Sample records for action potential characteristics

  1. Patch-Clamp Recording from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Improving Action Potential Characteristics through Dynamic Clamp (United States)

    Veerman, Christiaan C.; Zegers, Jan G.; Mengarelli, Isabella; Bezzina, Connie R.


    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for studying inherited cardiac arrhythmias and developing drug therapies to treat such arrhythmias. Unfortunately, until now, action potential (AP) measurements in hiPSC-CMs have been hampered by the virtual absence of the inward rectifier potassium current (IK1) in hiPSC-CMs, resulting in spontaneous activity and altered function of various depolarising and repolarising membrane currents. We assessed whether AP measurements in “ventricular-like” and “atrial-like” hiPSC-CMs could be improved through a simple, highly reproducible dynamic clamp approach to provide these cells with a substantial IK1 (computed in real time according to the actual membrane potential and injected through the patch-clamp pipette). APs were measured at 1 Hz using perforated patch-clamp methodology, both in control cells and in cells treated with all-trans retinoic acid (RA) during the differentiation process to increase the number of cells with atrial-like APs. RA-treated hiPSC-CMs displayed shorter APs than control hiPSC-CMs and this phenotype became more prominent upon addition of synthetic IK1 through dynamic clamp. Furthermore, the variability of several AP parameters decreased upon IK1 injection. Computer simulations with models of ventricular-like and atrial-like hiPSC-CMs demonstrated the importance of selecting an appropriate synthetic IK1. In conclusion, the dynamic clamp-based approach of IK1 injection has broad applicability for detailed AP measurements in hiPSC-CMs. PMID:28867785

  2. Simulation of action potential propagation in plants. (United States)

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


    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.

  3. Differential expression of hERG1 channel isoforms reproduces properties of native I(Kr and modulates cardiac action potential characteristics.

    Directory of Open Access Journals (Sweden)

    Anders Peter Larsen

    Full Text Available BACKGROUND: The repolarizing cardiac rapid delayed rectifier current, I(Kr, is composed of ERG1 channels. It has been suggested that two isoforms of the ERG1 protein, ERG1a and ERG1b, both contribute to I(Kr. Marked heterogeneity in the kinetic properties of native I(Kr has been described. We hypothesized that the heterogeneity of native I(Kr can be reproduced by differential expression of ERG1a and ERG1b isoforms. Furthermore, the functional consequences of differential expression of ERG1 isoforms were explored as a potential mechanism underlying native heterogeneity of action potential duration (APD and restitution. METHODOLOGY/PRINCIPAL FINDINGS: The results show that the heterogeneity of native I(Kr can be reproduced in heterologous expression systems by differential expression of ERG1a and ERG1b isoforms. Characterization of the macroscopic kinetics of ERG1 currents demonstrated that these were dependent on the relative abundance of ERG1a and ERG1b. Furthermore, we used a computational model of the ventricular cardiomyocyte to show that both APD and the slope of the restitution curve may be modulated by varying the relative abundance of ERG1a and ERG1b. As the relative abundance of ERG1b was increased, APD was gradually shortened and the slope of the restitution curve was decreased. CONCLUSIONS/SIGNIFICANCE: Our results show that differential expression of ERG1 isoforms may explain regional heterogeneity of I(Kr kinetics. The data demonstrate that subunit dependent changes in channel kinetics are important for the functional properties of ERG1 currents and hence I(Kr. Importantly, our results suggest that regional differences in the relative abundance of ERG1 isoforms may represent a potential mechanism underlying the heterogeneity of both APD and APD restitution observed in mammalian hearts.


    Directory of Open Access Journals (Sweden)

    Gurau Calin


    Full Text Available Advergames represent a new advertising concept that uses Internet technology to implement viral marketing campaigns. Despite the potential of this interactive advertising method, very few academic studies have been initiated to investigate the characteristics of advergames, and their influence on consumers’ perceptions and behaviour. Using secondary data, this paper attempts to evaluate the characteristics of effective advergames, and to analyse the effect of advergames on players’ perceptions and behaviour.

  5. Screening action potentials: The power of light

    Directory of Open Access Journals (Sweden)

    Lars eKaestner


    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.

  6. Introducing the Action Potential to Psychology Students (United States)

    Simon-Dack, Stephanie L.


    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…

  7. Characteristics of potential repository wastes

    International Nuclear Information System (INIS)

    Cowart, C.G.; Notz, K.J.


    This report presents the results of a fully documented peer review of DOE/RW-0184, Rev. 1, ''Characteristics of Potential Repository Wastes''. The peer review was chaired and administered by oak Ridge National Laboratory (ORNL) for the Department of Energy (DOE), Office of Civilian Radioactive Waste Management (OCRWM) and was conducted in accordance with OCRWM QA procedure QAAP 3.3 ''Peer Review'' for the purpose of quailing the document for use in OCRWM quality-affecting work. The peer reviewers selected represent a wide range of experience and knowledge particularly suitable for evaluating the subject matter. A total of 596 formal comments were documented by the seven peer review panels, and all were successfully resolved. The peers reached the conclusion that DOE/RW-0184, Rev. 1, is quality determined and suitable for use in quality-affecting work

  8. Characteristics of potential repository wastes

    International Nuclear Information System (INIS)

    Notz, K.J.


    The Office of Civilian Radioactive Waste Management (OCRWM) is responsible for the spent fuels and other wastes that will be disposed of in a geologic repository. The two major sources of these materials are commercial light-water reactor (LWR) spent fuel and immobilized high-level waste (HLW). Other wastes that may require long-term isolation include non-LWR spent fuels and miscellaneous sources such as activated metals. Detailed characterizations are required for all of these potential repository wastes. These characterizations include physical, chemical, and radiological properties. The latter must take into account decay as a function of time. This information has been extracted from primary data sources, evaluated, and assembled in a Characteristics Data Base which provides data in four formats: hard copy standard reports, menu-driven personal computer (PC) data bases, program-level PC data bases, and mainframe computer files. The Characteristics Data Base provides a standard set of self-consistent data to the various areas of responsibility including systems integration and waste stream analysis, storage, transportation, and geologic disposal. The data will be used for design studies, evaluation of alternatives, and system optimization by OCRWM and supporting contractors. 7 refs., 5 figs., 7 tabs

  9. Characteristics of complaints resulting in disciplinary actions against Danish GPs

    DEFF Research Database (Denmark)

    S, Birkeland; RD, Christensen; N, Damsbo


    The risk of being disciplined in connection with a complaint case causes distress to most general practitioners. The present study examined the characteristics of complaint cases resulting in disciplinary action.......The risk of being disciplined in connection with a complaint case causes distress to most general practitioners. The present study examined the characteristics of complaint cases resulting in disciplinary action....

  10. Ionic channels underlying the ventricular action potential in zebrafish embryo. (United States)

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


    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.

  11. Characteristics of potential repository wastes

    International Nuclear Information System (INIS)


    This document, and its associated appendices and microcomputer (PC) data bases, constitutes the reference OCRWM data base of physical and radiological characteristics data of radioactive wastes. This Characteristics Data Base (CDB) system includes data on spent nuclear fuel and high-level waste (HLW), which clearly require geologic disposal, and other wastes which may require long-term isolation, such as sealed radioisotope sources. The data base system was developed for OCRWM by the CDB Project at Oak Ridge National Laboratory. Various principal or official sources of these data provided primary information to the CDB Project which then used the ORIGEN2 computer code to calculate radiological properties. The data have been qualified by an OCRWM-sponsored peer review as suitable for quality-affecting work meeting the requirements of OCRWM's Quality Assurance Program. The wastes characterized in this report include: light-water reactor (LWR) spent fuel and immobilized HLW

  12. The Use of Ratiometric Fluorescence Measurements of the Voltage Sensitive Dye Di-4-ANEPPS to Examine Action Potential Characteristics and Drug Effects on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. (United States)

    Hortigon-Vinagre, M P; Zamora, V; Burton, F L; Green, J; Gintant, G A; Smith, G L


    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and higher throughput platforms have emerged as potential tools to advance cardiac drug safety screening. This study evaluated the use of high bandwidth photometry applied to voltage-sensitive fluorescent dyes (VSDs) to assess drug-induced changes in action potential characteristics of spontaneously active hiPSC-CM. Human iPSC-CM from 2 commercial sources (Cor.4U and iCell Cardiomyocytes) were stained with the VSD di-4-ANEPPS and placed in a specialized photometry system that simultaneously monitors 2 wavebands of emitted fluorescence, allowing ratiometric measurement of membrane voltage. Signals were acquired at 10 kHz and analyzed using custom software. Action potential duration (APD) values were normally distributed in cardiomyocytes (CMC) from both sources though the mean and variance differed significantly (APD 90 : 229 ± 15 ms vs 427 ± 49 ms [mean ± SD, P < 0.01]; average spontaneous cycle length: 0.99 ± 0.02 s vs 1.47 ± 0.35 s [mean ± SD, P < 0.01], Cor.4U vs iCell CMC, respectively). The 10-90% rise time of the AP (T rise ) was ∼6 ms and was normally distributed when expressed as 1/[Formula: see text] in both cell preparations. Both cell types showed a rate dependence analogous to that of adult human cardiac cells. Furthermore, nifedipine, ranolazine, and E4031 had similar effects on cardiomyocyte electrophysiology in both cell types. However, ranolazine and E4031 induced early after depolarization-like events and high intrinsic firing rates at lower concentrations in iCell CMC. These data show that VSDs provide a minimally invasive, quantitative, and accurate method to assess hiPSC-CM electrophysiology and detect subtle drug-induced effects for drug safety screening while highlighting a need to standardize experimental protocols across preparations. © The Author 2016. Published by Oxford University Press on behalf of the Society of

  13. 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.


    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

  14. Decoupling Action Potential Bias from Cortical Local Field Potentials

    Directory of Open Access Journals (Sweden)

    Stephen V. David


    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.

  15. Teachers in Action Research: Assumptions and Potentials (United States)

    Li, Yuen-Ling


    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.…

  16. Revealing gene action for production characteristics by inbreeding ...

    African Journals Online (AJOL)

    Revealing gene action for production characteristics by inbreeding, based on a long-term selection ... The gene action involved in the expression of production characters was investigated, using the effect of the theoretical inbreeding ..... and predicted selection responses for growth, fat and lean traits in mice. J. Anim. Sci.

  17. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties. (United States)

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


    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

  18. Compound sensory action potential in normal and pathological human nerves

    DEFF Research Database (Denmark)

    Krarup, Christian


    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...

  19. Conduction velocity of antigravity muscle action potentials. (United States)

    Christova, L; Kosarov, D; Christova, P


    The conduction velocity of the impulses along the muscle fibers is one of the parameters of the extraterritorial potentials of the motor units allowing for the evaluation of the functional state of the muscles. There are no data about the conduction velocities of antigravity muscleaction potentials. In this paper we offer a method for measuring conduction velocity of potentials of single MUs and the averaged potentials of the interference electromiogram (IEMG) lead-off by surface electrodes from mm. sternocleidomastoideus, trapezius, deltoideus (caput laterale) and vastus medialis. The measured mean values of the conduction velocity of antigravity muscles potentials can be used for testing the functional state of the muscles.

  20. Is action potential threshold lowest in the axon?

    NARCIS (Netherlands)

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


    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

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

    Directory of Open Access Journals (Sweden)

    Mary Jane Beilby


    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.

  2. Action potential propagation: ion current or intramembrane electric field? (United States)

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


    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.

  3. 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


    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....

  4. Selective effects of an octopus toxin on action potentials (United States)

    Dulhunty, Angela; Gage, Peter W.


    1. A lethal, water soluble toxin (Maculotoxin, MTX) with a molecular weight less than 540, can be extracted from the salivary glands of an octopus (Hapalochlaena maculosa). 2. MTX blocks action potentials in sartorius muscle fibres of toads without affecting the membrane potential. Delayed rectification is not inhibited by the toxin. 3. At low concentrations (10-6-10-5 g/ml.) MTX blocks action potentials only after a certain number have been elicited. The number of action potentials, which can be defined accurately, depends on the concentration of MTX and the concentration of sodium ions in the extracellular solution. 4. The toxin has no post-synaptic effect at the neuromuscular junction and it is concluded that it blocks neuromuscular transmission by inhibiting action potentials in motor nerve terminals. PMID:4330930

  5. Storage of energies - Translating potential into actions

    International Nuclear Information System (INIS)

    Signoret, Stephane; Mary, Olivier; Petitot, Pauline; Dejeu, Mathieu; De Santis, Audrey


    In this set of articles, a first one evokes issues discussed during a colloquium held in Paris by the European association for storage of energy, the possibilities mentioned about energy storage development in the French bill project for energy transition, and the importance of non-interconnected areas in the development of energy storage. A second article proposes an overview of developments and advances in energy storage in California which adopted suitable laws. The German situation is then briefly described: needs are still to be defined and a road map has been published in 2014, as technologies are expensive and the legal framework is still complex. The next article outlines the conditions of development of the power-to-gas sector (as a process of valorisation of excess electricity). An article gives an overview of technological developments in the field of electrochemical energy storage (batteries). The results of the PEPS study (a study on the potential of energy storage) in Europe are commented. An interview with a member of the French BRGM (Bureau of Mines) outlines the major role which underground storage could play in energy transition. The Seti project for an intelligent thermal energy storage and a better use of renewable energies is then presented. An article comments how to use foodstuff cold to make consumption cut-offs. A last article comments how superconductors could be used in the future for batteries. Few examples are briefly presented: a molten salt-based storage by Areva, a local production of green hydrogen in France, an innovating project of solar energy storage in Switzerland, and the Toucan solar plant in French Guyana

  6. Quadratic adaptive algorithm for solving cardiac action potential models. (United States)

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


    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

  7. 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


    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

  8. Fiber Optic Detection of Action Potentials in Axons

    National Research Council Canada - National Science Library

    Smela, Elisabeth


    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...

  9. 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...

  10. Inducing repetitive action potential firing in neurons via synthesized photoresponsive nanoscale cellular prostheses. (United States)

    Lu, Siyuan; Madhukar, Anupam


    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.

  11. A physical action potential generator: design, implementation and evaluation. (United States)

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


    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.

  12. Components of action potential repolarization in cerebellar parallel fibres. (United States)

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


    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.

  13. Compound sensory action potential in normal and pathological human nerves

    DEFF Research Database (Denmark)

    Krarup, Christian


    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....

  14. Membrane, action, and oscillatory potentials in simulated protocells (United States)

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


    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.

  15. Numerical investigation of action potential transmission in plants

    Directory of Open Access Journals (Sweden)

    Mariusz Pietruszka


    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.

  16. Characteristics of complaints resulting in disciplinary actions against Danish GPs. (United States)

    Birkeland, Søren; Depont Christensen, Rene; Damsbo, Niels; Kragstrup, Jakob


    The risk of being disciplined in connection with a complaint case causes distress to most general practitioners. The present study examined the characteristics of complaint cases resulting in disciplinary action. The Danish Patients' Complaints Board's decisions concerning general practice in 2007 were examined. Information on the motives for complaining, as well as patient and general practitioner characteristics, was extracted and the association with case outcome (disciplinary or no disciplinary action) was analysed. Variables included complaint motives, patient gender and age, urgency of illness, cancer diagnosis, healthcare settings (daytime or out-of-hours services), and general practitioner gender and professional seniority. Cases where the complaint motives involved a wish for placement of responsibility (OR = 2.35, p = 0.01) or a wish for a review of the general practitioner's competence (OR = 1.95, p = 0.02) were associated with increased odds of the general practitioner being disciplined. The odds of discipline decreased when the complaint was motivated by a feeling of being devalued (OR = 0.39, p = 0.02) or a request for an explanation (OR = 0.46, p = 0.01). With regard to patient and general practitioner characteristics, higher general practitioner professional seniority was associated with increased odds of discipline (OR = 1.97 per 20 additional years of professional seniority, p = 0.01). None of the other characteristics was statistically significantly associated with discipline in the multiple logistic regression model. Complaint motives and professional seniority were associated with decision outcomes. Further research is needed on the impact of professional seniority on performance.

  17. Pharmacists subjected to disciplinary action: characteristics and risk factors. (United States)

    Phipps, Denham L; Noyce, Peter R; Walshe, Kieran; Parker, Dianne; Ashcroft, Darren M


    OBJECTIVE To establish whether there are any characteristics of pharmacists that predict their likelihood of being subjected to disciplinary action. METHODS  The setting was the Royal Pharmaceutical Society of Great Britain's Disciplinary Committee. One hundred and seventeen pharmacists, all of whom had been referred to the Disciplinary Committee, were matched with a quota sample of 580 pharmacists who had not been subjected to disciplinary action but that matched the disciplined pharmacists on a set of demographic factors (gender, country of residence, year of registration). Frequency analysis and regression analysis were used to compare the two groups of pharmacists in terms of sector of work, ethnicity, age and country of training. Descriptive statistics were also obtained from the disciplined pharmacists to further explore characteristics of disciplinary cases and those pharmacists who undergo them. KEY FINDINGS  While a number of characteristics appeared to increase the likelihood of a pharmacist being referred to the disciplinary committee, only one of these - working in a community pharmacy - was statistically significant. Professional misconduct accounted for a greater proportion of referrals than did clinical malpractice, and approximately one-fifth of pharmacists who went before the Disciplinary Committee had previously been disciplined by the Society. CONCLUSIONS  This study provides initial evidence of pharmacist characteristics that are associated with an increased risk of being disciplined, based upon the data currently available. It is recommended that follow-up work is carried out using a more extensive dataset in order to confirm the statistical trends identified here. © 2011 The Authors. IJPP © 2011 Royal Pharmaceutical Society.

  18. Neuronal oscillations enhance stimulus discrimination by ensuring action potential precision

    DEFF Research Database (Denmark)

    Schaefer, Andreas T; Angelo, Kamilla; Spors, Hartwig


    generated membrane potential oscillations dramatically improve action potential (AP) precision by removing the membrane potential variance associated with jitter-accumulating trains of APs. This increased AP precision occurred irrespective of cell type and--at oscillation frequencies ranging from 3 to 65 Hz......Although oscillations in membrane potential are a prominent feature of sensory, motor, and cognitive function, their precise role in signal processing remains elusive. Here we show, using a combination of in vivo, in vitro, and theoretical approaches, that both synaptically and intrinsically......, membrane potential oscillations dramatically enhance the discriminatory capabilities of individual neurons and networks of cells and provide one attractive explanation for their abundance in neurophysiological systems....

  19. Spatiotemporal characteristics of motor actions by blind long jump athletes. (United States)

    Torralba, Miguel Angel; Padullés, José María; Losada, Jose Luis; López, Jose Luis


    Blind people depend on spatial and temporal representations to perform activities of daily living and compete in sport. The aim of this study is to determine the spatiotemporal characteristics of long jumps performed by blind athletes and compare findings with those reported for sighted athletes. We analysed a sample of 12 male athletes competing in the F11 Long Jump Finals at the Paralympic Games in London 2012. Performances were recorded using four high-speed cameras, and speeds were measured using a radar speed gun. The images were processed using validated image analysis software. The long jump run-up is shorter in blind athletes than in sighted athletes. We observed statistically significant differences for body centre of mass velocity and an increase in speed over the last three strides prior to take-off, contrasting with reports for sighted athletes and athletes with less severe visual impairment, who maintain or reduce their speed during the last stride. Stride length for the last three strides was the only spatial characteristic that was not significantly associated with effective jump distance. Blind long jumpers extend rather than shorten their last stride. Contact time with the take-off board is longer than that reported for sighted athletes. The actions of blind long jumpers, unlike those without disabilities, do not vary their leg actions during the final runway approach for optimal placement on the take-off board.

  20. Spatiotemporal characteristics of motor actions by blind long jump athletes (United States)

    Torralba, Miguel Angel; Padullés, José María; Losada, Jose Luis; López, Jose Luis


    Background Blind people depend on spatial and temporal representations to perform activities of daily living and compete in sport. Objective The aim of this study is to determine the spatiotemporal characteristics of long jumps performed by blind athletes and compare findings with those reported for sighted athletes. Methods We analysed a sample of 12 male athletes competing in the F11 Long Jump Finals at the Paralympic Games in London 2012. Performances were recorded using four high-speed cameras, and speeds were measured using a radar speed gun. The images were processed using validated image analysis software. Results The long jump run-up is shorter in blind athletes than in sighted athletes. We observed statistically significant differences for body centre of mass velocity and an increase in speed over the last three strides prior to take-off, contrasting with reports for sighted athletes and athletes with less severe visual impairment, who maintain or reduce their speed during the last stride. Stride length for the last three strides was the only spatial characteristic that was not significantly associated with effective jump distance. Blind long jumpers extend rather than shorten their last stride. Contact time with the take-off board is longer than that reported for sighted athletes. Conclusion The actions of blind long jumpers, unlike those without disabilities, do not vary their leg actions during the final runway approach for optimal placement on the take-off board. PMID:29018542

  1. Optical mapping of optogenetically shaped cardiac action potentials (United States)

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


    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

  2. TRH regulates action potential shape in cerebral cortex pyramidal neurons. (United States)

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


    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.

  3. 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.


    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

  4. Arsenic Trioxide Modulates the Central Snail Neuron Action Potential

    Directory of Open Access Journals (Sweden)

    Guan-Ling Lu


    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.

  5. Modelling in vivo action potential propagation along a giant axon. (United States)

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


    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.

  6. Warm Body Temperature Facilitates Energy Efficient Cortical Action Potentials (United States)

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


    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

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  9. Active action potential propagation but not initiation in thalamic interneuron dendrites (United States)

    Casale, Amanda E.; McCormick, David A.


    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

  10. Implementing participatory action research in Lithuania: potential and challenges

    Directory of Open Access Journals (Sweden)

    Gabija Jarašiūnaitė


    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.

  11. On the Analysis of Recurrence Characteristics at Variable Actions

    Directory of Open Access Journals (Sweden)

    Horea SANDI


    Full Text Available The paper is devoted to some methodological problems raised by the analysis of hazards due to variable actions having implications for the risk of damage to structures. The basic recurrence model used is that of Poissonian stochastic processes. The techniques of calibration of specific recurrence characteristics are discussed, adopting a critical point of view versus statistical analyses relying exclusively on data like annual maxima. The adoption of some types of distributions is critically discussed, from the point of view of their compatibility with the Poissonian model referred to. Only the Gumbel and Fréchet distributions are accepted as adequate for the purpose adopted. Starting from their common properties an unbounded family of distributions is proposed. This family makes it possible to adopt calibrations providing an approximation of unlimited closeness to observation samples. The case of a pluri-dimensional characterization of the randomness of observation data is then tackled, considering as an illustrative case the directional statistical analysis of sequences of wind events. Some specific expressions are proposed for the directional analysis, leading to a good approximation of observation samples. A case study relying on the expressions is then presented.

  12. Action Researchers' Perspectives about the Distinguishing Characteristics of Action Research: A Delphi and Learning Circles Mixed-Methods Study (United States)

    Rowell, Lonnie L.; Polush, Elena Yu; Riel, Margaret; Bruewer, Aaron


    The purpose of this study was to identify distinguishing characteristics of action research within the Action Research Special Interest Group of the American Educational Research Association. The authors sought to delineate the foundational framework endorsed by this community. The study was conducted during January-April 2012 and employed an…

  13. Jarosite characteristics and its utilisation potentials

    International Nuclear Information System (INIS)

    Pappu, Asokan; Saxena, Mohini; Asolekar, Shyam R.


    During metallic zinc extraction from zinc sulphide or sulphide ore, huge quantity of jarosite is being released universally as solid residues. The jarosite mainly contains iron, sulphur, zinc, calcium, lead, cadmium and aluminium. Jarosite released from such industrial process is complex and its quality and quantity make the task more complex for safe disposal. Apart from water contamination, jarosite already accumulated and its increasing annual production is a major source of pollution for surrounding environment including soil, vegetation and aquatic life and hence its disposal leads to major concern because of the stringent environmental protection regulations. An attempt was made to evaluate the characteristics of Indian jarosite with an objectives to understand its potentials for recycling and utilising as raw materials for developing value added products. Sand and Coal Combustion Residues (CCRs) was used as an admixture to attain good workability and detoxify the toxic substance in the jarosite. Result revealed that jarosite is silty clay loam in texture having 63.48% silt sized and 32.35% clay sized particles. The particle size of jarosite (D 9 = 16.21 ± 0.20 μm) is finer than the CCRs (D 9 = 19.72 ± 0.18 μm). The jarosite is nonuniform in structure and shape as compared to the CCRs having spherical, hollow shaped and some of them are cenosphere in nature. The major mineral phase of jarosite is Potassium Iron Sulphate Hydroxide {KFe 3 (SO 4 ) 2 (OH) 6 }and Iron Sulphate Hydrate {2Fe 2 O 3 SO 3 .5H 2 O}. In CCRs the dominant phases are quartz {SiO 2 }, mullite {3Al 2 O 3 .2SiO 2 } and hematite {Fe 2 O 3 }. The high electrical conductivity of jarosite (13.26 ± 0.437 dS/m) indicates that the presence of cations and anions are predominant over CCRs (0.498 ± 0.007 dS/m). The major portion of jarosite consists of iron (23.66 ± 0.18%), sulphur (12.23 ± 0.2%) and zinc (8.243 ± 0.075%). But CCRs main constituents are silicon ( 27.41 ± 0.74%), aluminium (15

  14. Direct detection of a single evoked action potential with MRS in Lumbricus terrestris. (United States)

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


    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.

  15. Widowhood Fantasies: Incidence, Characteristics, and Potential Function. (United States)

    Bear, Roberta Meyer; Flowers, Barbara P.

    Although some people fantasize about their spouse's possible death, the literature contains no reports of research on widowhood fantasies. The incidence, characteristics, and possible function of these fantasies were examined in individual interviews with 28 divorced and married men and women. Interview data were analyzed by calculating chi-square…

  16. Surface deformation during an action potential in pearled cells (United States)

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


    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.

  17. Perturbation analysis of spontaneous action potential initiation by stochastic ion channels

    KAUST Repository

    Keener, James P.; Newby, Jay M.


    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

  18. Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats. (United States)

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


    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

  19. The Potential of Deweyan-Inspired Action Research (United States)

    Stark, Jody L.


    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…

  20. Safety characteristics of potential waste transmutation systems

    International Nuclear Information System (INIS)

    Van Tuyle, G.J.


    For nuclear waste transmutation to alter significantly the need for geologic disposal of spent fuel from US Light-water reactors (LWRs), about 1.4% of the spent fuel (by mass) must be separated and transmuted. This includes the plutonium, the minor actinides, and four fission products: iodine. technetium, cesium and strontium. Regarding the actinides, fissioning of the plutonium, neptunium, americium, and curium generates a great deal of heat, so much so that most of the plutonium should be used to produce power. However, these actinides have some undesirable neutronic characteristics, and their utilization in reactors or subcritical (proton-accelerator) targets requires either a fast neutronic spectrum or a very high thermal-neutron flux. Transmutation of the fission products is generally by neutron capture, although this is difficult in the case of cesium and strontium. In this paper, various proposed means of transmuting the actinides and fission products are discussed, with the main focus being on the safety characteristics of each approach

  1. 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.


    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.

  2. Map-based model of the cardiac action potential

    Energy Technology Data Exchange (ETDEWEB)

    Pavlov, Evgeny A., E-mail: [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)


    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.

  3. Compound muscle action potential duration in critical illness neuromyopathy. (United States)

    Kramer, Christopher L; Boon, Andrea J; Harper, C Michel; Goodman, Brent P


    We sought to determine the specificity of compound muscle action potential (CMAP) durations and amplitudes in a large critical illness neuromyopathy (CINM) cohort relative to controls with other neuromuscular conditions. Fifty-eight patients with CINM who had been seen over a 17-year period were retrospectively studied. Electrodiagnostic findings of the CINM cohort were compared with patients with axonal peripheral neuropathy and myopathy due to other causes. Mean CMAP durations were prolonged, and mean CMAP amplitudes were severely reduced both proximally and distally in all nerves studied in the CINM cohort relative to the control groups. The specificity of prolonged CMAP durations for CINM approached 100% if they were encountered in more than 1 nerve. Prolonged, low-amplitude CMAPs occur more frequently and with greater severity in CINM patients than in neuromuscular controls with myopathy and axonal neuropathy and are highly specific for the diagnosis of CINM. Muscle Nerve 57: 395-400, 2018. © 2017 Wiley Periodicals, Inc.

