specific effects might play an important role. We initiated a comprehensive analysis of the effects of potential PGC-1α-activating drugs and pharmaceutically targeted the PPAR (bezafibrate, rosiglitazone), AMPK (AICAR, metformin) and Sirt1 (resveratrol) pathways in HeLa cells, neuronal cells and PGC-1α-deficient MEFs to get insight into cell type specificity and PGC-1α dependence of their working action. We used bezafibrate as a model drug to assess the effect on a tissue-specific level in a murine model. Not all analyzed drugs activate the PGC pathway or alter mitochondrial protein levels. However, they all affect supramolecular assembly of OXPHOS complexes and OXPHOS protein stability. In addition, a clear drug- and cell-type-specific influence on several cellular stress pathways as well as on post-translational modifications could be demonstrated, which might be relevant to fully understand the action of the analyzed drugs in the disease state. Importantly, the effect on the activation of mitochondrial biogenesis and stress response program upon drug treatment is PGC-1α dependent in MEFs demonstrating not only the pleiotropic effects of this molecule but points also to the working mechanism of the analyzed drugs. The definition of the action spectrum of the different drugs forms the basis for a defect-specific compensation strategy and a future personalized therapeutic approach.

The Effect of Health Education based on Health Belief Model on Preventive Actions of Synthetic Drugs Dependence in Male Students of Kerman, Iran

Directory of Open Access Journals (Sweden)

Seyed Saeed Mazloomy Mahmoodabad

2017-06-01

Conclusion: Findings indicated that by increase of HBM components' average scores, the average score of synthetic drug dependence preventive actions increased too. Therefore, results of the research confirm the effect and efficiency of HBM in making preventive actions of drug dependence. 

Effective corrective actions to enhance operational safety of nuclear installations

International Nuclear Information System (INIS)

2005-07-01

The safe operation of nuclear power plants around the world and the prevention of incidents in these installations remain key concerns for the nuclear community. In this connection the feedback of operating experience plays a major role: every nuclear plant operator needs to have a system in place to identify and feed back the lessons learned from operating experience and to implement effective corrective actions to prevent safety events from reoccurring. An effective operating experience programme also includes a proactive approach that is aimed at preventing the first-time occurrence of safety events. In April 2003, the IAEA issued the PROSPER guidelines for nuclear installations to strengthen and enhance their own operating experience process and for self-assessment on the effectiveness of the feedback process. Subsequently, in the course of the Operational Safety Review Teams missions conducted by the IAEA that focused on the operational safety practices of nuclear power plants, the IAEA enhanced the review of the operating experience in nuclear power plants by implementing a new module that is derived from these guidelines. In order to highlight the effective implementation of the operating experience programme and to provide practical assistance in this area, the IAEA organized workshops and conferences to discuss recent trends in operating experience. The IAEA also performed assistance and review missions at plants and corporate organizations. The IAEA is further developing advice and assistance on operating experience feedback programmes and is reporting on good practices. The present publication is the outcome of two years of coordinated effort involving the participation of experts of nuclear organizations in several Member States. It provides information and good practices for successfully establishing an effective corrective actions programme. This publication forms part of a series that develops the principles set forth in these guidelines

Momentum dependence of the symmetry potential and its influence on nuclear reactions

International Nuclear Information System (INIS)

Feng Zhaoqing

2011-01-01

A Skyrme-type momentum-dependent nucleon-nucleon force distinguishing isospin effect is parametrized and further implemented in the Lanzhou quantum molecular dynamics model, which leads to a splitting of nucleon effective mass in nuclear matter. Based on the isospin- and momentum-dependent transport model, we investigate the influence of momentum-dependent symmetry potential on several isospin-sensitive observables in heavy-ion collisions. It is found that symmetry potentials with and without the momentum dependence but corresponding to the same density dependence of the symmetry energy result in different distributions of the observables. The midrapidity neutron/proton ratios at high transverse momenta and the excitation functions of the total π - /π + and K 0 /K + yields are particularly sensitive to the momentum dependence of the symmetry potential.

Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

Energy Technology Data Exchange (ETDEWEB)

Takaoka, Yuki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Kawamoto, Seiji, E-mail: skawa@hiroshima-u.ac.jp [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Katayama, Akiko [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Nakano, Toshiaki [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Yamanaka, Yasushi; Takahashi, Miki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Shimada, Yayoi; Chiang, Kuei-Chen [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Ohmori, Naoya [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Aki, Tsunehiro [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Goto, Takeshi; Sato, Shuji [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Goto, Shigeru [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Iwao Hospital, Yufuin (Japan); Chen, Chao-Long [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Ono, Kazuhisa [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan)

2013-02-08

Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4{sup +}Foxp3{sup +} Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings.

Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

International Nuclear Information System (INIS)

Takaoka, Yuki; Kawamoto, Seiji; Katayama, Akiko; Nakano, Toshiaki; Yamanaka, Yasushi; Takahashi, Miki; Shimada, Yayoi; Chiang, Kuei-Chen; Ohmori, Naoya; Aki, Tsunehiro; Goto, Takeshi; Sato, Shuji; Goto, Shigeru; Chen, Chao-Long; Ono, Kazuhisa

2013-01-01

Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4 + Foxp3 + Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings

Reynolds-number dependence of turbulence enhancement on collision growth

Directory of Open Access Journals (Sweden)

R. Onishi

2016-10-01

Full Text Available This study investigates the Reynolds-number dependence of turbulence enhancement on the collision growth of cloud droplets. The Onishi turbulent coagulation kernel proposed in Onishi et al. (2015 is updated by using the direct numerical simulation (DNS results for the Taylor-microscale-based Reynolds number (Reλ up to 1140. The DNS results for particles with a small Stokes number (St show a consistent Reynolds-number dependence of the so-called clustering effect with the locality theory proposed by Onishi et al. (2015. It is confirmed that the present Onishi kernel is more robust for a wider St range and has better agreement with the Reynolds-number dependence shown by the DNS results. The present Onishi kernel is then compared with the Ayala–Wang kernel (Ayala et al., 2008a; Wang et al., 2008. At low and moderate Reynolds numbers, both kernels show similar values except for r2 ∼ r1, for which the Ayala–Wang kernel shows much larger values due to its large turbulence enhancement on collision efficiency. A large difference is observed for the Reynolds-number dependences between the two kernels. The Ayala–Wang kernel increases for the autoconversion region (r1, r2 < 40 µm and for the accretion region (r1 < 40 and r2 > 40 µm; r1 > 40 and r2 < 40 µm as Reλ increases. In contrast, the Onishi kernel decreases for the autoconversion region and increases for the rain–rain self-collection region (r1, r2 > 40 µm. Stochastic collision–coalescence equation (SCE simulations are also conducted to investigate the turbulence enhancement on particle size evolutions. The SCE with the Ayala–Wang kernel (SCE-Ayala and that with the present Onishi kernel (SCE-Onishi are compared with results from the Lagrangian Cloud Simulator (LCS; Onishi et al., 2015, which tracks individual particle motions and size evolutions in homogeneous isotropic turbulence. The SCE-Ayala and SCE-Onishi kernels show consistent

Polarization Dependence of Surface Enhanced Raman Scattering on a Single Dielectric Nanowire

Directory of Open Access Journals (Sweden)

Hua Qi

2012-01-01

Full Text Available Our measurements of surface enhanced Raman scattering (SERS on Ga2O3 dielectric nanowires (NWs core/silver composites indicate that the SERS enhancement is highly dependent on the polarization direction of the incident laser light. The polarization dependence of the SERS signal with respect to the direction of a single NW was studied by changing the incident light angle. Further investigations demonstrate that the SERS intensity is not only dependent on the direction and wavelength of the incident light, but also on the species of the SERS active molecule. The largest signals were observed on an NW when the incident 514.5 nm light was polarized perpendicular to the length of the NW, while the opposite phenomenon was observed at the wavelength of 785 nm. Our theoretical simulations of the polarization dependence at 514.5 nm and 785 nm are in good agreement with the experimental results.

How Recommender Systems in Technology-Enhanced Learning depend on Context

NARCIS (Netherlands)

Drachsler, Hendrik; Manouselis, Nikos

2009-01-01

Drachsler, H., & Manouselis, N. (2009). How Recommender Systems in Technology-Enhanced Learning depend on Context. Presentation given at the 1st workshop on Context-aware Recommender Systems for Learning at the Alpine Rendez-Vous 2009. November, 30 - December, 3, 2009, Garmisch-Patenkirchen,

The grounds for time dependent market potentials from dealers' dynamics

Science.gov (United States)

Yamada, K.; Takayasu, H.; Takayasu, M.

2008-06-01

We apply the potential force estimation method to artificial time series of market price produced by a deterministic dealer model. We find that dealers’ feedback of linear prediction of market price based on the latest mean price changes plays the central role in the market’s potential force. When markets are dominated by dealers with positive feedback the resulting potential force is repulsive, while the effect of negative feedback enhances the attractive potential force.

76 FR 21938 - Potential Environmental Impacts of the Proposed Runway 13 Extension and Associated Actions for...

Science.gov (United States)

2011-04-19

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Potential Environmental Impacts of the Proposed Runway 13 Extension and Associated Actions for the Devils Lake Regional Airport in Devils Lake, ND AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT). ACTION...

Determination of Nerve Fiber Diameter Distribution From Compound Action Potential: A Continuous Approach.

Science.gov (United States)

Un, M Kerem; Kaghazchi, Hamed

2018-01-01

When a signal is initiated in the nerve, it is transmitted along each nerve fiber via an action potential (called single fiber action potential (SFAP)) which travels with a velocity that is related with the diameter of the fiber. The additive superposition of SFAPs constitutes the compound action potential (CAP) of the nerve. The fiber diameter distribution (FDD) in the nerve can be computed from the CAP data by solving an inverse problem. This is usually achieved by dividing the fibers into a finite number of diameter groups and solve a corresponding linear system to optimize FDD. However, number of fibers in a nerve can be measured sometimes in thousands and it is possible to assume a continuous distribution for the fiber diameters which leads to a gradient optimization problem. In this paper, we have evaluated this continuous approach to the solution of the inverse problem. We have utilized an analytical function for SFAP and an assumed a polynomial form for FDD. The inverse problem involves the optimization of polynomial coefficients to obtain the best estimate for the FDD. We have observed that an eighth order polynomial for FDD can capture both unimodal and bimodal fiber distributions present in vivo, even in case of noisy CAP data. The assumed FDD distribution regularizes the ill-conditioned inverse problem and produces good results.

Quantitative analysis of single muscle fibre action potentials recorded at known distances

NARCIS (Netherlands)

Albers, B.A.; Put, J.H.M.; Wallinga, W.; Wirtz, P.

1989-01-01

In vivo records of single fibre action potentials (SFAPs) have always been obtained at unknown distance from the active muscle fibre. A new experimental method has been developed enabling the derivation of the recording distance in animal experiments. A single fibre is stimulated with an

A Novel Platform for the Potentiation of Therapeutic Antibodies Based on Antigen-Dependent Formation of IgG Hexamers at the Cell Surface

DEFF Research Database (Denmark)

de Jong, R. N.; Beurskens, F. J.; Verploegen, S.

2016-01-01

IgG antibodies can organize into ordered hexamers on cell surfaces after binding their antigen. These hexamers bind the first component of complement C1 inducing complement-dependent target cell killing. Here, we translated this natural concept into a novel technology platform (HexaBody technology......) for therapeutic antibody potentiation. We identified mutations that enhanced hexamer formation and complement activation by IgG1 antibodies against a range of targets on cells from hematological and solid tumor indications. IgG1 backbones with preferred mutations E345K or E430G conveyed a strong ability to induce...... conditional complement-dependent cytotoxicity (CDC) of cell lines and chronic lymphocytic leukemia (CLL) patient tumor cells, while retaining regular pharmacokinetics and biopharmaceutical developability. Both mutations potently enhanced CDC- and antibody-dependent cellular cytotoxicity (ADCC) of a type II CD...

Khat (Catha edulis Forsk. Dependence Potential and Pattern of Use in Saudi Arabia

Directory of Open Access Journals (Sweden)

Siddig Ibrahim Abdelwahab

2015-01-01

Full Text Available Background. Catha edulis Forsk. (Khat is used for its psychoactive effects among people in Africa and the Arabian Peninsula, although its utilization is illegal in some countries such as Saudi Arabia. This study examined the pattern of Khat use and assessed the applicability of the Drug Abuse Screening Test-10 (DAST-10 to measure Khat dependence. Methods. A pretested questionnaire was used to gather data from 603 respondents. Variables included demographic characteristics, pattern of use, reasons for Khat chewing, and DAST-10. Stepwise-logistic regression was used to explore predictors of Khat dependence. Results. The majority of the respondents were married, had a secondary school level of education, were employed, were younger than 35 years old, and were living in rural areas. Many chewers gave more than one reason for using Khat. It was mainly used to increase mental capacity, physical strength, and social entertainment, as well as enhance cheerfulness and orgasms. Statistical modeling of Khat dependence suggested that the most significant predictors were residence (OR = 1.67, P<0.02, frequency of Khat chewing (OR = 4.8, P<0.01, age of starting Khat chewing (OR = 1.15, P<0.01, and time of Khat effect (OR = 1.15, P<0.04. Conclusion. Our study provides important information on the pattern of Khat use and its potential to cause dependence.

Experience-dependent plasticity from eye opening enables lasting, visual cortex-dependent enhancement of motion vision.

Science.gov (United States)

Prusky, Glen T; Silver, Byron D; Tschetter, Wayne W; Alam, Nazia M; Douglas, Robert M

2008-09-24

Developmentally regulated plasticity of vision has generally been associated with "sensitive" or "critical" periods in juvenile life, wherein visual deprivation leads to loss of visual function. Here we report an enabling form of visual plasticity that commences in infant rats from eye opening, in which daily threshold testing of optokinetic tracking, amid otherwise normal visual experience, stimulates enduring, visual cortex-dependent enhancement (>60%) of the spatial frequency threshold for tracking. The perceptual ability to use spatial frequency in discriminating between moving visual stimuli is also improved by the testing experience. The capacity for inducing enhancement is transitory and effectively limited to infancy; however, enhanced responses are not consolidated and maintained unless in-kind testing experience continues uninterrupted into juvenile life. The data show that selective visual experience from infancy can alone enable visual function. They also indicate that plasticity associated with visual deprivation may not be the only cause of developmental visual dysfunction, because we found that experientially inducing enhancement in late infancy, without subsequent reinforcement of the experience in early juvenile life, can lead to enduring loss of function.

Nitrate-Dependent Iron Oxidation: A Potential Mars Metabolism

Science.gov (United States)

Price, Alex; Pearson, Victoria K.; Schwenzer, Susanne P.; Miot, Jennyfer; Olsson-Francis, Karen

2018-01-01

This work considers the hypothetical viability of microbial nitrate-dependent Fe2+ oxidation (NDFO) for supporting simple life in the context of the early Mars environment. This draws on knowledge built up over several decades of remote and in situ observation, as well as recent discoveries that have shaped current understanding of early Mars. Our current understanding is that certain early martian environments fulfill several of the key requirements for microbes with NDFO metabolism. First, abundant Fe2+ has been identified on Mars and provides evidence of an accessible electron donor; evidence of anoxia suggests that abiotic Fe2+ oxidation by molecular oxygen would not have interfered and competed with microbial iron metabolism in these environments. Second, nitrate, which can be used by some iron oxidizing microorganisms as an electron acceptor, has also been confirmed in modern aeolian and ancient sediment deposits on Mars. In addition to redox substrates, reservoirs of both organic and inorganic carbon are available for biosynthesis, and geochemical evidence suggests that lacustrine systems during the hydrologically active Noachian period (4.1–3.7 Ga) match the circumneutral pH requirements of nitrate-dependent iron-oxidizing microorganisms. As well as potentially acting as a primary producer in early martian lakes and fluvial systems, the light-independent nature of NDFO suggests that such microbes could have persisted in sub-surface aquifers long after the desiccation of the surface, provided that adequate carbon and nitrates sources were prevalent. Traces of NDFO microorganisms may be preserved in the rock record by biomineralization and cellular encrustation in zones of high Fe2+ concentrations. These processes could produce morphological biosignatures, preserve distinctive Fe-isotope variation patterns, and enhance preservation of biological organic compounds. Such biosignatures could be detectable by future missions to Mars with appropriate

Nitrate-Dependent Iron Oxidation: A Potential Mars Metabolism

Directory of Open Access Journals (Sweden)

Alex Price

2018-03-01

Full Text Available This work considers the hypothetical viability of microbial nitrate-dependent Fe2+ oxidation (NDFO for supporting simple life in the context of the early Mars environment. This draws on knowledge built up over several decades of remote and in situ observation, as well as recent discoveries that have shaped current understanding of early Mars. Our current understanding is that certain early martian environments fulfill several of the key requirements for microbes with NDFO metabolism. First, abundant Fe2+ has been identified on Mars and provides evidence of an accessible electron donor; evidence of anoxia suggests that abiotic Fe2+ oxidation by molecular oxygen would not have interfered and competed with microbial iron metabolism in these environments. Second, nitrate, which can be used by some iron oxidizing microorganisms as an electron acceptor, has also been confirmed in modern aeolian and ancient sediment deposits on Mars. In addition to redox substrates, reservoirs of both organic and inorganic carbon are available for biosynthesis, and geochemical evidence suggests that lacustrine systems during the hydrologically active Noachian period (4.1–3.7 Ga match the circumneutral pH requirements of nitrate-dependent iron-oxidizing microorganisms. As well as potentially acting as a primary producer in early martian lakes and fluvial systems, the light-independent nature of NDFO suggests that such microbes could have persisted in sub-surface aquifers long after the desiccation of the surface, provided that adequate carbon and nitrates sources were prevalent. Traces of NDFO microorganisms may be preserved in the rock record by biomineralization and cellular encrustation in zones of high Fe2+ concentrations. These processes could produce morphological biosignatures, preserve distinctive Fe-isotope variation patterns, and enhance preservation of biological organic compounds. Such biosignatures could be detectable by future missions to Mars with

Nitrate-Dependent Iron Oxidation: A Potential Mars Metabolism.

Science.gov (United States)

Price, Alex; Pearson, Victoria K; Schwenzer, Susanne P; Miot, Jennyfer; Olsson-Francis, Karen

2018-01-01

This work considers the hypothetical viability of microbial nitrate-dependent Fe 2+ oxidation (NDFO) for supporting simple life in the context of the early Mars environment. This draws on knowledge built up over several decades of remote and in situ observation, as well as recent discoveries that have shaped current understanding of early Mars. Our current understanding is that certain early martian environments fulfill several of the key requirements for microbes with NDFO metabolism. First, abundant Fe 2+ has been identified on Mars and provides evidence of an accessible electron donor; evidence of anoxia suggests that abiotic Fe 2+ oxidation by molecular oxygen would not have interfered and competed with microbial iron metabolism in these environments. Second, nitrate, which can be used by some iron oxidizing microorganisms as an electron acceptor, has also been confirmed in modern aeolian and ancient sediment deposits on Mars. In addition to redox substrates, reservoirs of both organic and inorganic carbon are available for biosynthesis, and geochemical evidence suggests that lacustrine systems during the hydrologically active Noachian period (4.1-3.7 Ga) match the circumneutral pH requirements of nitrate-dependent iron-oxidizing microorganisms. As well as potentially acting as a primary producer in early martian lakes and fluvial systems, the light-independent nature of NDFO suggests that such microbes could have persisted in sub-surface aquifers long after the desiccation of the surface, provided that adequate carbon and nitrates sources were prevalent. Traces of NDFO microorganisms may be preserved in the rock record by biomineralization and cellular encrustation in zones of high Fe 2+ concentrations. These processes could produce morphological biosignatures, preserve distinctive Fe-isotope variation patterns, and enhance preservation of biological organic compounds. Such biosignatures could be detectable by future missions to Mars with appropriate

Action potential-based MEA platform for in vitro screening of drug-induced cardiotoxicity using human iPSCs and rat neonatal myocytes.