  4. Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats. (United States)

    Forcelli, Patrick A; Soper, Colin; Duckles, Anne; Gale, Karen; Kondratyev, Alexei


    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.

  5. [Patterns of action potential firing in cortical neurons of neonatal mice and their electrophysiological property]. (United States)

    Furong, Liu; Shengtian, L I


    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.

  6. The monophasic action potential upstroke: a means of characterizing local conduction. (United States)

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


    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.

  7. Current-potential characteristics of electrochemical systems

    Energy Technology Data Exchange (ETDEWEB)

    Battaglia, Vincent S. [Univ. of California, Berkeley, CA (United States)


    This dissertation contains investigations in three distinct areas. Chapters 1 and 2 provide an analysis of the effects of electromagnetic phenomena during the initial stages of cell discharge. Chapter 1 includes the solution to Maxwell`s equations for the penetration of the axial component of an electric field into an infinitely long cylindrical conductor. Chapter 2 contains the analysis of the conductor included in a radial circuit. Chapter 3 provides a complete description of the equations that describe the growth of an oxide film. A finite difference program was written to solve the equations. The system investigated is the iron/iron oxide in a basic, aqueous solution. Chapters 4 and 5 include the experimental attempts for replacing formaldehyde with an innocuous reducing agent for electroless deposition. In chapter 4, current-versus-voltage curves are provided for a sodium thiosulfate bath in the presence of a copper disk electrode. Also provided are the cathodic polarization curves of a copper/EDTA bath in the presence of a copper electrode. Chapter 5 contains the experimental results of work done with sodium hypophosphite as a reducing agent. Mixed-potential-versus-time curves for solutions containing various combinations of copper sulfate, nickel chloride, and hypophosphite in the presence of a palladium disk electrode provide an indication of the reducing power of the solutions.

  8. Short latency compound action potentials from mammalian gravity receptor organs (United States)

    Jones, T. A.; Jones, S. M.


    Gravity receptor function was characterized in four mammalian species using far-field vestibular evoked potentials (VsEPs). VsEPs are compound action potentials of the vestibular nerve and central relays that are elicited by linear acceleration ramps applied to the cranium. Rats, mice, guinea pigs, and gerbils were studied. In all species, response onset occurred within 1.5 ms of the stimulus onset. Responses persisted during intense (116 dBSPL) wide-band (50 to 50 inverted question mark omitted inverted question mark000 Hz) forward masking, whereas auditory responses to intense clicks (112 dBpeSPL) were eliminated under the same conditions. VsEPs remained after cochlear extirpation but were eliminated following bilateral labyrinthectomy. Responses included a series of positive and negative peaks that occurred within 8 ms of stimulus onset (range of means at +6 dBre: 1.0 g/ms: P1=908 to 1062 micros, N1=1342 to 1475 micros, P2=1632 to 1952 micros, N2=2038 to 2387 micros). Mean response amplitudes at +6 dBre: 1.0 g/ms ranged from 0.14 to 0.99 microV. VsEP input/output functions revealed latency slopes that varied across peaks and species ranging from -19 to -51 micros/dB. Amplitude-intensity slopes also varied ranging from 0.04 to 0.08 microV/dB for rats and mice. Latency values were comparable to those of birds although amplitudes were substantially smaller in mammals. VsEP threshold values were considerably higher in mammals compared to birds and ranged from -8.1 to -10.5 dBre 1.0 g/ms across species. These results support the hypothesis that mammalian gravity receptors are less sensitive to dynamic stimuli than are those of birds.

  9. State and location dependence of action potential metabolic cost in cortical pyramidal neurons. (United States)

    Hallermann, Stefan; de Kock, Christiaan P J; Stuart, Greg J; Kole, Maarten H P


    Action potential generation and conduction requires large quantities of energy to restore Na(+) and K(+) ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na(+)/K(+) charge overlap as a measure of action potential energy efficiency, we found that action potential initiation in the axon initial segment (AIS) and forward propagation into the axon were energetically inefficient, depending on the resting membrane potential. In contrast, action potential backpropagation into dendrites was efficient. Computer simulations predicted that, although the AIS and nodes of Ranvier had the highest metabolic cost per membrane area, action potential backpropagation into the dendrites and forward propagation into axon collaterals dominated energy consumption in cortical pyramidal neurons. Finally, we found that the high metabolic cost of action potential initiation and propagation down the axon is a trade-off between energy minimization and maximization of the conduction reliability of high-frequency action potentials.

  10. [Cell phone communication: hygienic characteristics, biological action, standardization (a review)]. (United States)

    Gudina, M V; Volkotrub, L P


    The paper considers the topical issues concerning the functioning of the cellular communication system. It provides the hygienic characteristics of its individual elements. The factors influencing the size of an electromagnetic field generated by mobile phones are stated. Research data on the impact of electromagnetic radiation from a mobile phone on users' health are reviewed. The pivots of present-day Russian hygienic rating regarding the permissible exposures to nonionizing electromagnetic energy generated by the elements of the cellular communication system are identified.

  11. Identification of motivations for unsafe driving actions and potential countermeasures (United States)


    This report presents the findings of a preliminary investigation of drivers' motivations for selected unsafe driving actions (UDAs). The general objective of the study was to develop the test methods, procedures, and materials for collecting data for...

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


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


    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. ...

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


    ... 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...

  14. Ontogeny of vestibular compound action potentials in the domestic chicken (United States)

    Jones, S. M.; Jones, T. A.


    Compound action potentials of the vestibular nerve were measured from the surface of the scalp in 148 chickens (Gallus domesticus). Ages ranged from incubation day 18 (E18) to 22 days posthatch (P22). Responses were elicited using linear acceleration cranial pulses. Response thresholds decreased at an average rate of -0.45 dB/day. The decrease was best fit by an exponential model with half-maturity time constant of 5.1 days and asymptote of approximately -25.9 dB re:1.0 g/ms. Mean threshold approached within 3 dB of the asymptote by ages P6-P9. Similarly, response latencies decreased exponentially to within 3% of mature values at ages beyond P9. The half-maturity time constant for peripheral response peak latencies P1, N1, and P2 was comparable to thresholds and ranged from approximately 4.6 to 6.2 days, whereas central peaks (N2, P3, and N3) ranged from 2.9 to 3.4 days. Latency-intensity slopes for P1, N1, and P2 tended to decrease with age, reaching mature values within approximately 100 hours of hatching. Amplitudes increased as a function of age with average growth rates for response peaks ranging from 0.04 to 0.09 microV/day. There was no obvious asymptote to the growth of amplitudes over the ages studied. Amplitude-intensity slopes also increased modestly with age. The results show that gravity receptors are responsive to transient cranial stimuli as early as E19 in the chicken embryo. The functional response of gravity receptors continues to develop for many days after all major morphological structures are in place. Distinct maturational processes can be identified in central and peripheral neural relays. Functional improvements during maturation may result from refinements in the receptor epithelia, improvements in central and peripheral synaptic transmission, increased neural myelination, as well as changes in the mechanical coupling between the cranium and receptor organ.

  15. Basic Characteristics of Human Erroneous Actions during Test and Maintenance Activities Leading to Unplanned Reactor Trips

    International Nuclear Information System (INIS)

    Kim, Jae Whan; Park, Jin Kyun


    Test and maintenance (T and M) activities of nuclear power plants are essential for sustaining the safety of a power plant and maintaining the reliability of plant systems and components. However, the potential of human errors during T and M activities has also the potential to induce unplanned reactor trips or power derate or making safety-related systems unavailable. According to the major incident/accident reports of nuclear power plants in Korea, contribution of human errors takes up about 20% of the total events. The previous study presents that most of human-related unplanned reactor trip events during normal power operation are associated with T and M activities (63%), which are comprised of plant maintenance activities such as a 'periodic preventive maintenance (PPM)', a 'planned maintenance (PM)' and a 'corrective maintenance (CM)'. This means that T and M activities should be a major subject for reducing the frequency of human-related unplanned reactor trips. This paper aims to introduce basic characteristics of human erroneous actions involved in the test and maintenance-induced unplanned reactor trip events that have occurred between 1986 and 2006 in Korean nuclear power plants. The basic characteristics are described by dividing human erroneous actions into planning-based errors and execution-based errors. For the events associated with planning failures, they are, firstly, classified according to existence of the work procedure and then described for what aspects of the procedure or work plan have deficiency or problem. On the other hand, for the events associated with execution failures, they are described from the aspect of external error modes

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

    International Nuclear Information System (INIS)

    Montvay, I.; Gutbrod, F.


    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.)

  17. Dynamic characteristics of the thorax connected with the heart action. (United States)

    Juznic, G; Emri, I; Peterec, D; Prepadnik, M


    We determined the indices of local vibrations (resonance frequency, damping coefficient, stiffness constant, extinction time) and transfer function H(s) . 10(-6) for three somatotypes and three respiratory positions on 88 points of the thorax. The examinees were males (age 21 years). We found the resonance frequencies of 36.86--54.75 cps, damping coefficient (delta) 0.121--0.217. This means the damping is less than critical (delta = 1). We applied shocks (a force of 2 N) with a reflex hammer on 88 points of the thorax. The force diminished from the exciting place (say ictus) to the recording place (accelerometer on the sternum) from 2 to 0.2 N. The athletic type has the highest resonance frequency and stiffness constant; the leptosomic type has the highest damping; the longest extinction time belongs to the pyknic type. The pyknic type has also the highest value of the transfer function. The respiratory position (quiet respiration, Valsalva and Müller experiment) influences the values of the indices of local vibrations and of the transfer function. The influence is evident especially on the intercostal points: the transfer of the oscillations is alleviated at a higher stiffness of the thorax (Valsalva; the value of H(S) . 10(-6) rises from 7.00 to 9.39 sec2), it deteriorates at a small stiffness of the thorax (in Müller's experiment falls to 2.78 sec2). With the fall in the intrathoracic pressure the damping in the intercostal points decreases. On the basis of experiments the conclusion was made that a short testing of the thorax of an examinee will give the dynamic characteristics of the thorax (indices of local vibrations and transfer functions) of the individual. This procedure will alleviate the quantitative use of noninvasive mechanical methods in the assessment of the cardiovascular function.

  18. Understanding the Electrical Behavior of the Action Potential in Terms of Elementary Electrical Sources (United States)

    Rodriguez-Falces, Javier


    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,…

  19. [Effects of dauricine on action potentials and slow inward currents of guinea pig ventricular papillary muscles]. (United States)

    Li, S N; Zhang, K Y


    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.

  20. [Phenibut potentiation of the therapeutic action of antiparkinson agents]. (United States)

    Gol'dblat, Iu V; Lapin, I P


    It was observed in experiments on mice that the central action of phenibut (beta-phenyl-gamma-aminobutyric acid) diminished after destruction of brain dopaminergic neurons by 6-hydroxydopamine and after pretreatment with the dopamine receptor blocker haloperidol which suggests the dopaminergic component in the action of phenibut. In 13 of 16 patients receiving long-term treatment with antiparkinsonic drugs, addition of phenibut (0.25 g thrice daily for 10 days) resulted in marked clinical improvement with a significant increase of motor activity, as well as diminution of both rigidity and tremor. Follow-up showed a significant lowering of muscle tone of rigid muscles, augmentation of their strength and amplitude of movements. In 8 patients receiving phenibut without antiparkinsonic drugs the results were negligible.

  1. Consumer-Related Food Waste: Causes and Potential for Action

    DEFF Research Database (Denmark)

    Aschemann-Witzel, Jessica; Hooge, Ilona de; Amani, Pegah


    behaviors. We identify actions that governments, societal stakeholders and retailers can undertake to reduce consumer-related food waste, highlighting that synergistic actions between all parties are most promising. Further research should focus on exploring specific food waste contexts and interactions......In the past decade, food waste has received increased attention on both academic and societal levels. As a cause of negative economic, environmental and social effects, food waste is considered to be one of the sustainability issues that needs to be addressed. In developed countries, consumers...... are one of the biggest sources of food waste. To successfully reduce consumer-related food waste, it is necessary to have a clear understanding of the factors influencing food waste-related consumer perceptions and behaviors. The present paper presents the results of a literature review and expert...

  2. Oxidative shift in tissue redox potential increases beat-to-beat variability of action potential duration. (United States)

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


    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.

  3. Dynamics of action potential initiation in the GABAergic thalamic reticular nucleus in vivo. (United States)

    Muñoz, Fabián; Fuentealba, Pablo


    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.

  4. Consumer-Related Food Waste: Causes and Potential for Action

    Directory of Open Access Journals (Sweden)

    Jessica Aschemann-Witzel


    Full Text Available In the past decade, food waste has received increased attention on both academic and societal levels. As a cause of negative economic, environmental and social effects, food waste is considered to be one of the sustainability issues that needs to be addressed. In developed countries, consumers are one of the biggest sources of food waste. To successfully reduce consumer-related food waste, it is necessary to have a clear understanding of the factors influencing food waste-related consumer perceptions and behaviors. The present paper presents the results of a literature review and expert interviews on factors causing consumer-related food waste in households and supply chains. Results show that consumers’ motivation to avoid food waste, their management skills of food provisioning and food handling and their trade-offs between priorities have an extensive influence on their food waste behaviors. We identify actions that governments, societal stakeholders and retailers can undertake to reduce consumer-related food waste, highlighting that synergistic actions between all parties are most promising. Further research should focus on exploring specific food waste contexts and interactions more in-depth. Experiments and interventions in particular can contribute to a shift from analysis to solutions.

  5. 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


    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

  6. Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials (United States)

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


    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

  7. Imaging Action Potential in Single Mammalian Neurons by Tracking the Accompanying Sub-Nanometer Mechanical Motion. (United States)

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


    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.

  8. Readability, suitability, and characteristics of asthma action plans: examination of factors that may impair understanding. (United States)

    Yin, H Shonna; Gupta, Ruchi S; Tomopoulos, Suzy; Wolf, Michael S; Mendelsohn, Alan L; Antler, Lauren; Sanchez, Dayana C; Lau, Claudia Hillam; Dreyer, Benard P


    Recognition of the complexity of asthma management has led to the development of asthma treatment guidelines that include the recommendation that all pediatric asthma patients receive a written asthma action plan. We assessed the readability, suitability, and characteristics of asthma action plans, elements that contribute to the effectiveness of action plan use, particularly for those with limited literacy. This was a descriptive study of 30 asthma action plans (27 state Department of Health (DOH)-endorsed, 3 national action plans endorsed by 6 states). (1) readability (as assessed by Flesch Reading Ease, Flesch-Kincaid, Gunning Fog, Simple Measure of Gobbledygook, Forcast), (2) suitability (Suitability Assessment of Materials [SAM], adequate: ≥ 0.4; unsuitable: typography (30.0%), learning stimulation/motivation (26.7%), and graphics (13.3%). There were no statistically significant differences between the average grade level or SAM score of state DOH developed action plans and those from or adapted from national organizations. Plans varied with respect to terms used, symptoms included, and recommended actions. Specific improvements in asthma action plans could maximize patient and parent understanding of appropriate asthma management and could particularly benefit individuals with limited literacy skills.

  9. [Hardware Implementation of Numerical Simulation Function of Hodgkin-Huxley Model Neurons Action Potential Based on Field Programmable Gate Array]. (United States)

    Wang, Jinlong; Lu, Mai; Hu, Yanwen; Chen, Xiaoqiang; Pan, Qiangqiang


    Neuron is the basic unit of the biological neural system. The Hodgkin-Huxley (HH) model is one of the most realistic neuron models on the electrophysiological characteristic description of neuron. Hardware implementation of neuron could provide new research ideas to clinical treatment of spinal cord injury, bionics and artificial intelligence. Based on the HH model neuron and the DSP Builder technology, in the present study, a single HH model neuron hardware implementation was completed in Field Programmable Gate Array (FPGA). The neuron implemented in FPGA was stimulated by different types of current, the action potential response characteristics were analyzed, and the correlation coefficient between numerical simulation result and hardware implementation result were calculated. The results showed that neuronal action potential response of FPGA was highly consistent with numerical simulation result. This work lays the foundation for hardware implementation of neural network.

  10. [Loudness optimized registration of compound action potential in cochlear implant recipients]. (United States)

    Berger, Klaus; Hocke, Thomas; Hessel, Horst


    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.

  11. Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location. (United States)

    Crago, Patrick E; Makowski, Nathaniel S


    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.

  12. Potential characteristics that relate to teachers mathematics-related beliefs (United States)

    Purnomo, Y. W.; Aziz, T. A.; Pramudiani, P.; Darwis, S.; Suryadi, D.


    A characteristic of the persons was very potential to affect the beliefs they held. This study examines whether there was a significant difference between the beliefs factors with characteristics such as gender, teaching experience, certification status, and grade level assignments. There were 325 primary school teachers in East Jakarta who participated in this research. MANOVA was applied to analyze the data. The findings of this study indicate that only on teaching experience, there was a significant difference between the beliefs held by the teachers, i.e. teachers who have 11-20 years teaching experience were more likely to think absolute than constructivism. Moreover, there was no difference between each belief they held with the other characteristics.

  13. 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


    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

  14. Characteristic features of net information measures for constrained Coulomb potentials

    International Nuclear Information System (INIS)

    Patil, S H; Sen, K D; Watson, N A; Jr, H E Montgomery


    The dimensional analyses of the position and momentum variance based quantum mechanical Heisenberg uncertainty measure and the other useful net entropic information measures for the bound states of two constrained Coulomb potentials are reported for the first time. The potentials describe an electron moving in the central field due to a nucleus of charge Z with radius R defining the constraints as (a) the truncated potential given by -Z/(r n +R n ) 1/n , and (b) the radius of the impenetrable spherical wall. The net information measures for the two potentials are explicitly shown to be independent of the scaling of the set [Z, R] at a fixed value of ZR. Analytic proof is presented, for the first time, showing the presence of a characteristic extremum in the variation of the net information entropy as a function of the radius R with its location scaling as Z -1 . Numerical results are presented which support the validity of the scaling properties

  15. Distinct electrophysiological potentials for intention in action and prior intention for action

    DEFF Research Database (Denmark)

    Vinding, Mikkel C; Jensen, Mads; Overgaard, Morten


    The role of conscious intention in relation to motoric movements has become a major topic of investigation in neuroscience. Traditionally, reports of conscious intention have been compared to various features of the readiness-potential (RP) – an electrophysiological signal that appears before...... electrophysiological “intention potential” above the mid-frontal areas at the time participants formed a distal intention. This potential was only found when the distal intention was self-paced and not when the intention was formed in response to an external cue....

  16. Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential. (United States)

    Eickenscheidt, Max; Zeck, Günther


    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.

  17. Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells. (United States)

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


    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.

  18. Consequences of Converting Graded to Action Potentials upon Neural Information Coding and Energy Efficiency (United States)

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


    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

  19. State and location dependence of action potential metabolic cost in cortical pyramidal neurons

    NARCIS (Netherlands)

    Hallermann, Stefan; de Kock, Christiaan P. J.; Stuart, Greg J.; Kole, Maarten H. P.


    Action potential generation and conduction requires large quantities of energy to restore Na+ and K+ ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na+/K+ charge overlap as a measure of action

  20. State and location dependence of action potential metabolic cost in cortical pyramidal neurons

    NARCIS (Netherlands)

    Hallermann, S.; de Kock, C.P.J.; Stuart, G.J.; Kole, M.H.


    Action potential generation and conduction requires large quantities of energy to restore Na + and K + ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na +K + charge overlap as a measure of action

  1. 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.


    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

  2. Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes. (United States)

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


    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.

  3. 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


    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...

  4. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions. (United States)


    ... 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...

  5. Biophysical characteristics reveal neural stem cell differentiation potential.

    Directory of Open Access Journals (Sweden)

    Fatima H Labeed

    Full Text Available Distinguishing human neural stem/progenitor cell (huNSPC populations that will predominantly generate neurons from those that produce glia is currently hampered by a lack of sufficient cell type-specific surface markers predictive of fate potential. This limits investigation of lineage-biased progenitors and their potential use as therapeutic agents. A live-cell biophysical and label-free measure of fate potential would solve this problem by obviating the need for specific cell surface markers.We used dielectrophoresis (DEP to analyze the biophysical, specifically electrophysiological, properties of cortical human and mouse NSPCs that vary in differentiation potential. Our data demonstrate that the electrophysiological property membrane capacitance inversely correlates with the neurogenic potential of NSPCs. Furthermore, as huNSPCs are continually passaged they decrease neuron generation and increase membrane capacitance, confirming that this parameter dynamically predicts and negatively correlates with neurogenic potential. In contrast, differences in membrane conductance between NSPCs do not consistently correlate with the ability of the cells to generate neurons. DEP crossover frequency, which is a quantitative measure of cell behavior in DEP, directly correlates with neuron generation of NSPCs, indicating a potential mechanism to separate stem cells biased to particular differentiated cell fates.We show here that whole cell membrane capacitance, but not membrane conductance, reflects and predicts the neurogenic potential of human and mouse NSPCs. Stem cell biophysical characteristics therefore provide a completely novel and quantitative measure of stem cell fate potential and a label-free means to identify neuron- or glial-biased progenitors.

  6. Mirror, mirror on the wall..... A study into the characteristics of the facilitation of teachers who conduct action research

    NARCIS (Netherlands)

    Cornelissen, L.J.F.


    This article investigates the facilitation characteristics of teachers who conduct action research. A framework of the facilitation characteristics was constructed during a cyclic research process of literature research and semi-structured interviews with facilitators, teachers and experts. The

  7. In-vitro characterization of a cochlear implant system for recording of evoked compound action potentials (United States)


    Background Modern cochlear implants have integrated recording systems for measuring electrically evoked compound action potentials of the auditory nerve. The characterization of such recording systems is important for establishing a reliable basis for the interpretation of signals acquired in vivo. In this study we investigated the characteristics of the recording system integrated into the MED-EL PULSARCI100 cochlear implant, especially its linearity and resolution, in order to develop a mathematical model describing the recording system. Methods In-vitro setup: The cochlear implant, including all attached electrodes, was fixed in a tank of physiologic saline solution. Sinusoidal signals of the same frequency but with different amplitudes were delivered via a signal generator for measuring and recording on a single electrode. Computer simulations: A basic mathematical model including the main elements of the recording system, i.e. amplification and digitalization stage, was developed. For this, digital output for sinusoidal input signals of different amplitudes were calculated using in-vitro recordings as reference. Results Using an averaging of 100 measurements the recording system behaved linearly down to approximately -60 dB of the input signal range. Using the same method, a system resolution of 10 μV was determined for sinusoidal signals. The simulation results were in very good agreement with the results obtained from in-vitro experiments. Conclusions The recording system implemented in the MED-EL PULSARCI100 cochlear implant for measuring the evoked compound action potential of the auditory nerve operates reliably. The developed mathematical model provides a good approximation of the recording system. PMID:22531599

  8. BK channels regulate spontaneous action potential rhythmicity in the suprachiasmatic nucleus.

    Directory of Open Access Journals (Sweden)

    Jack Kent

    Full Text Available BACKGROUND: Circadian ( approximately 24 hr rhythms are generated by the central pacemaker localized to the suprachiasmatic nucleus (SCN of the hypothalamus. Although the basis for intrinsic rhythmicity is generally understood to rely on transcription factors encoded by "clock genes", less is known about the daily regulation of SCN neuronal activity patterns that communicate a circadian time signal to downstream behaviors and physiological systems. Action potentials in the SCN are necessary for the circadian timing of behavior, and individual SCN neurons modulate their spontaneous firing rate (SFR over the daily cycle, suggesting that the circadian patterning of neuronal activity is necessary for normal behavioral rhythm expression. The BK K(+ channel plays an important role in suppressing spontaneous firing at night in SCN neurons. Deletion of the Kcnma1 gene, encoding the BK channel, causes degradation of circadian behavioral and physiological rhythms. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis that loss of robust behavioral rhythmicity in Kcnma1(-/- mice is due to the disruption of SFR rhythms in the SCN, we used multi-electrode arrays to record extracellular action potentials from acute wild-type (WT and Kcnma1(-/- slices. Patterns of activity in the SCN were tracked simultaneously for up to 3 days, and the phase, period, and synchronization of SFR rhythms were examined. Loss of BK channels increased arrhythmicity but also altered the amplitude and period of rhythmic activity. Unexpectedly, Kcnma1(-/- SCNs showed increased variability in the timing of the daily SFR peak. CONCLUSIONS/SIGNIFICANCE: These results suggest that BK channels regulate multiple aspects of the circadian patterning of neuronal activity in the SCN. In addition, these data illustrate the characteristics of a disrupted SCN rhythm downstream of clock gene-mediated timekeeping and its relationship to behavioral rhythms.

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


    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


    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...

  10. Expert system characteristics and potential applications in safeguards

    International Nuclear Information System (INIS)

    Chapman, L.D.


    The general growth of expert, knowledge-based (KB) or rule based systems will significantly increase in the next three to five years. Improvements in computer hardware (speed, reduced size, power) and software (rule based, data based, user interfaces) in recent years are providing the foundations for the growth of expert systems. A byproduct of this growth will undoubtedly be the application of expert systems to various safeguards problems. Characteristics of these expert systems will involve 1) multiple rules governing an outcome, 2) confidence factors on individual variables and rule sets, 3) priority, cost, and risk based rule sets, and 4) the reasoning behind the advice or decision given by the expert system. This paper presents characteristics, structures, and examples of simple rule based systems. Potential application areas for these expert systems may include training, operations, management, designs, evaluations, and specific hardware operation

  11. Modeling of action potential generation in NG108-15 cells. (United States)

    Molnar, Peter; Hickman, James J


    In order to explore the possibility of identifying toxins based on their effect on the shape of action potentials, we created a computer model of the action potential generation in NG108-15 cells (a neuroblastoma/glioma hybrid cell line). To generate the experimental data for model validation, voltage-dependent sodium, potassium and high-threshold calcium currents, as well as action potentials, were recorded from NG108-15 cells with conventional whole-cell patch-clamp methods. Based on the classic Hodgkin-Huxley formalism and the linear thermodynamic description of the rate constants, ion-channel parameters were estimated using an automatic fitting method. Utilizing the established parameters, action potentials were generated using the Hodgkin-Huxley formalism and were fitted to the recorded action potentials. To demonstrate the applicability of the method for toxin detection and discrimination, the effect of tetrodotoxin (a sodium channel blocker) and tefluthrin (a pyrethroid that is a sodium channel opener) were studied. The two toxins affected the shape of the action potentials differently, and their respective effects were identified based on the predicted changes in the fitted parameters.

  12. NTD Silicon; Product Characteristics, Main Uses and Growth Potential

    International Nuclear Information System (INIS)

    Hansen, M. G.; Bjorling, C. F.


    Topsil is a specialised manufacturer of ultrapure float zone silicon since 1959, headquartered in Denmark. Topsil co-pioneered the invention of Neutron Transmutation Doped (NTD) monocrystalline silicon with research institute Risoe in the 1970s and has since then been world leading manufacturer of NTD silicon for the power market. This presentation will focus on NTD silicon; its characteristics, invention and main uses. It will address the trends of the power market and market projections for NTD, and discuss the growth potential in the years ahead, including larger silicon wafers and management of the NTD supply chain

  13. NTD Silicon; Product Characteristics, Main Uses and Growth Potential

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, M. G.; Bjorling, C. F. [Topsil Semiconductor Materials A/S, Odense (Denmark)


    Topsil is a specialised manufacturer of ultrapure float zone silicon since 1959, headquartered in Denmark. Topsil co-pioneered the invention of Neutron Transmutation Doped (NTD) monocrystalline silicon with research institute Risoe in the 1970s and has since then been world leading manufacturer of NTD silicon for the power market. This presentation will focus on NTD silicon; its characteristics, invention and main uses. It will address the trends of the power market and market projections for NTD, and discuss the growth potential in the years ahead, including larger silicon wafers and management of the NTD supply chain.