Science.gov (United States)

Jans, Danny; Callewaert, Geert; Krylychkina, Olga; Hoffman, Luis; Gullo, Francesco; Prodanov, Dimiter; Braeken, Dries

2017-09-01

Drug-induced cardiotoxicity poses a negative impact on public health and drug development. Cardiac safety pharmacology issues urged for the preclinical assessment of drug-induced ventricular arrhythmia leading to the design of several in vitro electrophysiological screening assays. In general, patch clamp systems allow for intracellular recordings, while multi-electrode array (MEA) technology detect extracellular activity. Here, we demonstrate a complementary metal oxide semiconductor (CMOS)-based MEA system as a reliable platform for non-invasive, long-term intracellular recording of cardiac action potentials at high resolution. Quinidine (8 concentrations from 10 -7 to 2.10 -5 M) and verapamil (7 concentrations from 10 -11 to 10 -5 M) were tested for dose-dependent responses in a network of cardiomyocytes. Electrophysiological parameters, such as the action potential duration (APD), rates of depolarization and repolarization and beating frequency were assessed. In hiPSC, quinidine prolonged APD with EC 50 of 2.2·10 -6 M. Further analysis indicated a multifactorial action potential prolongation by quinidine: (1) decreasing fast repolarization with IC 50 of 1.1·10 -6 M; (2) reducing maximum upstroke velocity with IC 50 of 2.6·10 -6 M; and (3) suppressing spontaneous activity with EC 50 of 3.8·10 -6 M. In rat neonatal cardiomyocytes, verapamil blocked spontaneous activity with EC 50 of 5.3·10 -8 M and prolonged the APD with EC 50 of 2.5·10 -8 M. Verapamil reduced rates of fast depolarization and repolarization with IC 50 s of 1.8 and 2.2·10 -7 M, respectively. In conclusion, the proposed action potential-based MEA platform offers high quality and stable long-term recordings with high information content allowing to characterize multi-ion channel blocking drugs. We anticipate application of the system as a screening platform to efficiently and cost-effectively test drugs for cardiac safety. Copyright © 2017 Elsevier Inc. All rights reserved.

Enhanced Y1-receptor-mediated vasoconstrictive action of neuropeptide Y (NPY) in superior mesenteric arteries in portal hypertension.

Science.gov (United States)

Wiest, Reiner; Jurzik, Lars; Moleda, Lukas; Froh, Matthias; Schnabl, Bernd; von Hörsten, Stephan; Schölmerich, Juergen; Straub, Rainer H

2006-03-01

Vascular hyporeactivity to catecholamines contributes to arterial vasodilation and hemodynamic dysregulation in portal hypertension. Neuropeptide Y (NPY) is a sympathetic neurotransmitter facilitating adrenergic vasoconstriction via Y1-receptors on the vascular smooth muscle. Therefore, we investigated its role for vascular reactivity in the superior mesenteric artery (SMA) of portal vein ligated (PVL) and sham operated rats. In vitro perfused SMA vascular beds of rats were tested for the cumulative dose-response to NPY dependent on the presence and level of alpha1-adrenergic vascular tone (methoxamine MT: 0.3-10 microM). Moreover, the effect of NPY (50 nM) on vascular responsiveness to alpha1-adrenergic stimulation (MT: 0.3-300 microM) was evaluated. Y1-receptor function was tested by Y1-selective inhibition using BIBP-3226 (1 microM). NPY dose-dependently and endothelium-independently enhanced MT-pre-constriction in SMA. This potentiation was increasingly effective with increasing adrenergic pre-stimulation and being more pronounced in PVL rats as compared to sham rats at high MT concentrations. NPY enhanced vascular contractility only in PVL rats correcting the adrenergic vascular hyporeactivity. Y1-receptor inhibition completely abolished NPY-evoked vasoconstrictive effects. NPY endothelium-independently potentiates adrenergic vasoconstriction via Y1-receptors being more pronounced in portal hypertension improving mesenteric vascular contractility and thereby correcting the splanchnic vascular hyporeactivity. This makes NPY a superior vasoconstrictor counterbalancing arterial vasodilation in portal hypertension.

Objective selection of EEG late potentials through residual dependence estimation of independent components

International Nuclear Information System (INIS)

Milanesi, M; James, C J; Martini, N; Menicucci, D; Gemignani, A; Ghelarducci, B; Landini, L

2009-01-01

This paper presents a novel method to objectively select electroencephalographic (EEG) cortical sources estimated by independent component analysis (ICA) in event-related potential (ERP) studies. A proximity measure based on mutual information is employed to estimate residual dependences of the components that are then hierarchically clustered based on these residual dependences. Next, the properties of each group of components are evaluated at each level of the hierarchical tree by two indices that aim to assess both cluster tightness and physiological reliability through a template matching process. These two indices are combined in three different approaches to bring to light the hierarchical structure of the cluster organizations. Our method is tested on a set of experiments with the purpose of enhancing late positive ERPs elicited by emotional picture stimuli. Results suggest that the best way to look for physiologically plausible late positive potential (LPP) sources is to explore in depth the tightness of those clusters that, taken together, best resemble the template. According to our results, after brain sources clustering, LPPs are always identified more accurately than from ensemble-averaged raw data. Since the late components of an ERP involve the same associative areas, regardless of the modality of stimulation or specific tasks administered, the proposed method can be simply adapted to other ERP studies, and extended from psychophysiological studies to pathological or sport training evaluation support

Applicability of anaerobic nitrate-dependent Fe(II) oxidation to microbial enhanced oil recovery (MEOR).

Science.gov (United States)

Zhu, Hongbo; Carlson, Han K; Coates, John D

2013-08-06

Microbial processes that produce solid-phase minerals could be judiciously applied to modify rock porosity with subsequent alteration and improvement of floodwater sweep in petroleum reservoirs. However, there has been little investigation of the application of this to enhanced oil recovery (EOR). Here, we investigate a unique approach of altering reservoir petrology through the biogenesis of authigenic rock minerals. This process is mediated by anaerobic chemolithotrophic nitrate-dependent Fe(II)-oxidizing microorganisms that precipitate iron minerals from the metabolism of soluble ferrous iron (Fe(2+)) coupled to the reduction of nitrate. This mineral biogenesis can result in pore restriction and reduced pore throat diameter. Advantageously and unlike biomass plugs, these biominerals are not susceptible to pressure or thermal degradation. Furthermore, they do not require continual substrate addition for maintenance. Our studies demonstrate that the biogenesis of insoluble iron minerals in packed-bed columns results in effective hydrology alteration and homogenization of heterogeneous flowpaths upon stimulated microbial Fe(2+) biooxidation. We also demonstrate almost 100% improvement in oil recovery from hydrocarbon-saturated packed-bed columns as a result of this metabolism. These studies represent a novel departure from traditional microbial EOR approaches and indicate the potential for nitrate-dependent Fe(2+) biooxidation to improve volumetric sweep efficiency and enhance both the quality and quantity of oil recovered.

Nuclear and Cytoplasmic Delivery of Lactoferrin in Glioma using Chitosan Nanoparticles: Cellular Location Dependent-Action of Lactoferrin.

Science.gov (United States)

Tammam, Salma N; Azzazy, Hassan M E; Lamprecht, Alf

2018-05-23

Lactoferrin (Lf) exerts anti-cancer effects on glioma, however, the exact mechanism remains unclear. Despite possessing a nuclear localization sequence (NLS), Lf was found to allocate only in the cytoplasm of glioma 261. Lf was therefore loaded into nuclear and cytoplasmic targeted nanoparticles (NPs) to determine whether nuclear delivery of Lf would enhance its anti-cancer effect. Upon treatment with 300 and 800 µg/mL Lf loaded chitosan NPs, nuclear targeted Lf-NPs showed 1.3 and 2.7 folds increase in cell viability, whereas cytoplasmic targeted Lf-NPs at 300 µg/mL decreased cell viability by 0.8 folds in comparison to free Lf and controls. Results suggest that the cytotoxicity of Lf on glioma is attributable to its cytoplasmic allocation. Nuclear delivery of Lf induced cell proliferation rather than cytotoxicity, indicating that the mode of action of Lf in glioma is cell location dependent. This calls for caution about the general use of Lf as an anti-cancer protein. Copyright © 2018. Published by Elsevier B.V.

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

Energy Technology Data Exchange (ETDEWEB)

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

1990-08-01

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

Interactive green street enhancement using light dependent sensors and actuators

NARCIS (Netherlands)

Wouters, Ivo; Chen, W.; Oorschot, van B.; Smeenk, W.

2008-01-01

We propose and demonstrate a design of an interactive green street facility using light dependent sensors and actuators for enhancing the social cohesion of people. We show that electronics and green design can have positive effect on social interaction in a neighbourhood by a design example, called

Experience of action depends on intention, not body movement

DEFF Research Database (Denmark)

Jensen, Mads; Vagnoni, Eleonora; Overgaard, Morten

2014-01-01

in memory. We found that recall of a voluntary action was unaffected by an incongruent involuntary movement. In contrast, recall of an involuntary movement was strongly influenced by an incongruent voluntary action. Our results demonstrate an “intentional capture” of body movement by voluntary actions......, in support of intentional theories of agency, but contrary to reconstructive theories. When asked to recall both actions and movements, people's responses are shaped by memory of what they intended to do, rather than by how their body moved....... effects that they produce. Intentions would then be mere confabulations, and not bona fide experiences. Previous work on voluntary action has focused on immediate experiences of authorship, and few studies have considered memory for voluntary actions. We devised an experiment in which both voluntary...

Ultrasonic Enhancement of Antibiotic Action on Escherichia coli Biofilms: an In Vivo Model

OpenAIRE

Rediske, Andrea M.; Roeder, Beverly L.; Brown, Maren K.; Nelson, Jared L.; Robison, Rachel L.; Draper, David O.; Schaalje, G. Bruce; Robison, Richard A.; Pitt, William G.

1999-01-01

Biofilm infections are a common complication of prosthetic devices in humans. Previous in vitro research has determined that low-frequency ultrasound combined with aminoglycoside antibiotics is an effective method of killing biofilms. We report the development of an in vivo model to determine if ultrasound enhances antibiotic action. Two 24-h-old Escherichia coli (ATCC 10798) biofilms grown on polyethylene disks were implanted subcutaneously on the backs of New Zealand White female rabbits, o...

Outcome producing potential influences twelve-month-olds' interpretation of a novel action as goal-directed.

Science.gov (United States)

Biro, Szilvia; Verschoor, Stephan; Coalter, Esther; Leslie, Alan M

2014-11-01

Learning about a novel, goal-directed action is a complex process. It requires identifying the outcome of the action and linking the action to its outcome for later use in new situations to predict the action or to anticipate its outcome. We investigated the hypothesis that linking a novel action to a salient change in the environment is critical for infants to assign a goal to the novel action. We report a study in which we show that 12-month-old infants, who were provided with prior experience with a novel action accompanied with a salient visible outcome in one context, can interpret the same action as goal-directed even in the absence of the outcome in another context. Our control condition shows that prior experience with the action, but without the salient effect, does not lead to goal-directed interpretation of the novel action. We also found that, for the case of 9-month-olds infants, prior experience with the outcome producing potential of the novel action does not facilitate a goal-directed interpretation of the action. However, this failure was possibly due to difficulties with generalizing the learnt association to another context rather than with linking the action to its outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

Body posture modulates action perception.

Science.gov (United States)

Zimmermann, Marius; Toni, Ivan; de Lange, Floris P

2013-04-03

Recent studies have highlighted cognitive and neural similarities between planning and perceiving actions. Given that action planning involves a simulation of potential action plans that depends on the actor's body posture, we reasoned that perceiving actions may also be influenced by one's body posture. Here, we test whether and how this influence occurs by measuring behavioral and cerebral (fMRI) responses in human participants predicting goals of observed actions, while manipulating postural congruency between their own body posture and postures of the observed agents. Behaviorally, predicting action goals is facilitated when the body posture of the observer matches the posture achieved by the observed agent at the end of his action (action's goal posture). Cerebrally, this perceptual postural congruency effect modulates activity in a portion of the left intraparietal sulcus that has previously been shown to be involved in updating neural representations of one's own limb posture during action planning. This intraparietal area showed stronger responses when the goal posture of the observed action did not match the current body posture of the observer. These results add two novel elements to the notion that perceiving actions relies on the same predictive mechanism as planning actions. First, the predictions implemented by this mechanism are based on the current physical configuration of the body. Second, during both action planning and action observation, these predictions pertain to the goal state of the action.

The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake.

Science.gov (United States)

Böhm, Jennifer; Scherzer, Sönke; Krol, Elzbieta; Kreuzer, Ines; von Meyer, Katharina; Lorey, Christian; Mueller, Thomas D; Shabala, Lana; Monte, Isabel; Solano, Roberto; Al-Rasheid, Khaled A S; Rennenberg, Heinz; Shabala, Sergey; Neher, Erwin; Hedrich, Rainer

2016-02-08

Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na(+)-rich animal and nutrition for the plant. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Field strength and dose dependence of contrast enhancement by gadolinium-based MR contrast agents

International Nuclear Information System (INIS)

Rinck, P.A.; Muller, R.N.

1999-01-01

The relaxivities r 1 and r 2 of magnetic resonance contrast agents and the T 1 relaxation time values of tissues are strongly field dependent. We present quantitative data and simulations of different gadolinium-based extracellular fluid contrast agents and the modulation of their contrast enhancement by the magnetic field to be able to answer the following questions: How are the dose and field dependences of their contrast enhancement? Is there an interrelationship between dose and field dependence? Should one increase or decrease doses at specific fields? Nuclear magnetic relaxation dispersion data were acquired for the following contrast agents: gadopentetate dimeglumine, gadoterate meglumine, gadodiamide injection, and gadoteridol injection, as well as for several normal and pathological human tissue samples. The magnetic field range stretched from 0.0002 to 4.7 T, including the entire clinical imaging range. The data acquired were then fitted with the appropriate theoretical models. The combination of the diamagnetic relaxation rates (R 1 = 1/T 1 and R 2 = 1/T 2 ) of tissues with the respective paramagnetic contributions of the contrast agents allowed the prediction of image contrast at any magnetic field. The results revealed a nearly identical field and dose-dependent increase of contrast enhancement induced by these contrast agents within a certain dose range. The target tissue concentration (TTC) was an important though nonlinear factor for enhancement. The currently recommended dose of 0.1 mmol/kg body weight seems to be a compromise close to the lower limits of diagnostically sufficient contrast enhancement for clinical imaging at all field strengths. At low field contrast enhancement might be insufficient. Adjustment of dose or concentration, or a new class of contrast agents with optimized relaxivity, would be a valuable contribution to a better diagnostic yield of contrast enhancement at all fields. (orig.)

β1-Adrenoceptor autoantibodies affect action potential duration and delayed rectifier potassium currents in guinea pigs.

Science.gov (United States)

Zhao, Yuhui; Huang, Haixia; Du, Yunhui; Li, Xiao; Lv, Tingting; Zhang, Suli; Wei, Hua; Shang, Jianyu; Liu, Ping; Liu, Huirong

2015-01-01

β1-Adrenoceptor autoantibodies (β1-AAs) affect the action potential duration (APD) in cardiomyocytes and are related to ventricular arrhythmias. The delayed rectifier potassium current (I K) plays a crucial role in APD, but the effects of β1-AAs on I K have not been completely illuminated. This work aimed to observe the effects of β1-AAs on I K and APD and further explore the mechanisms of β1-AA-mediated ventricular arrhythmias. β1-AAs were obtained from sera of patients with coronary heart disease (CHD) and nonsustained ventricular tachycardia. With whole-cell patch clamp technique, action potentials and I K were recorded. The results illustrated 0.1 μmol/L β1-AAs shortened APD at 50 % (APD50) and 90 % (APD90) of the repolarization. However, at 0.01 μmol/L, β1-AAs had no effects on either APD90 or APD50 (P > 0.05). At 0.001 μmol/L, β1-AAs significantly prolonged APD90 and APD50. Moreover, β1-AAs (0.001, 0.01, 0.1 μmol/L) dose-dependently increased the rapidly activating delayed rectifier potassium current (I Kr), but similarly decreased the slowly activating delayed rectifier potassium current (I Ks) and increased L-type calcium currents at the different concentrations. Taken together, the IKr increase induced by high β1-AA concentrations is responsible for a significant APD reduction which would contribute to repolarization changes and trigger the malignant ventricular arrhythmias in CHD patients.

Layer-dependent surface potential of phosphorene and anisotropic/layer-dependent charge transfer in phosphorene-gold hybrid systems.

Science.gov (United States)

Xu, Renjing; Yang, Jiong; Zhu, Yi; Yan, Han; Pei, Jiajie; Myint, Ye Win; Zhang, Shuang; Lu, Yuerui

2016-01-07

The surface potential and the efficiency of interfacial charge transfer are extremely important for designing future semiconductor devices based on the emerging two-dimensional (2D) phosphorene. Here, we directly measured the strong layer-dependent surface potential of mono- and few-layered phosphorene on gold, which is consistent with the reported theoretical prediction. At the same time, we used an optical way photoluminescence (PL) spectroscopy to probe charge transfer in the phosphorene-gold hybrid system. We firstly observed highly anisotropic and layer-dependent PL quenching in the phosphorene-gold hybrid system, which is attributed to the highly anisotropic/layer-dependent interfacial charge transfer.

A dual potassium channel activator improves repolarization reserve and normalizes ventricular action potentials

DEFF Research Database (Denmark)

Calloe, Kirstine; Di Diego, José M; Hansen, Rie Schultz

2016-01-01

in cultured canine cardiac myocytes and determined whether a dual K(+) current activator can normalize K(+) currents and restore action potential (AP) configuration. METHODS AND RESULTS: Ventricular myocytes were isolated and cultured for up to 48h. Current and voltage clamp recordings were made using patch...... of EADs. Our results suggest a potential benefit of K(+) current activators under conditions of reduced repolarization reserve including heart failure....

Molecular tilt-dependent and tyrosine-enhanced electron transfer across ITO/SAM/[DPPC–Au NP–Tyrosine] Janus nanoparticle junction

Energy Technology Data Exchange (ETDEWEB)

Sarangi, Nirod Kumar; Patnaik, Archita, E-mail: archita59@yahoo.com [Indian Institute of Technology Madras, Department of Chemistry (India)

2016-09-15

Enhanced interfacial electron transfer (ET) across the otherwise insulating indium tin oxide/alkanethiol self-assembled monolayer (SAM)/redox molecule junction was accomplished when a Janus gold nanoparticle (JNP) protected by bioinspired phosphatidylcholine (DPPC) lipid and tyrosine amino acid ligands was anchored on it. In addition to the most theoretical and experimental investigations on the distance-dependent ET across Metal–Organic SAM–Nanoparticle (NP) architectures, the current results succinctly illustrate molecular tilt angle of the SAM and the characteristic of JNP as key factors in expediting the ET rate via electron tunneling. In the absence of JNP, electron tunneling with a tunneling factor β = 1.1 Å{sup −1} across the SAM was the rate-limiting step, evidenced from electrochemical impedance spectroscopy (EIS). The apparent electron transfer rate constant (k{sub app}{sup 0}) for anchored SAM was enhanced by at least one order of magnitude than the DPPC-only protected nanoparticle, suggesting the potential role of tyrosine towards the enhanced ET. The asymmetric and biogenic nature of the construct sheds light on a potential bioelectronic device for novel electronic attributes.Graphical abstractEntry of TOC .