  14. Scoring radiologic characteristics to predict proliferative potential in meningiomas

    International Nuclear Information System (INIS)

    Hashiba, Tetsuo; Hashimoto, Naoya; Maruno, Motohiko; Izumoto, Shuichi; Suzuki, Tsuyoshi; Kagawa, Naoki; Yoshimine, Toshiki


    We investigated the feasibility of using radiologic characteristics to predict the proliferative potential in meningiomas. Our statistical analysis revealed that the presence of peritumoral edema, an ambiguous brain-tumor border, and irregular tumor shape were significantly correlated with a higher MIB-1 staining index (SI) value. We developed the following scoring system for specific features in each tumor: peritumoral edema (tumor with edema=1, tumor without edema=0); brain-tumor border (tumor with any ambiguous border=1, tumor circumscribed by a distinct rim=0); and tumor shape (tumor with irregular shape=1, tumor with smooth shape=0). Using Spearman's correlation coefficient analysis, we found a significant correlation (P<0.005) between total score calculated for each patient and SI value. Our findings suggest that the proliferative potential of meningiomas can be predicted using a less invasive preoperative examination focusing on the presence of peritumoral edema, ambiguous brain-tumor border, and irregular tumor shape. (author)

  15. Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron. (United States)

    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


    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

  16. Sensitivity to structure in action sequences: An infant event-related potential study. (United States)

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


    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.

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


    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

  18. Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds. (United States)

    Kimura, Kenji; Ohtubo, Yoshitaka; Tateno, Katsumi; Takeuchi, Keita; Kumazawa, Takashi; Yoshii, Kiyonori


    Taste receptor cells fire action potentials in response to taste substances to trigger non-exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole-cell recordings, and subsequently we identified their cell types immunologically with cell-type markers, an IP3 receptor (IP3 R3) for type II cells and a SNARE protein (SNAP-25) for type III cells. Cells not immunoreactive to these antibodies were examined as non-IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non-IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na(+) current density was similar in type II cells and type III cells, but it was significantly smaller in non-IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non-IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA-sensitive current density and TEA-insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. Effect of an educational game on university students' learning about action potentials. (United States)

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


    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.

  20. Effects of Acetylcholine and Noradrenalin on Action Potentials of Isolated Rabbit Sinoatrial and Atrial Myocytes (United States)

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


    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

  1. Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells (United States)

    Johnson, Stuart L.; Eckrich, Tobias; Kuhn, Stephanie; Zampini, Valeria; Franz, Christoph; Ranatunga, Kishani M.; Roberts, Terri P.; Masetto, Sergio; Knipper, Marlies; Kros, Corné J.; Marcotti, Walter


    Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion cells and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials are intrinsically generated by immature IHCs of altricial rodents and that apical IHCs exhibit bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter ACh, by fine-tuning the IHC’s resting membrane potential (Vm), is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the Vm of apical and basal IHCs by activating SK2 channels. We hypothesize that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway. PMID:21572434

  2. Perturbation analysis of spontaneous action potential initiation by stochastic ion channels

    KAUST Repository

    Keener, James P.


    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.

  3. [Effect of pulse magnetic field on distribution of neuronal action potential]. (United States)

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


    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.

  4. Environmental characteristics and utilization potential of metallurgical slag: Chapter 19 (United States)

    Piatak, Nadine; De Vivo, Benedetto; Belkin, Harvey E.; Lima, Annamaria


    Slag, an abundant byproduct from the pyrometallurgical processing of ores, can be an environmental liability or a valuable resource. The most common environmental impact of slag is from the leaching of potentially toxic elements, acidity, or alkalinity that may impact nearby soils and surface water and groundwater. Factors that influence its environmental behavior include physical characteristics, such as grain size and porosity, chemical composition with some slag being enriched in certain elements, the mineralogy and partitioning of elements in more or less reactive phases, water-slag interactions, and site conditions. Many of these same factors also influence its resource potential. For example, crystalline ferrous slag is most commonly used as construction aggregate, whereas glassy (i.e., granulated) slag is used in cement. Also, the calcium minerals found in ferrous slag result in useful applications in water treatment. In contrast, the high trace-element content of some base-metal slags makes the slags economically attractive for extraction of residual elements. An evaluation tool is used to help categorize a particular slag as an environmental hazard or valuable byproduct. Results for one type of slag, legacy steelmaking slag from the Chicago area in the USA, suggest the material has potential to be used for treating phosphate-rich or acidic waters; however, the pH and trace-element content of resulting solutions may warrant further examination.

  5. Potential Beneficiaries of the Obama Administration’s Executive Action Programs Deeply Embedded in US Society

    Directory of Open Access Journals (Sweden)

    Donald Kerwin


    Full Text Available The Obama administration has developed two broad programs to defer immigration enforcement actions against undocumented persons living in the United States: (1 Deferred Action for Parents of Americans and Lawful Permanent Residents (DAPA; and (2 Deferred Action for Childhood Arrivals (DACA. The DACA program, which began in August 2012, was expanded on November 20, 2014. DAPA and the DACA expansion (hereinafter referred to as “DACA-plus” are currently under review by the US Supreme Court and subject to an active injunction.This paper offers a statistical portrait of the intended direct beneficiaries of DAPA, DACA, and DACA-plus. It finds that potential DAPA, DACA, and DACA-plus recipients are deeply embedded in US society, with high employment rates, extensive US family ties, long tenure, and substantial rates of English-language proficiency. The paper also notes various groups that would benefit indirectly from the full implementation of DAPA and DACA or, conversely, would suffer from the removal of potential beneficiaries of these programs. For example, all those who would rely on the retirement programs of the US government will benefit from the high employment rates and relative youth of the DACA population, while many US citizens who rely on the income of a DAPA-eligible parent would fall into poverty or extreme poverty should that parent be removed from the United States.This paper offers an analysis of potential DAPA and DACA beneficiaries. In an earlier study, the authors made the case for immigration reform based on long-term trends related to the US undocumented population, including potential DAPA and DACA beneficiaries (Warren and Kerwin 2015. By contrast, this paper details the degree to which these populations have become embedded in US society. It also compares persons eligible for the original DACA program with those eligible for DACA-plus.As stated, the great majority of potential DAPA and DACA recipients enjoy strong family

  6. Prolonged action potential duration in cardiac ablation of PDK1 mice. (United States)

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


    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.

  7. Action Potential Dynamics in Fine Axons Probed with an Axonally Targeted Optical Voltage Sensor. (United States)

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


    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.

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

    International Nuclear Information System (INIS)

    Rivacoba, A.


    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

  9. Frequency decoding of periodically timed action potentials through distinct activity patterns in a random neural network

    International Nuclear Information System (INIS)

    Reichenbach, Tobias; Hudspeth, A J


    Frequency discrimination is a fundamental task of the auditory system. The mammalian inner ear, or cochlea, provides a place code in which different frequencies are detected at different spatial locations. However, a temporal code based on spike timing is also available: action potentials evoked in an auditory-nerve fiber by a low-frequency tone occur at a preferred phase of the stimulus—they exhibit phase locking—and thus provide temporal information about the tone's frequency. Humans employ this temporal information for discrimination of low frequencies. How might such temporal information be read out in the brain? Here we employ statistical and numerical methods to demonstrate that recurrent random neural networks in which connections between neurons introduce characteristic time delays, and in which neurons require temporally coinciding inputs for spike initiation, can perform sharp frequency discrimination when stimulated with phase-locked inputs. Although the frequency resolution achieved by such networks is limited by the noise in phase locking, the resolution for realistic values reaches the tiny frequency difference of 0.2% that has been measured in humans. (paper)

  10. Characteristics of nursing professionals and the practice of ecologically sustainable actions in the medication processes

    Directory of Open Access Journals (Sweden)

    Patricia de Oliveira Furukawa

    Full Text Available ABSTRACT Objectives: to verify the correlation between the characteristics of professionals and the practice of sustainable actions in the medication processes in an ICU, and to determine if interventions such as training and awareness can promote sustainable practices performed by nursing staff in the hospital. Methods: before-and-after design study using Lean Six Sigma methodology, applied in an intensive care unit. Nursing staff were observed regarding the practice of ecologically sustainable actions during medication processes (n = 324 cases for each group (pre and post-intervention through a data collection instrument. The processes analyzed involved 99 professionals in the pre-intervention phase and 97 in the post-intervention phase. Data were analyzed quantitatively and the association of variables was accomplished by means of statistical inference, according to the nature of the related variables. Results: the education level was the only characteristic that showed to be relevant to an increase in sustainable practices, with a statistically significant difference (p = 0.002. When comparing before and after the intervention, there was an increase in environmentally friendly actions with statistically significant differences (p = 0.001. Conclusions: the results suggest that institutions should encourage and invest in formal education, as well as training of health professionals to promote sustainable practices in the hospital.

  11. Calcium-Induced calcium release during action potential firing in developing inner hair cells. (United States)

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


    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

  12. A Parametric Computational Model of the Action Potential of Pacemaker Cells. (United States)

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


    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.

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

    DEFF Research Database (Denmark)

    Lewandowski, Rebecca; Procida, Kristina; Vaidyanathan, Ravi


    . 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...

  14. Improving Cardiac Action Potential Measurements: 2D and 3D Cell Culture. (United States)

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


    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.

  15. A phantom axon setup for validating models of action potential recordings. (United States)

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


    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 %.

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

    Directory of Open Access Journals (Sweden)

    Hester M Den Ruijter


    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.

  17. Selective effects of potassium elevations on glutamate signaling and action potential conduction in hippocampus. (United States)

    Meeks, Julian P; Mennerick, Steven


    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.

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


    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.

  19. Channel sialic acids limit hERG channel activity during the ventricular action potential. (United States)

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


    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.

  20. Potential need for re-definition of the highest priority recovery action in the Krsko SAG-1

    International Nuclear Information System (INIS)

    Bilic Zabric, T.; Basic, I.


    Replacement of old SG (Steam Generators) [7] and the characteristic of new ones throws the question of proper accident management strategy, which leans on philosophy that repair and recovery actions have first priority. In the current NPP Krsko SAMGs (Severe Accident Management Guidelines), water supply to the SG has priority over re-injection water into the core. NPP Krsko reconsidered the highest priority of SAG-1 (inject water to the SG), against the WOG (Westinghouse Owners Group) generic approach (inject water into the core) and potential revision of Severe Accident Phenomenology Evaluations using MAAP (Modular accident Analysis Program) 4.0.5 code. (author)

  1. 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.


    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

  2. 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


    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...

  3. Investigating a Potential Auxin-Related Mode of Hormetic/Inhibitory Action of the Phytotoxin Parthenin. (United States)

    Belz, Regina G


    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.

  4. Rosewood oil induces sedation and inhibits compound action potential in rodents. (United States)

    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


    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.

  5. Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance. (United States)

    Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca


    Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents.

  6. 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:


    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.

  7. What contributes to action plan enactment? Examining characteristics of physical activity plans. (United States)

    Fleig, Lena; Gardner, Benjamin; Keller, Jan; Lippke, Sonia; Pomp, Sarah; Wiedemann, Amelie U


    Individuals with chronic conditions can benefit from formulating action plans to engage in regular physical activity. However, the content and the successful translation of plans into action, so-called plan enactment, are rarely adequately evaluated. The aim of this study was to describe the content of user-specified plans and to examine whether participants were more likely to enact their plans if these plans were highly specific, viable, and instrumental. The study presents secondary analyses from a larger behavioural intervention in cardiac and orthopaedic rehabilitation. The content of 619 action plans from 229 participants was evaluated by two independent raters (i.e., qualitative analyses and ratings of specificity) and by participants themselves (i.e., instrumentality and viability). Plan enactment was also measured via self-reports. Multilevel analyses examined the relationship between these plan characteristics and subsequent plan enactment, and between plan enactment and aggregated physical activity. Participants preferred to plan leisure-time physical activities anchored around time-based cues. Specificity of occasion cues (i.e., when to act) and highly instrumental plans were positively associated with plan enactment. Interestingly, individuals who planned less specific behavioural responses (i.e., what to do) were more likely to enact their plans. Plan enactment was positively associated with aggregated behaviour. Interventions should not only emphasize the importance of planning, but also the benefits of formulating specific contextual cues. Planning of the behavioural response seems to require less precision. Allowing for some flexibility in executing the anticipated target behaviour seems to aid successful plan enactment. Statement of Contribution What is already known on this subject? Action planning interventions are efficacious in promoting health behaviour. Characteristics of plan content (i.e., specificity) matter for unconditional behaviour

  8. 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.


    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

  9. 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.


    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

  10. Youth Participatory Action Research and Educational Transformation: The Potential of Intertextuality as a Methodological Tool (United States)

    Bertrand, Melanie


    In this article, Melanie Bertrand explores the potential of using the concept of intertextuality--which captures the way snippets of written or spoken text from one source become incorporated into other sources--in the study and practice of youth participatory action research (YPAR). Though this collective and youth-centered form of research…

  11. Effect of an Educational Game on University Students' Learning about Action Potentials (United States)

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


    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…

  12. The Transformative Potential of Action Research and ICT in the Second Language (L2) Classroom (United States)

    Farren, Margaret; Crotty, Yvonne; Kilboy, Laura


    This study shows the transformative potential of action research and information and communications technology (ICT) in the second language (L2) classroom. Two enquiries from teacher-researchers are detailed in the article. Their engagement in a collaborative professional development Masters programme was pivotal in designing and implementing ICT…

  13. 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.


    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

  14. Sensitivity of the amplitude of the single muscle fibre action potential to microscopic volume conduction parameters

    NARCIS (Netherlands)

    Alberts, B.A.; Rutten, Wim; Wallinga, W.; Boom, H.B.K.


    A microscopic model of volume conduction was applied to examine the sensitivity of the single muscle fibre action potential to variations in parameters of the source and of the volume conductor, such as conduction velocity, intracellular conductivity and intracellular volume fraction. The model

  15. Anodal sensory nerve action potentials: From physiological understanding to potential clinical applicability. (United States)

    Leote, Joao; Pereira, Pedro; Cabib, Christopher; Cipullo, Federica; Valls-Sole, Josep


    Low-intensity electrical stimuli of digital nerves may generate a double peak potential (DPp), composed of a cathodal (caAP) and an anodal (anAP) potential in orthodromic recordings. We studied the effects on caAP and anAP of stimuli of variable intensity, duration, and frequency. We also applied a conditioning stimulus to study potential differences in recovery time. The anAP was obtained in 33 of 40 healthy subjects (82.5%) and 4 of 20 patients with various types of sensory neuropathies (20%). Changes in stimulus duration and intensity had reciprocal effects on the amplitude of the anAP and the caAP. There were significant differences in recovery time between caAP and anAP after a conditioning stimulus. The caAP and anAP are 2 interdependent waveforms generated by different effects of the same stimulus over axons at the verge of depolarization. Muscle Nerve 53: 897-905, 2016. © 2015 Wiley Periodicals, Inc.

  16. 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


    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....

  17. Two-Phase Gas-Liquid Flow Structure Characteristics under Periodic Cross Forces Action

    Directory of Open Access Journals (Sweden)

    V. V. Perevezentsev


    Full Text Available The article presents a study of two-phase gas-liquid flow under the action of periodic cross forces. The work objective is to obtain experimental data for further analysis and have structure characteristics of the two-phase flow movement. For research, to obtain data without disturbing effect on the flow were used optic PIV (Particle Image Visualization methods because of their noninvasiveness. The cross forces influence was provided by an experimental stand design to change the angular amplitudes and the periods of channel movement cycle with two-phase flow. In the range of volume gas rates was shown a water flow rate versus the inclination angle of immovable riser section and the characteristic angular amplitudes and periods of riser section inclination cycle under periodic cross forces. Data on distribution of average water velocity in twophase flow in abovementioned cases were also obtained. These data allowed us to draw a conclusion that a velocity distribution depends on the angular amplitude and on the period of the riser section roll cycle. This article belongs to publications, which study two-phase flows with no disturbing effect on them. Obtained data give an insight into understanding a pattern of twophase gas-liquid flow under the action of periodic cross forces and can be used to verify the mathematical models of the CFD thermo-hydraulic codes. In the future, the work development expects taking measurements with more frequent interval in the ranges of angular amplitudes and periods of the channel movement cycle and create a mathematical model to show the action of periodic cross forces on two-phase gas-liquid flow.

  18. Semiclassical expansion of quantum characteristics for many-body potential scattering problem

    International Nuclear Information System (INIS)

    Krivoruchenko, M.I.; Fuchs, C.; Faessler, A.


    In quantum mechanics, systems can be described in phase space in terms of the Wigner function and the star-product operation. Quantum characteristics, which appear in the Heisenberg picture as the Weyl's symbols of operators of canonical coordinates and momenta, can be used to solve the evolution equations for symbols of other operators acting in the Hilbert space. To any fixed order in the Planck's constant, many-body potential scattering problem simplifies to a statistical-mechanical problem of computing an ensemble of quantum characteristics and their derivatives with respect to the initial canonical coordinates and momenta. The reduction to a system of ordinary differential equations pertains rigorously at any fixed order in ℎ. We present semiclassical expansion of quantum characteristics for many-body scattering problem and provide tools for calculation of average values of time-dependent physical observables and cross sections. The method of quantum characteristics admits the consistent incorporation of specific quantum effects, such as non-locality and coherence in propagation of particles, into the semiclassical transport models. We formulate the principle of stationary action for quantum Hamilton's equations and give quantum-mechanical extensions of the Liouville theorem on conservation of the phase-space volume and the Poincare theorem on conservation of 2p-forms. The lowest order quantum corrections to the Kepler periodic orbits are constructed. These corrections show the resonance behavior. (Abstract Copyright [2007], Wiley Periodicals, Inc.)

  19. School Safety, Severe Disciplinary Actions, and School Characteristics: A Secondary Analysis of the School Survey on Crime and Safety (United States)

    Han, Seunghee; Akiba, Motoko


    On the basis of a secondary analysis of survey data collected from 1,872 secondary school principals in the 2005-2006 School Survey on Crime and Safety, we examined the frequency of and reasons for severe disciplinary actions and the relationship between school characteristics and severe disciplinary actions. We found that severe disciplinary…

  20. 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


    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.

  1. Quality characteristics of Greek fly ashes and potential uses

    Energy Technology Data Exchange (ETDEWEB)

    Skodras, G.; Grammelis, P.; Kakaras, E. [Institute for Solid Fuels Technology and Applications, Ptolemais (Greece); Karangelos, D.; Anagnostakis, M.; Hinis, E. [Nuclear Engineering Section, Mechanical Engineering Department, National Technical University of Athens, Athens (Greece)


    The main characteristics of fly ash from Greek coal-fired boilers are presented in this paper in relation to its exploitation potential. Both fuel and fly ash samples were collected and analyzed according to the ASTM Standards. Apart from the typical analyses (proximate, ultimate, ash analysis and calorific value), an ICP-AES spectrometer was used for the analysis of heavy metals in the ash. Experimental measurements in order to determine the radioactivity content of raw fuel and the fly ash were carried out as well. A representative fly ash sample from Ptolemais power plant was evaluated and tested as filler in Self-Compacting Concrete (SCC). Ashes from the Greek brown coal are classified in type C, most of the fly ash being produced in Ptolemais of Northern Greece, while the rest in Megalopolis. Ptolemais fly ash is rich in calcium compounds, while Megalopolis fly ash contains more pyrite. Increased heavy metal concentrations are observed in the fly ash samples of Greek coal. Greek fly ash appears to have not only pozzolanic but also hydraulic behaviour. Furthermore, Greek fly ash, depending on its origin, may have relatively high natural radioactivity content, reaching in the case of Megalopolis fly ash 1 kBq kg{sup -1} of {sup 226}Ra. The laboratory results showed that fly ashes can be a competitive substitute to conventional limestone filler material in SCC. Fly ash is mostly used in Greece in cement industry replacing cement clinker and aiming to the production of special types of Portland cements. However, a more aggressive utilisation strategy should be developed, since low quantities of the total produced fly ash are currently further utilised. (author)

  2. Restitution slope is principally determined by steady-state action potential duration. (United States)

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


    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

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


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


    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...

  4. Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells. (United States)

    Johnson, Stuart L; Eckrich, Tobias; Kuhn, Stephanie; Zampini, Valeria; Franz, Christoph; Ranatunga, Kishani M; Roberts, Terri P; Masetto, Sergio; Knipper, Marlies; Kros, Corné J; Marcotti, Walter


    Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials were intrinsically generated by immature IHCs of altricial rodents and that apical IHCs showed bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter acetylcholine fine-tunes the IHC's resting membrane potential (V(m)), and as such is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the V(m) of apical and basal IHCs by triggering small-conductance Ca(2+)-activated K(+) (SK2) channels. We propose that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway.

  5. The jumping action's indices of female volleyball players and their relation at some somatic characteristics

    Directory of Open Access Journals (Sweden)

    Stech M.


    Full Text Available In the paper the results of correlation analysis between of most significance jumping action's indices of high performance polish female volleyball players and their some somatic characteristics (stature, weight and body composition indices: BMI, FATkg, FAT%, FFMkg,FFM%, TBWkg and TBW% are presented. It has been found close correlation between of height of attack jump and stature (r=0,98, weight (r=0,76, FFMkg(r=0,88 and TBWkg (r=0,88. But correlation of height of attack jump with FFM% and TBW% was nonessential. Statistical essential correlation between basic indices of plyometric factor and FAT%, FFM% and TBW% indices (accordingly r = -0,65; 0,65 and 0,66 has been found. The results of the study may be taking into consideration in order to elaboration of effective jumping methods for volleyball players.

  6. Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart. (United States)

    Nagy, Norbert; Szél, Tamás; Jost, Norbert; Tóth, András; Gy Papp, Julius; Varró, András


    Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K(+) currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

  7. Spatial and frequency domain ring source models for the single muscle fiber action potential

    DEFF Research Database (Denmark)

    Henneberg, Kaj-åge; R., Plonsey


    In the paper, single-fibre models for the extracellular action potential are developed that will allow the potential to the evaluated at an arbitrary field point in the extracellular space. Fourier-domain models are restricted in that they evaluate potentials at equidistant points along a line...... parallel to the fibre axis. Consequently, they cannot easily evaluate the potential at the boundary nodes of a boundary-element electrode model. The Fourier-domain models employ axial-symmetric ring source models, and thereby provide higher accuracy that the line source model, where the source is lumped...... including anisotropy show that the spatial models require extreme care in the integration procedure owing to the singularity in the weighting functions. With adequate sampling, the spatial models can evaluate extracellular potentials with high accuracy....

  8. 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


    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

  9. Assessing transformational change potential: the case of the Tunisian cement Nationally Appropriate Mitigation Action (NAMA)

    DEFF Research Database (Denmark)

    Boodoo, Zyaad; Olsen, Karen Holm


    and documentation gathered during field work in Tunisia 2014–2015. The study finds that the NAMA design is not likely to lead to transformational change of the cement sector, since underlying factors accounting for lock-in are not properly tackled. Although the NAMA has enabled new and promising sectoral......To effectively address the root causes of carbon lock-in across developing countries, Nationally Appropriate Mitigation Actions (NAMAs) with transformational change characteristics are being supported by donors and finance mechanisms as a means to achieve ambitious nationally determined...... contributions (NDCs). However, there is still a scarcity of empirical studies on how transformational change policies and actions are designed and supported in practice. This article addresses such a gap in knowledge by combining theoretical insights from the multi-level perspective and transitions management...

  10. Cardiac action potential repolarization revisited: early repolarization shows all-or-none behaviour. (United States)

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


    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.

  11. Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites (United States)

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


    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

  12. Automated grouping of action potentials of human embryonic stem cell-derived cardiomyocytes. (United States)

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


    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.

  13. Determination of Nerve Fiber Diameter Distribution From Compound Action Potential: A Continuous Approach. (United States)

    Un, M Kerem; Kaghazchi, Hamed


    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.

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

    Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok


    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.

  15. Characteristics and potential role of M2 macrophages in COPD

    Directory of Open Access Journals (Sweden)

    He S


    Full Text Available Shengyang He, Lihua Xie, Junjuan Lu, Shenghua SunDepartment of Respiratory Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China Background: COPD is a multi-pathogenesis disease mainly caused by smoking. A further understanding of the mechanism of smoking-related COPD might contribute to preventions and treatments of this disease in the early stages. This study was designed to identify the characteristics of M2 macrophages in COPD for a better understanding about their potential role.Materials and methods: COPD models were built in the C57BL/6 mouse by cigarette smoke (CS exposure combined with intraperitoneal injection of cigarette smoke extract (CSE. The modeling efficiency was evaluated by lung function and hematoxylin and eosin (H&E staining. The number of different macrophage phenotypes was detected by immunohistochemical staining (IHS of CD206, CD86 and CD68 on the lung tissue paraffin section. The RAW264.7 cells were polarized toward the M2 phenotype by interleukin IL-4 and confirmed by a flow cytometer. The gene expression levels of TGF-βRII, Smad2, Smad3 and Smad7 in CSE-treated M2 macrophages were detected by real-time reverse transcription polymerase chain reaction (RT-PCR. The expression levels of TGF-β/Smad pathway-related makers (TGF-βRII, p-Smad2, p-Smad3, Smad7 and TGF-β in alveolar M2 macrophages were detected by two consecutive paraffin section IHS.Results: The COPD model is well established, which is confirmed by the lung function test and lung H&E staining. The whole number of macrophages and the ratio of M2/M1 phenotype are both increased (p<0.05. The level of CD206+ cells in IL-4-stimulated RAW264.7 cells is up to 93.4%, which is confirmed by a flow cytometer. The gene expression of TGF-βRII, Smad2, Smad3 and Smad7 are all enhanced (p<0.05 in CES-treated M2 macrophages, which is detected by RT-PCR. The protein levels of TGF-β/Smad pathway-related markers are

  16. Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction. (United States)

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


    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.


    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: [Center for Cosmology and Particle Physics, Department of Physics, New York University, 4 Washington Place, New York, NY 10003 (United States)


    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.

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

    Directory of Open Access Journals (Sweden)

    Dimitrios Zikos


    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.

  19. Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential. (United States)

    Desbois, Andrew P; Smith, Valerie J


    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.

  20. Event-related potential effects of superior action anticipation in professional badminton players. (United States)

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


    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.

  1. The real-time link between person perception and action: brain potential evidence for dynamic continuity. (United States)

    Freeman, Jonathan B; Ambady, Nalini; Midgley, Katherine J; Holcomb, Phillip J


    Using event-related potentials, we investigated how the brain extracts information from another's face and translates it into relevant action in real time. In Study 1, participants made between-hand sex categorizations of sex-typical and sex-atypical faces. Sex-atypical faces evoked negativity between 250 and 550 ms (N300/N400 effects), reflecting the integration of accumulating sex-category knowledge into a coherent sex-category interpretation. Additionally, the lateralized readiness potential revealed that the motor cortex began preparing for a correct hand response while social category knowledge was still gradually evolving in parallel. In Study 2, participants made between-hand eye-color categorizations as part of go/no-go trials that were contingent on a target's sex. On no-go trials, although the hand did not actually move, information about eye color partially prepared the motor cortex to move the hand before perception of sex had finalized. Together, these findings demonstrate the dynamic continuity between person perception and action, such that ongoing results from face processing are immediately and continuously cascaded into the motor system over time. The preparation of action begins based on tentative perceptions of another's face before perceivers have finished interpreting what they just saw. © 2010 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business

  2. Biosynthesis of silver nanoparticles using Sida acuta extract for antimicrobial actions and corrosion inhibition potential. (United States)

    Idrees, Muhammad; Batool, Saima; Kalsoom, Tanzila; Raina, Sadaf; Sharif, Hafiz Muhammad Adeel; Yasmeen, Summera


    Nanotechnology exhibits a multidisciplinary area and gained interests for researchers. Nanoparticles produced via physical and chemical methods affects ecosystem drastically. Green synthesis is the charming technique that is inexpensive and safe for the environment. This study aimed to explore the antibacterial actions of as-synthesized silver nanoparticles (Ag-NPs) against Escherichia coli, Staphylococcus aureus and Streptococcus faecalis. Also, the anti-corrosion actions confirmed that the Ag-NPs proved as good inhibitors. In this way, Ag-NPs were prepared via biosynthesis technique by consuming the ground leaves and stem of 'Sida acuta' as a capping agent. The Ag-NPs were formed by irradiation of the aqueous solution of silver nitrate (AgNO 3 ) with extract of S. acuta stem and leaves. The as-synthesized reaction mixture of Ag-NPs was found to exhibit an absorbance band at 446-447 nm, by an UV/VIS spectrophotometer, which is a characteristic of Ag-NPs due to the surface plasmon resonance absorption band. The X-ray diffraction and transmission electron microscopy (TEM) were used for the confirmation of Ag-NPs' variety dimension, morphology and dispersion. The infrared spectra confirmed the bio-fabrication of the Ag-NPs displayed the existence of conceivable functional groups responsible for the bio-reduction and capping. The antimicrobial actions were measured and the zone of inhibition was compared with standard antibiotics.

  3. Waste management implications of concentrating slimes - characteristics and potential problems

    International Nuclear Information System (INIS)


    This report describes the geotechnical, geochemical and environmental characteristics of fine-grained uranium tailings (slimes) which may influence both short- and long-term management of slime-enriched uranium tailings impoundments. Properties of slimes are compared and contrasted with those of sand tailings using field and laboratory data primarily from naturally segregated tailings in the Elliot Lake area, Ontario and Northern Saskatchewan uranium-bearing regions of Canada. Key management considerations are included

  4. Somatic characteristics and efficiency of technical-tactical actions of basketball players at the stage of special basic preparation

    Directory of Open Access Journals (Sweden)

    Tymanski R.


    Full Text Available The article deals with an analysis of correlation between the efficiency of technical-tactical actions and some somatic characteristics of APE&S team (Gdansk basketball players. A close positive correlation between attack action's efficiency with smaller absolute and percentage content of the fat component and with a higher percentage (but no absolute content of fatless mass has been found. A higher manifestation of defense actions efficiency has been found in the basketball players with more content of fat the component in the body.

  5. Voltage-gated sodium channel expression and action potential generation in differentiated NG108-15 cells. (United States)

    Liu, Jinxu; Tu, Huiyin; Zhang, Dongze; Zheng, Hong; Li, Yu-Long


    The generation of action potential is required for stimulus-evoked neurotransmitter release in most neurons. Although various voltage-gated ion channels are involved in action potential production, the initiation of the action potential is mainly mediated by voltage-gated Na+ channels. In the present study, differentiation-induced changes of mRNA and protein expression of Na+ channels, Na+ currents, and cell membrane excitability were investigated in NG108-15 cells. Whole-cell patch-clamp results showed that differentiation (9 days) didn't change cell membrane excitability, compared to undifferentiated state. But differentiation (21 days) induced the action potential generation in 45.5% of NG108-15 cells (25/55 cells). In 9-day-differentiated cells, Na+ currents were mildly increased, which was also found in 21-day differentiated cells without action potential. In 21-day differentiated cells with action potential, Na+ currents were significantly enhanced. Western blot data showed that the expression of Na+ channels was increased with differentiated-time dependent manner. Single-cell real-time PCR data demonstrated that the expression of Na+ channel mRNA was increased by 21 days of differentiation in NG108-15 cells. More importantly, the mRNA level of Na+ channels in cells with action potential was higher than that in cells without action potential. Differentiation induces expression of voltage-gated Na+ channels and action potential generation in NG108-15 cells. A high level of the Na+ channel density is required for differentiation-triggered action potential generation.

  6. An Excel‐based implementation of the spectral method of action potential alternans analysis (United States)

    Pearman, Charles M.


    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

  7. An Excel-based implementation of the spectral method of action potential alternans analysis. (United States)

    Pearman, Charles M


    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.

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

    Directory of Open Access Journals (Sweden)

    Anne-Kathrin Theis


    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.

  9. Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications. (United States)

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


    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.


    Directory of Open Access Journals (Sweden)

    Svetlana V. Kirilicheva


    Full Text Available Aim. The article describes the tourist potential of two large museums of the Krasnodar Territory, the Krasnodar State Historical and Archaeological Museum-Reserve named after E.D. Felitsyn and Krasnodar Regional Art Museum named after F.A. Kovalenko. Much attention is paid to the classification of museums in the Krasnodar Territory. Methods. In the study were used a comparative-geographical method, a systematic approach, an analysis of statistical-mathematical materials and an analysis of the leisure profile of citizens. Findings. A comparative assessment of the potential of two large museums of the region is given. We also conducted an analysis of the survey data of the leisure profile among the townspeople in the city of Krasnodar in order to identify which of the museums is more popular. The main indicators such as the number of storage units, the total exposition and exhibition area, the number of sightseeing visits and mass events, the number of educational programs and exhibitions, the number of employees were examined and analyzed. Distinctions between museums are also noted. Conclusions. An analysis of these data showed that both museums have sufficient tourist potential to represent the city and get acquainted with the city through museums. The results of an analysis of events held in museums to attract visitors are presented. The sufficient tourist potential of two large museums for representation of the city and region is defined. The directions for their development as objects of tourism are proposed.

  11. Outcome producing potential influences twelve-month-olds' interpretation of a novel action as goal-directed. (United States)

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


    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.

  12. Single K ATP channel opening in response to action potential firing in mouse dentate granule neurons. (United States)

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


    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.

  13. The Effects of Action Potential Stimulation on Pain, Swelling and Function of Patients with Knee Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Razieh Sepehri


    Full Text Available Background: Knee osteoarthritis (OA is one of the most prevalent joint diseases. Electrical muscle stimulation is effective to improve its symptoms. Today, action potential stimulation (APS with various currents and periods is used to treat OA. This study aims at analyzing the effect of action potential stimulation in improving knee OA symptoms. Materials and Methods: In this clinical trial, patients with mild to moderate knee OA divided randomly in two groups each had 15 people. Along with the conventional exercises of physiotherapy, one group received 16 minutes action potential stimulation with the lowest intensity (sensible; but the other group besides receiving the conventional exercises of physiotherapy was connected into a plugged off machine for 16 minutes. Certain variables were measured and recorded four times. Results: Comparing the variables before and after intervention did not show any meaningful difference between the two groups. But within group, pain with p=0.0001 showed a meaningful decrease. Decreasing of swelling (inflammation in group 1 and 2 was meaningful with p<0.001 and p<0.001, respectively. For group 1, knee flexion range was improved meaningfully between first and fourth times as p<0.031, but it was not meaningful for group 2. Duration of 50 meters walking and step up and down from three steps significantly decreased in both groups. Conclusion: Although there was no significant difference in variables between two groups, but within both groups’ pain and swelling decreased and functional ability increased, thus, it can be concluded that type of APS does not play a key role in treating knee OA.

  14. Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells. (United States)

    Tait, Luke; Wedgwood, Kyle; Tsaneva-Atanasova, Krasimira; Brown, Jon T; Goodfellow, Marc


    The entorhinal cortex is a crucial component of our memory and spatial navigation systems and is one of the first areas to be affected in dementias featuring tau pathology, such as Alzheimer's disease and frontotemporal dementia. Electrophysiological recordings from principle cells of medial entorhinal cortex (layer II stellate cells, mEC-SCs) demonstrate a number of key identifying properties including subthreshold oscillations in the theta (4-12 Hz) range and clustered action potential firing. These single cell properties are correlated with network activity such as grid firing and coupling between theta and gamma rhythms, suggesting they are important for spatial memory. As such, experimental models of dementia have revealed disruption of organised dorsoventral gradients in clustered action potential firing. To better understand the mechanisms underpinning these different dynamics, we study a conductance based model of mEC-SCs. We demonstrate that the model, driven by extrinsic noise, can capture quantitative differences in clustered action potential firing patterns recorded from experimental models of tau pathology and healthy animals. The differential equation formulation of our model allows us to perform numerical bifurcation analyses in order to uncover the dynamic mechanisms underlying these patterns. We show that clustered dynamics can be understood as subcritical Hopf/homoclinic bursting in a fast-slow system where the slow sub-system is governed by activation of the persistent sodium current and inactivation of the slow A-type potassium current. In the full system, we demonstrate that clustered firing arises via flip bifurcations as conductance parameters are varied. Our model analyses confirm the experimentally suggested hypothesis that the breakdown of clustered dynamics in disease occurs via increases in AHP conductance. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Action potential propagation recorded from single axonal arbors using multi-electrode arrays. (United States)

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


    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.

  16. Conduction velocity of action potentials measured from unidimensional latency-topography in human and frog skeletal muscle fibers. (United States)

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


    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.

  17. Potential and Geochemical Characteristics of Geothermal Resources in Eastern Macedonia


    Spasovski, Orce


    Geothermal explorations in the Republic of Macedonia were intensified in the 70's, during the first effects from the energetic crisis. As a result of those explorations, there were established over 50 springs with mineral and thermo-mineral water, with maximum potential of over 1400 l/s and evidenced reserves as deposit for exploitation of around 1000 l/s, with temperature higher than the mean season swings for this part of the Earth in the range 20-79 °C, accumulated quantities of geothe...

  18. Comparative investigations of manual action representations: evidence that chimpanzees represent the costs of potential future actions involving tools. (United States)

    Frey, Scott H; Povinelli, Daniel J


    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.

  19. Ionization from short-range potential under action of electromagnetic field of complex configuration

    CERN Document Server

    Rodionov, V N; Kravtsova, G A


    The transcendental equation for the complex energy is obtained on the basis of the exactly solvable 3D model of the short-acting potential and the Green time function in the intensive electromagnetic field, constituting the combination of the constant magnetic field and the circular-polarization wave field. The electron quasistationary states parameters in the delta-potential with an account of the action of the intensive external field of complex configuration are calculated. The problem on the possibility of stabilizing the bound states decay of the spinor and scalar particles through the intensive magnetic field is clarified. It is established that the obtained results regime the reexamination of the accepted notion on the stabilizing role of the strong magnetic field by the atoms ionization

  20. Potentiating action of propofol at GABAA receptors of retinal bipolar cells

    DEFF Research Database (Denmark)

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


    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...

  1. Traditional Japanese medicines inhibit compound action potentials in the frog sciatic nerve. (United States)

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


    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.

  2. Effects of acoustic noise on the auditory nerve compound action potentials evoked by electric pulse trains. (United States)

    Nourski, Kirill V; Abbas, Paul J; Miller, Charles A; Robinson, Barbara K; Jeng, Fuh-Cherng


    This study investigated the effects of acoustic noise on the auditory nerve compound action potentials in response to electric pulse trains. Subjects were adult guinea pigs, implanted with a minimally invasive electrode to preserve acoustic sensitivity. Electrically evoked compound action potentials (ECAP) were recorded from the auditory nerve trunk in response to electric pulse trains both during and after the presentation of acoustic white noise. Simultaneously presented acoustic noise produced a decrease in ECAP amplitude. The effect of the acoustic masker on the electric probe was greatest at the onset of the acoustic stimulus and it was followed by a partial recovery of the ECAP amplitude. Following cessation of the acoustic noise, ECAP amplitude recovered over a period of approximately 100-200 ms. The effects of the acoustic noise were more prominent at lower electric pulse rates (interpulse intervals of 3 ms and higher). At higher pulse rates, the ECAP adaptation to the electric pulse train alone was larger and the acoustic noise, when presented, produced little additional effect. The observed effects of noise on ECAP were the greatest at high electric stimulus levels and, for a particular electric stimulus level, at high acoustic noise levels.

  3. Biophysical foundations for the study of the electrical excitability and action potential propagation in myocardium

    International Nuclear Information System (INIS)

    Suarez Antola, R.


    The electric current flow in the heterogeneous and anysotropic volume conductor of the myocardium is studied. The equations of bidomain theory are derived using an approach framed in the theory of averaged fields, introducing microscopic, mesoscopic and macroscopic spatial scales. However, the procedure, compatible with the histological and the anatomical details of the organ, is different from the multiple scale asymptotic expansions usually applied in homogeneization problems. A probabilistic approach framed in large numbers theorems is used to derive the equation for membrane ionic current from the stochastic activity of the channels at the microscopic level. An operational procedure suitable to define a sharp bidomain boundary from the fuzzy distribution of structural details and physical properties at the histological level is given. The problem of threshold is studied. The sizes and shapes of critical masses of cardiac cells that must be depolarized above threshold in order to produce a propagated action potential are determined by an approximate analytical procedure. The concept of family of threshold patterns for the emergence of action potentials in the heart is introduced. This concept is applied to discuss the conditions of emergence of ectopic focus. Analytical formulae are derived, for the time constant and the rheobase for electrical stimulation of the myocardium. These formulae are in good agreement with known experimental results. New experiments that could be done to confirm or reject them are suggested

  4. The effect of recording site on extracted features of motor unit action potential. (United States)

    Artuğ, N Tuğrul; Goker, Imran; Bolat, Bülent; Osman, Onur; Kocasoy Orhan, Elif; Baslo, M Baris


    Motor unit action potential (MUAP), which consists of individual muscle fiber action potentials (MFAPs), represents the electrical activity of the motor unit. The values of the MUAP features are changed by denervation and reinnervation in neurogenic involvement as well as muscle fiber loss with increased diameter variability in myopathic diseases. The present study is designed to investigate how increased muscle fiber diameter variability affects MUAP parameters in simulated motor units. In order to detect this variation, simulated MUAPs were calculated both at the innervation zone where the MFAPs are more synchronized, and near the tendon, where they show increased temporal dispersion. Reinnervation in neurogenic state increases MUAP amplitude for the recordings at both the innervation zone and near the tendon. However, MUAP duration and the number of peaks significantly increased in a case of myopathy for recordings near the tendon. Furthermore, of the new features, "number of peaks×spike duration" was found as the strongest indicator of MFAP dispersion in myopathy. MUAPs were also recorded from healthy participants in order to investigate the biological counterpart of the simulation data. MUAPs which were recorded near to tendon revealed significantly prolonged duration and decreased amplitude. Although the number of peaks was increased by moving the needle near to tendon, this was not significant. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. The Influence of Glutamate on Axonal Compound Action Potential In Vitro. (United States)

    Abouelela, Ahmed; Wieraszko, Andrzej


    Background  Our previous experiments demonstrated modulation of the amplitude of the axonal compound action potential (CAP) by electrical stimulation. To verify assumption that glutamate released from axons could be involved in this phenomenon, the modification of the axonal CAP induced by glutamate was investigated. Objectives  The major objective of this research is to verify the hypothesis that axonal activity would trigger the release of glutamate, which in turn would interact with specific axonal receptors modifying the amplitude of the action potential. Methods  Segments of the sciatic nerve were exposed to exogenous glutamate in vitro, and CAP was recorded before and after glutamate application. In some experiments, the release of radioactive glutamate analog from the sciatic nerve exposed to exogenous glutamate was also evaluated. Results  The glutamate-induced increase in CAP was blocked by different glutamate receptor antagonists. The effect of glutamate was not observed in Ca-free medium, and was blocked by antagonists of calcium channels. Exogenous glutamate, applied to the segments of sciatic nerve, induced the release of radioactive glutamate analog, demonstrating glutamate-induced glutamate release. Immunohistochemical examination revealed that axolemma contains components necessary for glutamatergic neurotransmission. Conclusion  The proteins of the axonal membrane can under the influence of electrical stimulation or exogenous glutamate change membrane permeability and ionic conductance, leading to a change in the amplitude of CAP. We suggest that increased axonal activity leads to the release of glutamate that results in changes in the amplitude of CAPs.

  6. Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions. (United States)

    Dutta, Sara; Mincholé, Ana; Quinn, T Alexander; Rodriguez, Blanca


    Acute myocardial ischemia is one of the main causes of sudden cardiac death. The mechanisms have been investigated primarily in experimental and computational studies using different animal species, but human studies remain scarce. In this study, we assess the ability of four human ventricular action potential models (ten Tusscher and Panfilov, 2006; Grandi et al., 2010; Carro et al., 2011; O'Hara et al., 2011) to simulate key electrophysiological consequences of acute myocardial ischemia in single cell and tissue simulations. We specifically focus on evaluating the effect of extracellular potassium concentration and activation of the ATP-sensitive inward-rectifying potassium current on action potential duration, post-repolarization refractoriness, and conduction velocity, as the most critical factors in determining reentry vulnerability during ischemia. Our results show that the Grandi and O'Hara models required modifications to reproduce expected ischemic changes, specifically modifying the intracellular potassium concentration in the Grandi model and the sodium current in the O'Hara model. With these modifications, the four human ventricular cell AP models analyzed in this study reproduce the electrophysiological alterations in repolarization, refractoriness, and conduction velocity caused by acute myocardial ischemia. However, quantitative differences are observed between the models and overall, the ten Tusscher and modified O'Hara models show closest agreement to experimental data. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Mesenchymal stem cells: biological characteristics and potential clinical applications

    DEFF Research Database (Denmark)

    Kassem, Moustapha


    are among the first stem cell types to be introduced in the clinic. Several studies have demonstrated the possible use of MSC in systemic transplantation for systemic diseases, local implantation for local tissue defects, as a vehicle for genes in gene therapy protocols or to generate transplantable tissues...... and organs in tissue engineering protocols. Before their widespread use in therapy, methods allowing the generation of large number of cells without affecting their differentiation potential as well as technologies that overcome immunological rejection (in case allogenic transplantation) must be developed.......Mesenchymal stem cells (MSC) are clonogenic, non-hematpoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages, for example, osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages, for example, neuronal...

  8. Required characteristics of Paenibacillus polymyxa JB-0501 as potential probiotic. (United States)

    Naghmouchi, Karim; Baah, John; Cudennec, Benoit; Drider, Djamel


    The ability of Paenibacillus polymyxa to inhibit the growth of Escherichia coli generic ATCC 25922 (Escherichia coli ATCC 25922) and to adhere to monolayers of the enterocyte-like human cell line Caco-2 was evaluated. P. polymyxa JB-0501 (P. polymyxa JB-0501), found in a livestock feed probiotic supplement, was compared to P. polymyxa reference strain ATCC 43685 and ATCC 7070 (P. polymyxa ATCC) in terms of carbohydrate utilization and resistance to lysozyme, acid, bile salts, and hydrogen peroxide. JB-0501 grew at pH 4.5 and at H2O2 concentrations less than 7.3 μg/ml and presented a higher affinity to hexadecane and decane. Bile salts at 0.2 % inhibited the growth of all three strains. P. polymyxa JB-0501 and P. polymyxa ATCC 43865 adhered to Caco-2 cell monolayers. The percentage of cells that adhered ranged from about 0.35 to 6.5 % and was partially proportional to the number applied. Contact time (from 15 min to 1 h) had little impact on adhesion. P. polymyxa JB-0501 inhibited the growth of E. coli ATCC 25922, as proven by the diffusion tests in agar. Taken together, these results suggested that P. polymyxa JB-0501 has the potential probiotic properties to justify its consideration as a livestock feed supplement.

  9. 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

  10. Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells. (United States)

    Yang, Li-Zhen; Zhu, Yi-Chun


    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.

  11. Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation. (United States)

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


    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

  12. [Potential distribution and geographic characteristics of wild populations of Vanilla planifolia (Orchidaceae) Oaxaca, Mexico]. (United States)

    Hernandez-Ruiz, Jesús; Herrera-Cabrera, B Edgar; Delgado-Alvarado, Adriana; Salazar-Rojas, Víctor M; Bustamante-Gonzalez, Ángel; Campos-Contreras, Jorge E; Ramírez-Juarez, Javier


    Wild specimens of Vanilla planifolia represent a vital part of this resource primary gene pool, and some plants have only been reported in Oaxaca, Mexico. For this reason, we studied its geographical distribution within the state, to locate and describe the ecological characteristics of the areas where they have been found, in order to identify potential areas of establishment. The method comprised four stages: 1) the creation of a database with herbarium records, 2) the construction of the potential distribution based on historical herbarium records for the species, using the model of maximum entropy (MaxEnt) and 22 bioclimatic variables as predictors; 3) an in situ systematic search of individuals, based on herbarium records and areas of potential distribution in 24 municipalities, to determine the habitat current situation and distribution; 4) the description of the environmental factors of potential ecological niches generated by MaxEnt. A review of herbarium collections revealed a total of 18 records of V. planifolia between 1939 and 1998. The systematic search located 28 plants distributed in 12 sites in 95 364 Km(2). The most important variables that determined the model of vanilla potential distribution were: precipitation in the rainy season (61.9 %), soil moisture regime (23.4 %) and precipitation during the four months of highest rainfall (8.1 %). The species potential habitat was found to be distributed in four zones: wet tropics of the Gulf of Mexico, humid temperate, humid tropical, and humid temperate in the Pacific. Precipitation oscillated within the annual ranges of 2 500 to 4 000 mm, with summer rains, and winter precipitation as 5 to 10 % of the total. The moisture regime and predominating climate were udic type I (330 to 365 days of moisture) and hot humid (Am/A(C) m). The plants were located at altitudes of 200 to 1 190 masl, on rough hillsides that generally make up the foothills of mountain systems, with altitudes of 1 300 to 2 500 masl. In

  13. Characteristics of nursing professionals and the practice of ecologically sustainable actions in the medication processes. (United States)

    Furukawa, Patricia de Oliveira; Cunha, Isabel Cristina Kowal Olm; Pedreira, Mavilde da Luz Gonçalves; Marck, Patricia Beryl


    to verify the correlation between the characteristics of professionals and the practice of sustainable actions in the medication processes in an ICU, and to determine if interventions such as training and awareness can promote sustainable practices performed by nursing staff in the hospital. before-and-after design study using Lean Six Sigma methodology, applied in an intensive care unit. Nursing staff were observed regarding the practice of ecologically sustainable actions during medication processes (n = 324 cases for each group (pre and post-intervention)) through a data collection instrument. The processes analyzed involved 99 professionals in the pre-intervention phase and 97 in the post-intervention phase. Data were analyzed quantitatively and the association of variables was accomplished by means of statistical inference, according to the nature of the related variables. the education level was the only characteristic that showed to be relevant to an increase in sustainable practices, with a statistically significant difference (p = 0.002). When comparing before and after the intervention, there was an increase in environmentally friendly actions with statistically significant differences (p = 0.001). the results suggest that institutions should encourage and invest in formal education, as well as training of health professionals to promote sustainable practices in the hospital. verificar la correlación entre las características de los profesionales y la práctica de acciones sustentables en los procesos de medicación en una UTI y determinar si intervenciones como capacitación y concientización logran promover la práctica de acciones sustentables por el equipo de enfermería en el hospital. estudio antes y después usando la metodología Lean Seis Sigma, aplicada en una unidad de terapia intensiva. El equipo de enfermería fue observado referente a la práctica de acciones ecológicamente sustentables durante los procesos de medicación (n = 324 casos

  14. Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart (United States)

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


    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.

  15. The Belem Framework for Action: Harnessing the Power and Potential of Adult Learning and Education for a Viable Future (United States)

    Adult Learning, 2012


    This article presents the Belem Framework for Action. This framework focuses on harnessing the power and potential of adult learning and education for a viable future. This framework begins with a preamble on adult education and towards lifelong learning.

  16. Prediction of Thorough QT study results using action potential simulations based on ion channel screens. (United States)

    Mirams, Gary R; Davies, Mark R; Brough, Stephen J; Bridgland-Taylor, Matthew H; Cui, Yi; Gavaghan, David J; Abi-Gerges, Najah


    Detection of drug-induced pro-arrhythmic risk is a primary concern for pharmaceutical companies and regulators. Increased risk is linked to prolongation of the QT interval on the body surface ECG. Recent studies have shown that multiple ion channel interactions can be required to predict changes in ventricular repolarisation and therefore QT intervals. In this study we attempt to predict the result of the human clinical Thorough QT (TQT) study, using multiple ion channel screening which is available early in drug development. Ion current reduction was measured, in the presence of marketed drugs which have had a TQT study, for channels encoded by hERG, CaV1.2, NaV1.5, KCNQ1/MinK, and Kv4.3/KChIP2.2. The screen was performed on two platforms - IonWorks Quattro (all 5 channels, 34 compounds), and IonWorks Barracuda (hERG & CaV1.2, 26 compounds). Concentration-effect curves were fitted to the resulting data, and used to calculate a percentage reduction in each current at a given concentration. Action potential simulations were then performed using the ten Tusscher and Panfilov (2006), Grandi et al. (2010) and O'Hara et al. (2011) human ventricular action potential models, pacing at 1Hz and running to steady state, for a range of concentrations. We compared simulated action potential duration predictions with the QT prolongation observed in the TQT studies. At the estimated concentrations, simulations tended to underestimate any observed QT prolongation. When considering a wider range of concentrations, and conventional patch clamp rather than screening data for hERG, prolongation of ≥5ms was predicted with up to 79% sensitivity and 100% specificity. This study provides a proof-of-principle for the prediction of human TQT study results using data available early in drug development. We highlight a number of areas that need refinement to improve the method's predictive power, but the results suggest that such approaches will provide a useful tool in cardiac safety

  17. Electrophysiologic evaluation of lumbosacral single nerve roots using compound muscle action potentials. (United States)

    Ogura, Taku; Shikata, Hideto; Hase, Hitoshi; Mori, Masaki; Hayashida, Taturo; Osawa, Toru; Mikami, Yasuo; Kubo, Toshikazu


    Transcutaneous electrical stimulation applied to the vertebral column produces compound muscle action potentials (CMAPs) from the leg muscles. Using this method, we evaluated the efferent pathways of the lumbosacral nerve roots. The subjects were 26 healthy volunteers and 31 patients with lumbar disc herniation (LDH). CMAP recordings were obtained from the bilateral vastus medialis, tibialis anterior, extensor digitorum brevis, and abductor hallucis muscles using low-output-impedance stimulation. In normal subjects, the CMAP latency increased linearly with the distance between the stimulating electrode and the recording electrode, with little difference in latency between the left and the right sides in each subject. The CMAP amplitude was significantly lower in the patients with LDH, and the latency was also prolonged when the stimulating electrode was placed above the lesion. This technique may thus be a useful noninvasive method for assessing lumbosacral nerve root function in patients with LDH.

  18. Sensory nerve action potentials and sensory perception in women with arthritis of the hand. (United States)

    Calder, Kristina M; Martin, Alison; Lydiate, Jessica; MacDermid, Joy C; Galea, Victoria; MacIntyre, Norma J


    Arthritis of the hand can limit a person's ability to perform daily activities. Whether or not sensory deficits contribute to the disability in this population remains unknown. The primary purpose of this study was to determine if women with osteoarthritis (OA) or rheumatoid arthritis (RA) of the hand have sensory impairments. Sensory function in the dominant hand of women with hand OA or RA and healthy women was evaluated by measuring sensory nerve action potentials (SNAPs) from the median, ulnar and radial nerves, sensory mapping (SM), and vibratory and current perception thresholds (VPT and CPT, respectively) of the second and fifth digits. All SNAP amplitudes were significantly lower for the hand OA and hand RA groups compared with the healthy group (p sensory fibers in the median, ulnar and radial nerves. Less apparent were losses in conduction speed or sensory perception.

  19. Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke

    Directory of Open Access Journals (Sweden)

    Wentao Li


    Full Text Available Fingolimod (FTY720 is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720’s mechanisms of action in stroke

  20. Action Potential Modulation of Neural Spin Networks Suggests Possible Role of Spin

    CERN Document Server

    Hu, H P


    In this paper we show that nuclear spin networks in neural membranes are modulated by action potentials through J-coupling, dipolar coupling and chemical shielding tensors and perturbed by microscopically strong and fluctuating internal magnetic fields produced largely by paramagnetic oxygen. We suggest that these spin networks could be involved in brain functions since said modulation inputs information carried by the neural spike trains into them, said perturbation activates various dynamics within them and the combination of the two likely produce stochastic resonance thus synchronizing said dynamics to the neural firings. Although quantum coherence is desirable and may indeed exist, it is not required for these spin networks to serve as the subatomic components for the conventional neural networks.