Action potential propagation recorded from single axonal arbors using multi-electrode arrays.

Science.gov (United States)

Tovar, Kenneth R; Bridges, Daniel C; Wu, Bian; Randall, Connor; Audouard, Morgane; Jang, Jiwon; Hansma, Paul K; Kosik, Kenneth S

2018-04-11

We report the presence of co-occurring extracellular action potentials (eAPs) from cultured mouse hippocampal neurons among groups of planar electrodes on multi-electrode arrays (MEAs). The invariant sequences of eAPs among co-active electrode groups, repeated co-occurrences and short inter-electrode latencies are consistent with action potential propagation in unmyelinated axons. Repeated eAP co-detection by multiple electrodes was widespread in all our data records. Co-detection of eAPs confirms they result from the same neuron and allows these eAPs to be isolated from all other spikes independently of spike sorting algorithms. We averaged co-occurring events and revealed additional electrodes with eAPs that would otherwise be below detection threshold. We used these eAP cohorts to explore the temperature sensitivity of action potential propagation and the relationship between voltage-gated sodium channel density and propagation velocity. The sequence of eAPs among co-active electrodes 'fingerprints' neurons giving rise to these events and identifies them within neuronal ensembles. We used this property and the non-invasive nature of extracellular recording to monitor changes in excitability at multiple points in single axonal arbors simultaneously over several hours, demonstrating independence of axonal segments. Over several weeks, we recorded changes in inter-electrode propagation latencies and ongoing changes in excitability in different regions of single axonal arbors. Our work illustrates how repeated eAP co-occurrences can be used to extract physiological data from single axons with low electrode density MEAs. However, repeated eAP co-occurrences leads to over-sampling spikes from single neurons and thus can confound traditional spike-train analysis.

Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer

Science.gov (United States)

Charité, Jeroen; McFadden, David G.; Merlo, Giorgio; Levi, Giovanni; Clouthier, David E.; Yanagisawa, Masashi; Richardson, James A.; Olson, Eric N.

2001-01-01

Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix–loop–helix transcription factor dHAND is also required for craniofacial development, and in endothelin-1 (ET-1) mutant embryos, dHAND expression in the branchial arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to dHAND transcription, we analyzed the dHAND gene for cis-regulatory elements that control transcription in the branchial arches. We describe an evolutionarily conserved dHAND enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for branchial arch expression. By comparing protein binding to these sites in branchial arch extracts from endothelin receptor A (EdnrA) mutant and wild-type mouse embryos, we identified Dlx6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion, Dlx6 was down-regulated in branchial arches from EdnrA mutant mice. These results suggest that Dlx6 acts as an intermediary between ET-1 signaling and dHAND transcription during craniofacial morphogenesis. PMID:11711438

Influence of interface potential on the effective mass in Ge nanostructures

International Nuclear Information System (INIS)

Barbagiovanni, E. G.; Cosentino, S.; Terrasi, A.; Mirabella, S.; Lockwood, D. J.; Costa Filho, R. N.

2015-01-01

The role of the interface potential on the effective mass of charge carriers is elucidated in this work. We develop a new theoretical formalism using a spatially dependent effective mass that is related to the magnitude of the interface potential. Using this formalism, we studied Ge quantum dots (QDs) formed by plasma enhanced chemical vapour deposition (PECVD) and co-sputtering (sputter). These samples allowed us to isolate important consequences arising from differences in the interface potential. We found that for a higher interface potential, as in the case of PECVD QDs, there is a larger reduction in the effective mass, which increases the confinement energy with respect to the sputter sample. We further understood the action of O interface states by comparing our results with Ge QDs grown by molecular beam epitaxy. It is found that the O states can suppress the influence of the interface potential. From our theoretical formalism, we determine the length scale over which the interface potential influences the effective mass

Culture-dependent and culture-independent characterization of potentially functional biphenyl-degrading bacterial community in response to extracellular organic matter from Micrococcus luteus.

Science.gov (United States)

Su, Xiao-Mei; Liu, Yin-Dong; Hashmi, Muhammad Zaffar; Ding, Lin-Xian; Shen, Chao-Feng

2015-05-01

Biphenyl (BP)-degrading bacteria were identified to degrade various polychlorinated BP (PCB) congers in long-term PCB-contaminated sites. Exploring BP-degrading capability of potentially useful bacteria was performed for enhancing PCB bioremediation. In the present study, the bacterial composition of the PCB-contaminated sediment sample was first investigated. Then extracellular organic matter (EOM) from Micrococcus luteus was used to enhance BP biodegradation. The effect of the EOM on the composition of bacterial community was investigated by combining with culture-dependent and culture-independent methods. The obtained results indicate that Proteobacteria and Actinobacteria were predominant community in the PCB-contaminated sediment. EOM from M. luteus could stimulate the activity of some potentially difficult-to-culture BP degraders, which contribute to significant enhancement of BP biodegradation. The potentially difficult-to-culture bacteria in response to EOM addition were mainly Rhodococcus and Pseudomonas belonging to Gammaproteobacteria and Actinobacteria respectively. This study provides new insights into exploration of functional difficult-to-culture bacteria with EOM addition and points out broader BP/PCB degrading, which could be employed for enhancing PCB-bioremediation processes. © 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Therapeutic potential of the original incretin hormone glucose-dependent insulinotropic polypeptide: diabetes, obesity, osteoporosis and Alzheimer's disease?

Science.gov (United States)

Irwin, Nigel; Gault, Victor; Flatt, Peter R

2010-09-01

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that potentiates nutrient-induced insulin release. To date, the physiological importance of GIP has received much less attention than its younger sister incretin hormone glucagon-like peptide-1. Thus, it is worthwhile to refocus on this important and somewhat neglected incretin hormone. The potential role of GIP as a treatment option for type 2 diabetes is highlighted. Furthermore, the use of GIP as a new therapeutic option for obesity, osteoporosis and cognitive impairment is also considered. Long-acting GIP receptor agonists offer a potential new class of antidiabetic drugs. Furthermore, recent observations suggest an as yet untapped potential for GIP agonists in the treatment of osteoporosis and cognitive impairment. In addition, GIP is known to play a role in lipid metabolism and fat deposition. Accordingly, both genetic and chemical ablation of GIP signalling in mice with obesity-diabetes can protect against, or reverse, many of the obesity-associated metabolic disturbances. This review focuses on preclinical data generated to date. GIP-based therapeutics have potential for the treatment of type 2 diabetes and obesity, with the possibility of further beneficial actions in osteoporosis and cognitive decline.

Transportation Security : federal action needed to enhance security efforts : statement of Peter Guerrero, Director, Physical Infrastructure Issues

Science.gov (United States)

2003-09-09

Mr. Guerrero's testimony examines (1) challenges in securing the nation's transportation system; (2) actions transportation operators, as well as state and local governments, have taken since September 11 to enhance security; (3) the federal role in ...

Dependent Human Error Probability Assessment

International Nuclear Information System (INIS)

Simic, Z.; Mikulicic, V.; Vukovic, I.

2006-01-01

This paper presents an assessment of the dependence between dynamic operator actions modeled in a Nuclear Power Plant (NPP) PRA and estimate the associated impact on Core damage frequency (CDF). This assessment was done improve HEP dependencies implementation inside existing PRA. All of the dynamic operator actions modeled in the NPP PRA are included in this assessment. Determining the level of HEP dependence and the associated influence on CDF are the major steps of this assessment. A decision on how to apply the results, i.e., should permanent HEP model changes be made, is based on the resulting relative CDF increase. Some CDF increase was selected as a threshold based on the NPP base CDF value and acceptance guidelines from the Regulatory Guide 1.174. HEP dependence resulting in a CDF increase of > 5E-07 would be considered potential candidates for specific incorporation into the baseline model. The approach used to judge the level of dependence between operator actions is based on dependency level categories and conditional probabilities developed in the Handbook of Human Reliability Analysis with Emphasis on Nuclear Power Plant Applications NUREG/CR-1278. To simplify the process, NUREG/CR-1278 identifies five levels of dependence: ZD (zero dependence), LD (low dependence), MD (moderate dependence), HD (high dependence), and CD (complete dependence). NUREG/CR-1278 also identifies several qualitative factors that could be involved in determining the level of dependence. Based on the NUREG/CR-1278 information, Time, Function, and Spatial attributes were judged to be the most important considerations when determining the level of dependence between operator actions within an accident sequence. These attributes were used to develop qualitative criteria (rules) that were used to judge the level of dependence (CD, HD, MD, LD, ZD) between the operator actions. After the level of dependence between the various HEPs is judged, quantitative values associated with the

Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Science.gov (United States)

Rubi, Lena; Eckert, Daniel; Boehm, Stefan; Hilber, Karlheinz; Koenig, Xaver

2017-04-01

Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

One nuclear calcium transient induced by a single burst of action potentials represents the minimum signal strength in activity-dependent transcription in hippocampal neurons.

Science.gov (United States)

Yu, Yan; Oberlaender, Kristin; Bengtson, C Peter; Bading, Hilmar

2017-07-01

Neurons undergo dramatic changes in their gene expression profiles in response to synaptic stimulation. The coupling of neuronal excitation to gene transcription is well studied and is mediated by signaling pathways activated by cytoplasmic and nuclear calcium transients. Despite this, the minimum synaptic activity required to induce gene expression remains unknown. To address this, we used cultured hippocampal neurons and cellular compartment analysis of temporal activity by fluorescence in situ hybridization (catFISH) that allows detection of nascent transcripts in the cell nucleus. We found that a single burst of action potentials, consisting of 24.4±5.1 action potentials during a 6.7±1.9s depolarization of 19.5±2.0mV causing a 9.3±0.9s somatic calcium transient, is sufficient to activate transcription of the immediate early gene arc (also known as Arg3.1). The total arc mRNA yield produced after a single burst-induced nuclear calcium transient was very small and, compared to unstimulated control neurons, did not lead to a significant increase in arc mRNA levels measured using quantitative reverse transcriptase PCR (qRT-PCR) of cell lysates. Significantly increased arc mRNA levels became detectable in hippocampal neurons that had undergone 5-8 consecutive burst-induced nuclear calcium transients at 0.05-0.15Hz. These results indicate that a single burst-induced nuclear calcium transient can activate gene expression and that transcription is rapidly shut off after synaptic stimulation has ceased. Copyright © 2017 Elsevier Ltd. All rights reserved.

General Solvent-dependent Strategy toward Enhanced Oxygen Reduction Reaction in Graphene/Metal Oxide Nanohybrids: Effects of Nitrogen-containing Solvent

Science.gov (United States)

Kao, Wei-Yao; Chen, Wei-Quan; Chiu, Yu-Hsiang; Ho, Yu-Hsuan; Chen, Chun-Hu

2016-11-01

A general solvent-dependent protocol directly influencing the oxygen reduction reaction (ORR) in metal oxide/graphene nanohybrids has been demonstrated. We conducted the two-step synthesis of cobalt oxide/N-doped graphene nanohybrids (CNG) with solvents of water, ethanol, and dimethylformamide (DMF), representing tree typical categories of aqueous, polar organic, and organic N-containing solvents commonly adopted for graphene nanocomposites preparation. The superior ORR performance of the DMF-hybrids can be attributed to the high nitrogen-doping, aggregation-free hybridization, and unique graphene porous structures. As DMF is the more effective N-source, the spectroscopic results support a catalytic nitrogenation potentially mediated by cobalt-DMF coordination complexes. The wide-distribution of porosity (covering micro-, meso-, to macro-pore) and micron-void assembly of graphene may further enhance the diffusion kinetics for ORR. As the results, CNG by DMF-synthesis exhibits the high ORR activities close to Pt/C (i.e. only 8 mV difference of half-wave potential with electron transfer number of 3.96) with the better durability in the alkaline condition. Additional graphene hybrids comprised of iron and manganese oxides also show the superior ORR activities by DMF-synthesis, confirming the general solvent-dependent protocol to achieve enhanced ORR activities.

Action Research’s Potential to Foster Institutional Change for Urban Water Management

Directory of Open Access Journals (Sweden)

Dimitrios Zikos

2013-04-01

Full Text Available The paper discusses the potential of action research to meet the challenges entailed in institutional design for urban water management. Our overall aim is to briefly present action research and discuss its methodological merits with regard to the challenges posed by the different conceptual bases for extrapolating the effects of institutional design on institutional change. Thus, our aim is to explore how Action Research meets the challenge of scoping the field in an open fashion for determining the appropriate mechanisms of institutional change and supporting the emerging of new water institutions. To accomplish this aim, we select the Water Framework Directive (WFD as an illustrative driving force requiring changes in water management practices and implying the need for the emergence of new institutions. We employ a case of urban water management in the Volos Metropolitan Area, part of the Thessaly region in Greece, where a Pilot River Basin Plan was implemented. By applying action research and being involved in a long process of interaction between stakeholders, we examine the emergence of new institutions dealing with urban water management under the general principles of the major driving force for change: the WFD.

Event-related potential effects of superior action anticipation in professional badminton players.

Science.gov (United States)

Jin, Hua; Xu, Guiping; Zhang, John X; Gao, Hongwei; Ye, Zuoer; Wang, Pin; Lin, Huiyan; Mo, Lei; Lin, Chong-De

2011-04-04

The ability to predict the trajectory of a ball based on the opponent's body kinematics has been shown to be critical to high-performing athletes in many sports. However, little is known about the neural correlates underlying such superior ability in action anticipation. The present event-related potential study compared brain responses from professional badminton players and non-player controls when they watched video clips of badminton games and predicted a ball's landing position. Replicating literature findings, the players made significantly more accurate judgments than the controls and showed better action anticipation. Correspondingly, they showed enlarged amplitudes of two ERP components, a P300 peaking around 350ms post-stimulus with a parietal scalp distribution and a P2 peaking around 250ms with a posterior-occipital distribution. The P300 effect was interpreted to reflect primed access and/or directing of attention to game-related memory representations in the players facilitating their online judgment of related actions. The P2 effect was suggested to reflect some generic learning effects. The results identify clear neural responses that differentiate between different levels of action anticipation associated with sports expertise. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Different Dose-Dependent Modes of Action of C-Type Natriuretic Peptide on Pseudomonas aeruginosa Biofilm Formation

Directory of Open Access Journals (Sweden)

Florie Desriac

2018-04-01

Full Text Available We have previously shown that the C-type Natriuretic Peptide (CNP, a peptide produced by lungs, is able to impact Pseudomonas aeruginosa physiology. In the present work, the effect of CNP at different concentrations on P. aeruginosa biofilm formation was studied and the mechanisms of action of this human hormone on P. aeruginosa were deciphered. CNP was shown to inhibit dynamic biofilm formation in a dose-dependent manner without affecting the bacterial growth at any tested concentrations. The most effective concentrations were 1 and 0.1 µM. At 0.1 µM, the biofilm formation inhibition was fully dependent on the CNP sensor protein AmiC, whereas it was only partially AmiC-dependent at 1 µM, revealing the existence of a second AmiC-independent mode of action of CNP on P. aeruginosa. At 1 µM, CNP reduced both P. aeruginosa adhesion on glass and di-rhamnolipid production and also increased the bacterial membrane fluidity. The various effects of CNP at 1 µM and 0.1 µM on P. aeruginosa shown here should have major consequences to design drugs for biofilm treatment or prevention.

ICRF-enhanced plasma potentials in the SOL of Alcator C-Mod

Energy Technology Data Exchange (ETDEWEB)

Ochoukov, R.; Whyte, D. G.; Brunner, D.; LaBombard, B.; Lipschultz, B.; Terry, J. L.; Wukitch, S. J. [PSFC MIT, NW17, 175 Albany Street, Cambridge, MA 02139 (United States); D' Ippolito, D. A.; Myra, J. R. [Lodestar Research Corporation, 2400 Central Avenue, Boulder, Colorado 80301 (United States)

2014-02-12

We performed an extensive survey of the plasma potential in the scrape-off layer (SOL) of Ion Cyclotron Range-of Frequencies (ICRF)-heated discharges on Alcator C-Mod. Our results show that plasma potentials are enhanced in the presence of ICRF power and plasma potential values of >100 V are often observed. Such potentials are high enough to induce sputtering of high-Z molybdenum (Mo) plasma facing components by deuterium ions on C-Mod. For comparison, the plasma potential in Ohmic discharges is typically less than 10 V, well below the threshold needed to induce Mo sputtering by deuterium ions. ICRF-enhanced plasma potentials are observed in the SOL regions that both magnetically map and do not map to active ICRF antennas. Regions that magnetically map to active ICRF antennas are accessible to slow waves directly launched by the antennas and these regions experience plasma potential enhancement that is partially consistent with the slow wave rectification mechanism. One of the most defining features of the slow wave rectification is a threshold appearance of significant plasma potentials (>100 V) when the dimensionless rectification parameter Λ{sub −o} is above unity and this trend is observed experimentally. We also observe ICRF-enhanced plasma potentials >100 V in regions that do not magnetically map to the active antennas and, hence, are not accessible for slow waves launched directly by the active antennas. However, unabsorbed fast waves can reach these regions. The general trend that we observe in these 'un-mapped' regions is that the plasma potential scales with the strength of the local RF wave fields with the fast wave polarization and the highest plasma potentials are observed in discharges with the highest levels of unabsorbed ICRF power. Similarly, we find that core Mo levels scale with the level of unabsorbed ICRF power suggesting a link between plasma potentials in the SOL and the strength of the impurity source.

Directional growth of Ag nanorod from polymeric silver cyanide: A potential substrate for concentration dependent SERS signal enhancement leading to melamine detection

Science.gov (United States)

Roy, Anindita; Sahoo, Ramkrishna; Chowdhury, Joydeep; Bhattacharya, Tara Shankar; Agarwal, Ratnesh; Pal, Tarasankar

2017-08-01

Attention has been directed to prepare exclusive one-dimensional silver nanostructure from the linear inorganic polymer AgCN. Successive color change from yellow to orange, to red and finally to green reflects the evolution of high yielding Ag nanorods (NRs) from well-known -[Ag-CN]- chains of polymeric AgCN at room temperature. The parental 1D morphology of AgCN is retained within the as-synthesized Ag NRs. So we could successfully exploit the Ag NR for surface-enhanced Raman scattering (SERS) studies for sensing a popular milk adulterant melamine down to picomolar level. We observed interesting concentration dependent selective SERS band enhancement of melamine. The enhanced 1327 cm- 1 SERS signal intensity at lower concentration (10- 9 and 10- 12 M) of melamine speaks for the preferential participation of -C-N of melamine molecule with Ag surface. On the other hand, '-NH2' group together with ring 'N' participation of melamine molecule onto Ag surface suggested an adsorptive stance at higher (10- 3-10- 7 M) concentration range. Thus the binding modes of the molecule at the Ag surface justify its fluxional behavior.

Potential dependent superiority of gold nanoparticles in comparison to iodinated contrast agents

International Nuclear Information System (INIS)

Jackson, Price A.; Rahman, Wan Nordiana W. Abd.; Wong, Christopher J.; Ackerly, Trevor; Geso, Moshi

2010-01-01

Purpose: To identify the benefits in image contrast enhancement using gold nanoparticles (AuNPs) compared to conventional iodinated contrast media. Materials and methods: Gold nanoparticles and iodinated contrast media were evaluated for contrast enhancement at various X-ray tube potentials in an imaging phantom. Iopromide and AuNP suspension were equalized according to molar concentration of radiopaque element (0.5077 Mol/L). Contrast-to-noise ratio is used to quantify contrast enhancement. Both projectional radiographic (40-80 kVp) and computed tomography (CT) (80-140kVp) imaging modalities were examined. Results and conclusions: Findings indicate 89% improvement in CNR at low energies near the mammographic range (40 kVp). However, as expected no significant difference in enhancement was observed at potentials commonly used for angiography (around 80 kVp) probably due to the k-edge influence for iodine. At the highest energies typically available in computed tomography, significant improvement in contrast enhancement using gold nanoparticles is obtained, 114% greater CNR than that produced by iodine at 140 kVp. Experimental findings for 70-120 kVp spectra correlate well with the theoretical calculations based on linear attenuation coefficients. Superior attenuation of gold nanoparticles at low and high kVp potentials support their further (pre)clinical evaluation.

Analysis of electrically evoked compound action potential of the auditory nerve in children with bilateral cochlear implants.

Science.gov (United States)

Caldas, Fernanda Ferreira; Cardoso, Carolina Costa; Barreto, Monique Antunes de Souza Chelminski; Teixeira, Marina Santos; Hilgenberg, Anacléia Melo da Silva; Serra, Lucieny Silva Martins; Bahmad Junior, Fayez

2016-01-01

The cochlear implant device has the capacity to measure the electrically evoked compound action potential of the auditory nerve. The neural response telemetry is used in order to measure the electrically evoked compound action potential of the auditory nerve. To analyze the electrically evoked compound action potential, through the neural response telemetry, in children with bilateral cochlear implants. This is an analytical, prospective, longitudinal, historical cohort study. Six children, aged 1-4 years, with bilateral cochlear implant were assessed at five different intervals during their first year of cochlear implant use. There were significant differences in follow-up time (p=0.0082) and electrode position (p=0.0019) in the T-NRT measure. There was a significant difference in the interaction between time of follow-up and electrode position (p=0.0143) when measuring the N1-P1 wave amplitude between the three electrodes at each time of follow-up. The electrically evoked compound action potential measurement using neural response telemetry in children with bilateral cochlear implants during the first year of follow-up was effective in demonstrating the synchronized bilateral development of the peripheral auditory pathways in the studied population. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Action of caffeine on x-irradiated HeLa cells. VII. Evidence that caffeine enhances expression of potentially lethal radiation damage

International Nuclear Information System (INIS)

Beetham, K.L.; Tolmach, L.J.

1984-01-01

HeLa cells irradiated with 2 Gy of 220-kV X rays suffer a 60-70% loss of colony-forming ability which is increased to 90% by postirradiation treatment with 10 mM caffeine for 6 hr. The detailed postirradiation patterns of cell death and sister-cell fusion in such cultures and in cultures in which the colony-forming ability was brought to about the same level by treatment with a larger (4 Gy) X-ray dose alone or by longer (48 hr) treatment with 10 mM caffeine alone were recorded by time-lapse cinemicrography. Because the patterns of cell death and fusion differ radically in irradiated and in caffeine-treated cultures, the response of the additional cells killed by the combined treatment can be identified as X-ray induced rather than caffeine induced. The appearance of cultures after several days of incubation confirms the similarity of the post-treatment patterns of proliferation in cultures suffering enhanced killing to those occurring in cultures treated with larger doses of X rays alone. It is concluded that x rays do not sensitize cells to caffeine, but rather that caffeine enhanced the expression of potentially lethal radiation-induced damage

Temperature dependence in interatomic potentials and an improved potential for Ti

International Nuclear Information System (INIS)

Ackland, G J

2012-01-01

The process of deriving an interatomic potentials represents an attempt to integrate out the electronic degrees of freedom from the full quantum description of a condensed matter system. In practice it is the derivatives of the interatomic potentials which are used in molecular dynamics, as a model for the forces on a system. These forces should be the derivative of the free energy of the electronic system, which includes contributions from the entropy of the electronic states. This free energy is weakly temperature dependent, and although this can be safely neglected in many cases there are some systems where the electronic entropy plays a significant role. Here a method is proposed to incorporate electronic entropy in the Sommerfeld approximation into empirical potentials. The method is applied as a correction to an existing potential for titanium. Thermal properties of the new model are calculated, and a simple method for fixing the melting point and solid-solid phase transition temperature for existing models fitted to zero temperature data is presented.

Enhancement of delayed-rectifier potassium conductance by low concentrations of local anaesthetics in spinal sensory neurones

Science.gov (United States)

Olschewski, Andrea; Wolff, Matthias; Bräu, Michael E; Hempelmann, Gunter; Vogel, Werner; Safronov, Boris V

2002-01-01

Combining the patch-clamp recordings in slice preparation with the ‘entire soma isolation' method we studied action of several local anaesthetics on delayed-rectifier K+ currents in spinal dorsal horn neurones.Bupivacaine, lidocaine and mepivacaine at low concentrations (1–100 μM) enhanced delayed-rectifier K+ current in intact neurones within the spinal cord slice, while exhibiting a partial blocking effect at higher concentrations (>100 μM). In isolated somata 0.1–10 μM bupivacaine enhanced delayed-rectifier K+ current by shifting its steady-state activation characteristic and the voltage-dependence of the activation time constant to more negative potentials by 10–20 mV.Detailed analysis has revealed that bupivacaine also increased the maximum delayed-rectifier K+ conductance by changing the open probability, rather than the unitary conductance, of the channel.It is concluded that local anaesthetics show a dual effect on delayed-rectifier K+ currents by potentiating them at low concentrations and partially suppressing at high concentrations. The phenomenon observed demonstrated the complex action of local anaesthetics during spinal and epidural anaesthesia, which is not restricted to a suppression of Na+ conductance only. PMID:12055132

Path integral solution for some time-dependent potential

International Nuclear Information System (INIS)

Storchak, S.N.

1989-12-01

The quantum-mechanical problem with a time-dependent potential is solved by the path integral method. The solution is obtained by the application of the previously derived general formula for rheonomic homogeneous point transformation and reparametrization in the path integral. (author). 4 refs

Caffeine potentiates or protects against radiation-induced DNA and chromosomal damage in human lymphocytes depending on temperature and concentration

International Nuclear Information System (INIS)

Stoilov, L.M.; Mullenders, L.H.F.; Natarajan, A.T.

1994-01-01

The effect of caffeine on radiation-induced chromosomal aberrations and DNA strand breaks in unstimulated human lymphocytes was investigated. When present prior to and during the radiation exposure, caffeine treatment was found to cause either potentiation or protection against induction of chromosomal aberrations depending on the concentration and temperature. When the nucleoid sedimentation technique was applied, enhancement or reduction of radiation-induced DNA strand breaks by caffeine was also found to be dependent on temperature and caffeine concentration. It is proposed that caffeine, in addition to its suspected ability to influence DNA repair, can also influence the induction of DNA damage, leading to alterations in the yield of chromosomal aberrations

Caffeine potentiates or protects against radiation-induced DNA and chromosomal damage in human lymphocytes depending on temperature and concentration

Energy Technology Data Exchange (ETDEWEB)

Stoilov, L.M. (Department of Molecular Genetics, Institute of Genetics, Sofia (Bulgaria)); Mullenders, L.H.F.; Natarajan, A.T. (J.A. Cohen Institute, Interuniversity Research Institute for Radiopathology and Radiation Protection, Leiden (Netherlands))

1994-12-01

The effect of caffeine on radiation-induced chromosomal aberrations and DNA strand breaks in unstimulated human lymphocytes was investigated. When present prior to and during the radiation exposure, caffeine treatment was found to cause either potentiation or protection against induction of chromosomal aberrations depending on the concentration and temperature. When the nucleoid sedimentation technique was applied, enhancement or reduction of radiation-induced DNA strand breaks by caffeine was also found to be dependent on temperature and caffeine concentration. It is proposed that caffeine, in addition to its suspected ability to influence DNA repair, can also influence the induction of DNA damage, leading to alterations in the yield of chromosomal aberrations.

Action Learning: Avoiding Conflict or Enabling Action

Science.gov (United States)

Corley, Aileen; Thorne, Ann

2006-01-01

Action learning is based on the premise that action and learning are inextricably entwined and it is this potential, to enable action, which has contributed to the growth of action learning within education and management development programmes. However has this growth in action learning lead to an evolution or a dilution of Revan's classical…

Potential enhancements to addressing programmatic risk in the tank waste remediation system (TWRS) program

International Nuclear Information System (INIS)

Brothers, A.; Fassbender, L.; Bilyard, G.; Levine, L.

1996-04-01

Pacific Northwest National Laboratory (PNNL) conducted a Tank Waste Remediation System (TWRS) Risk Management methodology development task. The objective of this task was to develop risk management methodology focused on (1) the use of programmatic risk information in making TWRS architecture selection decisions and (2) the identification/evaluation/selection of TWRS risk-handling actions. Methods for incorporating programmatic risk/uncertainty estimates into trade studies are provided for engineers/analysts. Methods for identifying, evaluating, and selecting risk-handling actions are provided for managers. The guidance provided in this report is designed to help decision-makers make difficult judgments. Current approaches to architecture selection decisions and identification/evaluation/selection of risk-handling actions are summarized. Three categories of sources of programmatic risk (parametric, external, and organizational) are examined. Multiple analytical approaches are presented to enhance the current alternative generation and analysis (AGA) and risk-handling procedures. Appendix A describes some commercially available risk management software tools and Appendix B provides a brief introduction to quantification of risk attitudes. The report provides three levels of analysis for enhancing the AGA Procedure: (1) qualitative discussion coupled with estimated uncertainty ranges for scores in the alternatives-by-criteria matrix; (2) formal elicitation of probability distributions for the alternative scores; and (3) a formal, more structured, comprehensive risk analysis. A framework is also presented for using the AGA programmatic risk analysis results in making better decisions. The report also presents two levels of analysis for evaluation and selection of risk-handling actions: (1) qualitative analysis and judgmental rankings of alternative actions, and (2) Simple Multi-Attribute Rating Technique (SMART)

Chemical Potential Tuning and Enhancement of Thermoelectric Properties in Indium Selenides.

Science.gov (United States)

Rhyee, Jong-Soo; Kim, Jin Hee

2015-03-20

Researchers have long been searching for the materials to enhance thermoelectric performance in terms of nano scale approach in order to realize phonon-glass-electron-crystal and quantum confinement effects. Peierls distortion can be a pathway to enhance thermoelectric figure-of-merit ZT by employing natural nano-wire-like electronic and thermal transport. The phonon-softening known as Kohn anomaly, and Peierls lattice distortion decrease phonon energy and increase phonon scattering, respectively, and, as a result, they lower thermal conductivity. The quasi-one-dimensional electrical transport from anisotropic band structure ensures high Seebeck coefficient in Indium Selenide. The routes for high ZT materials development of In₄Se₃ - δ are discussed from quasi-one-dimensional property and electronic band structure calculation to materials synthesis, crystal growth, and their thermoelectric properties investigations. The thermoelectric properties of In₄Se₃ - δ can be enhanced by electron doping, as suggested from the Boltzmann transport calculation. Regarding the enhancement of chemical potential, the chlorine doped In₄Se₃ - δ Cl 0.03 compound exhibits high ZT over a wide temperature range and shows state-of-the-art thermoelectric performance of ZT = 1.53 at 450 °C as an n -type material. It was proven that multiple elements doping can enhance chemical potential further. Here, we discuss the recent progress on the enhancement of thermoelectric properties in Indium Selenides by increasing chemical potential.

Experience of action depends on intention, not body movement: an experiment on memory for mens rea.

Science.gov (United States)

Jensen, Mads; Vagnoni, Eleonora; Overgaard, Morten; Haggard, Patrick

2014-03-01

How do we know whether our own actions were voluntary or involuntary? Intentional theories of sense of agency suggest that we consciously perceive the intentions that accompany our actions, but reconstructive theories suggest that we perceive our actions only through the body movements and other effects that they produce. Intentions would then be mere confabulations, and not bona fide experiences. Previous work on voluntary action has focused on immediate experiences of authorship, and few studies have considered memory for voluntary actions. We devised an experiment in which both voluntary action and involuntary movement always occurred at the same time, but could either involve the same hand (congruent condition), or different hands (incongruent condition). When signals from the voluntary and involuntary movements involved different hands, they could therefore potentially interfere in memory. We found that recall of a voluntary action was unaffected by an incongruent involuntary movement. In contrast, recall of an involuntary movement was strongly influenced by an incongruent voluntary action. Our results demonstrate an "intentional capture" of body movement by voluntary actions, in support of intentional theories of agency, but contrary to reconstructive theories. When asked to recall both actions and movements, people's responses are shaped by memory of what they intended to do, rather than by how their body moved. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Chun-Lei Zhang

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

Comparing topological charge definitions using topology fixing actions

International Nuclear Information System (INIS)

Bruckmann, Falk; Gruber, Florian; Jansen, Karl; Marinkovic, Marina; Urbach, Carsten; Wagner, Marc

2009-05-01

We investigate both the hyperbolic action and the determinant ratio action designed to fix the topological charge on the lattice. We show to what extent topology is fixed depending on the parameters of these actions, keeping the physical situation fixed. At the same time the agreement between different definitions of topological charge - the field theoretic and the index definition - is directly correlated to the degree topology is fixed. Moreover, it turns out that the two definitions agree very well. We also study finite volume effects arising in the static potential and related quantities due to topology fixing. (orig.)

Dosis Facit Sanitatem—Concentration-Dependent Effects of Resveratrol on Mitochondria

Directory of Open Access Journals (Sweden)

Corina T. Madreiter-Sokolowski

2017-10-01

Full Text Available The naturally occurring polyphenol, resveratrol (RSV, is known for a broad range of actions. These include a positive impact on lifespan and health, but also pro-apoptotic anti-cancer properties. Interestingly, cell culture experiments have revealed a strong impact of RSV on mitochondrial function. The compound was demonstrated to affect mitochondrial respiration, structure and mass of mitochondria as well as mitochondrial membrane potential and, ultimately, mitochondria-associated cell death pathways. Notably, the mitochondrial effects of RSV show a very strict and remarkable concentration dependency: At low concentrations, RSV (<50 μM fosters cellular antioxidant defense mechanisms, activates AMP-activated protein kinase (AMPK- and sirtuin 1 (SIRT1-linked pathways and enhances mitochondrial network formation. These mechanisms crucially contribute to the cytoprotective effects of RSV against toxins and disease-related damage, in vitro and in vivo. However, at higher concentrations, RSV (>50 μM triggers changes in (sub-cellular Ca2+ homeostasis, disruption of mitochondrial membrane potential and activation of caspases selectively yielding apoptotic cancer cell death, in vitro and in vivo. In this review, we discuss the promising therapeutic potential of RSV, which is most probably related to the compound’s concentration-dependent manipulation of mitochondrial function and structure.

Spin-dependent potentials from lattice QCD

International Nuclear Information System (INIS)

Koma, Y.

2006-09-01

The spin-dependent corrections to the static inter-quark potential are phenomenologically relevant to describing the fine and hyperfine spin splitting of the heavy quarkonium spectra. We investigate these corrections, which are represented as the field strength correlators on the quark-antiquark source, in SU(3) lattice gauge theory. We use the Polyakov loop correlation function as the quark-antiquark source, and by employing the multi-level algorithm, we obtain remarkably clean signals for these corrections up to intermediate distances of around 0.6 fm. Our observation suggests several new features of the corrections. (orig.)

Disrupting the ventral premotor cortex interferes with the contribution of action observation to use-dependent plasticity.

Science.gov (United States)

Cantarero, Gabriela; Galea, Joseph M; Ajagbe, Loni; Salas, Rachel; Willis, Jeff; Celnik, Pablo

2011-12-01

Action observation (AO), observing another individual perform an action, has been implicated in several higher cognitive processes including forming basic motor memories. Previous work has shown that physical practice (PP) results in cortical motor representational changes, referred to as use-dependent plasticity (UDP), and that AO combined with PP potentiates UDP in both healthy adults and stroke patients. In humans, AO results in activation of the ventral premotor cortex (PMv), however, whether this PMv activation has a functional contribution to UDP is not known. Here, we studied the effects disruption of PMv has on UDP when subjects performed PP combined with AO (PP + AO). Subjects participated in two randomized crossover sessions measuring the amount of UDP resulting from PP + AO while receiving disruptive (1 Hz) TMS over the fMRI-activated PMv or over frontal cortex (Sham). We found that, unlike the sham session, disruptive TMS over PMv reduced the beneficial contribution of AO to UDP. To ensure that disruption of PMv was specifically interfering with the contribution of AO and not PP, subjects completed two more control sessions where they performed only PP while receiving disruptive TMS over PMv or frontal cortex. We found that the magnitude of UDP for both control sessions was similar to PP + AO with TMS over PMv. These findings suggest that the fMRI activation found in PMv during AO studies is functionally relevant to task performance, at least for the beneficial effects that AO exerts over motor training.

Effect of an Educational Game on University Students' Learning about Action Potentials

Science.gov (United States)

Luchi, Kelly Cristina Gaviao; Montrezor, Luís Henrique; Marcondes, Fernanda K.

2017-01-01

The aim of this study was to evaluate the effect of an educational game that is used for teaching the mechanisms of the action potentials in cell membranes. The game was composed of pieces representing the intracellular and extracellular environments, ions, ion channels, and the Na+-K+-ATPase pump. During the game activity, the students arranged…

Action potential conduction between a ventricular cell model and an isolated ventricular cell

NARCIS (Netherlands)

Wilders, R.; Kumar, R.; Joyner, R. W.; Jongsma, H. J.; Verheijck, E. E.; Golod, D.; van Ginneken, A. C.; Goolsby, W. N.

1996-01-01

We used the Luo and Rudy (LR) mathematical model of the guinea pig ventricular cell coupled to experimentally recorded guinea pig ventricular cells to investigate the effects of geometrical asymmetry on action potential propagation. The overall correspondence of the LR cell model with the recorded

Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure

Science.gov (United States)

Brinkman, Adam S.; Murali, Sangita G.; Hitt, Stacy; Solverson, Patrick M.; Holst, Jens J.