  1. Sensory action potentials of the maxillary nerve: a methodologic study with clinical implications

    DEFF Research Database (Denmark)

    Thygesen, Torben; Baad-Hansen, Lene; Svensson, Peter


    PURPOSE: Recently, recording of sensory nerve action potentials (SNAPs) of the inferior alveolar nerve (IAN) was described and is used as a diagnostic test of traumatic neuropathic trigeminal disorders. The technique is limited to IAN damage; therefore, we adapted the technique to the maxillary...... nerve, which is also frequently injured by either trauma or orthognathic surgery. PATIENTS AND METHODS: Fourteen healthy volunteers participated in this methodologic study in which the infraorbital nerve (ION) was stimulated with 2 needle electrodes. The SNAPs were recorded from the maxillary nerve...... difference. Repeated tests within a session test demonstrated no significant differences in the latency data (ANOVA: P= .225) or amplitude data (ANOVA: P= .44). Stimulus-response curves indicated that the SNAPs saturated at 5.1+/-4.4 mA stimulus intensity. In 1 subject, stimulation of the mental nerve...

  2. Molecular motions that shape the cardiac action potential: Insights from voltage clamp fluorometry. (United States)

    Zhu, Wandi; Varga, Zoltan; Silva, Jonathan R


    Very recently, voltage-clamp fluorometry (VCF) protocols have been developed to observe the membrane proteins responsible for carrying the ventricular ionic currents that form the action potential (AP), including those carried by the cardiac Na(+) channel, NaV1.5, the L-type Ca(2+) channel, CaV1.2, the Na(+)/K(+) ATPase, and the rapid and slow components of the delayed rectifier, KV11.1 and KV7.1. This development is significant, because VCF enables simultaneous observation of ionic current kinetics with conformational changes occurring within specific channel domains. The ability gained from VCF, to connect nanoscale molecular movement to ion channel function has revealed how the voltage-sensing domains (VSDs) control ion flux through channel pores, mechanisms of post-translational regulation and the molecular pathology of inherited mutations. In the future, we expect that this data will be of great use for the creation of multi-scale computational AP models that explicitly represent ion channel conformations, connecting molecular, cell and tissue electrophysiology. Here, we review the VCF protocol, recent results, and discuss potential future developments, including potential use of these experimental findings to create novel computational models. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. β1-Adrenoceptor autoantibodies affect action potential duration and delayed rectifier potassium currents in guinea pigs. (United States)

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


    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.

  4. Sodium Channel β2 Subunits Prevent Action Potential Propagation Failures at Axonal Branch Points. (United States)

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


    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

  5. Modulation of KCNQ1 alternative splicing regulates cardiac IKs and action potential repolarization. (United States)

    Lee, Hsiang-Chun; Rudy, Yoram; Po-Yuan, Phd; Sheu, Sheng-Hsiung; Chang, Jan-Gowth; Cui, Jianmin


    Slow delayed-rectifier potassium current (IKs) channels, made of the pore-forming KCNQ1 and auxiliary KCNE1 subunits, play a key role in determining action potential duration (APD) in cardiac myocytes. The consequences of drug-induced KCNQ1 splice alteration remain unknown. To study the modulation of KCNQ1 alternative splicing by amiloride and the consequent changes in IKs and action potentials (APs) in ventricular myocytes. Canine endocardial, midmyocardial, and epicardial ventricular myocytes were isolated. Levels of KCNQ1a and KCNQ1b as well as a series of splicing factors were quantified by using the reverse transcriptase-polymerase chain reaction and Western blot. The effect of amiloride-induced changes in the KCNQ1b/total KCNQ1 ratio on AP was measured by using whole-cell patch clamp with and without isoproterenol. With 50 μmol/L of amiloride for 6 hours, KCNQ1a at transcriptional and translational levels increased in midmyocardial myocytes but decreased in endo- and epicardial myocytes. Likewise, changes in splicing factors in midmyocardial were opposite to that in endo- and epicardial myocytes. In midmyocardial myocytes amiloride shortened APD and decreased isoproterenol-induced early afterdepolarizations significantly. The same amiloride-induced effects were demonstrated by using human ventricular myocyte model for AP simulations under beta-adrenergic stimulation. Moreover, amiloride reduced the transmural dispersion of repolarization in pseudo-electrocardiogram. Amiloride regulates IKs and APs with transmural differences and reduces arrhythmogenicity through the modulation of KCNQ1 splicing. We suggested that the modulation of KCNQ1 splicing may help prevent arrhythmia. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  6. Effect of microbial action on the corrosion potential of austenitic alloy containers for high-level nuclear waste

    International Nuclear Information System (INIS)

    Angell, P.; Dunn, D.S.; Cragnolino, G.A.


    The safe disposal of high-level nuclear waste (HLW) entails the ability to ensure the integrity of waste containers for prolonged time periods. It is generally accepted that under certain conditions, microbial action may change local benign environments to those in which localized corrosion can be actively promoted. The use of repassivation potential (E rp ) in relation to the value of the corrosion potential (E corr ) has been proposed as a means of assessing the propensity of a metallic material to localized corrosion. Microbial activity is known to influence E corr however, the precise mechanism is unresolved. Shewanella putrefaciens, a bacteria with many of the characteristics of sulfate-reducing bacteria (SRB), are being grown under controlled conditions on 316L stainless steel (SS) surfaces to understand the relationship between E corr and metabolic activity. It has been observed that the growth of the bacteria under aerobic conditions, without the production of metabolic sulfide, leads to only minor variation in E corr . These changes possibly correlate to the periods of active bacterial growth

  7. Sympathetic Nervous Regulation of Calcium and Action Potential Alternans in the Intact Heart. (United States)

    Winter, James; Bishop, Martin J; Wilder, Catherine D E; O'Shea, Christopher; Pavlovic, Davor; Shattock, Michael J


    Rationale: Arrhythmogenic cardiac alternans are thought to be an important determinant for the initiation of ventricular fibrillation. There is limited information on the effects of sympathetic nerve stimulation (SNS) on alternans in the intact heart and the conclusions of existing studies, focused on investigating electrical alternans, are conflicted. Meanwhile, several lines of evidence implicate instabilities in Ca handling, not electrical restitution, as the primary mechanism underpinning alternans. Despite this, there have been no studies on Ca alternans and SNS in the intact heart. The present study sought to address this, by application of voltage and Ca optical mapping for the simultaneous study of APD and Ca alternans in the intact guinea pig heart during direct SNS. Objective : To determine the effects of SNS on APD and Ca alternans in the intact guinea pig heart and to examine the mechanism(s) by which the effects of SNS are mediated. Methods and Results : Studies utilized simultaneous voltage and Ca optical mapping in isolated guinea pig hearts with intact innervation. Alternans were induced using a rapid dynamic pacing protocol. SNS was associated with rate-independent shortening of action potential duration (APD) and the suppression of APD and Ca alternans, as indicated by a shift in the alternans threshold to faster pacing rates. Qualitatively similar results were observed with exogenous noradrenaline perfusion. In contrast with previous reports, both SNS and noradrenaline acted to flatten the slope of the electrical restitution curve. Pharmacological block of the slow delayed rectifying potassium current (I Ks ), sufficient to abolish I Ks -mediated APD-adaptation, partially reversed the effects of SNS on pacing-induced alternans. Treatment with cyclopiazonic acid, an inhibitor of the sarco(endo)plasmic reticulum ATPase, had opposite effects to that of SNS, acting to increase susceptibility to alternans, and suggesting that accelerated Ca reuptake

  8. EVALUATION in vitro OF THE ACTION OF Lactobacillus plantarum WITH PROBIOTIC CHARACTERISTICS ON Yersinia pseudotuberculosis

    Directory of Open Access Journals (Sweden)

    Henry Jurado-Gámez


    Full Text Available With the objective to check the potential probiotic of Lactobacillus plantarum on one of themost frequent diseases in guinea pig (Cavia porcellus caused by Yersinia pseudotuberculosis, tests were conducted of inhibition and comparisonin front of antibiotics, showing favorable results, the inhibitt othe pathogenic bacterium. It valued by HPLC the possible peptides produced by L. plantarum, characterizing an presence of two peptides. Tests were performed for the selection of lactic bacteria which showed the following profile: catalase-negative, not producer of gas, resistant to bile salts (0, 5%, 1%, 2% and 3%, pH (2,5, 3,5 and 7,6 and temperature of 38 at 45°C. Also determined the characteristics of the kinetics of fermentation, using two mediums, where it is evaluated CFU/ mL, pH, consumption of total sugars (mg/L and production of lactic acid (%; Lactobacillus plantarum reached the exponential phase of growth in the mediums MRS and Pro, at the 12 and 14:24 hours, with values of 7,0x1011 UFC/mL and 5,0x1013 UFC/mL, respectively. A design of blocks was applied at random with two treatments and eleven blocks, the result allowed to determine that it doesn’t exist significant statistical differences (P>0,05 between the proposed means, but if between the hours of evaluation (P <0,05.

  9. Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells (United States)

    Saung, Wint Thu; Foskett, J. Kevin


    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

  10. A second-generation computational modeling of cardiac electrophysiology: response of action potential to ionic concentration changes and metabolic inhibition. (United States)

    Alaa, Nour Eddine; Lefraich, Hamid; El Malki, Imane


    Cardiac arrhythmias are becoming one of the major health care problem in the world, causing numerous serious disease conditions including stroke and sudden cardiac death. Furthermore, cardiac arrhythmias are intimately related to the signaling ability of cardiac cells, and are caused by signaling defects. Consequently, modeling the electrical activity of the heart, and the complex signaling models that subtend dangerous arrhythmias such as tachycardia and fibrillation, necessitates a quantitative model of action potential (AP) propagation. Yet, many electrophysiological models, which accurately reproduce dynamical characteristic of the action potential in cells, have been introduced. However, these models are very complex and are very time consuming computationally. Consequently, a large amount of research is consecrated to design models with less computational complexity. This paper is presenting a new model for analyzing the propagation of ionic concentrations and electrical potential in space and time. In this model, the transport of ions is governed by Nernst-Planck flux equation (NP), and the electrical interaction of the species is described by a new cable equation. These set of equations form a system of coupled partial nonlinear differential equations that is solved numerically. In the first we describe the mathematical model. To realize the numerical simulation of our model, we proceed by a finite element discretization and then we choose an appropriate resolution algorithm. We give numerical simulations obtained for different input scenarios in the case of suicide substrate reaction which were compared to those obtained in literature. These input scenarios have been chosen so as to provide an intuitive understanding of dynamics of the model. By accessing time and space domains, it is shown that interpreting the electrical potential of cell membrane at steady state is incorrect. This model is general and applies to ions of any charge in space and time

  11. Regulation and regulatory role of WNT signaling in potentiating FSH action during bovine dominant follicle selection.

    Directory of Open Access Journals (Sweden)

    P S P Gupta

    Full Text Available Follicular development occurs in wave like patterns in monotocous species such as cattle and humans and is regulated by a complex interaction of gonadotropins with local intrafollicular regulatory molecules. To further elucidate potential mechanisms controlling dominant follicle selection, granulosa cell RNA harvested from F1 (largest and F2 (second largest follicles isolated at predeviation (PD and onset of diameter deviation (OD stages of the first follicular wave was subjected to preliminary RNA transcriptome analysis. Expression of numerous WNT system components was observed. Hence experiments were performed to test the hypothesis that WNT signaling modulates FSH action on granulosa cells during follicular waves. Abundance of mRNA for WNT pathway members was evaluated in granulosa cells harvested from follicles at emergence (EM, PD, OD and early dominance (ED stages of the first follicular wave. In F1 follicles, abundance of CTNNB1 and DVL1 mRNAs was higher and AXIN2 mRNA was lower at ED versus EM stages and DVL1 and FZD6 mRNAs were higher and AXIN2 mRNA was lower in F1 versus F2 follicle at the ED stage. Bovine granulosa cells were treated in vitro with increasing doses of the WNT inhibitor IWR-1+/- maximal stimulatory dose of FSH. IWR-1 treatment blocked the FSH-induced increase in granulosa cell numbers and reduced the FSH-induced increase in estradiol. Granulosa cells were also cultured in the presence or absence of FSH +/- IWR-1 and hormonal regulation of mRNA for WNT pathway members and known FSH targets determined. FSH treatment increased CYP19A1, CCND2, CTNNB1, AXIN2 and FZD6 mRNAs and the stimulatory effect on CYP19A1 mRNA was reduced by IWR-1. In contrast, FSH reduced CARTPT mRNA and IWR-1 partially reversed the inhibitory effect of FSH. Results support temporal and hormonal regulation and a potential role for WNT signaling in potentiating FSH action during dominant follicle selection.

  12. Backpropagating Action Potentials Enable Detection of Extrasynaptic Glutamate by NMDA Receptors

    Directory of Open Access Journals (Sweden)

    Yu-Wei Wu


    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.

  13. Human neural tuning estimated from compound action potentials in normal hearing human volunteers (United States)

    Verschooten, Eric; Desloovere, Christian; Joris, Philip X.


    The sharpness of cochlear frequency tuning in humans is debated. Evoked otoacoustic emissions and psychophysical measurements suggest sharper tuning in humans than in laboratory animals [15], but this is disputed based on comparisons of behavioral and electrophysiological measurements across species [14]. Here we used evoked mass potentials to electrophysiologically quantify tuning (Q10) in humans. We combined a notched noise forward masking paradigm [9] with the recording of trans tympanic compound action potentials (CAP) from masked probe tones in awake human and anesthetized monkey (Macaca mulatta). We compare our results to data obtained with the same paradigm in cat and chinchilla [16], and find that CAP-Q10values in human are ˜1.6x higher than in cat and chinchilla and ˜1.3x higher than in monkey. To estimate frequency tuning of single auditory nerve fibers (ANFs) in humans, we derive conversion functions from ANFs in cat, chinchilla, and monkey and apply these to the human CAP measurements. The data suggest that sharp cochlear tuning is a feature of old-world primates.

  14. Non-linear entropy functionals and a characteristic invariant of symmetry group actions on infinite quantum systems

    International Nuclear Information System (INIS)

    Hudetz, T.


    We review the development of the non-Abelian generalization of the Kolmogorov-Sinai(KS) entropy invariant, as initated by Connes and Stormer and completed by Connes, Narnhofer and Thirring only recently. As an introduction and motivation, the classical KS theory is reformulated in terms of Abelian W * -algebras. Finally, we describe simple physical applications of the developed characteristic invariant to space-time symmetry group actions on infinite quantum systems. 42 refs. (Author)


    Directory of Open Access Journals (Sweden)

    Stech M.


    Full Text Available The purpose of this study was to develop generalized and individual models of the jump actions of skilled female volleyball players. The main prerequisite for the development of the jump actions models were the results of our earlier studies of factor structure of jump actions of 10 sportswomen of the Polish volleyball team "Gedania" (Premier League in the preparatory and competitive periods of the annual cycle of preparation. The athletes age was 22.0 +- 2.9 years, the sports experience - 8.1 +- 3.1 years, body height - 181.9 +- 8.4 years and body weight - 72.8 +- 10.8 kg. Mathematical and statistical processing of the data (the definition of M ± SD and significant differences between the samples was performed using a standard computer program "STATISTICA 7,0". Based on the analysis of the factor structure of 20 jump actions of skilled women volleyball players determined to within 5 of the most informative indexes and their tentative values recommended for the formation of a generalized model of this structure. Comparison of individual models of jump actions of skilled women volleyball players with their generalized models in different periods of preparation can be used for the rational choice of means and methods for the increasing of the training process efficiency.

  16. Action without Action Planning: The Potential of the Career Thinking Session in Enabling Transformational Career Learning and Development (United States)

    Bassot, Barbara


    This paper examines the potential of the Career Thinking Session (CTS) model to career guidance and counselling practice with young people. A qualitative research study is presented, focusing on the case study of a client involved in the transition to higher education. The setting for the research is described and the origins of the CTS are…

  17. Melatonin: Action as antioxidant and potential applications in human disease and aging

    International Nuclear Information System (INIS)

    Bonnefont-Rousselot, Dominique; Collin, Fabrice


    This review aims at describing the beneficial properties of melatonin related to its antioxidant effects. Oxidative stress, i.e., an imbalance between the production of reactive oxygen species and antioxidant defences, is involved in several pathological conditions such as cardiovascular or neurological disease, and in aging. Therefore, research for antioxidants has developed. However, classical antioxidants often failed to exhibit beneficial effects, especially in metabolic diseases. Melatonin has been shown as a specific antioxidant due to its amphiphilic feature that allows it to cross physiological barriers, thereby reducing oxidative damage in both lipid and aqueous cell environments. Studies on the antioxidant action of melatonin are reported, with a special mention to water gamma radiolysis as a method to produce oxygen-derived free radicals, and on structure-activity relationships of melatonin derivatives. Mass spectrometry-based techniques have been developed to identify melatonin oxidation products. Besides its ability to scavenge several radical species, melatonin regulates the activity of antioxidant enzymes (indirect antioxidant properties). Efficient detection methods confirmed the presence of melatonin in several plant products. Therapeutic potential of melatonin relies either on increasing melatonin dietary intake or on supplementation with supraphysiological dosages. Clinical trials showed that melatonin could be efficient in preventing cell damage, as well under acute (sepsis, asphyxia in newborns) as under chronic (metabolic and neurodegenerative diseases, cancer, inflammation, aging). Its global action on oxidative stress, together with its rhythmicity that plays a role in several metabolic functions, lead melatonin to be of great interest for future clinical research in order to improve public health.

  18. Comment on "Penetration of Action Potentials During Collision in the Median and Lateral Giant Axons of Invertebrates"

    DEFF Research Database (Denmark)

    Berg, Rune W.; Stauning, Marius Tving; Sorensen, Jakob Balslev


    The action potential (AP) is an electrical impulse elicited by depolarization of the neuronal membrane from the resting membrane potential (around − 70 mV). It propagates along the axon, allowing for rapid and distant communication. Recently, it was claimed that two APs traveling in opposite...

  19. The nucleon-nucleon correlations and the integral characteristics of the potential distributions in nuclei

    International Nuclear Information System (INIS)

    Knyaz'kov, O.M.; Kukhtina, I.N.


    The integral characteristics of the potential distribution in nuclei, namely the volume integrals, moments and mean square radii are studied in the framework of the semimicroscopic approach to the interaction of low energy nucleons with nuclei on the base of the exchange nucleon-nucleon correlations and the density dependence of effective forces. The ratio of the normalized multipole moments of potential and matter distributions is investigated. The energy dependence of the integral characteristics is analyzed. 15 refs.; 2 tabs

  20. Ventricular action potential adaptation to regular exercise: role of β-adrenergic and KATP channel function. (United States)

    Wang, Xinrui; Fitts, Robert H


    Regular exercise training is known to affect the action potential duration (APD) and improve heart function, but involvement of β-adrenergic receptor (β-AR) subtypes and/or the ATP-sensitive K + (K ATP ) channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel-running or control groups; they were anesthetized after 6-8 wk of training, and myocytes were isolated. Exercise training significantly increased APD of apex and base myocytes at 1 Hz and decreased APD at 10 Hz. Ca 2+ transient durations reflected the changes in APD, while Ca 2+ transient amplitudes were unaffected by wheel running. The nonselective β-AR agonist isoproterenol shortened the myocyte APD, an effect reduced by wheel running. The isoproterenol-induced shortening of APD was largely reversed by the selective β 1 -AR blocker atenolol, but not the β 2 -AR blocker ICI 118,551, providing evidence that wheel running reduced the sensitivity of the β 1 -AR. At 10 Hz, the K ATP channel inhibitor glibenclamide prolonged the myocyte APD more in exercise-trained than control rats, implicating a role for this channel in the exercise-induced APD shortening at 10 Hz. A novel finding of this work was the dual importance of altered β 1 -AR responsiveness and K ATP channel function in the training-induced regulation of APD. Of physiological importance to the beating heart, the reduced response to adrenergic agonists would enhance cardiac contractility at resting rates, where sympathetic drive is low, by prolonging APD and Ca 2+ influx; during exercise, an increase in K ATP channel activity would shorten APD and, thus, protect the heart against Ca 2+ overload or inadequate filling. NEW & NOTEWORTHY Our data demonstrated that regular exercise prolonged the action potential and Ca 2+ transient durations in myocytes isolated from apex and base regions at 1-Hz and shortened both at 10-Hz stimulation. Novel findings were that wheel running shifted the

  1. 3D Interest Point Detection using Local Surface Characteristics with Application in Action Recognition

    DEFF Research Database (Denmark)

    Holte, Michael Boelstoft


    . The proposed Difference-of-Normals (DoN) 3D IP detector operates on the surface mesh, and evaluates the surface structure (curvature) locally (per vertex) in the mesh data. We present an exam- ple of application in action recognition from a sequence of 3-dimensional geometrical data, where local 3D motion de...

  2. Correlates of a single cortical action potential in the epidural EEG (United States)

    Teleńczuk, Bartosz; Baker, Stuart N; Kempter, Richard; Curio, Gabriel


    To identify the correlates of a single cortical action potential in surface EEG, we recorded simultaneously epidural EEG and single-unit activity in the primary somatosensory cortex of awake macaque monkeys. By averaging over EEG segments coincident with more than hundred thousand single spikes, we found short-lived (≈ 0.5 ms) triphasic EEG deflections dominated by high-frequency components > 800 Hz. The peak-to-peak amplitude of the grand-averaged spike correlate was 80 nV, which matched theoretical predictions, while single-neuron amplitudes ranged from 12 to 966 nV. Combining these estimates with post-stimulus-time histograms of single-unit responses to median-nerve stimulation allowed us to predict the shape of the evoked epidural EEG response and to estimate the number of contributing neurons. These findings establish spiking activity of cortical neurons as a primary building block of high-frequency epidural EEG, which thus can serve as a quantitative macroscopic marker of neuronal spikes. PMID:25554430

  3. Action potential energy efficiency varies among neuron types in vertebrates and invertebrates.

    Directory of Open Access Journals (Sweden)

    Biswa Sengupta


    Full Text Available The initiation and propagation of action potentials (APs places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na(+ and K(+ currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin-Huxley model of the squid axon, optimizing the kinetics or number of Na(+ and K(+ channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost.

  4. A novel framework for feature extraction in multi-sensor action potential sorting. (United States)

    Wu, Shun-Chi; Swindlehurst, A Lee; Nenadic, Zoran


    Extracellular recordings of multi-unit neural activity have become indispensable in neuroscience research. The analysis of the recordings begins with the detection of the action potentials (APs), followed by a classification step where each AP is associated with a given neural source. A feature extraction step is required prior to classification in order to reduce the dimensionality of the data and the impact of noise, allowing source clustering algorithms to work more efficiently. In this paper, we propose a novel framework for multi-sensor AP feature extraction based on the so-called Matched Subspace Detector (MSD), which is shown to be a natural generalization of standard single-sensor algorithms. Clustering using both simulated data and real AP recordings taken in the locust antennal lobe demonstrates that the proposed approach yields features that are discriminatory and lead to promising results. Unlike existing methods, the proposed algorithm finds joint spatio-temporal feature vectors that match the dominant subspace observed in the two-dimensional data without needs for a forward propagation model and AP templates. The proposed MSD approach provides more discriminatory features for unsupervised AP sorting applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Benefits of Nut Consumption on Insulin Resistance and Cardiovascular Risk Factors: Multiple Potential Mechanisms of Actions

    Directory of Open Access Journals (Sweden)

    Yoona Kim


    Full Text Available Epidemiological and clinical studies have indicated that nut consumption could be a healthy dietary strategy to prevent and treat type 2 diabetes (T2DM and related cardiovascular disease (CVD. The objective of this review is to examine the potential mechanisms of action of nuts addressing effects on glycemic control, weight management, energy balance, appetite, gut microbiota modification, lipid metabolism, oxidative stress, inflammation, endothelial function and blood pressure with a focus on data from both animal and human studies. The favourable effects of nuts could be explained by the unique nutrient composition and bioactive compounds in nuts. Unsaturated fatty acids (monounsaturated fatty acids and polyunsaturated fatty acids present in nuts may play a role in glucose control and appetite suppression. Fiber and polyphenols in nuts may also have an anti-diabetic effect by altering gut microbiota. Nuts lower serum cholesterol by reduced cholesterol absorption, inhibition of HMG-CoA reductase and increased bile acid production by stimulation of 7-α hydroxylase. Arginine and magnesium improve inflammation, oxidative stress, endothelial function and blood pressure. In conclusion, nuts contain compounds that favourably influence glucose homeostasis, weight control and vascular health. Further investigations are required to identify the most important mechanisms by which nuts decrease the risk of T2DM and CVD.

  6. Boron-doped nanocrystalline diamond microelectrode arrays monitor cardiac action potentials. (United States)

    Maybeck, Vanessa; Edgington, Robert; Bongrain, Alexandre; Welch, Joseph O; Scorsone, Emanuel; Bergonzo, Philippe; Jackman, Richard B; Offenhäusser, Andreas


    The expansion of diamond-based electronics in the area of biological interfacing has not been as thoroughly explored as applications in electrochemical sensing. However, the biocompatibility of diamond, large safe electrochemical window, stability, and tunable electronic properties provide opportunities to develop new devices for interfacing with electrogenic cells. Here, the fabrication of microelectrode arrays (MEAs) with boron-doped nanocrystalline diamond (BNCD) electrodes and their interfacing with cardiomyocyte-like HL-1 cells to detect cardiac action potentials are presented. A nonreductive means of structuring doped and undoped diamond on the same substrate is shown. The resulting BNCD electrodes show high stability under mechanical stress generated by the cells. It is shown that by fabricating the entire surface of the MEA with NCD, in patterns of conductive doped, and isolating undoped regions, signal detection may be improved up to four-fold over BNCD electrodes passivated with traditional isolators. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Directory of Open Access Journals (Sweden)

    Domenico F Galati


    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.

  8. Multifocal fluorescence microscope for fast optical recordings of neuronal action potentials. (United States)

    Shtrahman, Matthew; Aharoni, Daniel B; Hardy, Nicholas F; Buonomano, Dean V; Arisaka, Katsushi; Otis, Thomas S


    In recent years, optical sensors for tracking neural activity have been developed and offer great utility. However, developing microscopy techniques that have several kHz bandwidth necessary to reliably capture optically reported action potentials (APs) at multiple locations in parallel remains a significant challenge. To our knowledge, we describe a novel microscope optimized to measure spatially distributed optical signals with submillisecond and near diffraction-limit resolution. Our design uses a spatial light modulator to generate patterned illumination to simultaneously excite multiple user-defined targets. A galvanometer driven mirror in the emission path streaks the fluorescence emanating from each excitation point during the camera exposure, using unused camera pixels to capture time varying fluorescence at rates that are ∼1000 times faster than the camera's native frame rate. We demonstrate that this approach is capable of recording Ca(2+) transients resulting from APs in neurons labeled with the Ca(2+) sensor Oregon Green Bapta-1 (OGB-1), and can localize the timing of these events with millisecond resolution. Furthermore, optically reported APs can be detected with the voltage sensitive dye DiO-DPA in multiple locations within a neuron with a signal/noise ratio up to ∼40, resolving delays in arrival time along dendrites. Thus, the microscope provides a powerful tool for photometric measurements of dynamics requiring submillisecond sampling at multiple locations. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  9. Action Potential Energy Efficiency Varies Among Neuron Types in Vertebrates and Invertebrates (United States)

    Sengupta, Biswa; Stemmler, Martin; Laughlin, Simon B.; Niven, Jeremy E.


    The initiation and propagation of action potentials (APs) places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na+ and K+ currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin–Huxley model of the squid axon, optimizing the kinetics or number of Na+ and K+ channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost. PMID:20617202

  10. Direction-selective circuitry in rat retina develops independently of GABAergic, cholinergic and action potential activity.

    Directory of Open Access Journals (Sweden)

    Le Sun

    Full Text Available The ON-OFF direction selective ganglion cells (DSGCs in the mammalian retina code image motion by responding much more strongly to movement in one direction. They do so by receiving inhibitory inputs selectively from a particular sector of processes of the overlapping starburst amacrine cells, a type of retinal interneuron. The mechanisms of establishment and regulation of this selective connection are unknown. Here, we report that in the rat retina, the morphology, physiology of the ON-OFF DSGCs and the circuitry for coding motion directions develop normally with pharmacological blockade of GABAergic, cholinergic activity and/or action potentials for over two weeks from birth. With recent results demonstrating light independent formation of the retinal DS circuitry, our results strongly suggest the formation of the circuitry, i.e., the connections between the second and third order neurons in the visual system, can be genetically programmed, although emergence of direction selectivity in the visual cortex appears to require visual experience.

  11. The transformative potential of action research and ICT in the Second Language (L2 classroom

    Directory of Open Access Journals (Sweden)

    Farren Margaret


    Full Text Available This study shows the transformative potential of action research and information and communications technology (ICT in the second language (L2 classroom. Two enquiries from teacher-researchers are detailed in the article. Their engagement in a collaborative professional development Masters programme was pivotal in designing and implementing ICT creatively in their classroom. Gee (2008 advocates the use of the preferred media of our classroom students in order to address their learning. Prensky (2001 urges us to feel the fear and do it anyway with our digital native classes. A post-primary teacher and a primary teacher show us how they felt the fear, did it and transformed aspects of their own teaching in the process. The Masters programme required the teachers to engage with innovative practices, informed by their own values, and integrate technologies that were new to them into their repertoire of classroom strategies. Peer validation meetings with colleagues enabled meaningful insights to emerge from the research. The teachers improve and transform their second language (L2 practice in collaboration and validation with others.

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

    Directory of Open Access Journals (Sweden)

    M.R. Moreira


    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.

  13. Variations in interpulse interval of double action potentials during propagation in single neurons. (United States)

    Villagran-Vargas, Edgar; Rodríguez-Sosa, Leonardo; Hustert, Reinhold; Blicher, Andreas; Laub, Katrine; Heimburg, Thomas


    In this work, we analyzed the interpulse interval (IPI) of doublets and triplets in single neurons of three biological models. Pulse trains with two or three spikes originate from the process of sensory mechanotransduction in neurons of the locust femoral nerve, as well as through spontaneous activity both in the abdominal motor neurons and the caudal photoreceptor of the crayfish. We show that the IPI for successive low-frequency single action potentials, as recorded with two electrodes at two different points along a nerve axon, remains constant. On the other hand, IPI in doublets either remains constant, increases or decreases by up to about 3 ms as the pair propagates. When IPI increases, the succeeding pulse travels at a slower speed than the preceding one. When IPI is reduced, the succeeding pulse travels faster than the preceding one and may exceed the normal value for the specific neuron. In both cases, IPI increase and reduction, the speed of the preceding pulse differs slightly from the normal value, therefore the two pulses travel at different speeds in the same nerve axon. On the basis of our results, we may state that the effect of attraction or repulsion in doublets suggests a tendency of the spikes to reach a stable configuration. We strongly suggest that the change in IPI during spike propagation of doublets opens up a whole new realm of possibilities for neural coding and may have major implications for understanding information processing in nervous systems. Copyright © 2012 Wiley Periodicals, Inc.

  14. Burst analysis tool for developing neuronal networks exhibiting highly varying action potential dynamics

    Directory of Open Access Journals (Sweden)

    Fikret Emre eKapucu


    Full Text Available In this paper we propose a firing statistics based neuronal network burst detection algorithm for neuronal networks exhibiting highly variable action potential dynamics. Electrical activity of neuronal networks is generally analyzed by the occurrences of spikes and bursts both in time and space. Commonly accepted analysis tools employ burst detection algorithms based on predefined criteria. However, maturing neuronal networks, such as those originating from human embryonic stem cells (hESC, exhibit highly variable network structure and time-varying dynamics. To explore the developing burst/spike activities of such networks, we propose a burst detection algorithm which utilizes the firing statistics based on interspike interval (ISI histograms. Moreover, the algorithm calculates interspike interval thresholds for burst spikes as well as for pre-burst spikes and burst tails by evaluating the cumulative moving average and skewness of the ISI histogram. Because of the adaptive nature of the proposed algorithm, its analysis power is not limited by the type of neuronal cell network at hand. We demonstrate the functionality of our algorithm with two different types of microelectrode array (MEA data recorded from spontaneously active hESC-derived neuronal cell networks. The same data was also analyzed by two commonly employed burst detection algorithms and the differences in burst detection results are illustrated. The results demonstrate that our method is both adaptive to the firing statistics of the network and yields successful burst detection from the data. In conclusion, the proposed method is a potential tool for analyzing of hESC-derived neuronal cell networks and thus can be utilized in studies aiming to understand the development and functioning of human neuronal networks and as an analysis tool for in vitro drug screening and neurotoxicity assays.

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

    Directory of Open Access Journals (Sweden)

    F Woodward Hopf


    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.

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


    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.

  17. Action Potential Shortening and Impairment of Cardiac Function by Ablation of Slc26a6. (United States)

    Sirish, Padmini; Ledford, Hannah A; Timofeyev, Valeriy; Thai, Phung N; Ren, Lu; Kim, Hyo Jeong; Park, Seojin; Lee, Jeong Han; Dai, Gu; Moshref, Maryam; Sihn, Choong-Ryoul; Chen, Wei Chun; Timofeyeva, Maria Valeryevna; Jian, Zhong; Shimkunas, Rafael; Izu, Leighton T; Chiamvimonvat, Nipavan; Chen-Izu, Ye; Yamoah, Ebenezer N; Zhang, Xiao-Dong


    Intracellular pH (pH i ) is critical to cardiac excitation and contraction; uncompensated changes in pH i impair cardiac function and trigger arrhythmia. Several ion transporters participate in cardiac pH i regulation. Our previous studies identified several isoforms of a solute carrier Slc26a6 to be highly expressed in cardiomyocytes. We show that Slc26a6 mediates electrogenic Cl - /HCO 3 - exchange activities in cardiomyocytes, suggesting the potential role of Slc26a6 in regulation of not only pH i , but also cardiac excitability. To test the mechanistic role of Slc26a6 in the heart, we took advantage of Slc26a6 knockout ( Slc26a6 -/ - ) mice using both in vivo and in vitro analyses. Consistent with our prediction of its electrogenic activities, ablation of Slc26a6 results in action potential shortening. There are reduced Ca 2+ transient and sarcoplasmic reticulum Ca 2+ load, together with decreased sarcomere shortening in Slc26a6 -/ - cardiomyocytes. These abnormalities translate into reduced fractional shortening and cardiac contractility at the in vivo level. Additionally, pH i is elevated in Slc26a6 -/ - cardiomyocytes with slower recovery kinetics from intracellular alkalization, consistent with the Cl - /HCO 3 - exchange activities of Slc26a6. Moreover, Slc26a6 -/ - mice show evidence of sinus bradycardia and fragmented QRS complex, supporting the critical role of Slc26a6 in cardiac conduction system. Our study provides mechanistic insights into Slc26a6, a unique cardiac electrogenic Cl - /HCO 3 - transporter in ventricular myocytes, linking the critical roles of Slc26a6 in regulation of pH i , excitability, and contractility. pH i is a critical regulator of other membrane and contractile proteins. Future studies are needed to investigate possible changes in these proteins in Slc26a6 -/ - mice. © 2017 American Heart Association, Inc.

  18. Potential Beneficiaries of the Obama Administration’s Executive Action Programs Deeply Embedded in US Society


    Donald Kerwin; Robert Warren


    The Obama administration has developed two broad programs to defer immigration enforcement actions against undocumented persons living in the United States: (1) Deferred Action for Parents of Americans and Lawful Permanent Residents (DAPA); and (2) Deferred Action for Childhood Arrivals (DACA). The DACA program, which began in August 2012, was expanded on November 20, 2014. DAPA and the DACA expansion (hereinafter referred to as “DACA-plus”) are currently under review by the US Supreme Court ...

  19. Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. (United States)

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


    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.

  20. The energy cost of action potential propagation in dopamine neurons: clues to susceptibility in Parkinson's disease. (United States)

    Pissadaki, Eleftheria K; Bolam, J Paul


    Dopamine neurons of the substantia nigra pars compacta (SNc) are uniquely sensitive to degeneration in Parkinson's disease (PD) and its models. Although a variety of molecular characteristics have been proposed to underlie this sensitivity, one possible contributory factor is their massive, unmyelinated axonal arbor that is orders of magnitude larger than other neuronal types. We suggest that this puts them under such a high energy demand that any stressor that perturbs energy production leads to energy demand exceeding supply and subsequent cell death. One prediction of this hypothesis is that those dopamine neurons that are selectively vulnerable in PD will have a higher energy cost than those that are less vulnerable. We show here, through the use of a biology-based computational model of the axons of individual dopamine neurons, that the energy cost of axon potential propagation and recovery of the membrane potential increases with the size and complexity of the axonal arbor according to a power law. Thus SNc dopamine neurons, particularly in humans, whose axons we estimate to give rise to more than 1 million synapses and have a total length exceeding 4 m, are at a distinct disadvantage with respect to energy balance which may be a factor in their selective vulnerability in PD.

  1. Toxicity, sublethal effects, and potential modes of action of select fungicides on freshwater fish and invertebrates (United States)

    Elskus, Adria A.


    Despite decades of agricultural and urban use of fungicides and widespread detection of these pesticides in surface waters, relatively few data are available on the effects of fungicides on fish and invertebrates in the aquatic environment. Nine fungicides are reviewed in this report: azoxystrobin, boscalid, chlorothalonil, fludioxonil, myclobutanil, fenarimol, pyraclostrobin, pyrimethanil, and zoxamide. These fungicides were identified as emerging chemicals of concern because of their high or increasing global use rates, detection frequency in surface waters, or likely persistence in the environment. A review of the literature revealed significant sublethal effects of fungicides on fish, aquatic invertebrates, and ecosystems, including zooplankton and fish reproduction, fish immune function, zooplankton community composition, metabolic enzymes, and ecosystem processes, such as leaf decomposition in streams, among other biological effects. Some of these effects can occur at fungicide concentrations well below single-species acute lethality values (48- or 96-hour concentration that effects a response in 50 percent of the organisms, that is, effective concentration killing 50 percent of the organisms in 48 or 96 hours) and chronic sublethal values (for example, 21-day no observed adverse effects concentration), indicating that single-species toxicity values may dramatically underestimate the toxic potency of some fungicides. Fungicide modes of toxic action in fungi can sometimes reflect the biochemical and (or) physiological effects of fungicides observed in vertebrates and invertebrates; however, far more studies are needed to explore the potential to predict effects in nontarget organisms based on specific fungicide modes of toxic action. Fungicides can also have additive and (or) synergistic effects when used with other fungicides and insecticides, highlighting the need to study pesticide mixtures that occur in surface waters. For fungicides that partition to

  2. Associations between motor unit action potential parameters and surface EMG features. (United States)

    Del Vecchio, Alessandro; Negro, Francesco; Felici, Francesco; Farina, Dario


    The surface interference EMG signal provides some information on the neural drive to muscles. However, the association between neural drive to muscle and muscle activation has long been debated with controversial indications due to the unavailability of motor unit population data. In this study, we clarify the potential and limitations of interference EMG analysis to infer motor unit recruitment strategies with an experimental investigation of several concurrently active motor units and of the associated features of the surface EMG. For this purpose, we recorded high-density surface EMG signals during linearly increasing force contractions of the tibialis anterior muscle, up to 70% of maximal force. The recruitment threshold (RT), conduction velocity (MUCV), median frequency (MDF MU ), and amplitude (RMS MU ) of action potentials of 587 motor units from 13 individuals were assessed and associated with features of the interference EMG. MUCV was positively associated with RT ( R 2 = 0.64 ± 0.14), whereas MDF MU and RMS MU showed a weaker relation with RT ( R 2 = 0.11 ± 0.11 and 0.39 ± 0.24, respectively). Moreover, the changes in average conduction velocity estimated from the interference EMG predicted well the changes in MUCV ( R 2 = 0.71), with a strong association to ankle dorsiflexion force ( R 2 = 0.81 ± 0.12). Conversely, both the average EMG MDF and RMS were poorly associated with motor unit recruitment. These results clarify the limitations of EMG spectral and amplitude analysis in inferring the neural strategies of muscle control and indicate that, conversely, the average conduction velocity could provide relevant information on these strategies. NEW & NOTEWORTHY The surface EMG provides information on the neural drive to muscles. However, the associations between EMG features and neural drive have been long debated due to unavailability of motor unit population data. Here, by using novel highly accurate decomposition of the EMG, we related motor unit

  3. Motor Unit Action Potential Clustering—Theoretical Consideration for Muscle Activation during a Motor Task

    Directory of Open Access Journals (Sweden)

    Michael J. Asmussen


    Full Text Available During dynamic or sustained isometric contractions, bursts of muscle activity appear in the electromyography (EMG signal. Theoretically, these bursts of activity likely occur because motor units are constrained to fire temporally close to one another and thus the impulses are “clustered” with short delays to elicit bursts of muscle activity. The purpose of this study was to investigate whether a sequence comprised of “clustered” motor unit action potentials (MUAP can explain spectral and amplitude changes of the EMG during a simulated motor task. This question would be difficult to answer experimentally and thus, required a model to study this type of muscle activation pattern. To this end, we modeled two EMG signals, whereby a single MUAP was either convolved with a randomly distributed impulse train (EMG-rand or a “clustered” sequence of impulses (EMG-clust. The clustering occurred in windows lasting 5–100 ms. A final mixed signal of EMG-clust and EMG-rand, with ratios (1:1–1:10, was also modeled. A ratio of 1:1 would indicate that 50% of MUAP were randomly distributed, while 50% of “clustered” MUAP occurred in a given time window (5–100 ms. The results of the model showed that clustering MUAP caused a downshift in the mean power frequency (i.e., ~30 Hz with the largest shift occurring with a cluster window of 10 ms. The mean frequency shift was largest when the ratio of EMG-clust to EMG-rand was high. Further, the clustering of MUAP also caused a substantial increase in the amplitude of the EMG signal. This model potentially explains an activation pattern that changes the EMG spectra during a motor task and thus, a potential activation pattern of muscles observed experimentally. Changes in EMG measurements during fatiguing conditions are typically attributed to slowing of conduction velocity but could, per this model, also result from changes of the clustering of MUAP. From a clinical standpoint, this type of muscle

  4. Impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.

    Directory of Open Access Journals (Sweden)

    Jussi T Koivumäki

    Full Text Available Electrophysiological studies of the human heart face the fundamental challenge that experimental data can be acquired only from patients with underlying heart disease. Regarding human atria, there exist sizable gaps in the understanding of the functional role of cellular Ca²+ dynamics, which differ crucially from that of ventricular cells, in the modulation of excitation-contraction coupling. Accordingly, the objective of this study was to develop a mathematical model of the human atrial myocyte that, in addition to the sarcolemmal (SL ion currents, accounts for the heterogeneity of intracellular Ca²+ dynamics emerging from a structurally detailed sarcoplasmic reticulum (SR. Based on the simulation results, our model convincingly reproduces the principal characteristics of Ca²+ dynamics: 1 the biphasic increment during the upstroke of the Ca²+ transient resulting from the delay between the peripheral and central SR Ca²+ release, and 2 the relative contribution of SL Ca²+ current and SR Ca²+ release to the Ca²+ transient. In line with experimental findings, the model also replicates the strong impact of intracellular Ca²+ dynamics on the shape of the action potential. The simulation results suggest that the peripheral SR Ca²+ release sites define the interface between Ca²+ and AP, whereas the central release sites are important for the fire-diffuse-fire propagation of Ca²+ diffusion. Furthermore, our analysis predicts that the modulation of the action potential duration due to increasing heart rate is largely mediated by changes in the intracellular Na+ concentration. Finally, the results indicate that the SR Ca²+ release is a strong modulator of AP duration and, consequently, myocyte refractoriness/excitability. We conclude that the developed model is robust and reproduces many fundamental aspects of the tight coupling between SL ion currents and intracellular Ca²+ signaling. Thus, the model provides a useful framework for future

  5. Study of crotoxin mechanism of action to mammary carcinomas and evaluation of its potential as a radiopharmaceutical

    International Nuclear Information System (INIS)

    Silveira, Marina Bicalho


    Crotoxin, the main component of Crotalus durissus terrificus snake venom, has been studied since 1938. It is a natural polypeptidic complex with pharmacological potential because of its antitumoral properties which has attracted great interest for diagnosis and therapy of oncological diseases. However, Crotoxin mechanism of action and sites of specific interaction on tumor cells are still misunderstood. Breast cancer is the second most frequent type in the world and the most common cancer in women. About 30 to 60% of mammary tumors overexpress epidermal growth factor receptor (EGFR), a transmembrane protein related to cell proliferation. Since literature has reported that Crotoxin antitumoral effect is more potent on cells with EGFR overexpression the objectives of this work were to evaluate Crotoxin cytotoxic effects on mammary tumor cells human breast carcinoma (MCF-7) and Ehrlich tumor cells (murine ascitics carcinoma), and to investigate the specific molecular interaction of Crotoxin on Ehrlich tumor cells. Initially, Crotoxin was radiolabelled with iodine-125 ( 125 I-Crotoxin) and iodine-131 ( 131 I-Crotoxin). Saturation and competition assay were carried out to characterize Crotoxin in vitro interaction; Crotoxin biodistribution studies and singlephoton emission computed tomography (SPECT) of mice bearing Ehrlich tumor have been evaluated to describe in vivo interaction. Our results showed that Crotoxin presented cytotoxic effect against Ehrlich with DL 50 in vitro (concentration of compound which is lethal for 50% of cells) of about one micromolar, but did not present significant effect against MCF-7. Morphological alterations characteristic of apoptosis suggests programmed cell death. 125 I-Crotoxin interaction with Ehrlich tumor cells was saturable with approximately 70% specificity, and presented K d =24.98 nmol/L and B max =16,570 sites/cell for low affinity binding sites and K d =0.06 nmol/L and B max =210 sites/cell high affinity binding sites

  6. Facilitating Youth to Take Sustainability Actions: The Potential of Peer Education (United States)

    de Vreede, Catherine; Warner, Alan; Pitter, Robert


    Peer education is an understudied yet valuable strategy for sustainability educators in shifting youth to take action for sustainability. This case study conceptualizes the change process in facilitating youth to take sustainability actions, and explores the benefits, dynamics, and challenges of peer education as a strategy in facilitating change.…

  7. Action potential influences spatial perception: Evidence for genuine top-down effects on perception. (United States)

    Witt, Jessica K


    The action-specific account of spatial perception asserts that a perceiver's ability to perform an action, such as hitting a softball or walking up a hill, impacts the visual perception of the target object. Although much evidence is consistent with this claim, the evidence has been challenged as to whether perception is truly impacted, as opposed to the responses themselves. These challenges have recently been organized as six pitfalls that provide a framework with which to evaluate the empirical evidence. Four case studies of action-specific effects are offered as evidence that meets the framework's high bar, and thus that demonstrates genuine perceptual effects. That action influences spatial perception is evidence that perceptual and action-related processes are intricately and bidirectionally linked.

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

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


    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

  9. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids (United States)

    Covey, Dan P.; Bunner, Kendra D.; Schuweiler, Douglas R.; Cheer, Joseph F.; Garris, Paul A.


    The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

  10. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids. (United States)

    Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A


    The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

  11. Dynamics of action potential backpropagation in basal dendrites of prefrontal cortical pyramidal neurons. (United States)

    Zhou, Wen-Liang; Yan, Ping; Wuskell, Joseph P; Loew, Leslie M; Antic, Srdjan D


    Basal dendrites of neocortical pyramidal neurons are relatively short and directly attached to the cell body. This allows electrical signals arising in basal dendrites to strongly influence the neuronal output. Likewise, somatic action potentials (APs) should readily propagate back into the basilar dendritic tree to influence synaptic plasticity. Two recent studies, however, determined that sodium APs are severely attenuated in basal dendrites of cortical pyramidal cells, so that they completely fail in distal dendritic segments. Here we used the latest improvements in the voltage-sensitive dye imaging technique (Zhou et al., 2007) to study AP backpropagation in basal dendrites of layer 5 pyramidal neurons of the rat prefrontal cortex. With a signal-to-noise ratio of > 15 and minimal temporal averaging (only four sweeps) we were able to sample AP waveforms from the very last segments of individual dendritic branches (dendritic tips). We found that in short- (< 150 microm) and medium (150-200 microm in length)-range basal dendrites APs backpropagated with modest changes in AP half-width or AP rise-time. The lack of substantial changes in AP shape and dynamics of rise is inconsistent with the AP-failure model. The lack of substantial amplitude boosting of the third AP in the high-frequency burst also suggests that in short- and medium-range basal dendrites backpropagating APs were not severely attenuated. Our results show that the AP-failure concept does not apply in all basal dendrites of the rat prefrontal cortex. The majority of synaptic contacts in the basilar dendritic tree actually received significant AP-associated electrical and calcium transients.

  12. Electrically evoked compound action potentials artefact rejection by independent component analysis: procedure automation. (United States)

    Akhoun, Idrick; McKay, Colette; El-Deredy, Wael


    Independent-components-analysis (ICA) successfully separated electrically-evoked compound action potentials (ECAPs) from the stimulation artefact and noise (ECAP-ICA, Akhoun et al., 2013). This paper shows how to automate the ECAP-ICA artefact cancellation process. Raw-ECAPs without artefact rejection were consecutively recorded for each stimulation condition from at least 8 intra-cochlear electrodes. Firstly, amplifier-saturated recordings were discarded, and the data from different stimulus conditions (different current-levels) were concatenated temporally. The key aspect of the automation procedure was the sequential deductive source categorisation after ICA was applied with a restriction to 4 sources. The stereotypical aspect of the 4 sources enables their automatic classification as two artefact components, a noise and the sought ECAP based on theoretical and empirical considerations. The automatic procedure was tested using 8 cochlear implant (CI) users and one to four stimulus electrodes. The artefact and noise sources were successively identified and discarded, leaving the ECAP as the remaining source. The automated ECAP-ICA procedure successfully extracted the correct ECAPs compared to standard clinical forward masking paradigm in 22 out of 26 cases. ECAP-ICA does not require extracting the ECAP from a combination of distinct buffers as it is the case with regular methods. It is an alternative that does not have the possible bias of traditional artefact rejections such as alternate-polarity or forward-masking paradigms. The ECAP-ICA procedure bears clinical relevance, for example as the artefact rejection sub-module of automated ECAP-threshold detection techniques, which are common features of CI clinical fitting software. Copyright © 2014. Published by Elsevier B.V.

  13. Impedance and electrically evoked compound action potential (ECAP drop within 24 hours after cochlear implantation.

    Directory of Open Access Journals (Sweden)

    Joshua Kuang-Chao Chen

    Full Text Available Previous animal study revealed that post-implantation electrical detection levels significantly declined within days. The impact of cochlear implant (CI insertion on human auditory pathway in terms of impedance and electrically evoked compound action potential (ECAP variation within hours after surgery remains unclear, since at this time frequency mapping can only commence weeks after implantation due to factors associated with wound conditions. The study presented our experiences with regards to initial switch-on within 24 hours, and thus the findings about the milieus inside cochlea within the first few hours after cochlear implantation in terms of impedance/ECAP fluctuations. The charts of fifty-four subjects with profound hearing impairment were studied. A minimal invasive approach was used for cochlear implantation, characterized by a small skin incision (≈ 2.5 cm and soft techniques for cochleostomy. Impedance/ECAP was measured intro-operatively and within 24 hours post-operatively. Initial mapping within 24 hours post-operatively was performed in all patients without major complications. Impedance/ECAP became significantly lower measured within 24 hours post-operatively as compared with intra-operatively (p<0.001. There were no differences between pre-operative and post-operative threshold for air-conduction hearing. A significant drop of impedance/ECAP in one day after cochlear implantation was revealed for the first time in human beings. Mechanisms could be related to the restoration of neuronal sensitivity to the electrical stimulation, and/or the interaction between the matrix enveloping the electrodes and the electrical stimulation of the initial switch-on. Less wound pain/swelling and soft techniques both contributed to the success of immediate initial mapping, which implied a stable micro-environment inside the cochlea despite electrodes insertion. Our research invites further studies to correlate initial impedance/ECAP changes

  14. Recording single neurons' action potentials from freely moving pigeons across three stages of learning. (United States)

    Starosta, Sarah; Stüttgen, Maik C; Güntürkün, Onur


    While the subject of learning has attracted immense interest from both behavioral and neural scientists, only relatively few investigators have observed single-neuron activity while animals are acquiring an operantly conditioned response, or when that response is extinguished. But even in these cases, observation periods usually encompass only a single stage of learning, i.e. acquisition or extinction, but not both (exceptions include protocols employing reversal learning; see Bingman et al.(1) for an example). However, acquisition and extinction entail different learning mechanisms and are therefore expected to be accompanied by different types and/or loci of neural plasticity. Accordingly, we developed a behavioral paradigm which institutes three stages of learning in a single behavioral session and which is well suited for the simultaneous recording of single neurons' action potentials. Animals are trained on a single-interval forced choice task which requires mapping each of two possible choice responses to the presentation of different novel visual stimuli (acquisition). After having reached a predefined performance criterion, one of the two choice responses is no longer reinforced (extinction). Following a certain decrement in performance level, correct responses are reinforced again (reacquisition). By using a new set of stimuli in every session, animals can undergo the acquisition-extinction-reacquisition process repeatedly. Because all three stages of learning occur in a single behavioral session, the paradigm is ideal for the simultaneous observation of the spiking output of multiple single neurons. We use pigeons as model systems, but the task can easily be adapted to any other species capable of conditioned discrimination learning.

  15. Developmental impairment of compound action potential in the optic nerve of myelin mutant taiep rats. (United States)

    Roncagliolo, Manuel; Schlageter, Carol; León, Claudia; Couve, Eduardo; Bonansco, Christian; Eguibar, José R


    The taiep rat is a myelin mutant with an initial hypomyelination, followed by a progressive demyelination of the CNS. The neurological correlates start with tremor, followed by ataxia, immobility episodes, epilepsy and paralysis. The optic nerve, an easily-isolable central tract fully myelinated by oligodendrocytes, is a suitable preparation to evaluate the developmental impairment of central myelin. We examined the ontogenic development of optic nerve compound action potentials (CAP) throughout the first 6 months of life of control and taiep rats. Control optic nerves (ON) develop CAPs characterized by three waves. Along the first month, the CAPs of taiep rats showed a delayed maturation, with lower amplitudes and longer latencies than controls; at P30, the conduction velocity has only a third of the normal value. Later, as demyelination proceeds, the conduction velocity of taiep ONs begins to decrease and CAPs undergo a gradual temporal dispersion. CAPs of control and taiep showed differences in their pharmacological sensitivity to TEA and 4-AP, two voltage dependent K+ channel-blockers. As compared with TEA, 4-AP induced a significant increase of the amplitudes and a remarkable broadening of CAPs. After P20, unlike controls, the greater sensitivity to 4-AP exhibited by taiep ONs correlates with the detachment and retraction of paranodal loops suggesting that potassium conductances could regulate the excitability as demyelination of CNS axons progresses. It is concluded that the taiep rat, a long-lived mutant, provides a useful model to study the consequences of partial demyelination and the mechanisms by which glial cells regulate the molecular organization and excitability of axonal membranes during development and disease.