2012-01-01

Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 μg·kg−1·day−1), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral reference group. Animals underwent massive distal bowel resection followed by jejunocolic anastomosis and placement of jugular catheters. Starting on postoperative day 4, rats in the EN groups were allowed ad libitum access to EN. Groups provided PN + EN + GLP-2 had their rate of PN reduced by 0.25 ml/day starting on postoperative day 6. Groups provided PN + EN + GLP-2 demonstrated significantly greater body weight gain with similar energy intake and a safe 80% reduction in PN compared with TPN ± GLP-2. Groups provided PN + EN + GLP-2 for 7 or 18 days showed similar body weight gain, residual jejunal length, and digestive capacity. Groups provided PN + EN + GLP-2 showed increased jejunal GLP-2 receptor (GLP-2R), insulin-like growth factor-I (IGF-I), and IGF-binding protein-5 (IGFBP-5) expression. Treatment with TPN + GLP-2 demonstrated increased jejunal expression of epidermal growth factor. Cessation of GLP-2 after 7 days with continued EN sustained the majority of intestinal adaption and significantly increased expression of colonic proglucagon compared with PN + EN + GLP-2 for 18 days, and increased plasma GLP-2 concentrations compared with TPN alone. In summary, EN potentiate the intestinotrophic actions of GLP-2 by improving body weight gain allowing for a safe 80% reduction in PN with increased jejunal expression of GLP-2R, IGF-I, and IGFBP-5 following distal bowel

Exact effective action for (1+1)-dimensional fermions in an Abelian background at finite temperature and chemical potential

International Nuclear Information System (INIS)

Maciel, Soraya G.; Perez, Silvana

2008-01-01

In this paper we study the effects of a nonzero chemical potential in (1+1)-dimensional quantum field models at finite temperature. We particularly consider massless fermions in an Abelian gauge field background and calculate the effective action by evaluating the n-point functions. We find that the structure of the amplitudes corresponds to a generalization of the structure noted earlier in a calculation without a chemical potential (the associated integrals carry the dependence on the chemical potential). Our calculation shows that the chiral anomaly is unaffected by the presence of a chemical potential at finite temperature. However, unlike in the absence of a chemical potential, odd point functions do not vanish. We trace this to the fact that in the presence of a chemical potential the generalized charge conjugation symmetry of the theory allows for such amplitudes. In fact, we find that all the even point functions are even functions of μ, while the odd point functions are odd functions of μ which is consistent with this generalized charge conjugation symmetry. We show that the origin of the structure of the amplitudes is best seen from a formulation of the theory in terms of left- and right-handed spinors. The calculations are also much simpler in this formulation and it clarifies many other aspects of the theory.

Pathological prolongation of action potential duration as a cause of the reduced alpha-adrenoceptor-mediated negative inotropy in streptozotocin-induced diabetic mice myocardium.

Science.gov (United States)

Kanae, Haruna; Hamaguchi, Shogo; Wakasugi, Yumi; Kusakabe, Taichi; Kato, Keisuke; Namekata, Iyuki; Tanaka, Hikaru

2017-11-01

Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice. Cromakalim shortened the action potential duration and increased the negative inotropy in streptozotocin-treated mice. These results suggest that the reduced α-adrenoceptor-mediated inotropy in the diabetic mouse myocardium is partly due to its prolonged action potential. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Grasp it loudly! Supporting actions with semantically congruent spoken action words.

Directory of Open Access Journals (Sweden)

Raphaël Fargier

Full Text Available Evidence for cross-talk between motor and language brain structures has accumulated over the past several years. However, while a significant amount of research has focused on the interaction between language perception and action, little attention has been paid to the potential impact of language production on overt motor behaviour. The aim of the present study was to test whether verbalizing during a grasp-to-displace action would affect motor behaviour and, if so, whether this effect would depend on the semantic content of the pronounced word (Experiment I. Furthermore, we sought to test the stability of such effects in a different group of participants and investigate at which stage of the motor act language intervenes (Experiment II. For this, participants were asked to reach, grasp and displace an object while overtly pronouncing verbal descriptions of the action ("grasp" and "put down" or unrelated words (e.g. "butterfly" and "pigeon". Fine-grained analyses of several kinematic parameters such as velocity peaks revealed that when participants produced action-related words their movements became faster compared to conditions in which they did not verbalize or in which they produced words that were not related to the action. These effects likely result from the functional interaction between semantic retrieval of the words and the planning and programming of the action. Therefore, links between (action language and motor structures are significant to the point that language can refine overt motor behaviour.

Teachers in Action Research: Assumptions and Potentials

Science.gov (United States)

Li, Yuen-Ling

2008-01-01

Research literature has long indicated that action research may stimulate practitioners themselves to actively evaluate the quality of their practice. This study is designed to report the use of action research for the development of early years professional practice by analyzing the pre-project and the post-project video-filmed teaching events.…

Preoperative examination of potential renal transplant donors: value of gadolinium-enhanced 3D-MR-angiography in comparison with DSA and urography

International Nuclear Information System (INIS)

Winterer, J.T.; Paul, G.; Einert, A.; Altehoefer, C.; Uhrmeister, P.; Laubenberger, J.

2000-01-01

Purpose: To assess a contrast-enhanced standardized MRA protocol for the presurgical evaluation of potential renal transplant donors. Methods: Twenty-three potential donors for renal transplantations were examined with gadolinium-enhanced, two-phase MR angiograms (1.5 T) and DSA/urography for the number of renal arteries, the presence of aberrant arterial and venous branches, renal artery stenoses and anatomy of the renal collecting system and ureters. The diagnostic value was assessed by evaluating different image processing modalities and interobserver variability. Results: Using maximum intensity projections (MIP) together with multiplanar reformatting (MPR), accessory arteries were detected with a sensitivity/specificity of 100%/98%. Depending on diagnostic experience, exclusive evaluation of MIP yielded a sensitivitiy/specificity of 67-100%/95-100%. Using MIP/MPR, venous depiction was good in 80%, with MIP solely in 30-40%. At least the proximal third of the ureter was visible in 67%. Conclusion: MPR/MIP evaluation of two-phase, contrast-enhanced MRA provides an excellent depiction of renal vessel anatomy for presurgical evaluation of renal transplant donors. Exclusive MIP assessment is less reliable and depends strongly on the examiner's experience. For sufficient visualization of the ureters, either additional measurements or low-dose diuretic injection have to be performed. (orig.) [de

Activity-Dependent Plasticity of Spike Pauses in Cerebellar Purkinje Cells

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Giorgio Grasselli

2016-03-01

Full Text Available The plasticity of intrinsic excitability has been described in several types of neurons, but the significance of non-synaptic mechanisms in brain plasticity and learning remains elusive. Cerebellar Purkinje cells are inhibitory neurons that spontaneously fire action potentials at high frequencies and regulate activity in their target cells in the cerebellar nuclei by generating a characteristic spike burst-pause sequence upon synaptic activation. Using patch-clamp recordings from mouse Purkinje cells, we find that depolarization-triggered intrinsic plasticity enhances spike firing and shortens the duration of spike pauses. Pause plasticity is absent from mice lacking SK2-type potassium channels (SK2−/− mice and in occlusion experiments using the SK channel blocker apamin, while apamin wash-in mimics pause reduction. Our findings demonstrate that spike pauses can be regulated through an activity-dependent, exclusively non-synaptic, SK2 channel-dependent mechanism and suggest that pause plasticity—by altering the Purkinje cell output—may be crucial to cerebellar information storage and learning.

OH radicals from the indirect actions of X-rays induce cell lethality and mediate the majority of the oxygen enhancement effect.

Science.gov (United States)

Hirayama, Ryoichi; Ito, Atsushi; Noguchi, Miho; Matsumoto, Yoshitaka; Uzawa, Akiko; Kobashi, Gen; Okayasu, Ryuichi; Furusawa, Yoshiya

2013-11-01

We examined OH radical-mediated indirect actions from X irradiation on cell killing in wild-type Chinese hamster ovary cell lines (CHO and AA8) under oxic and hypoxic conditions, and compared the contribution of direct and indirect actions under both conditions. The contribution of indirect action on cell killing can be estimated from the maximum degree of protection by dimethylsulfoxide, which suppresses indirect action by quenching OH radicals without affecting the direct action of X rays on cell killing. The contributions of indirect action on cell killing of CHO cells were 76% and 50% under oxic and hypoxic conditions, respectively, and those for AA8 cells were 85% and 47%, respectively. Therefore, the indirect action on cell killing was enhanced by oxygen during X irradiation in both cell lines tested. Oxygen enhancement ratios (OERs) at the 10% survival level (D10 or LD90) for CHO and AA8 cells were 2.68 ± 0.15 and 2.76 ± 0.08, respectively. OERs were evaluated separately for indirect and direct actions, which gave the values of 3.75 and 2.01 for CHO, and 4.11 and 1.32 for AA8 cells, respectively. Thus the generally accepted OER value of ∼3 is best understood as the average of the OER values for both indirect and direct actions. These results imply that both indirect and direct actions on cell killing require oxygen for the majority of lethal DNA damage, however, oxygen plays a larger role in indirect than for direct effects. Conversely, the lethal damage induced by the direct action of X rays are less affected by oxygen concentration.

Effects of terpineol on the compound action potential of the rat sciatic nerve

Directory of Open Access Journals (Sweden)

M.R. Moreira

2001-10-01

Full Text Available Terpineol, a volatile terpenoid alcohol of low toxicity, is widely used in the perfumery industry. It is an important chemical constituent of the essential oil of many plants with widespread applications in folk medicine and in aromatherapy. The effects of terpineol on the compound action potential (CAP of rat sciatic nerve were studied. Terpineol induced a dose-dependent blockade of the CAP. At 100 µM, terpineol had no demonstrable effect. At 300 µM terpineol, peak-to-peak amplitude and conduction velocity of CAP were significantly reduced at the end of 180-min exposure of the nerve to the drug, from 3.28 ± 0.22 mV and 33.5 ± 7.05 m/s, respectively, to 1.91 ± 0.51 mV and 26.2 ± 4.55 m/s. At 600 µM, terpineol significantly reduced peak-to-peak amplitude and conduction velocity from 2.97 ± 0.55 mV and 32.8 ± 3.91 m/s to 0.24 ± 0.23 mV and 2.72 ± 2.72 m/s, respectively (N = 5. All these effects developed slowly and were reversible upon 180-min washout.

An Excel‐based implementation of the spectral method of action potential alternans analysis

Science.gov (United States)

Pearman, Charles M.

2014-01-01

Abstract Action potential (AP) alternans has been well established as a mechanism of arrhythmogenesis and sudden cardiac death. Proper interpretation of AP alternans requires a robust method of alternans quantification. Traditional methods of alternans analysis neglect higher order periodicities that may have greater pro‐arrhythmic potential than classical 2:1 alternans. The spectral method of alternans analysis, already widely used in the related study of microvolt T‐wave alternans, has also been used to study AP alternans. Software to meet the specific needs of AP alternans analysis is not currently available in the public domain. An AP analysis tool is implemented here, written in Visual Basic for Applications and using Microsoft Excel as a shell. This performs a sophisticated analysis of alternans behavior allowing reliable distinction of alternans from random fluctuations, quantification of alternans magnitude, and identification of which phases of the AP are most affected. In addition, the spectral method has been adapted to allow detection and quantification of higher order regular oscillations. Analysis of action potential morphology is also performed. A simple user interface enables easy import, analysis, and export of collated results. PMID:25501439

Genetic or pharmacological reduction of PERK enhances cortical-dependent taste learning.

Science.gov (United States)

Ounallah-Saad, Hadile; Sharma, Vijendra; Edry, Efrat; Rosenblum, Kobi

2014-10-29

Protein translation initiation is controlled by levels of eIF2α phosphorylation (p-eIF2α) on Ser51. In addition, increased p-eIF2α levels impair long-term synaptic plasticity and memory consolidation, whereas decreased levels enhance them. Levels of p-eIF2α are determined by four kinases, of which protein kinase RNA-activated (PKR), PKR-like endoplastic reticulum kinase (PERK), and general control nonderepressible 2 are extensively expressed in the mammalian mature brain. Following identification of PERK as the major kinase to determine basal levels of p-eIF2α in primary neuronal cultures, we tested its function as a physiological constraint of memory consolidation in the cortex, the brain structure suggested to store, at least in part, long-term memories in the mammalian brain. To that aim, insular cortex (IC)-dependent positive and negative forms of taste learning were used. Genetic reduction of PERK expression was accomplished by local microinfusion of a lentivirus harboring PERK Short hairpin RNA, and pharmacological inhibition was achieved by local microinfusion of a PERK-specific inhibitor (GSK2606414) to the rat IC. Both genetic reduction of PERK expression and pharmacological inhibition of its activity reduced p-eIF2α levels and enhanced novel taste learning and conditioned taste aversion, but not memory retrieval. Moreover, enhanced extinction was observed together with enhanced associative memory, suggesting increased cortical-dependent behavioral plasticity. The results suggest that, by phosphorylating eIF2α, PERK functions in the cortex as a physiological constraint of memory consolidation, and its downregulation serves as cognitive enhancement. Copyright © 2014 the authors 0270-6474/14/3314624-09$15.00/0.

The potential use of mobile technology: enhancing accessibility and ...

African Journals Online (AJOL)

The potential use of mobile technology: enhancing accessibility and communication in a blended ... South African Journal of Education ... Recommendations, limitations of the present study, and suggestions for future research were made.

Chemical Potential Tuning and Enhancement of Thermoelectric Properties in Indium Selenides

Directory of Open Access Journals (Sweden)

Jong-Soo Rhyee

2015-03-01

Full Text Available Researchers have long been searching for the materials to enhance thermoelectric performance in terms of nano scale approach in order to realize phonon-glass-electron-crystal and quantum confinement effects. Peierls distortion can be a pathway to enhance thermoelectric figure-of-merit ZT by employing natural nano-wire-like electronic and thermal transport. The phonon-softening known as Kohn anomaly, and Peierls lattice distortion decrease phonon energy and increase phonon scattering, respectively, and, as a result, they lower thermal conductivity. The quasi-one-dimensional electrical transport from anisotropic band structure ensures high Seebeck coefficient in Indium Selenide. The routes for high ZT materials development of In4Se3−δ are discussed from quasi-one-dimensional property and electronic band structure calculation to materials synthesis, crystal growth, and their thermoelectric properties investigations. The thermoelectric properties of In4Se3−δ can be enhanced by electron doping, as suggested from the Boltzmann transport calculation. Regarding the enhancement of chemical potential, the chlorine doped In4Se3−δCl0.03 compound exhibits high ZT over a wide temperature range and shows state-of-the-art thermoelectric performance of ZT = 1.53 at 450 °C as an n-type material. It was proven that multiple elements doping can enhance chemical potential further. Here, we discuss the recent progress on the enhancement of thermoelectric properties in Indium Selenides by increasing chemical potential.

Size and shape dependent deprotonation potential and proton affinity of nanodiamond

International Nuclear Information System (INIS)

Barnard, Amanda S; Per, Manolo C

2014-01-01

Many important reactions in biology and medicine involve proton abstraction and transfer, and it is integral to applications such as drug delivery. Unlike electrons, which are quantum mechanically delocalized, protons are instantaneously localized on specific residues in these reactions, which can be a distinct advantage. However, the introduction of nanoparticles, such as non-toxic nanodiamonds, to this field complicates matters, as the number of possible sites increases as the inverse radius of the particle. In this paper we present >10 4 simulations that map the size- and shape-dependence of the deprotonation potential and proton affinity of nanodiamonds in the range 1.8–2.7 nm in average diameter. We find that while the average deprotonation potential and proton affinities decrease with size, the site-specific values are inhomogeneous over the surface of the particles, exhibiting strong shape-dependence. The proton affinity is strongly facet-dependent, whereas the deprotonation potential is edge/corner-dependent, which creates a type of spatial hysteresis in the transfer of protons to and from the nanodiamond, and provides new opportunities for selective functionalization. (paper)

Size and shape dependent deprotonation potential and proton affinity of nanodiamond

Science.gov (United States)

Barnard, Amanda S.; Per, Manolo C.

2014-11-01

Many important reactions in biology and medicine involve proton abstraction and transfer, and it is integral to applications such as drug delivery. Unlike electrons, which are quantum mechanically delocalized, protons are instantaneously localized on specific residues in these reactions, which can be a distinct advantage. However, the introduction of nanoparticles, such as non-toxic nanodiamonds, to this field complicates matters, as the number of possible sites increases as the inverse radius of the particle. In this paper we present \\gt {{10}4} simulations that map the size- and shape-dependence of the deprotonation potential and proton affinity of nanodiamonds in the range 1.8-2.7 nm in average diameter. We find that while the average deprotonation potential and proton affinities decrease with size, the site-specific values are inhomogeneous over the surface of the particles, exhibiting strong shape-dependence. The proton affinity is strongly facet-dependent, whereas the deprotonation potential is edge/corner-dependent, which creates a type of spatial hysteresis in the transfer of protons to and from the nanodiamond, and provides new opportunities for selective functionalization.

The three body problem with energy dependent potentials

International Nuclear Information System (INIS)

Kim, Y.E.; McKay, C.M.; McKellar, B.H.J.

1975-10-01

It is shown how to generalize the three body equations of Faddeev, and of Karlsson and Zeiger, to include the case when the two body potential is energy dependent. Such generalizations will prove useful in the three nucleon problem and in three body models of nuclear reactions. (author)

Temperature dependence of radiation effects in polyethylene

International Nuclear Information System (INIS)

Wu, G; Katsumura, Y.; Kudoh, H.; Morita, Y.; Seguchi, T.

2000-01-01

Temperature dependence of crosslinking and gas evolution under γ-irradiation was studied for high-density and low-density polyethylene samples in the 30-360degC range. It was found that crosslinking was the predominant process up to 300degC and the gel point decreased with increasing temperature. At above 300degC, however, the gel fraction at a given dose decreased rapidly with temperature and the action of radiation turned to enhance polyethylene degradation. Yields of H 2 and hydrocarbon gases increased with temperature and the compositions of hydrocarbons were dose dependent. (author)

Sodium Channel β2 Subunits Prevent Action Potential Propagation Failures at Axonal Branch Points.

Science.gov (United States)

Cho, In Ha; Panzera, Lauren C; Chin, Morven; Hoppa, Michael B

2017-09-27

Neurotransmitter release depends on voltage-gated Na + channels (Na v s) to propagate an action potential (AP) successfully from the axon hillock to a synaptic terminal. Unmyelinated sections of axon are very diverse structures encompassing branch points and numerous presynaptic terminals with undefined molecular partners of Na + channels. Using optical recordings of Ca 2+ and membrane voltage, we demonstrate here that Na + channel β2 subunits (Na v β2s) are required to prevent AP propagation failures across the axonal arborization of cultured rat hippocampal neurons (mixed male and female). When Na v β2 expression was reduced, we identified two specific phenotypes: (1) membrane excitability and AP-evoked Ca 2+ entry were impaired at synapses and (2) AP propagation was severely compromised with >40% of axonal branches no longer responding to AP-stimulation. We went on to show that a great deal of electrical signaling heterogeneity exists in AP waveforms across the axonal arborization independent of axon morphology. Therefore, Na v β2 is a critical regulator of axonal excitability and synaptic function in unmyelinated axons. SIGNIFICANCE STATEMENT Voltage-gated Ca 2+ channels are fulcrums of neurotransmission that convert electrical inputs into chemical outputs in the form of vesicle fusion at synaptic terminals. However, the role of the electrical signal, the presynaptic action potential (AP), in modulating synaptic transmission is less clear. What is the fidelity of a propagating AP waveform in the axon and what molecules shape it throughout the axonal arborization? Our work identifies several new features of AP propagation in unmyelinated axons: (1) branches of a single axonal arborization have variable AP waveforms independent of morphology, (2) Na + channel β2 subunits modulate AP-evoked Ca 2+ -influx, and (3) β2 subunits maintain successful AP propagation across the axonal arbor. These findings are relevant to understanding the flow of excitation in the

Ambiance-dependent agglomeration and surface-enhanced Raman spectroscopy response of self-assembled silver nanoparticles for plasmonic photovoltaic devices

Science.gov (United States)

Gwamuri, Jephias; Venkatesan, Ragavendran; Sadatgol, Mehdi; Mayandi, Jeyanthinath; Guney, Durdu O.; Pearce, Joshua M.