  16. Effects of estragole on the compound action potential of the rat sciatic nerve

    Directory of Open Access Journals (Sweden)

    J.H. Leal-Cardoso


    Full Text Available Estragole, a relatively nontoxic terpenoid ether, is an important constituent of many essential oils with widespread applications in folk medicine and aromatherapy and known to have potent local anesthetic activity. We investigated the effects of estragole on the compound action potential (CAP of the rat sciatic nerve. The experiments were carried out on sciatic nerves dissected from Wistar rats. Nerves, mounted in a moist chamber, were stimulated at a frequency of 0.2 Hz, with electric pulses of 50-100-µs duration at 10-20 V, and evoked CAP were monitored on an oscilloscope and recorded on a computer. CAP control parameters were: peak-to-peak amplitude (PPA, 9.9 ± 0.55 mV (N = 15, conduction velocity, 92.2 ± 4.36 m/s (N = 15, chronaxy, 45.6 ± 3.74 µs (N = 5, and rheobase, 3.9 ± 0.78 V (N = 5. Estragole induced a dose-dependent blockade of the CAP. At 0.6 mM, estragole had no demonstrable effect. At 2.0 and 6.0 mM estragole, PPA was significantly reduced at the end of 180-min exposure of the nerve to the drug to 85.6 ± 3.96 and 13.04 ± 1.80% of control, respectively. At 4.0 mM, estragole significantly altered PPA, conduction velocity, chronaxy, and rheobase (P <= 0.05, ANOVA; N = 5 to 49.3 ± 6.21 and 77.7 ± 3.84, 125.9 ± 10.43 and 116.7 ± 4.59%, of control, respectively. All of these effects developed slowly and were reversible upon a 300-min wash-out. The data show that estragole dose-dependently blocks nerve excitability.

  17. Inter-subject variability in human atrial action potential in sinus rhythm versus chronic atrial fibrillation.

    Directory of Open Access Journals (Sweden)

    Carlos Sánchez

    Full Text Available Human atrial electrophysiology exhibits high inter-subject variability in both sinus rhythm (SR and chronic atrial fibrillation (cAF patients. Variability is however rarely investigated in experimental and theoretical electrophysiological studies, thus hampering the understanding of its underlying causes but also its implications in explaining differences in the response to disease and treatment. In our study, we aim at investigating the ability of populations of human atrial cell models to capture the inter-subject variability in action potential (AP recorded in 363 patients both under SR and cAF conditions.Human AP recordings in atrial trabeculae (n = 469 from SR and cAF patients were used to calibrate populations of computational SR and cAF atrial AP models. Three populations of over 2000 sampled models were generated, based on three different human atrial AP models. Experimental calibration selected populations of AP models yielding AP with morphology and duration in range with experimental recordings. Populations using the three original models can mimic variability in experimental AP in both SR and cAF, with median conductance values in SR for most ionic currents deviating less than 30% from their original peak values. All cAF populations show similar variations in G(K1, G(Kur and G(to, consistent with AF-related remodeling as reported in experiments. In all SR and cAF model populations, inter-subject variability in I(K1 and I(NaK underlies variability in APD90, variability in I(Kur, I(CaL and I(NaK modulates variability in APD50 and combined variability in Ito and I(Kur determines variability in APD20. The large variability in human atrial AP triangulation is mostly determined by I(K1 and either I(NaK or I(NaCa depending on the model.Experimentally-calibrated human atrial AP models populations mimic AP variability in SR and cAF patient recordings, and identify potential ionic determinants of inter-subject variability in human atrial AP

  18. Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility. (United States)

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


    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

  19. Synthesis of sulfenamides, derivatives of morpholine, 4-aminomorpholine and thiomorpholine as compounds of potential radioprotective action

    Energy Technology Data Exchange (ETDEWEB)

    Strzelczyk, M.; Kucharski, A. (Wojskowa Akademia Medyczna, Lodz (Poland))


    Sulfenamides belong to the group of compounds displaying radioprotective action. Their mechanism of action is based mainly on the protection against oxygenation. Six compounds were synthetized four of which i.e. 3-nitrophenylothiomorpholine, 2,4-dinitrophenylothiomorpholine, 2,4-dinitrophenylothio-4-aminomorpholine and 2,4-dinitrophenylothiothiomorpholine were to date not described in the literature. The structure of the synthetized compounds was confirmed by elementary and infrared spectral analysis.

  20. Acute effects of ethanol on action potential and intracellular Ca2+ transient in cardiac ventricular cells: a simulation study

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Bébarová, M.; Christé, G.; Šimurdová, M.; Šimurda, J.


    Roč. 54, č. 5 (2016), s. 753-762 ISSN 0140-0118 Institutional support: RVO:61388998 Keywords : ethanol * cardiomyocyte * action potential * rat ventricular cell model * human ventricular cell model Subject RIV: BO - Biophysics Impact factor: 1.916, year: 2016

  1. Flattening of the electrocardiographic T-wave is a sign of proarrhythmic risk and a reflection of action potential triangulation

    DEFF Research Database (Denmark)

    Bhuiyan, Tanveer Ahmed; Graff, Claus; Kanters, J.K.


    Drug-induced triangulation of the cardiac action potential is associated with increased risk of arrhythmic events. It has been suggested that triangulation causes a flattening of the electrocardiographic T-wave but the relationship between triangulation, T-wave flattening and onset of arrhythmia ...

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


    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.

  3. Field-aligned current density versus electric potential characteristics for magnetospheric flux tubes

    International Nuclear Information System (INIS)

    Lemaire, J.; Scherer, M.


    The field-aligned current density (Jsub(tot)) is a non-linear function of the applied potential difference (phi) between the ionosphere and the magnetosphere. This nonlinear function has been calculated for plasma boundary conditions typical in a dayside cusp magnetic flux tube. The J-characteristic of such a flux tube changes when the temperatures of the warm magnetospheric electrons and of the cold ionospheric electrons are modified; it changes also when the relative density of the warm plasma is modified; the presence of trapped secondary electrons changes also the J-characteristic. The partial currents contributed by the warm and cold electrons, and by warm and cold ions are illustrated. The dynamic characteristic of an electric circuit depends on the static characteristic of each component of the sytem: i.e. the resistive ionosphere, the return current region, and the region of particle precipitation whose field-aligned current/voltage characteristics have been studied in this article

  4. Nanoelectronics-biology frontier: From nanoscopic probes for action potential recording in live cells to three-dimensional cyborg tissues


    Duan, Xiaojie; Fu, Tian-Ming; Liu, Jia; Lieber, Charles M.


    Semiconductor nanowires configured as the active channels of field-effect transistors (FETs) have been used as detectors for high-resolution electrical recording from single live cells, cell networks, tissues and organs. Extracellular measurements with substrate supported silicon nanowire (SiNW) FETs, which have projected active areas orders of magnitude smaller than conventional microfabricated multielectrode arrays (MEAs) and planar FETs, recorded action potential and field potential signa...

  5. Governance issues, potentials and failures of participative collective action in the Kafue Flats, Zambia

    Directory of Open Access Journals (Sweden)

    Harry Nixon Chabwela


    2004 for creating by-laws based on initiatives of local staff of the Department of Fisheries, local interest groups and researchers. A broad local debate on how to manage the fisheries in a sustainable way and develop locally based by-laws for joint management of fisheries gives good potential for success and appears promising for the future of fisheries in Kafue Flats. Despite many difficulties it is an example of local collective action in order to scale up governance of common-pool resources.

  6. Photophysical properties, photodegradation characteristics, and lasing action for coumarin dye C540A in polymeric media (United States)

    Jones, Guilford, II; Huang, Zhennian; Pacheco, Dennis P., Jr.; Russell, Jeffrey A.


    Tunable solid-state dye lasers operating in the blue-green spectral region are attractive for a variety of applications. An important consideration in assessing the viability of this technology is the service life of the gain medium, which is presently limited by dye photodegradation. In this study, solid polymeric samples consisting of the coumarin dye C540A in modified PMMA were subjected to controlled photodegradation tests. The excitation laser was a flashlamp-pumped dye laser operating at 440 nm with a pulse duration of 1 μs. A complementary set of data was obtained for dye in solution phase for comparison purposes. Photophysical properties of C540A in water solution of polymethacrylic acid (PMAA) have been investigated with a view to assess the suitability of the sequestering polymer (PMAA) as an effective additive to facilitate use of a water medium for highly efficient blue-green dye lasers. Lasing action of C540A in aqueous PMAA has been realized using flashlamp-pumped laser system, yielding excellent laser efficiencies superior to that achieved in ethanolic solutions with the same dye. Laser characterization of dye in media included measurement of laser threshold, slope efficiency, pulse duration and output wavelength.

  7. Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons. (United States)

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


    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.

  8. The Potential of General Classroom Observation: Turkish EFL Teachers' Perceptions, Sentiments, and Readiness for Action (United States)

    Merç, Ali


    The purpose of this study was to determine Turkish EFL teachers' attitudes towards classroom observation. 204 teachers from different school settings responded to an online questionnaire. Data were analyzed according to three types of attitudes towards classroom observation: perceptions, sentiments, and readiness for action. The findings revealed…

  9. Acupuncture therapy: mechanism of action, efficacy, and safety: a potential intervention for psychogenic disorders? (United States)


    Scientific bases for the mechanism of action of acupuncture in the treatment of pain and the pathogenic mechanism of acupuncture points are briefly summarized. The efficacy and safety of acupuncture therapy is discussed based on the results of German clinical trials. A conclusion on the role for acupuncture in the treatment of psychogenic disorders could not be reached. PMID:24444292

  10. Consolidated Quarterly Report: Number of potential release sites subject to corrective action

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, John R.; Cochran, John R.


    This Sandia National Laboratories, New Mexico Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) fulfills all quarterly reporting requirements set forth in the Resource Conservation and Recovery Act Facility Operating Permit and the Compliance Order on Consent. The 12 sites in the corrective action process are listed in Table I-1.

  11. Motivations and possible actions of potential criminal adversaries of US nuclear programs

    International Nuclear Information System (INIS)

    Bass, G.; Jenkins, B.; Kellen, K.; Krofcheek, J.; Petty, G.; Reinstedt, R.; Ronfeldt, D.


    The motivations that might impel individuals or groups to undertake criminal actions against US nuclear facilities or programs are explored in the report (R and R-2554-SL) from which this note is taken. The analysis involves examination of the motivations behind nuclear-related crimes that have already occurred and of those behind analogous nonnuclear crimes

  12. On the Potentials for Synergy Between COST Action TU1406 and the JCSS

    DEFF Research Database (Denmark)

    Nielsen, Michael Havbro Faber

    On of the main challenges of COST Action TU1406 is to identify, categorize and to the extent possible represent performance indicators of roadway bridges in a manner supporting decision making for their service life integrity management. This calls for an information consistent approach accounting...

  13. Preparing Social Justice Oriented Teachers: The Potential Role of Action Research in the PDS (United States)

    Dodman, Stephanie L.; Lai, Kerri; Campet, Melissa; Cavallero-Lotocki, Renee; Hopkins, Aaron; Onidi, Christine


    Deliberate investigation into practice is an essential of the National Association for Professional Development Schools' defining elements of a Professional Development School (PDS). This article reports on the pilot efforts of one PDS as it initiated deliberate investigation through action research with a small group of teacher candidates. The…

  14. From Fiction to Fact to Potential Action: Generating Prosocial Attitudes and Behaviors Using Young Adult Literature (United States)

    Hays, Alice


    This dissertation investigates the impact reading Young Adult Literature (YAL) has on students' empathetic responses as well as their capacity to take action regarding a social justice issue chosen by the student. Drawing on data from a 10th grade honors classroom at a Title 1 school in the Southwest, this ethnographic case study investigates how…

  15. New Sides of Aldosterone Action in Cardiovascular System as Potential Targets for Therapeutic Intervention. (United States)

    Kolodziejczyk, Patrycjusz; Gromotowicz-Poplawska, Anna; Aleksiejczuk, Michal; Chabielska, Ewa; Tutka, Piotr; Miltyk, Wojciech


    Aldosterone, the main mineralocorticoid hormone, plays a crucial role in the regulation of electrolyte homeostasis and blood pressure. Although, this role is undoubtedly important, it is not a hormonal action that attracts the most attention. Aldosterone seems to be very important important as a local messenger in the pathology of cardiovascular diseases (CVD). In the last few years, the attention was focused on the correlation between raised aldosterone level and increased risk of cardiovascular events. It has been demonstrated that aldosterone contributes to fibrosis, inflammation, endothelial dysfunction, fibrinolytic disordes, and oxidative stress leading to CVD development and progression. It used to be thought that the effects of aldosterone are mediated via classic nuclear receptors - mineralocorticoid receptors (MR). Now we know that the mechanism of aldosterone action in cardiovascular system is much more complex, since experimental and clinical studies indicate that MR blockade may be not sufficient to abolish aldosterone-incuced harmful effects in the cardiovascular system. Therefore, the involvement of some other than MR, receptors and factors is suggested. Moreover, in addition to the generally known genomic action of aldosterone, which involves MR activation, the nongenomic pathways are postulated in the mode of hormone action. More and more attention is focused on the membrane-coupled receptors, which mediate the rapid effects of aldosterone and have been already confirmed in different cells and tissues of a cardiovascular system. The confirmation of multiple mechanisms of aldosterone action opens a new perspective for more effective therapeutic intervention in aldosterone-related CVD. Copyright© Bentham Science Publishers; For any queries, please email at

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

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


    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.

  17. Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells (United States)

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


    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

  18. NMR Pore Structure and Dynamic Characteristics of Sandstone Caused by Ambient Freeze-Thaw Action

    Directory of Open Access Journals (Sweden)

    Bo Ke


    Full Text Available For a deeper understanding of the freeze-thaw weathering effects on the microstructure evolution and deterioration of dynamic mechanical properties of rock, the present paper conducted the nuclear magnetic resonance (NMR tests and impact loading experiments on sandstone under different freeze-thaw cycles. The results of NMR test show that, with the increase of freeze-thaw cycles, the pores expand and pores size tends to be uniform. The experimental results show that the stress-strain curves all go through four stages, namely, densification, elasticity, yielding, and failure. The densification curve is shorter, and the slope of elasticity curve decreases as the freeze-thaw cycles increase. With increasing freeze-thaw cycles, the dynamic peak stress decreases and energy absorption of sandstone increases. The dynamic failure form is an axial splitting failure, and the fragments increase and the size diminishes with increasing freeze-thaw cycles. The higher the porosity is, the more severe the degradation of dynamic characteristics is. An increase model for the relationships between the porosity or energy absorption and freeze-thaw cycles number was built to reveal the increasing trend with the freeze-thaw cycles increase; meanwhile, a decay model was built to predict the dynamic compressive strength degradation of rock after repeated freeze-thaw cycles.

  19. Real time estimation of generation, extinction and flow of muscle fibre action potentials in high density surface EMG. (United States)

    Mesin, Luca


    Developing a real time method to estimate generation, extinction and propagation of muscle fibre action potentials from bi-dimensional and high density surface electromyogram (EMG). A multi-frame generalization of an optical flow technique including a source term is considered. A model describing generation, extinction and propagation of action potentials is fit to epochs of surface EMG. The algorithm is tested on simulations of high density surface EMG (inter-electrode distance equal to 5mm) from finite length fibres generated using a multi-layer volume conductor model. The flow and source term estimated from interference EMG reflect the anatomy of the muscle, i.e. the direction of the fibres (2° of average estimation error) and the positions of innervation zone and tendons under the electrode grid (mean errors of about 1 and 2mm, respectively). The global conduction velocity of the action potentials from motor units under the detection system is also obtained from the estimated flow. The processing time is about 1 ms per channel for an epoch of EMG of duration 150 ms. A new real time image processing algorithm is proposed to investigate muscle anatomy and activity. Potential applications are proposed in prosthesis control, automatic detection of optimal channels for EMG index extraction and biofeedback. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Feature-Specific Event-Related Potential Effects to Action- and Sound-Related Verbs during Visual Word Recognition. (United States)

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


    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.

  1. Personal contextual characteristics and cognitions: predicting child abuse potential and disciplinary style. (United States)

    Rodriguez, Christina M


    According to Social Information Processing theory, parents' cognitive processes influence their decisions to engage in physical maltreatment, although cognitions occur in the context of other aspects of the parents' life. The present study investigated whether cognitive processes (external locus of control, inappropriate developmental expectations) predicted child abuse potential and overreactive disciplinary style beyond personal contextual factors characteristic of the parent (hostility, stress, and coping). 363 parents were recruited online. Results highlight the relative importance of the contextual characteristics (particularly stress, avoidant coping, and irritability) relative to cognitive processes in predicting abuse potential and overreactive discipline strategies, although an external locus of control also significantly contributed. Findings do not support that parents' developmental expectations uniquely predict elevated abuse risk. Results indicate stressed parents who utilize avoidance coping strategies are more likely to use overreactive discipline and report increased abuse potential. Findings are discussed with regard to implications for prevention/intervention efforts.

  2. The potential for multi-disciplinary primary health care services to take action on the social determinants of health: actions and constraints. (United States)

    Baum, Frances E; Legge, David G; Freeman, Toby; Lawless, Angela; Labonté, Ronald; Jolley, Gwyneth M


    The Commission on the Social Determinants of Health and the World Health Organization have called for action to address the social determinants of health. This paper considers the extent to which primary health care services in Australia are able to respond to this call. We report on interview data from an empirical study of primary health care centres in Adelaide and Alice Springs, Australia. Sixty-eight interviews were held with staff and managers at six case study primary health care services, regional health executives, and departmental funders to explore how their work responded to the social determinants of health and the dilemmas in doing so. The six case study sites included an Aboriginal Community Controlled Organisation, a sexual health non-government organisation, and four services funded and managed by the South Australian government. While respondents varied in the extent to which they exhibited an understanding of social determinants most were reflexive about the constraints on their ability to take action. Services' responses to social determinants included delivering services in a way that takes account of the limitations individuals face from their life circumstances, and physical spaces in the primary health care services being designed to do more than simply deliver services to individuals. The services also undertake advocacy for policies that create healthier communities but note barriers to them doing this work. Our findings suggest that primary health care workers are required to transverse "dilemmatic space" in their work. The absence of systematic supportive policy, frameworks and structure means that it is hard for PHC services to act on the Commission on the Social Determinants of Health's recommendations. Our study does, however, provide evidence of the potential for PHC services to be more responsive to social determinants given more support and by building alliances with communities and social movements. Further research on the value

  3. Microelectrode array measurement of potassium ion channel remodeling on the field action potential duration in rapid atrial pacing rabbits model. (United States)

    Sun, Juan; Yan, Huang; Wugeti, Najina; Guo, Yujun; Zhang, Ling; Ma, Mei; Guo, Xingui; Jiao, Changan; Xu, Wenli; Li, Tianqi


    Atrial fibrillation (AF) arises from abnormalities in atrial structure and electrical activity. Microelectrode arrays (MEA) is a real-time, nondestructive measurement of the resting and action potential signal, from myocardial cells, to the peripheral circuit of electrophysiological activity. This study examined the field action potential duration (fAPD) of the right atrial appendage (RAA) by MEA in rapid atrial pacing (RAP) in the right atrium of rabbits. In addition, this study also investigated the effect of potassium ion channel blockers on fAPD. 40 New Zealand white rabbits of either sex were randomly divided into 3 groups: 1) the control, 2) potassium ion channel blocker (TEA, 4-Ap and BaCl2), and 3) amiodarone groups. The hearts were quickly removed and right atrial appendage sectioned (slice thickness 500 μm). Each slice was perfused with Tyrode's solution and continuously stimulated for 30 minutes. Sections from the control group were superfused with Tyrode's solution for 10 minutes, while the blocker groups and amiodarone were both treated with their respective compounds for 10 minutes each. The fAPD of RAA and action field action potential morphology were measured using MEA. In non-pace (control) groups, fAPD was 188.33 ± 18.29 ms after Tyrode's solution superfusion, and 173.91 ± 6.83 ms after RAP. In pace/potassium ion channel groups, TEA and BaCl2 superfusion prolonged atrial field action potential (fAPD) (control vs blocker: 176.67 ± 8.66 ms vs 196.11 ± 10.76 ms, 182.22 ± 12.87 ms vs 191.11 ± 13.09 ms with TEA and BaCl2 superfusion, respectively, P action potential in animal heart slices. After superfusing potassium ion channel blockers, fAPD was prolonged. These results suggest that Ito, IKur and IK1 remodel and mediate RAP-induced atrial electrical remodeling. Amiodarone alter potassium ion channel activity (Ito, IKur, IK1 and IKs), shortening fAPD.

  4. Diosgenin, 4-hydroxyisoleucine, and fiber from fenugreek: mechanisms of actions and potential effects on metabolic syndrome. (United States)

    Fuller, Scott; Stephens, Jacqueline M


    Metabolic syndrome and its complications continue to rise in prevalence and show no signs of abating in the immediate future. Therefore, the search for effective treatments is a high priority in biomedical research. Products derived from botanicals have a time-honored history of use in the treatment of metabolic diseases including type 2 diabetes. Trigonella foenum-graecum, commonly known as fenugreek, is an annual herbaceous plant that has been a staple of traditional herbal medicine in many cultures. Although fenugreek has been studied in both clinical and basic research settings, questions remain about its efficacy and biologic mechanisms of action. Diosgenin, 4-hydroxyisoleucine, and the fiber component of the plant are the most intensively studied bioactive constituents present in fenugreek. These compounds have been demonstrated to exert beneficial effects on several physiologic markers including glucose tolerance, inflammation, insulin action, liver function, blood lipids, and cardiovascular health. Although insights into the molecular mechanisms underlying the favorable effects of fenugreek have been gained, we still do not have definitive evidence establishing its role as a therapeutic agent in metabolic disease. This review aims to summarize the currently available evidence on the physiologic effects of the 3 best-characterized bioactive compounds of fenugreek, with particular emphasis on biologic mechanisms of action relevant in the context of metabolic syndrome. © 2015 American Society for Nutrition.

  5. A multiscale approach to modelling electrochemical processes occurring across the cell membrane with application to transmission of action potentials. (United States)

    Richardson, G


    By application of matched asymptotic expansions, a simplified partial differential equation (PDE) model for the dynamic electrochemical processes occurring in the vicinity of a membrane, as ions selectively permeate across it, is formally derived from the Poisson-Nernst-Planck equations of electrochemistry. It is demonstrated that this simplified model reduces itself, in the limit of a long thin axon, to the cable equation used by Hodgkin and Huxley to describe the propagation of action potentials in the unmyelinated squid giant axon. The asymptotic reduction from the simplified PDE model to the cable equation leads to insights that are not otherwise apparent; these include an explanation of why the squid giant axon attains a diameter in the region of 1 mm. The simplified PDE model has more general application than the Hodgkin-Huxley cable equation and can, e.g. be used to describe action potential propagation in myelinated axons and neuronal cell bodies.

  6. The study on the characteristic of Shuangqiao fault and the ore-control action of it in Daqiaowu deposit

    International Nuclear Information System (INIS)

    Han Xiaozhong; Hui Xiaochao; Wang Mingtai; Liu Rongrong; Liu Quan; Tang Jiangwei; Jin Miaozhang


    Shuangqiao fault is the most important one to control uranium ore bodies in Daqiaowu district of Quzhou area, Zhejiang province, but there is the obvious argument about the attitude which results in the restriction of the U- prognosis in the area. It aims at finding out the movement and ore-control action of the fault by the study on the characteristic of geometry and kinematics. and combining with geophysics in the depth. The Shuangqiao fault's trend is SE instead of NW by researching, and it has the polygenetic movement. There are two obvious stages of tension about the Shuangqiao fault which tally with the two stages of mineralization in Daqiaowu deposit to show the controlled action to ore bodies by it. By the study in-depth, the Shuangqiao fault can lead the metallogenic hydrothermal, and the secondary faults which connect with it can store the ore bodies. The point that the hanging side of fault can control the ore bodies is put forward by making a synthesis of tectonic assembled form and ore-control factors in Daqiaowu deposit. This view is approved by exploration to provide the reference for disposition of uranium prospecting. (authors)

  7. Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice. (United States)

    Herde, Michel K; Herbison, Allan E


    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.

  8. A simulation of T-wave alternans vectocardiographic representation performed by changing the ventricular heart cells action potential duration. (United States)

    Janusek, D; Kania, M; Zaczek, R; Zavala-Fernandez, H; Maniewski, R


    The presence of T wave alternans (TWA) in the surface ECG signals has been recognized as a marker of electrical instability, and is hypothesized to be related to patients at increased risk for ventricular arrhythmias. In this paper we present a TWA simulation study. The TWA phenomenon was simulated by changing the duration of the ventricular heart cells action potential. The magnitude was calculated in the surface ECG with the use of the time domain method. The spatially concordant TWA, where during one heart beat all ventricular cells display a short-duration action potential and during the next beat they exhibit a long-duration action potential, as well as the discordant TWA, where at least one region is out of phase, was simulated. The vectocardiographic representation was employed. The obtained results showed a high level of T-loop pattern and location disturbances connected to the discordant TWA simulation in contrast to the concordant one. This result may be explained by the spatial heterogeneity of the ventricular repolarization process, which could be higher for the discordant TWA than for the concordant TWA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Coupled iterated map models of action potential dynamics in a one-dimensional cable of cardiac cells

    International Nuclear Information System (INIS)

    Wang Shihong; Xie Yuanfang; Qu Zhilin


    Low-dimensional iterated map models have been widely used to study action potential dynamics in isolated cardiac cells. Coupled iterated map models have also been widely used to investigate action potential propagation dynamics in one-dimensional (1D) coupled cardiac cells, however, these models are usually empirical and not carefully validated. In this study, we first developed two coupled iterated map models which are the standard forms of diffusively coupled maps and overcome the limitations of the previous models. We then determined the coupling strength and space constant by quantitatively comparing the 1D action potential duration profile from the coupled cardiac cell model described by differential equations with that of the coupled iterated map models. To further validate the coupled iterated map models, we compared the stability conditions of the spatially uniform state of the coupled iterated maps and those of the 1D ionic model and showed that the coupled iterated map model could well recapitulate the stability conditions, i.e. the spatially uniform state is stable unless the state is chaotic. Finally, we combined conduction into the developed coupled iterated map model to study the effects of coupling strength on wave stabilities and showed that the diffusive coupling between cardiac cells tends to suppress instabilities during reentry in a 1D ring and the onset of discordant alternans in a periodically paced 1D cable

  10. Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Poulet, Claire; Diness, Jonas Goldin


    (+) currents by ∼15% and prolonged action potential duration (APD), but no effect was observed in myocytes from AF patients. In trabeculae muscle strips from right atrial appendages of SR patients, both compounds increased APD and effective refractory period, and depolarized the resting membrane potential......, while only NS8593 induced these effects in tissue from AF patients. SK channel inhibition did not alter any electrophysiological parameter in human interventricular septum tissue. CONCLUSIONS: SK channels are present in human atria where they participate in repolarization. SK2 and SK3 were down...

  11. Comment on "Penetration of Action Potentials During Collision in the Median and Lateral Giant Axons of Invertebrates" (United States)

    Berg, Rune W.; Stauning, Marius Tving; Sørensen, Jakob Balslev; Jahnsen, Henrik


    The action potential (AP) is an electrical impulse elicited by depolarization of the neuronal membrane from the resting membrane potential (around -70 mV ). It propagates along the axon, allowing for rapid and distant communication. Recently, it was claimed that two APs traveling in opposite direction will pass unhindered through each other (penetrate) upon collision [Gonzalez-Perez et al.Phys. Rev. X 4, 031047 (2014), 10.1103/PhysRevX.4.031047]. We tested this claim under carefully controlled conditions and found that we cannot reproduce penetration. Instead, APs consistently annihilated upon collision. This is consistent with a vast body of literature.