2017-07-01

The agglomeration/dewetting process of thin silver films provides a scalable method of obtaining self-assembled nanoparticles (SANPs) for plasmonics-based thin-film solar photovoltaic (PV) devices. We show the effect of annealing ambiance on silver SANP average size, particle/cluster finite shape, substrate area coverage/particle distribution, and how these physical parameters influence optical properties and surface-enhanced Raman scattering (SERS) responses of SANPs. Statistical analysis performed indicates that generally Ag SANPs processed in the presence of a gas (argon and nitrogen) ambiance tend to have smaller average size particles compared to those processed under vacuum. Optical properties are observed to be highly dependent on particle size, separation distance, and finite shape. The greatest SERS enhancement was observed for the argon-processed samples. There is a correlation between simulation and experimental data that indicate argon-processed AgNPs have a great potential to enhance light coupling when integrated to thin-film PV.

Probing the density dependence of the symmetry potential in intermediate-energy heavy ion collisions

International Nuclear Information System (INIS)

Li Qingfeng; Li Zhuxia; Soff, Sven; Gupta, Raj K; Bleicher, Marcus; Stoecker, Horst

2005-01-01

Based on the ultrarelativistic quantum molecular dynamics model, the effects of the density-dependent symmetry potential for baryons and of the Coulomb potential for produced mesons are investigated for neutron-rich heavy ion collisions at intermediate energies. The calculated results of the Δ - /Δ ++ and π - /π + production ratios show a clear beam-energy dependence on the density-dependent symmetry potential, which is stronger for the π - /π + ratio close to the pion production threshold. The Coulomb potential of the mesons changes the transverse momentum distribution of the π - /π + ratio significantly, though it alters only slightly the π - and π + total yields. The π - yields, especially at midrapidity or at low transverse momenta and the π - /π + ratios at low transverse momenta are shown to be sensitive probes of the density-dependent symmetry potential in dense nuclear matter. The effect of the density-dependent symmetry potential on the production of both K 0 and K + mesons is also investigated

Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid

DEFF Research Database (Denmark)

Rinaldi, Tania; Kulangara, Karina; Antoniello, Katia

2007-01-01

as the commonly linked kinase calcium/calmodulin-dependent protein kinase II. Synaptic plasticity experiments between pairs of pyramidal neurons revealed an augmented postsynaptic form of long-term potentiation. These results indicate that VPA significantly enhances NMDA receptor-mediated transmission and causes......Valproic acid (VPA) is a powerful teratogen causing birth defects in humans, including autism spectrum disorder (ASD), if exposure occurs during the first trimester of embryogenesis. Learning and memory alterations are common symptoms of ASD, but underlying molecular and synaptic alterations remain...

Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.

Science.gov (United States)

Devenyi, Ryan A; Ortega, Francis A; Groenendaal, Willemijn; Krogh-Madsen, Trine; Christini, David J; Sobie, Eric A

2017-04-01

Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias. Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information-rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re-parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K + current and a drastic decrease in the slow delayed rectifier K + current, and this prediction was validated experimentally. Subsequent simulations with the adjusted model generated the clinically relevant prediction that the slow delayed rectifier is better able to stabilize the action potential and suppress pro-arrhythmic events than the rapid delayed rectifier. In summary, iterative coupling of

Enhancing School Asthma Action Plans: Qualitative Results from Southeast Minnesota Beacon Stakeholder Groups

Science.gov (United States)

Egginton, Jason S.; Textor, Lauren; Knoebel, Erin; McWilliams, Deborah; Aleman, Marty; Yawn, Barbara

2013-01-01

Background: This study explores ways southeast Minnesota schools currently address asthma problems, identifies areas for improvement, and assesses the potential value of asthma action plans (AAPs) in schools. Methods: Focus groups were used to query stakeholder groups on asthma care in schools. Groups were held separately for elementary school…

Study of antineoplastic action of novel isomeric derivatives of 4-thiazolidinone

Directory of Open Access Journals (Sweden)

М. R. Fil

2014-12-01

Full Text Available Pyrazole- and aryl-substituted derivatives of 4-thiazolidinone belong to a perspective group of compounds with potential antitumor action. Earlier, we have demonstrated high toxicity in vitro of several 4-thiazolidinones derivatives towards tumor cell lines. To further enhance the antitumor activity of novel 4-thiazolidinones, their chemical scaffold was optimized, and new pyrazole-thiazolidinones were synthesized. That allowed us to combine in one molecule the potential pharmacophore centres of previously tested compounds. As a result, “hybrid” 4-thiazolidinones exhibit higher toxicity in vitro toward tumor cells of various origin. The molecular mechanisms of antineoplastic activity of these compounds and intensity of induction of apoptosis strongly depended on the position of the substituent in the thiazolidinone cycle. In particular, Les-3661 compound, containing pyrazoline fragment in the 4th position of thiazolidinone core, exhibits 14 times higher cytotoxic activity towards tumor cells (LC50 = 3 µM in comparison to its 2-substituted isomer Les-3713 (LC50 = 42 µM. It is demonstrated that in terms of underlying molecular mechanisms for cytotoxic effect the Les-3661 compound induced caspase-8 and caspase-9 dependent mixed-type of apoptosis, while Les-3713 induced apoptosis mediated only by the caspase-8.

Wetland Resources Action Planning (WRAP) toolkit

DEFF Research Database (Denmark)

Bunting, Stuart W.; Smith, Kevin G.; Lund, Søren

2013-01-01

The Wetland Resources Action Planning (WRAP) toolkit is a toolkit of research methods and better management practices used in HighARCS (Highland Aquatic Resources Conservation and Sustainable Development), an EU-funded project with field experiences in China, Vietnam and India. It aims to communi......The Wetland Resources Action Planning (WRAP) toolkit is a toolkit of research methods and better management practices used in HighARCS (Highland Aquatic Resources Conservation and Sustainable Development), an EU-funded project with field experiences in China, Vietnam and India. It aims...... to communicate best practices in conserving biodiversity and sustaining ecosystem services to potential users and to promote the wise-use of aquatic resources, improve livelihoods and enhance policy information....

Joint action modulates motor system involvement during action observation in 3-year-olds

NARCIS (Netherlands)

Meyer, M.; Hunnius, S.; Elk, M. van; Ede, F.L. van; Bekkering, H.

2011-01-01

When we are engaged in a joint action, we need to integrate our partner's actions with our own actions. Previous research has shown that in adults the involvement of one's own motor system is enhanced during observation of an action partner as compared to during observation of an individual actor.

Action dependent heuristic dynamic programming based residential energy scheduling with home energy inter-exchange

International Nuclear Information System (INIS)

Xu, Yancai; Liu, Derong; Wei, Qinglai

2015-01-01

Highlights: • The algorithm is developed in the two-household energy management environment. • We develop the absent energy penalty cost for the first time. • The algorithm has ability to keep adapting in real-time operations. • Its application can lower total costs and achieve better load balancing. - Abstract: Residential energy scheduling is a hot topic nowadays in the background of energy saving and environmental protection worldwide. To achieve this objective, a new residential energy scheduling algorithm is developed for energy management, based on action dependent heuristic dynamic programming. The algorithm works under the circumstance of residential real-time pricing and two adjacent housing units with energy inter-exchange, which can reduce the overall cost and enhance renewable energy efficiency after long-term operation. It is designed to obtain the optimal control policy to manage the directions and amounts of electricity energy flux. The algorithm’s architecture is mainly constructed based on neural networks, denoting the learned characteristics in the linkage of layers. To get close to real situations, many constraints such as maximum charging/discharging power of batteries are taken into account. The absent energy penalty cost is developed for the first time as a part of the performance index function. When the environment changes, the residential energy scheduling algorithm gains new features and keeps adapting in real-time operations. Simulation results show that the developed algorithm is beneficial to energy conversation

Substance P enhances proliferation and paracrine potential of adipose-derived stem cells in vitro

International Nuclear Information System (INIS)

Kim, Suna; Piao, Jiyuan; Son, Youngsook; Hong, Hyun Sook

2017-01-01

Stem cells have tremendous promise to treat intractable diseases. Notably, adipose-derived stem cells (ADSCs) are actively being investigated because of ease of sampling and high repopulation capacity in vitro. ADSCs can exert a therapeutic effect through differentiation and paracrine potential, and these actions have been proven in many diseases, including cutaneous and inflammatory diseases. Transplantation of ADSCs necessitates therapeutic quantities and thus, long term ex vivo culture of ADSCs. However, this procedure can impair the activity of ADSCs and provoke cellular senescence, leading to low efficacy in vivo. Accordingly, strategies to restore cellular activity and inhibit senescence of stem cells during ex vivo culture are needed for stem cell-based therapies. This study evaluated a potential supplementary role of Substance P (SP) in ADSC ex vivo culture. After confirming that the ADSC cell cycle was damaged by passage 6 (p6), ADSCs at p6 were cultured with SP, and their proliferation rates, cumulative cell numbers, cytokine profiles, and impact on T/endothelial cells were assessed. Long-term culture weakened proliferation ability and secretion of the cytokines, transforming growth factor-beta 1 (TGF-beta1), vascular endothelial growth factor (VEGF), and stromal cell derived factor-1 alpha (SDF-1alpha) in ADSCs. However, SP treatment reduced the population doubling time (PDT), enabling gain of a sufficient number of ADSCs at early passages. In addition, SP restored cytokine secretion, enhancing the ADSC-mediated paracrine effect on T cell and human umbilical vein endothelial cells (HUVECs). Taken together, these results suggest that SP can retain the therapeutic effect of ADSCs by elevating their proliferative and paracrine potential in ex vivo culture. - Highlights: • Long-term culture of ADSCs leads to cell senescence. • Paracrine potential of ADSC decreases as passage number increases. • SP enhances the weakened proliferation capacity of

Fcγ-receptor IIa-mediated Src Signaling Pathway Is Essential for the Antibody-Dependent Enhancement of Ebola Virus Infection.

Directory of Open Access Journals (Sweden)

Wakako Furuyama

2016-12-01

Full Text Available Antibody-dependent enhancement (ADE of Ebola virus (EBOV infection has been demonstrated in vitro, raising concerns about the detrimental potential of some anti-EBOV antibodies. ADE has been described for many viruses and mostly depends on the cross-linking of virus-antibody complexes to cell surface Fc receptors, leading to enhanced infection. However, little is known about the molecular mechanisms underlying this phenomenon. Here we show that Fcγ-receptor IIa (FcγRIIa-mediated intracellular signaling through Src family protein tyrosine kinases (PTKs is required for ADE of EBOV infection. We found that deletion of the FcγRIIa cytoplasmic tail abolished EBOV ADE due to decreased virus uptake into cellular endosomes. Furthermore, EBOV ADE, but not non-ADE infection, was significantly reduced by inhibition of the Src family protein PTK pathway, which was also found to be important to promote phagocytosis/macropinocytosis for viral uptake into endosomes. We further confirmed a significant increase of the Src phosphorylation mediated by ADE. These data suggest that antibody-EBOV complexes bound to the cell surface FcγRIIa activate the Src signaling pathway that leads to enhanced viral entry into cells, providing a novel perspective for the general understanding of ADE of virus infection.

Enhancing action of LSD on neuronal responsiveness to serotonin in a brain structure involved in obsessive-compulsive disorder.

Science.gov (United States)

Zghoul, Tarek; Blier, Pierre

2003-03-01

Potent serotonin (5-HT) reuptake inhibitors are the only drugs that consistently exert a therapeutic action in obsessive-compulsive disorder (OCD). Given that some hallucinogens were reported to exert an anti-OCD effect outlasting their psychotomimetic action, possible modifications of neuronal responsiveness to 5-HT by LSD were examined in two rat brain structures: one associated with OCD, the orbitofrontal cortex (OFC), and another linked to depression, the hippocampus. The effects of concurrent microiontophoretic application of LSD and 5-HT were examined on neuronal firing rate in the rat OFC and hippocampus under chloral hydrate anaesthesia. In order to determine whether LSD could also exert a modification of 5-HT neuronal responsiveness upon systemic administration, after a delay when hallucinosis is presumably no longer present, it was given once daily (100 microg/kg i.p.) for 4 d and the experiments were carried out 24 h after the last dose. LSD attenuated the firing activity of OFC neurons, and enhanced the inhibitory effect of 5-HT when concomitantly ejected on the same neurons. In the hippocampus, LSD also decreased firing rate by itself but decreased the inhibitory action of 5-HT. The inhibitory action of 5-HT was significantly greater in the OFC, but smaller in the hippocampus, when examined after subacute systemic administration of LSD. It is postulated that some hallucinogens could have a beneficial action in OCD by enhancing the responsiveness to 5-HT in the OFC, and not necessarily in direct relation to hallucinosis. The latter observation may have theoretical implications for the pharmacotherapy of OCD.

Tunnelling in a time dependent quartic potential: Possible implications for cosmology

International Nuclear Information System (INIS)

Kabir, R; Mukherjee, A

2014-01-01

The theory of a real scalar field with an arbitrary potential plays an important role in cosmology, particularly in the context of inflationary scenarios. However, in most applications, the potential is treated as independent of time, whereas in an evolving universe, for example, before the onset of inflation, the potential is actually likely to be changing with time. As pointed out by Berry in the context of single-particle quantum mechanics, the existence of multiple time scales can lead to results that are qualitatively different from those obtained with a static potential. The present paper reports on numerical investigations in a scalar field theory with a double-well potential that depends explicitly on time. The transition rate per unit volume for the decay of the false vacuum is found to depend strongly on time. Possible implications for old inflation are discussed

Dynamic noise from action errors enhances network reciprocity in the prisoner's dilemma game

International Nuclear Information System (INIS)

Tanimoto, Jun; Ogasawara, Takashi

2015-01-01

Inspired by the fact that people make mistakes in a transient, fluctuating or chaotic environment, we establish a spatial prisoner's dilemma model where an agent commits action errors proportionally varying with the increasing/decreasing rate of the global cooperation fraction. A series of numerical simulations reveal that the cooperation level is enhanced in games in which the stag hunt (SH)-type dilemma is dominant; however, it is slightly diminished in games in which the chicken-type dilemma is dominant, compared with the standard network reciprocity model. Intensive analysis reveals that the noise created by the action error contribute to the spatial expansion of a cooperators' cluster, because a dilemma that is less chicken-type and more SH-type makes it disadvantageous for defectors to neighbor cooperators. Our finding, that errors in behavior in a chaotic environment contribute to the evolution of cooperation, might aim to explain the problem of how network reciprocity works. (paper)

Enhancement of soft X-ray lasing action with thin blade radiators

Science.gov (United States)

Suckewer, Szymon; Skinner, Charles H.; Voorhees, David R.

1988-01-01

An enhancement of approximately 100 of stimulated emission over spontaneous emission of the CVI 182 Angstrom line was obtained in a recombining magnetically confined plasma column. The plasma was formed by focusing a CO.sub.2 laser beam on a carbon disc. A magnetic solenoid produced a strong magnetic field which confined the plasma to the shape of a column. A single thin carbon blade extended parallel to the plasma column and served to make the column axially more uniform and also acted as a heat sink. Axial and transverse measurements of the soft X-ray lasing action were made from locations off-set from the central axis of the plasma column. Multiple carbon blades located at equal intervals around the plasma column were also found to produce acceptable results. According to another embodiment 10 a thin coating of aluminum or magnesium was placed on the carbon disc and blade. The Z of the coating should preferably be at least 5 greater than the Z of the target. Measurements of the soft X-rays generated at 182 Angstroms showed a significant increase in intensity enhancement.

Spontaneous processing of functional and non-functional action sequences

DEFF Research Database (Denmark)

Nielbo, Kristoffer Laigaard; Sørensen, Jesper

2011-01-01

as sub-categories of non-functional behavior (i.e., actions lacking causal coherence and a necessary integration between subparts). New insights in human action processing can help us explain how cognition might vary depending on the type of behavior processed. Using an event segmentation paradigm, we...... conducted two experiments eliciting differences in participants' response patterns to functional and non-functional actions. Participants consistently segmented non-functional action sequences into smaller units indicating either an attentional shift to the level of gesture analysis or a problem...... of representational integration. Experimental studies of non-functional behavior can strengthen explanations of recurrent features of human action processing, such as ritual and ritualized behavior, as well as indicate potential sources and effects of breakdown of the system....

Parametric enhancement of the tunneling transmission through a potential barrier

International Nuclear Information System (INIS)

Tanaka, Masatoshi; Iwata, Giiti.

1992-01-01

A possibility of indicated of enhancing the tunneling transmission of particle incident on a potential barrier with the aid of an auxiliary potential parametrically in resonance with incident particles. For a simple auxiliary potential, a train of two-step square wells, examples are presented in which the ratio of the transmission coefficients with and without the auxiliary potential can be very large, e.g. (2n + 1) 2L , where n is the positive integer and L the number of the period of the auxiliary potential. (author)

Time-dependent image potential at a metal surface

International Nuclear Information System (INIS)

Alducin, M.; Diez Muino, R.; Juaristi, J.I.

2003-01-01

Transient effects in the image potential induced by a point charge suddenly created in front of a metal surface are studied. The time evolution of the image potential is calculated using linear response theory. Two different time scales are defined: (i) the time required for the creation of the image potential and (ii) the time it takes to converge to its stationary value. Their dependence on the distance of the charge to the surface is discussed. The effect of the electron gas damping is also analyzed. For a typical metallic density, the order of magnitude of the creation time is 0.1 fs, whereas for a charge created close to the surface the convergence time is around 1-2 fs

The augmenting action of banana tree juice on skeletal muscle contraction.

Science.gov (United States)

Singh, Y N; Dryden, W F

1990-01-01

An extract obtained from juice expressed from the stem of the plantain banana tree (Musa sapientum L., var. paradisiaca) induces twitch augmentation in skeletal muscles. The mechanism of this action was investigated in the mouse hemi-diaphragm preparation. Directly evoked twitches and potassium induced (K+) contractures were both augmented by the extract. Twitch augmentation was partly dependent on extracellular Ca2+. The action on K(+)-contractures was unaffected by tetrodotoxin, but the rate of relaxation was enhanced in the absence of extracellular calcium (0[Ca2+]o). Muscle contracture induced by high concentrations of extract was also augmented in 0[Ca2+]o and in the presence of the Ca2(+)-channel blocking agent, nifedipine. The time course of the contracture was shortened in 0[Ca2+]o, but not by nifedipine. Nifedipine enhanced the augmenting effect of the extract on twitches but shortened the time-course of this action. In addition, a muscle contracture was superimposed on the twitching muscle at higher concentrations of nifedipine. Manganese, on the other hand, reduced or abolished the augmenting action of the extract. The results are consistent with an action of banana tree juice on the molecule responsible for excitation-contraction coupling in skeletal muscle, resulting in a labilization of intracellular Ca2+.

Conglutinin exhibits a complement-dependent enhancement of the respiratory burst of phagocytes stimulated by E. coli

DEFF Research Database (Denmark)

Friis, P; Svehag, S E; Andersen, Ove

1991-01-01

. Conglutinin enhances, in a dose-dependent manner, the respiratory burst of spleen cells stimulated with serum-opsonized Escherichia coli. The enhancement was only demonstrable in the presence of a functional complement system. The conglutinin-mediated enhancement of the respiratory burst was inhibited...

Gaming to see: action video gaming is associated with enhanced processing of masked stimuli.

Science.gov (United States)

Pohl, Carsten; Kunde, Wilfried; Ganz, Thomas; Conzelmann, Annette; Pauli, Paul; Kiesel, Andrea

2014-01-01

Recent research revealed that action video game players outperform non-players in a wide range of attentional, perceptual and cognitive tasks. Here we tested if expertise in action video games is related to differences regarding the potential of shortly presented stimuli to bias behavior. In a response priming paradigm, participants classified four animal pictures functioning as targets as being smaller or larger than a reference frame. Before each target, one of the same four animal pictures was presented as a masked prime to influence participants' responses in a congruent or incongruent way. Masked primes induced congruence effects, that is, faster responses for congruent compared to incongruent conditions, indicating processing of hardly visible primes. Results also suggested that action video game players showed a larger congruence effect than non-players for 20 ms primes, whereas there was no group difference for 60 ms primes. In addition, there was a tendency for action video game players to detect masked primes for some prime durations better than non-players. Thus, action video game expertise may be accompanied by faster and more efficient processing of shortly presented visual stimuli.

Gaming to see: Action Video Gaming is associated with enhanced processing of masked stimuli

Directory of Open Access Journals (Sweden)

Carsten ePohl

2014-02-01

Full Text Available Recent research revealed that action video game players outperform non-players in a wide range of attentional, perceptual and cognitive tasks. Here we tested if expertise in action video games is related to differences regarding the potential of shortly presented stimuli to bias behaviour. In a response priming paradigm, participants classified four animal pictures functioning as targets as being smaller or larger than a reference frame. Before each target, one of the same four animal pictures was presented as a masked prime to influence participants’ responses in a congruent or incongruent way. Masked primes induced congruence effects, that is, faster responses for congruent compared to incongruent conditions, indicating processing of hardly visible primes. Results also suggested that action video game players showed a larger congruence effect than non-players for 20 ms primes, whereas there was no group difference for 60 ms primes. In addition, there was a tendency for action video game players to detect masked primes for some prime durations better than non-players. Thus, action video game expertise may be accompanied by faster and more efficient processing of shortly presented visual stimuli.

Lectin-dependent enhancement of Ebola virus infection via soluble and transmembrane C-type lectin receptors.

Directory of Open Access Journals (Sweden)

Matthew Brudner

Full Text Available Mannose-binding lectin (MBL is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion

Lectin-dependent enhancement of Ebola virus infection via soluble and transmembrane C-type lectin receptors.

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Brudner, Matthew; Karpel, Marshall; Lear, Calli; Chen, Li; Yantosca, L Michael; Scully, Corinne; Sarraju, Ashish; Sokolovska, Anna; Zariffard, M Reza; Eisen, Damon P; Mungall, Bruce A; Kotton, Darrell N; Omari, Amel; Huang, I-Chueh; Farzan, Michael; Takahashi, Kazue; Stuart, Lynda; Stahl, Gregory L; Ezekowitz, Alan B; Spear, Gregory T; Olinger, Gene G; Schmidt, Emmett V; Michelow, Ian C

2013-01-01

Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active

Pumice stones as potential in-situ burning enhancer

DEFF Research Database (Denmark)

Rojas Alva, U.; Andersen, Bjørn Skjønning; Jomaas, Grunde

2018-01-01

Small-scale and mid-scale experiments were conducted in order to evaluate pumice stones as a potential enhancement for in-situ burning (ISB). Four oil types, several emulsification degrees of one crude oil were studied. In general, it was observed that the pumice stones did not improve the burning...... and after the burn, thus bringing the oil into the water column. Finally, the species production of CO and CO2 was not reduced. Based on the presented results, pumice stones have a negative impact on the efficiency of ISB, and they are ruled out as an ISB enhancer and should not be used in relation to ISB....

An Excel-based implementation of the spectral method of action potential alternans analysis.

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Pearman, Charles M

2014-12-01

Action potential (AP) alternans has been well established as a mechanism of arrhythmogenesis and sudden cardiac death. Proper interpretation of AP alternans requires a robust method of alternans quantification. Traditional methods of alternans analysis neglect higher order periodicities that may have greater pro-arrhythmic potential than classical 2:1 alternans. The spectral method of alternans analysis, already widely used in the related study of microvolt T-wave alternans, has also been used to study AP alternans. Software to meet the specific needs of AP alternans analysis is not currently available in the public domain. An AP analysis tool is implemented here, written in Visual Basic for Applications and using Microsoft Excel as a shell. This performs a sophisticated analysis of alternans behavior allowing reliable distinction of alternans from random fluctuations, quantification of alternans magnitude, and identification of which phases of the AP are most affected. In addition, the spectral method has been adapted to allow detection and quantification of higher order regular oscillations. Analysis of action potential morphology is also performed. A simple user interface enables easy import, analysis, and export of collated results. © 2014 The Author. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Brain training with non-action video games enhances aspects of cognition in older adults: a randomized controlled trial

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Ballesteros, Soledad; Prieto, Antonio; Mayas, Julia; Toril, Pilar; Pita, Carmen; Ponce de León, Laura; Reales, José M.; Waterworth, John

2014-01-01

Age-related cognitive and brain declines can result in functional deterioration in many cognitive domains, dependency, and dementia. A major goal of aging research is to investigate methods that help to maintain brain health, cognition, independent living and wellbeing in older adults. This randomized controlled study investigated the effects of 20 1-h non-action video game training sessions with games selected from a commercially available package (Lumosity) on a series of age-declined cognitive functions and subjective wellbeing. Two groups of healthy older adults participated in the study, the experimental group who received the training and the control group who attended three meetings with the research team along the study. Groups were similar at baseline on demographics, vocabulary, global cognition, and depression status. All participants were assessed individually before and after the intervention, or a similar period of time, using neuropsychological tests and laboratory tasks to investigate possible transfer effects. The results showed significant improvements in the trained group, and no variation in the control group, in processing speed (choice reaction time), attention (reduction of distraction and increase of alertness), immediate and delayed visual recognition memory, as well as a trend to improve in Affection and Assertivity, two dimensions of the Wellbeing Scale. Visuospatial working memory (WM) and executive control (shifting strategy) did not improve. Overall, the current results support the idea that training healthy older adults with non-action video games will enhance some cognitive abilities but not others. PMID:25352805

Brain training with non-action video games enhances aspects of cognition in older adults: a randomized controlled trial.

Science.gov (United States)

Ballesteros, Soledad; Prieto, Antonio; Mayas, Julia; Toril, Pilar; Pita, Carmen; Ponce de León, Laura; Reales, José M; Waterworth, John

2014-01-01

Age-related cognitive and brain declines can result in functional deterioration in many cognitive domains, dependency, and dementia. A major goal of aging research is to investigate methods that help to maintain brain health, cognition, independent living and wellbeing in older adults. This randomized controlled study investigated the effects of 20 1-h non-action video game training sessions with games selected from a commercially available package (Lumosity) on a series of age-declined cognitive functions and subjective wellbeing. Two groups of healthy older adults participated in the study, the experimental group who received the training and the control group who attended three meetings with the research team along the study. Groups were similar at baseline on demographics, vocabulary, global cognition, and depression status. All participants were assessed individually before and after the intervention, or a similar period of time, using neuropsychological tests and laboratory tasks to investigate possible transfer effects. The results showed significant improvements in the trained group, and no variation in the control group, in processing speed (choice reaction time), attention (reduction of distraction and increase of alertness), immediate and delayed visual recognition memory, as well as a trend to improve in Affection and Assertivity, two dimensions of the Wellbeing Scale. Visuospatial working memory (WM) and executive control (shifting strategy) did not improve. Overall, the current results support the idea that training healthy older adults with non-action video games will enhance some cognitive abilities but not others.

Variable Action Potential Backpropagation during Tonic Firing and Low-Threshold Spike Bursts in Thalamocortical But Not Thalamic Reticular Nucleus Neurons.

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Connelly, William M; Crunelli, Vincenzo; Errington, Adam C

2017-05-24

Backpropagating action potentials (bAPs) are indispensable in dendritic signaling. Conflicting Ca 2+ -imaging data and an absence of dendritic recording data means that the extent of backpropagation in thalamocortical (TC) and thalamic reticular nucleus (TRN) neurons remains unknown. Because TRN neurons signal electrically through dendrodendritic gap junctions and possibly via chemical dendritic GABAergic synapses, as well as classical axonal GABA release, this lack of knowledge is problematic. To address this issue, we made two-photon targeted patch-clamp recordings from rat TC and TRN neuron dendrites to measure bAPs directly. These recordings reveal that "tonic"' and low-threshold-spike (LTS) "burst" APs in both cell types are always recorded first at the soma before backpropagating into the dendrites while undergoing substantial distance-dependent dendritic amplitude attenuation. In TC neurons, bAP attenuation strength varies according to firing mode. During LTS bursts, somatic AP half-width increases progressively with increasing spike number, allowing late-burst spikes to propagate more efficiently into the dendritic tree compared with spikes occurring at burst onset. Tonic spikes have similar somatic half-widths to late burst spikes and undergo similar dendritic attenuation. In contrast, in TRN neurons, AP properties are unchanged between LTS bursts and tonic firing and, as a result, distance-dependent dendritic attenuation remains consistent across different firing modes. Therefore, unlike LTS-associated global electrical and calcium signals, the spatial influence of bAP signaling in TC and TRN neurons is more restricted, with potentially important behavioral-state-dependent consequences for synaptic integration and plasticity in thalamic neurons. SIGNIFICANCE STATEMENT In most neurons, action potentials (APs) initiate in the axosomatic region and propagate into the dendritic tree to provide a retrograde signal that conveys information about the level of

Multiple antidepressant potential modes of action of curcumin: a review of its anti-inflammatory, monoaminergic, antioxidant, immune-modulating and neuroprotective effects.

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Lopresti, Adrian L; Hood, Sean D; Drummond, Peter D

2012-12-01

Curcumin is the principal curcuminoid of the popular Indian spice turmeric and has attracted increasing attention for the treatment of a range of conditions. Research into its potential as a treatment for depression is still in its infancy, although several potential antidepressant mechanisms of action have been identified. Research completed to date on the multiple effects of curcumin is reviewed in this paper, with a specific emphasis on the biological systems that are compromised in depression. The antidepressant effects of curcumin in animal models of depression are summarised, and its influence on neurotransmitters such as serotonin and dopamine is detailed. The effects of curcumin in moderating hypothalamus-pituitary-adrenal disturbances, lowering inflammation and protecting against oxidative stress, mitochondrial damage, neuroprogression and intestinal hyperpermeability, all of which are compromised in major depressive disorder, are also summarised. With increasing interest in natural treatments for depression, and efforts to enhance current treatment outcomes, curcumin is presented as a promising novel, adjunctive or stand-alone natural antidepressant.

Investigating a Potential Auxin-Related Mode of Hormetic/Inhibitory Action of the Phytotoxin Parthenin.

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Belz, Regina G

2016-01-01

Parthenin is a metabolite of Parthenium hysterophorus and is believed to contribute to the weed's invasiveness via allelopathy. Despite the potential of parthenin to suppress competitors, low doses stimulate plant growth. This biphasic action was hypothesized to be auxin-like and, therefore, an auxin-related mode of parthenin action was investigated using two approaches: joint action experiments with Lactuca sativa, and dose-response experiments with auxin/antiauxin-resistant Arabidopsis thaliana genotypes. The joint action approach comprised binary mixtures of subinhibitory doses of the auxin 3-indoleacetic acid (IAA) mixed with parthenin or one of three reference compounds [indole-3-butyric acid (IBA), 2,3,5-triiodobenzoic acid (TIBA), 2-(p-chlorophenoxy)-2-methylpropionic acid (PCIB)]. The reference compounds significantly interacted with IAA at all doses, but parthenin interacted only at low doses indicating that parthenin hormesis may be auxin-related, in contrast to its inhibitory action. The genetic approach investigated the response of four auxin/antiauxin-resistant mutants and a wildtype to parthenin or two reference compounds (IAA, PCIB). The responses of mutant plants to the reference compounds confirmed previous reports, but differed from the responses observed for parthenin. Parthenin stimulated and inhibited all mutants independent of resistance. This provided no indication for an auxin-related action of parthenin. Therefore, the hypothesis of an auxin-related inhibitory action of parthenin was rejected in two independent experimental approaches, while the hypothesis of an auxin-related stimulatory effect could not be rejected.

Therapeutic treatments potentially mediated by melatonin receptors: potential clinical uses in the prevention of osteoporosis, cancer and as an adjuvant therapy.

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Witt-Enderby, Paula A; Radio, Nicholas M; Doctor, John S; Davis, Vicki L

2006-11-01

Melatonin's therapeutic potential is grossly underestimated because its functional roles are diverse and its mechanism(s) of action are complex and varied. Melatonin produces cellular effects via a variety of mechanisms in a receptor independent and dependent manner. In addition, melatonin is a chronobiotic agent secreted from the pineal gland during the hours of darkness. This diurnal release of melatonin impacts the sensitivity of melatonin receptors throughout a 24-hr period. This changing sensitivity probably contributes to the narrow therapeutic window for use of melatonin in treating sleep disorders, that is, at the light-to-dark (dusk) or dark-to-light (dawn) transition states. In addition to the cyclic changes in melatonin receptors, many genes cycle over the 24-hr period, independent or dependent upon the light/dark cycle. Interestingly, many of these genes support a role for melatonin in modulating metabolic and cardiovascular physiology as well as bone metabolism and immune function and detoxification of chemical agents and cancer reduction. Melatonin also enhances the actions of a variety of drugs or hormones; however, the role of melatonin receptors in modulating these processes is not known. The goal of this review is to summarize the evidence related to the utility of melatonin as a therapeutic agent by focusing on its other potential uses besides sleep disorders. In particular, its use in cancer prevention, osteoporosis and, as an adjuvant to other therapies are discussed. Also, the role that melatonin and, particularly, its receptors play in these processes are highlighted.

Idiosyncratic representation of peripersonal space depends on the success of one's own motor actions, but also the successful actions of others!

Science.gov (United States)

Coello, Yann; Quesque, François; Gigliotti, Maria-Francesca; Ott, Laurent; Bruyelle, Jean-Luc

2018-01-01

decreased amplitude of manual reaching actions was accompanied by an increase of peripersonal space representation, which was not due to the mere presence of a confederate (control experiment). We conclude that reward-dependent modulation of objects values in the environment modifies the representation of peripersonal space, when resulting from either self-generated motor actions or observation of motor actions performed by a confederate.

Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors

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Etame, Arnold B.

The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non

Learning-dependent and -independent enhancement of mitral/tufted cell glomerular odor responses following olfactory fear conditioning in awake mice.

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Ross, Jordan M; Fletcher, Max L

2018-04-18

Associative fear learning produces fear toward the conditioned stimulus (CS) and often generalization, the expansion of fear from the CS to similar, unlearned stimuli. However, how fear learning affects early sensory processing of learned and unlearned stimuli in relation to behavioral fear responses to these stimuli remains unclear. We subjected male and female mice expressing the fluorescent calcium indicator GCaMP3 in olfactory bulb mitral and tufted cells to a classical olfactory fear conditioning paradigm. We then used awake, in vivo calcium imaging to quantify learning-induced changes in glomerular odor responses, which constitute the first site of olfactory processing in the brain. The results demonstrate that odor-shock pairing non-specifically enhances glomerular odor representations in a learning-dependent manner and increases representational similarity between the CS and non-conditioned odors, potentially priming the system towards generalization of learned fear. Additionally, CS-specific glomerular enhancements remain even when associative learning is blocked, suggesting two separate mechanisms lead to enhanced glomerular responses following odor-shock pairings. SIGNIFICANCE STATEMENT In the olfactory bulb (OB), odors are uniquely coded in a spatial map that represents odor identity, making the OB a unique model system for investigating how learned fear alters sensory processing. Classical fear conditioning causes fear of the conditioned stimulus (CS) and of neutral stimuli, known as generalization. Combining fear conditioning with fluorescent calcium imaging of OB glomeruli, we found enhanced glomerular responses of the CS as well as neutral stimuli in awake mice, which mirrors fear generalization. We report that CS and neutral stimuli enhancements are, respectively, learning- independent and learning-dependent. Together, these results reveal distinct mechanisms leading to enhanced OB processing of fear-inducing stimuli and provide important

Examination of mechanisms underlying enhanced memory performance in action video game players: a pilot study.

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Li, Xianchun; Cheng, Xiaojun; Li, Jiaying; Pan, Yafeng; Hu, Yi; Ku, Yixuan

2015-01-01

Previous studies have shown enhanced memory performance resulting from extensive action video game playing. The mechanisms underlying the cognitive benefit were investigated in the current study. We presented two types of retro-cues, with variable intervals to memory array (Task 1) or test array (Task 2), during the retention interval in a change detection task. In Task 1, action video game players demonstrated steady performance while non-action video game players showed decreased performance as cues occurred later, indicating their performance difference increased as the cue-to-memory-array intervals became longer. In Task 2, both participant groups increased their performance at similar rates as cues presented later, implying the performance difference in two groups were irrespective of the test-array-to-cue intervals. These findings suggested that memory benefit from game plays is not attributable to the higher ability of overcoming interference from the test array, but to the interactions between the two processes of protection from decay and resistance from interference, or from alternative hypotheses. Implications for future studies were discussed.

The Harmonic Potential Theorem for a Quantum System with Time-Dependent Effective Mass

International Nuclear Information System (INIS)

Lai Meng-Yun; Xiao Duan-Liang; Pan Xiao-Yin

2015-01-01

We investigate the many-body wave function of a quantum system with time-dependent effective mass, confined by a harmonic potential with time-dependent frequency, and perturbed by a time-dependent spatially homogeneous electric field. It is found that the wave function is comprised of a phase factor times the solution to the unperturbed time-dependent Schrödinger equation with the latter being translated by a time-dependent value that satisfies the classical driven equation of motion. The wave function reduces to that of the harmonic potential theorem wave function when both the effective mass and frequency are static. An example of application is also given. (paper)

The influence of D2O, perchlorate, and variation in temperature on the potential-dependent contractile function of frog skeletal muscle

International Nuclear Information System (INIS)

Foulks, J.G.; Morishita, L.

1985-01-01

D 2 O and perchlorate manifest opposing effects on the contractile function of skeletal muscle (amplitude of twitches and maximum K contractures, potential dependence of contraction and inactivation), and when combined the influence of one may effectively antagonize that of the other. The ratio of perchlorate concentrations required to produce effects of equal intensity, (e.g., twitch enhancement and restoration of maximum K contractures in media lacking divalent cations or containing a depressant concentration of a cationic amphipath) in H 2 O and D 2 O solutions was generally rather constant. These findings are compatible with the view that both agents can influence contractile function by virtue of their effects on solvent structure. In the absence of divalent cations, the effects of reduced temperature resemble those of D 2 O whereas the effects of increased temperature resemble those of the chaotropic anion. However, in other media, variation in temperature was found to result in additional nonsolvent effects so that low temperature could oppose rather than enhance the effects of D 2 O. These observations are discussed in terms of a model which postulates a role for solvent influences on the kinetics of two separate potential-dependent conformational transitions of membrane proteins which mediate the activation and inactivation of contraction in skeletal muscle

Action potential generation requires a high sodium channel density in the axon initial segment

NARCIS (Netherlands)

Kole, Maarten H. P.; Ilschner, Susanne U.; Kampa, Björn M.; Williams, Stephen R.; Ruben, Peter C.; Stuart, Greg J.

2008-01-01

The axon initial segment ( AIS) is a specialized region in neurons where action potentials are initiated. It is commonly assumed that this process requires a high density of voltage-gated sodium ( Na(+)) channels. Paradoxically, the results of patch-clamp studies suggest that the Na(+) channel

Solvent-dependent fluorescence enhancement and piezochromism of a carbazole-substituted naphthopyran

Energy Technology Data Exchange (ETDEWEB)

Liu, Lihui; Wang, Aixia [Faculty of Chemistry, Northeast Normal University, Changchun 130024 (China); Wang, Guang, E-mail: wangg923@nenu.edu.cn [Faculty of Chemistry, Northeast Normal University, Changchun 130024 (China); Munyentwari, Alexis [Faculty of Chemistry, Northeast Normal University, Changchun 130024 (China); Zhou, Yihan, E-mail: yhzhou@ciac.ac.cn [National Analytical Research Center of Electrochemistry and Spectroscopy, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China)

2015-09-15

A novel carbazole-substituted naphthopyran, 3,3-bis-(4-carbazolylphenyl)-[3H]-naphtho[2,1-b]pyran (CzNP) was designed and synthesized. The new compound exhibited normal photochromism in dichloromethane solution and the UV irradiation did not influence its fluorescence. On the contrary, the fluorescence of CzNP in N,N-dimethylformamide (DMF) was intensively enhanced to 29 times after 60 min of the UV irradiation and this enhanced fluorescence can be quenched by addition of triethylamine (TEA). The study of enhanced extent of fluorescence of CzNP in solvents with different polarities and in mixed solvents demonstrated that the enhanced fluorescence is dependent on the polarity of solvents. The larger the polarity of solvent was, the stronger was the fluorescence of CzNP. CzNP also exhibited piezochromic performance and the pressure led to the cleavage of the C–O bond of pyran ring. - Highlights: • A carbazole-substituted photochromic naphthopyran was designed and synthesized. • The fluorescence was enhanced under the existence of DMF and UV irradiation. • The polarity of solvent was the dominating factor to affect the fluorescence. • The new compound also displayed piezochromic performance.

Selection-for-action in visual search.

Science.gov (United States)

Hannus, Aave; Cornelissen, Frans W; Lindemann, Oliver; Bekkering, Harold

2005-01-01

Grasping an object rather than pointing to it enhances processing of its orientation but not its color. Apparently, visual discrimination is selectively enhanced for a behaviorally relevant feature. In two experiments we investigated the limitations and targets of this bias. Specifically, in Experiment 1 we were interested to find out whether the effect is capacity demanding, therefore we manipulated the set-size of the display. The results indicated a clear cognitive processing capacity requirement, i.e. the magnitude of the effect decreased for a larger set size. Consequently, in Experiment 2, we investigated if the enhancement effect occurs only at the level of behaviorally relevant feature or at a level common to different features. Therefore we manipulated the discriminability of the behaviorally neutral feature (color). Again, results showed that this manipulation influenced the action enhancement of the behaviorally relevant feature. Particularly, the effect of the color manipulation on the action enhancement suggests that the action effect is more likely to bias the competition between different visual features rather than to enhance the processing of the relevant feature. We offer a theoretical account that integrates the action-intention effect within the biased competition model of visual selective attention.

Effects of momentum-dependent symmetry potential on heavy-ion collisions induced by neutron-rich nuclei

International Nuclear Information System (INIS)

Li Baoan; Das, Champak B.; Das Gupta, Subal; Gale, Charles

2004-01-01

Using an isospin- and momentum-dependent transport model we study effects of the momentum-dependent symmetry potential on heavy-ion collisions induced by neutron-rich nuclei. It is found that symmetry potentials with and without the momentum-dependence but corresponding to the same density-dependent symmetry energy E sym (ρ) lead to significantly different predictions on several E sym (ρ)-sensitive experimental observables especially for energetic nucleons. The momentum- and density-dependence of the symmetry potential have to be determined simultaneously in order to extract the E sym (ρ) accurately. The isospin asymmetry of midrapidity nucleons at high transverse momenta is particularly sensitive to the momentum-dependence of the symmetry potential. It is thus very useful for investigating accurately the equation of state of dense neutron-rich matter

Detection of Subtle Context-Dependent Model Inaccuracies in High-Dimensional Robot Domains.

Science.gov (United States)

Mendoza, Juan Pablo; Simmons, Reid; Veloso, Manuela

2016-12-01

Autonomous robots often rely on models of their sensing and actions for intelligent decision making. However, when operating in unconstrained environments, the complexity of the world makes it infeasible to create models that are accurate in every situation. This article addresses the problem of using potentially large and high-dimensional sets of robot execution data to detect situations in which a robot model is inaccurate-that is, detecting context-dependent model inaccuracies in a high-dimensional context space. To find inaccuracies tractably, the robot conducts an informed search through low-dimensional projections of execution data to find parametric Regions of Inaccurate Modeling (RIMs). Empirical evidence from two robot domains shows that this approach significantly enhances the detection power of existing RIM-detection algorithms in high-dimensional spaces.

The influence of action on episodic memory: a virtual reality study.

Science.gov (United States)

Plancher, Gaën; Barra, Julien; Orriols, Eric; Piolino, Pascale

2013-01-01

A range of empirical findings suggest that active learning is important for memory. However, few studies have focused on the mechanisms underlying this enactment effect in episodic memory using complex environments. Research using virtual reality has yielded inconsistent results. We postulated that the effect of action depends on the degree of interaction with the environment and freedom in the planning of an itinerary. To test these hypotheses, we disentangled the interaction and planning components of action to investigate whether each enhances factual and spatial memory. Seventy-two participants (36 male and 36 female) explored a virtual town in one of three experimental conditions: (a) a passive condition where participants were immersed as passenger of the car (no interaction, no planning); (b) a planning-only condition (the subject chose the itinerary but did not drive the car); (c) an interaction-only condition (the subject drove the car but the itinerary was fixed). We found that itinerary choice and motor control both enhanced spatial memory, while factual memory was impaired by online motor control. The role of action in memory is discussed.

Radioprotection by murine and human tumor-necrosis factor; Dose-dependent effects on hematopoiesis in the mouse

Energy Technology Data Exchange (ETDEWEB)

Sloerdal, L; Muench, M O; Warren, D J; Moore, M A.S. [James Ewing Laboratory of Developmental Hematopoiesis, Memorial Sloan-Kettering Cancer Center, New York (USA)

1989-01-01

Tumor-necrosis factor (TNF) has been shown to confer significant radioprotection in murine models. Herein, we demonstrate a dose-dependent enhancement of hematological recovery when single doses of either murine or human recombinant TNF are administered prior to irradiation. In addition to its action upon leukocytes and erythocytes, TNF also alleviates radiation-induced thrombocytopenia in the mouse. These effects on circulating blood constituents are further reflected in increased numbers of both primitive (CFU-S) and more differentiated (CFU-GM, CFU-Mega) hematopoietic progenitors in TNF-treated animals. This suggests that TNF exerts it radioprotective effects on a pool of primitive multi-potential hematopoietic cells. (author).

Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats.

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Forcelli, Patrick A; Soper, Colin; Duckles, Anne; Gale, Karen; Kondratyev, Alexei

2013-12-01

Phenobarbital is the most commonly utilized drug for neonatal seizures. However, questions regarding safety and efficacy of this drug make it particularly compelling to identify adjunct therapies that could boost therapeutic benefit. One potential adjunct therapy is melatonin. Melatonin is used clinically in neonatal and pediatric populations, and moreover, it exerts anticonvulsant actions in adult rats. However, it has not been previously evaluated for anticonvulsant effects in neonatal rats. Here, we tested the hypothesis that melatonin would exert anticonvulsant effects, either alone, or in combination with phenobarbital. Postnatal day (P)7 rats were treated with phenobarbital (0-40mg/kg) and/or melatonin (0-80mg/kg) prior to chemoconvulsant challenge with pentylenetetrazole (100mg/kg). We found that melatonin significantly potentiated the anticonvulsant efficacy of phenobarbital, but did not exert anticonvulsant effects on its own. These data provide additional evidence for the further examination of melatonin as an adjunct therapy in neonatal/pediatric epilepsy. Copyright © 2013 Elsevier B.V. All rights reserved.

An efficient and accurate method to obtain the energy-dependent Green function for general potentials

International Nuclear Information System (INIS)

Kramer, T; Heller, E J; Parrott, R E

2008-01-01

Time-dependent quantum mechanics provides an intuitive picture of particle propagation in external fields. Semiclassical methods link the classical trajectories of particles with their quantum mechanical propagation. Many analytical results and a variety of numerical methods have been developed to solve the time-dependent Schroedinger equation. The time-dependent methods work for nearly arbitrarily shaped potentials, including sources and sinks via complex-valued potentials. Many quantities are measured at fixed energy, which is seemingly not well suited for a time-dependent formulation. Very few methods exist to obtain the energy-dependent Green function for complicated potentials without resorting to ensemble averages or using certain lead-in arrangements. Here, we demonstrate in detail a time-dependent approach, which can accurately and effectively construct the energy-dependent Green function for very general potentials. The applications of the method are numerous, including chemical, mesoscopic, and atomic physics

Size-dependent abnormal thermo-enhanced luminescence of ytterbium-doped nanoparticles.

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Cui, Xiangshui; Cheng, Yao; Lin, Hang; Huang, Feng; Wu, Qingping; Wang, Yuansheng

2017-09-21

Thermal quenching above 300 K is widely expected in photoluminescence. Luminescence quenching is usually ascribed to the non-radiative relaxation of excited electrons to the ground state of the activators, during which a high temperature always plays a role in pushing the excited electrons towards the quenching channels, leading to thermal quenching. For the lanthanide-doped nanoparticles, however, there is a special luminescence quenching channel that does not exist in their bulk counterparts, i.e., energy migration-induced surface quenching. Herein, a size-dependent abnormal thermal enhancement of luminescence in the temperature range of 300 K to 423 K in the ytterbium-doped fluoride nanoparticles is presented for the first time. Importantly, in this work, we originally demonstrate that the energy migration-induced surface quenching can be suppressed by increasing temperature, which results in the abnormal thermal enhancement of luminescence. According to the temperature-dependent X-ray diffraction and lifetime analyses, an underlying mechanism based on the effect of thermal lattice expansion on ytterbium-mediated energy migration is proposed. This new finding adds new insights to the size effect on the luminescent characteristics of nanoparticles, which could be utilized to construct some unique nanostructures, especially for many important temperature-related purposes, such as thermal sensing technology.

Action-Dependent Photobiomodulation on Health, Suboptimal Health, and Disease

Directory of Open Access Journals (Sweden)

Timon Cheng-Yi Liu

2014-01-01

Full Text Available The global photobiomodulation (PBM on an organism was studied in terms of function-specific homeostasis (FSH and scale-free functional network in this paper. A function can be classified into a normal function in its FSH and a dysfunctional function far from its FSH. An FSH-specific stress (FSS disrupting an FSH can also be classified into a successful stress in its FSS-specific homeostasis (FSSH and a chronic stress far from its FSSH. The internal functions of an organism can be divided into essential, special nonessential, and general nonessential functions. Health may be defined as a state of an organism in which all the essential and special nonessential functions are normal or their stresses are successful. Suboptimal health may be defined as a state of a disease-free organism in which only some special nonessential functions are dysfunctional in comparison with its healthy state. Disease may be defined as a state of an organism which is not in both health and suboptimal health. The global PBM of health, suboptimal health, or disease suggested that the PBM may depend on the organism action.

Monte Carlo determination of the spin-dependent potentials

International Nuclear Information System (INIS)

Campostrini, M.; Moriarty, K.J.M.; Rebbi, C.

1987-05-01

Calculation of the bound states of heavy quark systems by a Hamiltonian formulation based on an expansion of the interaction into inverse powers of the quark mass is discussed. The potentials for the spin-orbit and spin-spin coupling between quark and antiquark, which are responsible for the fine and hyperfine splittings in heavy quark spectroscopy, are expressed as expectation values of Wilson loop factors with suitable insertions of chromomagnetic or chromoelectric fields. A Monte Carlo simulation has been used to evaluate the expectation values and, from them, the spin-dependent potentials. The Monte Carlo calculation is reported to show a long-range, non-perturbative component in the interaction

Enhanced K+-channel-mediated endothelium-dependent local and conducted dilation of small mesenteric arteries from ApoE−/− mice

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Beleznai, Timea; Takano, Hiromichi; Hamill, Claire; Yarova, Polina; Douglas, Gillian; Channon, Keith; Dora, Kim

2011-01-01

Aims Agonists that evoke smooth muscle cell hyperpolarization have the potential to stimulate both local and conducted dilation. We investigated whether the endothelium-dependent vasodilators acetylcholine (ACh) and SLIGRL stimulated conducted dilation and whether this was altered by deficiency in apolipoprotein E (ApoE−/−). Methods and results Isolated mesenteric arteries were cannulated, pressurized, and precontracted with phenylephrine. Agonists were either added to the bath to study local dilation or were restricted to one end of arteries to study conducted dilation. An enhanced sensitivity to both ACh and SLIGRL was observed in mesenteric arteries from ApoE−/− mice compared with wild-type controls. Inhibition of nitric oxide (NO) synthase blocked ACh responses, but had no effect on maximum dilation to SLIGRL. SLIGRL increased endothelial cell Ca2+, hyperpolarized smooth muscle cells, and fully dilated arteries. The NO-independent dilation to SLIGRL was blocked with high [KCl] or Ca2+-activated K+-channel blockers. The hyperpolarization and dilation to SLIGRL passed through the artery to at least 2.5 mm upstream. The conducted dilation was not affected by a deficit in ApoE and could also be stimulated by ACh, suggesting NO itself could stimulate conducted dilation. Conclusion In small mesenteric arteries of ApoE−/− mice, NO-independent dilation is enhanced. Since both NO-dependent and -independent pathways can stimulate local and conducted dilation, the potential for reducing vascular resistance is improved in these vessels. PMID:21690174

Action of Obestatin in Skeletal Muscle Repair: Stem Cell Expansion, Muscle Growth, and Microenvironment Remodeling

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Gurriarán-Rodríguez, Uxía; Santos-Zas, Icía; González-Sánchez, Jessica; Beiroa, Daniel; Moresi, Viviana; Mosteiro, Carlos S; Lin, Wei; Viñuela, Juan E; Señarís, José; García-Caballero, Tomás; Casanueva, Felipe F; Nogueiras, Rubén; Gallego, Rosalía; Renaud, Jean-Marc; Adamo, Sergio; Pazos, Yolanda; Camiña, Jesús P

2015-01-01

The development of therapeutic strategies for skeletal muscle diseases, such as physical injuries and myopathies, depends on the knowledge of regulatory signals that control the myogenic process. The obestatin/GPR39 system operates as an autocrine signal in the regulation of skeletal myogenesis. Using a mouse model of skeletal muscle regeneration after injury and several cellular strategies, we explored the potential use of obestatin as a therapeutic agent for the treatment of trauma-induced muscle injuries. Our results evidenced that the overexpression of the preproghrelin, and thus obestatin, and GPR39 in skeletal muscle increased regeneration after muscle injury. More importantly, the intramuscular injection of obestatin significantly enhanced muscle regeneration by simulating satellite stem cell expansion as well as myofiber hypertrophy through a kinase hierarchy. Added to the myogenic action, the obestatin administration resulted in an increased expression of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) and the consequent microvascularization, with no effect on collagen deposition in skeletal muscle. Furthermore, the potential inhibition of myostatin during obestatin treatment might contribute to its myogenic action improving muscle growth and regeneration. Overall, our data demonstrate successful improvement of muscle regeneration, indicating obestatin is a potential therapeutic agent for skeletal muscle injury and would benefit other myopathies related to muscle regeneration. PMID:25762009

Changes in time and frequency related aspects of motor unit action potentials during fatigue

NARCIS (Netherlands)

Wallinga, W.; Bouwens, Jeroen S.; Baten, Christian T.M.

1996-01-01

During fatigue the shape of motor unit action potentials (MUAPs) change. Characteristics of the MUAPs described before concern several time related aspects. No attention has been given to the frequency spectrum changes of MUAPS. The median frequency of MUAPS has now been determined for motor units

Map-based model of the cardiac action potential

International Nuclear Information System (INIS)

Pavlov, Evgeny A.; Osipov, Grigory V.; Chan, C.K.; Suykens, Johan A.K.

2011-01-01

A simple computationally efficient model which is capable of replicating the basic features of cardiac cell action potential is proposed. The model is a four-dimensional map and demonstrates good correspondence with real cardiac cells. Various regimes of cardiac activity, which can be reproduced by the proposed model, are shown. Bifurcation mechanisms of these regimes transitions are explained using phase space analysis. The dynamics of 1D and 2D lattices of coupled maps which model the behavior of electrically connected cells is discussed in the context of synchronization theory. -- Highlights: → Recent experimental-data based models are complicated for analysis and simulation. → The simplified map-based model of the cardiac cell is constructed. → The model is capable for replication of different types of cardiac activity. → The spatio-temporal dynamics of ensembles of coupled maps are investigated. → Received data are analyzed in context of biophysical processes in the myocardium.

Map-based model of the cardiac action potential

Energy Technology Data Exchange (ETDEWEB)

Pavlov, Evgeny A., E-mail: genie.pavlov@gmail.com [Department of Computational Mathematics and Cybernetics, Nizhny Novgorod State University, 23, Gagarin Avenue, 603950 Nizhny Novgorod (Russian Federation); Osipov, Grigory V. [Department of Computational Mathematics and Cybernetics, Nizhny Novgorod State University, 23, Gagarin Avenue, 603950 Nizhny Novgorod (Russian Federation); Chan, C.K. [Institute of Physics, Academia Sinica, 128 Sec. 2, Academia Road, Nankang, Taipei 115, Taiwan (China); Suykens, Johan A.K. [K.U. Leuven, ESAT-SCD/SISTA, Kasteelpark Arenberg 10, B-3001 Leuven (Heverlee) (Belgium)

2011-07-25

A simple computationally efficient model which is capable of replicating the basic features of cardiac cell action potential is proposed. The model is a four-dimensional map and demonstrates good correspondence with real cardiac cells. Various regimes of cardiac activity, which can be reproduced by the proposed model, are shown. Bifurcation mechanisms of these regimes transitions are explained using phase space analysis. The dynamics of 1D and 2D lattices of coupled maps which model the behavior of electrically connected cells is discussed in the context of synchronization theory. -- Highlights: → Recent experimental-data based models are complicated for analysis and simulation. → The simplified map-based model of the cardiac cell is constructed. → The model is capable for replication of different types of cardiac activity. → The spatio-temporal dynamics of ensembles of coupled maps are investigated. → Received data are analyzed in context of biophysical processes in the myocardium.

The Influence of Glutamate on Axonal Compound Action Potential In Vitro.

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