  12. Geothermal Potential Based on Physical Characteristics of the Region (Case Study: Mount Karang, Pandeglang Regency and Banten Province

    Directory of Open Access Journals (Sweden)

    Russel Fhillipo


    Full Text Available This research is about geothermal potential of Mount Karang, Banten Province which is based on the characteristics of the region. This research method used is geochemistry sample of hot springs and integrated with GIS method for spatial of geothermal potential. Based on the geothermal potential, Mount Karang is divided into three regions, ie high potential, normal potential, and low potential. The high geothermal potential region covers an area of 24.16 Km2 and which there are Cisolong and Banjar 2 hot springs. The normal potential covers Kawah hot spring. Index of the fault of Mount Karang region is one of the significant physical characteristics to determine geothermal potential.

  13. Conservation laws of wave action and potential enstrophy for Rossby waves in a stratified atmosphere (United States)

    Straus, D. M.


    The evolution of wave energy, enstrophy, and wave motion for atmospheric Rossby waves in a variable mean flow are discussed from a theoretical and pedagogic standpoint. In the absence of mean flow gradients, the wave energy density satisfies a local conservation law, with the appropriate flow velocity being the group velocity. In the presence of mean flow variations, wave energy is not conserved, but wave action is, provided the mean flow is independent of longitude. Wave enstrophy is conserved for arbitrary variations of the mean flow. Connections with Eliassen-Palm flux are also discussed.

  14. Adaptation decision-making in the Nordic Countries: assessing the potential for joint action

    DEFF Research Database (Denmark)

    Juhola, Sirkku; Goodsite, Michael Evan; Davis, Marion


    on the issue. This paper explores the potential for Nordic cooperation on adaptation; specifically, for the development of a regional adaptation strategy. In particular, it addresses two questions (1) What is the current state of adaptation in the Nordic countries? and (2) What are the potential benefits...

  15. A novel technique for phase synchrony measurement from the complex motor imaginary potential of combined body and limb action (United States)

    Zhou, Zhong-xing; Wan, Bai-kun; Ming, Dong; Qi, Hong-zhi


    In this study, we proposed and evaluated the use of the empirical mode decomposition (EMD) technique combined with phase synchronization analysis to investigate the human brain synchrony of the supplementary motor area (SMA) and primary motor area (M1) during complex motor imagination of combined body and limb action. We separated the EEG data of the SMA and M1 into intrinsic mode functions (IMFs) using the EMD method and determined the characteristic IMFs by power spectral density (PSD) analysis. Thereafter, the instantaneous phases of the characteristic IMFs were obtained by the Hilbert transformation, and the single-trial phase-locking value (PLV) features for brain synchrony measurement between the SMA and M1 were investigated separately. The classification performance suggests that the proposed approach is effective for phase synchronization analysis and is promising for the application of a brain-computer interface in motor nerve reconstruction of the lower limbs.

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

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


    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.

  17. Alternative fuel cycle options: performance characteristics and impact on nuclear power growth potential

    International Nuclear Information System (INIS)

    Chang, Y.I.; Till, C.E.; Rudolph, R.R.; Deen, J.R.; King, M.J.


    The fuel utilization characteristics for LWR, SSCR, CANDU and LMFBR reactor concepts are quantified for various fuel cycle options, including once-through cycles, thorium cycles, and denatured cycles. The implications of various alternative reactor deployment strategies on the long-term nuclear power growth potential are then quantified in terms of the maximum nuclear capacity that can be achieved and the growth pattern over time, subject to the constraint of a fixed uranium-resource base. The overall objective of this study is to shed light on any large differences in the long-term potential that exist between various alternative reactor/fuel cycle deployment strategies

  18. Anaesthetics stop diverse plant organ movements, affect endocytic vesicle recycling and ROS homeostasis, and block action potentials in Venus flytraps. (United States)

    Yokawa, K; Kagenishi, T; Pavlovic, A; Gall, S; Weiland, M; Mancuso, S; Baluška, F


    Anaesthesia for medical purposes was introduced in the 19th century. However, the physiological mode of anaesthetic drug actions on the nervous system remains unclear. One of the remaining questions is how these different compounds, with no structural similarities and even chemically inert elements such as the noble gas xenon, act as anaesthetic agents inducing loss of consciousness. The main goal here was to determine if anaesthetics affect the same or similar processes in plants as in animals and humans. A single-lens reflex camera was used to follow organ movements in plants before, during and after recovery from exposure to diverse anaesthetics. Confocal microscopy was used to analyse endocytic vesicle trafficking. Electrical signals were recorded using a surface AgCl electrode. Mimosa leaves, pea tendrils, Venus flytraps and sundew traps all lost both their autonomous and touch-induced movements after exposure to anaesthetics. In Venus flytrap, this was shown to be due to the loss of action potentials under diethyl ether anaesthesia. The same concentration of diethyl ether immobilized pea tendrils. Anaesthetics also impeded seed germination and chlorophyll accumulation in cress seedlings. Endocytic vesicle recycling and reactive oxygen species (ROS) balance, as observed in intact Arabidopsis root apex cells, were also affected by all anaesthetics tested. Plants are sensitive to several anaesthetics that have no structural similarities. As in animals and humans, anaesthetics used at appropriate concentrations block action potentials and immobilize organs via effects on action potentials, endocytic vesicle recycling and ROS homeostasis. Plants emerge as ideal model objects to study general questions related to anaesthesia, as well as to serve as a suitable test system for human anaesthesia. © The Authors 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail:

  19. Influence of unharmonic changes of plasma potential on the Langmuir probe characteristics for a grounded probe

    International Nuclear Information System (INIS)

    Surda, V.


    A theory is presented of the deformation of Langmuir probe characteristics by the presence of a.c. plasma potential oscillations at the space charge layer around the probe, making allowance for the fundamental frequency and the second harmonic. It is applicable particularly to the determination of the electron temperature in actual high-frequency discharges with a Maxwellian electron energy distribution. The effect of an a.c. signal on the ion current is also treated. (author). 8 figs., 14 refs

  20. Biphasic response of action potential duration to metabolic inhibition in rabbit and human ventricular myocytes: role of transient outward current and ATP-regulated potassium current

    NARCIS (Netherlands)

    Verkerk, A. O.; Veldkamp, M. W.; van Ginneken, A. C.; Bouman, L. N.


    Inhibition of cell metabolism is associated with significant changes in action potential duration. The aim of this study was to investigate the time course of the changes in action potential duration during metabolic inhibition and to determine what changes in membrane currents are responsible. The

  1. Matrix metalloproteinase-13 downregulation and potential cartilage protective action of the Korean Red Ginseng preparation

    Directory of Open Access Journals (Sweden)

    Je Hyeong Lee


    Conclusion: Some preparations from Korean Red Ginseng and ginseng leaves, particularly GDF/F4, may possess the protective activity against cartilage degradation in joint disorders, and may have potential as new therapeutic agents.

  2. IARC use of oxidative stress as key mode of action characteristic for facilitating cancer classification: Glyphosate case example illustrating a lack of robustness in interpretative implementation. (United States)

    Bus, James S


    The International Agency for Research on Cancer (IARC) has formulated 10 key characteristics of human carcinogens to incorporate mechanistic data into cancer hazard classifications. The analysis used glyphosate as a case example to examine the robustness of IARC's determination of oxidative stress as "strong" evidence supporting a plausible cancer mechanism in humans. The IARC analysis primarily relied on 14 human/mammalian studies; 19 non-mammalian studies were uninformative of human cancer given the broad spectrum of test species and extensive use of formulations and aquatic testing. The mammalian studies had substantial experimental limitations for informing cancer mechanism including use of: single doses and time points; cytotoxic/toxic test doses; tissues not identified as potential cancer targets; glyphosate formulations or mixtures; technically limited oxidative stress biomarkers. The doses were many orders of magnitude higher than human exposures determined in human biomonitoring studies. The glyphosate case example reveals that the IARC evaluation fell substantially short of "strong" supporting evidence of oxidative stress as a plausible human cancer mechanism, and suggests that other IARC monographs relying on the 10 key characteristics approach should be similarly examined for a lack of robust data integration fundamental to reasonable mode of action evaluations. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Terazima, E; Yoshino, M


    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.

  4. Assessing potential targets of calcium action in light-modulated gravitropism (United States)

    Roux, S. J.


    Light, through the mediation of the pigment phytochrome, modulates the gravitropic response of the shoots and roots of many plants. The transduction of both light and gravity stimuli appears to involve Ca(2+)-regulated steps, one or more of which may represent points of intersection between the two transduction chains. To be confident that Ca2+ plays a critical role in stimulus-response coupling for gravitropism, it will be important to identify specific targets of Ca2+ action whose function can be clearly linked to the regulation of growth. Calcium typically exerts its influence on cell metabolism through binding to and activating key regulatory proteins. The three best characterized of these proteins in plants are the calmodulins, calcium-dependent protein kinases, and annexins. In this review we summarize what is known about the structure and function of these proteins and speculate on how their activation by Ca2+ could influence the differential growth response of gravitropism.

  5. Methodological considerations for characterizing potential antioxidant actions of bioactive components in plant foods. (United States)

    Aruoma, Okezie I


    The study of free radicals and antioxidants in biology is producing medical revolution that promises a new age of health and disease management. From prevention of the oxidative reactions in foods, pharmaceuticals and cosmetics to the role of reactive oxygen species (ROS) in chronic degenerative diseases including cancer, autoimmune, inflammatory, cardiovascular and neurodegenerative (e.g. Alzheimer's disease, Parkinson's disease, multiple sclerosis, Downs syndrome) and aging challenges continue to emerge from difficulties associated with methods used in evaluating antioxidant actions in vivo. Our interest presently is focused on development of neurodegeneration models based on the integrity of neuronal cells in the central nervous system and how they are protected by antioxidants when challenged by neurotoxins as well as Fenton chemistry models based on the profile of polyunsaturated fatty acids (PUFAs) for the assessment of antioxidant actions in vivo. Use continues to be made of several in vitro analytical tools to characterise the antioxidant propensity of bioactive compounds in plant foods and supplements. For example, the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), total oxidant scavenging capacity (TOSC), the deoxyribose assay, assays involving oxidative DNA damage, assays involving reactive nitrogen intermediates (e.g. ONOO(-)), Trolox equivalent antioxidant capacity (TEAC) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. There is need to agree governance on in vitro antioxidant methods based on an understanding of the mechanisms involved. Because some of the assays are done in non-physiological pH values, it is impossible to extrapolate the results to physiological environment. The consensus of opinion is that a mix of these tools should be used in assessing the antioxidant activities in vitro. The proof of bio-efficacy must emanate from application of reliable in vivo models where markers of baseline oxidative

  6. HMGB1 Inhibition During Zymosan-Induced Inflammation: The Potential Therapeutic Action of Riboflavin. (United States)

    Mazur-Bialy, Agnieszka Irena; Pocheć, Ewa


    Sepsis, also known as systemic inflammatory response syndrome, is a life-threatening condition caused by a pathogenic agent and leading to multiple organ dysfunction syndrome. One of the factors responsible for the excessive intensification of the inflammatory response in the course of inflammation is high-mobility group protein B1 (HMGB1). HMG-1 is a nuclear protein which, after being released to the intercellular space, has a highly pro-inflammatory effect and acts as a late mediator of lethal damage. The purpose of this study was to examine whether the anti-inflammatory action of riboflavin is accompanied by inhibition of HMGB1 release during peritoneal inflammation and zymosan stimulation of macrophages. Peritonitis was induced in male BALB/c and C57BL/6J mice via intraperitoneal injection of zymosan (40 mg/kg). RAW 264.7 macrophages were activated with zymosan (250 µg/ml). Riboflavin (mice, 50 mg/kg; RAW 264.7, 25 µg/ml) was administered 30 min before zymosan, simultaneously with, or 2, 4, 6 h after zymosan. Additionally, mRNA expression of HMGB1 and its intracellular and serum levels were evaluated. The research showed that riboflavin significantly reduces both the expression and the release of HMGB1; however, the effect of riboflavin was time-dependent. The greatest efficacy was found when riboflavin was given 30 min prior to zymosan, and also 2 and 4 h (C57BL/6J; RAW 264.7) or 4 and 6 h (BALB/c) after zymosan. Research showed that riboflavin influences the level of HMGB1 released in the course of inflammation; however, further study is necessary to determine its mechanisms of action.

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

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


    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.

  8. Potential Molecular Mechanisms on the Role of the Sigma-1 Receptor in the Action of Cocaine and Methamphetamine (United States)

    Yasui, Yuko; Su, Tsung-Ping


    The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum membrane protein that involves a wide range of physiological functions. The Sig-1R has been shown to bind psychostimulants including cocaine and methamphetamine (METH) and thus has been implicated in the actions of those psychostimulants. For example, it has been demonstrated that the Sig-1R antagonists mitigate certain behavioral and cellular effects of psychostimulants including hyperactivity and neurotoxicity. Thus, the Sig-1R has become a potential therapeutic target of medication development against drug abuse that differs from traditional monoamine-related strategies. In this review, we will focus on the molecular mechanisms of the Sig-1R and discuss in such a manner with a hope to further understand or unveil unexplored relations between the Sig-1R and the actions of cocaine and METH, particularly in the context of cellular biological relevance. PMID:27088037

  9. NS5806 partially restores action potential duration but fails to ameliorate calcium transient dysfunction in a computational model of canine heart failure

    DEFF Research Database (Denmark)

    Maleckar, Mary M; Lines, Glenn T; Koivumäki, Jussi T


    AIMS: The study investigates how increased Ito, as mediated by the activator NS5806, affects excitation-contraction coupling in chronic heart failure (HF). We hypothesized that restoring spike-and-dome morphology of the action potential (AP) to a healthy phenotype would be insufficient to restore...... the intracellular Ca(2) (+) transient (CaT), due to HF-induced remodelling of Ca(2+) handling. METHODS AND RESULTS: An existing mathematical model of the canine ventricular myocyte was modified to incorporate recent experimental data from healthy and failing myocytes, resulting in models of both healthy and HF...... ionic processes with a focus on calcium transients (CaT), how these were altered in HF across the ventricular wall, and the subsequent effects of varying compound concentration in HF. Heart failure model variants recapitulated a characteristic increase in AP duration (APD) in the disease...

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

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


    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.

  11. Characteristics of Ampel bamboo as a biomass energy source potential in Bali (United States)

    Sucipta, M.; Putra Negara, D. N. K.; Tirta Nindhia, T. G.; Surata, I. W.


    Currently, non-renewable fossil energy dominates utilization of the world energy need for many applications. Efforts has been developed to find alternative renewable energy sources, due to fossil energy availability is diminishing. And one of renewable energy source is from biomass. The aim of this research is to determine characteristics of the Ampel bamboo (Bambusa vulgaris) as an energy potential of biomass. The Ampel bamboo’s characteristics possessed are evaluated based on its chemical composition; moisture, volatile, ash, and fixed carbon through proximate analysis; and also carbon, hydrogen and nitrogen content through ultimate analysis. From the Thermo-gravimetric analysis (TGA) indicates that Ampel bamboo contains of about 18.10% hemicelluloses, 47.75% cellulose and 18.86% lignin. While from the ultimate analysis results in the content of carbon, hydrogen, and Nitrogen of Ampel bamboo are 39.75%, 5.75% and 0% respectively. With such characteristics, it indicates that Ampel bamboo has an attractive potential as a renewable energy source.

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

    Czech Academy of Sciences Publication Activity Database

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


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

  13. Virtual Burglary: Exploring the Potential of Virtual Reality to Study Burglary in Action

    NARCIS (Netherlands)

    van Sintemaartensdijk, I.; van Prooijen, J-W.; van Gelder, J-L.; Otte, M.; Nee, Claire; Demetriou, Andrew


    Objectives: This article explores the potential of virtual reality (VR) to study burglary by measuring user responses on the subjective, physiological, and behavioral levels. Furthermore, it examines the influence of individual dispositions, such as sensation seeking and self-control, on behavior

  14. Influence of High Hydrostatic Pressure Technology on Wine Chemical and Sensorial Characteristics: Potentialities and Drawbacks. (United States)

    Nunes, Cláudia; Santos, Mickael C; Saraiva, Jorge A; Rocha, Sílvia M; Coimbra, Manuel A

    During last years, scientific research on high hydrostatic pressure (HHP) as a nonthermal processing technology for preservation or aging of wine has increased substantially. HHP between 200 and 500MPa is able to inactivate bacteria and yeasts in red and white wines, suggesting that it may be used for wine preservation. However, these treatments have been shown to promote changes on sensorial and physicochemical characteristics in both red and white wines, not immediately in the first month, but along storage. The changes are observed in wine color, aroma, and taste due mainly to reactions of phenolic compounds, sugars, and proteins. These reactions have been associated with those observed during wine aging, leading to aged-like wine characteristics perceived by sensorial analysis. This chapter will present the influence of HHP technology on wine chemical and sensorial characteristics, criticaly discussing its potentialities and drawbacks. The appropriate use of HHP, based on the scientific knowledge of the reactions occuring in wine promoted by HHP, will allow to exploit this technology for wine production achieving distinct characteristics to address particular market and consumer demands. © 2017 Elsevier Inc. All rights reserved.

  15. Monoamine Oxidase-A Inhibition and Associated Antioxidant Activity in Plant Extracts with Potential Antidepressant Actions

    Directory of Open Access Journals (Sweden)

    Tomás Herraiz


    Full Text Available Monoamine oxidase (MAO catalyzes the oxidative deamination of amines and neurotransmitters and is involved in mood disorders, depression, oxidative stress, and adverse pharmacological reactions. This work studies the inhibition of human MAO-A by Hypericum perforatum, Peganum harmala, and Lepidium meyenii, which are reported to improve and affect mood and mental conditions. Subsequently, the antioxidant activity associated with the inhibition of MAO is determined in plant extracts for the first time. H. perforatum inhibited human MAO-A, and extracts from flowers gave the highest inhibition (IC50 of 63.6 μg/mL. Plant extracts were analyzed by HPLC-DAD-MS and contained pseudohypericin, hypericin, hyperforin, adhyperforin, hyperfirin, and flavonoids. Hyperforin did not inhibit human MAO-A and hypericin was a poor inhibitor of this isoenzyme. Quercetin and flavonoids significantly contributed to MAO-A inhibition. P. harmala seed extracts highly inhibited MAO-A (IC50 of 49.9 μg/L, being a thousand times more potent than H. perforatum extracts owing to its content of β-carboline alkaloids (harmaline and harmine. L. meyenii root (maca extracts did not inhibit MAO-A. These plants may exert protective actions related to antioxidant effects. Results in this work show that P. harmala and H. perforatum extracts exhibit antioxidant activity associated with the inhibition of MAO (i.e., lower production of H2O2.

  16. Potential Mechanism of Action of meso-Dihydroguaiaretic Acid on Mycobacterium tuberculosis H37Rv

    Directory of Open Access Journals (Sweden)

    Aldo F. Clemente-Soto


    Full Text Available The isolation and characterization of the lignan meso-dihydroguaiaretic acid (MDGA from Larrea tridentata and its activity against Mycobacterial tuberculosis has been demonstrated, but no information regarding its mechanism of action has been documented. Therefore, in this study we carry out the gene expression from total RNA obtained from M. tuberculosis H37Rv treated with MDGA using microarray technology, which was validated by quantitative real time polymerase chain reaction. Results showed that the alpha subunit of coenzyme A transferase of M. tuberculosis H37Rv is present in both geraniol and 1-and 2-methylnaphthalene degradation pathways, which are targeted by MDGA. This assumption was supported by molecular docking which showed stable interaction between MDGA with the active site of the enzyme. We propose that inhibition of coenzyme A transferase of M. tuberculosis H37Rv results in the accumulation of geraniol and 1-and 2-methylnaphtalene inside bacteria, causing membrane destabilization and death of the pathogen. The natural product MDGA is thus an attractive template to develop new anti-tuberculosis drugs, because its target is different from those of known anti-tubercular agents.

  17. Barriers, facilitators, and potential strategies for increasing HPV vaccination: A statewide assessment to inform action

    Directory of Open Access Journals (Sweden)

    Kathleen B. Cartmell


    Full Text Available Objective: The objective was to investigate how state level strategies in South Carolina could maximize HPV vaccine uptake. Design: An environmental scan identified barriers, facilitators, and strategies for improving HPV vaccination in South Carolina. Interviews were conducted with state leaders from relevant organizations such as public health agencies, medical associations, K-12 schools, universities, insurers, and cancer advocacy organizations. A thematic content analysis design was used. Digital interview files were transcribed, a data dictionary was created and data were coded using the data dictionary. Results: Thirty four interviews were conducted with state leaders. Barriers to HPV vaccination included lack of HPV awareness, lack of provider recommendation, HPV vaccine concerns, lack of access and practice-level barriers. Facilitators included momentum for improving HPV vaccination, school-entry Tdap requirement, pharmacy-based HPV vaccination, state immunization registry, HEDIS measures and HPV vaccine funding. Strategies for improving HPV vaccination fell into three categories: 1 addressing lack of awareness about the importance of HPV vaccination among the public and providers; 2 advocating for policy changes around HPV vaccine coverage, vaccine education, and pharmacy-based vaccination; and 3 coordination of efforts. Discussion: A statewide environmental scan generated a blueprint for action to be used to improve HPV vaccination in the state. Keywords: HPV, HPV vaccines, Cervical cancer, Prevention, Health systems, Barriers, Facilitators, Strategies, South Carolina

  18. Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro. (United States)

    Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C; Mennerick, Steven


    Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (-astrocyte) within the same culture dish. -Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform and arrival time of axonal

  19. Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts (United States)

    Markes, Alexander R.; Okundaye, Amenawon O.; Qu, Zhilin; Mende, Ulrike; Choi, Bum-Rak


    Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs) and/or cardiac fibroblasts (CFs) and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair. PMID:29715271

  20. Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts.

    Directory of Open Access Journals (Sweden)

    Tae Yun Kim

    Full Text Available Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs and/or cardiac fibroblasts (CFs and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair.


    Directory of Open Access Journals (Sweden)

    Haryono Setiyo Huboyo


    Full Text Available Two rural communities using fuel wood energy in mountainous and coastal areas of Java island in Indonesia have been surveyed to know their household characteristics and the related potential indoor air pollution issues. By random sampling, we characterized fuel wood users only. The fuel wood use was mainly due to economic reason since some of the users were categorized as low-income families. Communities in the mountainous area were exposed to higher risk of indoor air pollution than those in coastal area due to their house characteristics and behavior during cooking. Both communities, however, were aware of indoor air pollution issues and indicated the sources. They also prioritized the factors to be controlled, which they perceived as the main cause of indoor air pollution problem.

  2. A code to compute the action-angle transformation for a particle in an abritrary potential well

    International Nuclear Information System (INIS)

    Berg, J.S.; Warnock, R.L.


    For a Vlasov treatment of longitudinal stability under an arbitrary wake field, with the solution of the Haiessinski equation as the unperturbed distribution, it is important to have the action-angle transformation for the distorted potential well in a convenient form. The authors have written a code that gives the transformation q,p → J, φ, with q(J,φ) as a Fourier series in φ, the Fourier coefficients and the Hamiltonian H(J) being spline functions of J in C 2 (having continuous second derivatives)

  3. Overexpression of the Large-Conductance, Ca2+-Activated K+ (BK) Channel Shortens Action Potential Duration in HL-1 Cardiomyocytes. (United States)

    Stimers, Joseph R; Song, Li; Rusch, Nancy J; Rhee, Sung W


    Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line. Expression of hBKα had minimal effects on expression levels of other ion channels with the exception of a small but significant reduction in Kv11.1. Patch-clamped hBKα expressing HL-1 cells exhibited an outward voltage- and Ca2+-sensitive K+ current, which was inhibited by the BK channel blocker iberiotoxin (100 nM). This BK current phenotype was not detected in untransfected HL-1 cells or in HL-1 null cells sham-transfected with an empty vector. Importantly, APD in hBKα-expressing HL-1 cells averaged 14.3 ± 2.8 ms (n = 10), which represented a 53% reduction in APD compared to HL-1 null cells lacking BKα expression. APD in the latter cells averaged 31.0 ± 5.1 ms (n = 13). The shortened APD in hBKα-expressing cells was restored to normal duration by 100 nM iberiotoxin, suggesting that a repolarizing K+ current attributed to BK channels accounted for action potential shortening. These findings provide initial proof-of-concept that the introduction of hBKα channels into a cardiac cell line can shorten APD, and raise the possibility that gene-based interventions to increase hBKα channels in cardiac cells may hold promise as a therapeutic strategy for long QT syndrome.

  4. Whey protein potentiates the intestinotrophic action of glucagon-like peptide-2 in parenterally fed rats

    DEFF Research Database (Denmark)

    Liu, Xiaowen; Murali, Sangita G; Holst, Jens J


    protein component, casein, soy, or whey protein, potentiates the intestinal growth response to GLP-2 in rats with PN-induced mucosal hypoplasia. Rats received PN and continuous intravenous infusion of GLP-2 (100 microg/kg/day) for 7 days. Six EN groups received PN+GLP-2 for days 1-3 and partial PN+GLP-2...... plus EN for days 4-7. EN was provided by ad libitum intake of a semielemental liquid diet with different protein sources: casein, hydrolyzed soy, whey protein concentrate (WPC), and hydrolyzed WPC+casein. Controls received PN+GLP-2 alone. EN induced significantly greater jejunal sucrase activity...... whey protein, and not casein or soy, potentiated the ability of GLP-2 to reverse PN-induced mucosal hypoplasia and further increase ileal villus height, crypt depth, and mucosa cellularity compared with PN+GLP-2 alone, P whey protein to induce greater mucosal surface area...

  5. Navy Ship Maintenance: Action Needed to Maximize New Contracting Strategys Potential Benefits (United States)


    implementation of the new strategy, the Navy conducted market research and pilot-tested attributes of the strategy with pilot maintenance periods for a...readiness strategy and, in 2015, introduction of a new contracting strategy for ship repair, referred to as MAC-MO. House Report 114-102 accompanying the...Maintenance Letter 1 Background 3 Market Research and Piloting Helped Inform Roll-out of MAC-MO Strategy, Which Offers Potential Benefits

  6. 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


    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.

  7. The potential role of cotinine in the cognitive and neuroprotective actions of nicotine. (United States)

    Buccafusco, Jerry J; Terry, Alvin V


    Cotinine is a primary metabolite of nicotine that has been suggested in many studies in animals and in humans to exert measurable effects on aspects of on-going behavior or on cognitive function. Much of the interest in cotinine derives from its long pharmacological half-life (15-19 hours) relative to nicotine (2-3 hours). Despite decades of study focusing on nicotine as the predominant behaviorally active component of tobacco, there continue to be aspects of the pharmacology of the drug that have yet to be explained. For example, nicotine can evoke a protracted behavioral response, i.e., in great excess of the presence of the drug in the plasma. Also, there is often a striking differential between the potency for nicotine-induced behavioral responses in humans and animals, and its potency as a cholinergic agonist, neurochemically. One possibility that may explain one or more of these properties of nicotine is the presence of a long-lived bioactive metabolite or breakdown product of nicotine such as cotinine. Preliminary data in support of this hypothesis are consistent with the ability of cotinine to improve performance accuracy on delayed matching task by macaque monkeys, and in reversing apomorphine-induced deficits in prepulse inhibition of acoustic startle in rats. The drug also was shown to be as potent as nicotine in the ability to act as a cytoprotective agent in cells that express a neuronal cholinergic phenotype. This new appreciation for the role of cotinine in nicotine's actions, and as a pharmacological agent in its own right, particularly in aspects of cognitive function and for neuroprotection, ultimately may be applied towards the treatment of Alzheimer's disease and related disorders, and for various psychiatric syndromes.

  8. Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish. (United States)

    Opler, Lewis A; Opler, Mark G A; Arnsten, Amy F T


    This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia.


    Opler, Lewis A.; Opler, Mark G.; Arnsten, Amy F.T.


    This paper reviews the anti-depressant actions of the N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, ketamine, and offers a potential neural mechanism for intranasal ketamine’s ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5–40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (e.g. Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia. PMID:25619798

  10. Review article: potential mechanisms of action of rifaximin in the management of irritable bowel syndrome with diarrhoea. (United States)

    Pimentel, M


    The role of gut microbiota in the pathophysiology of irritable bowel syndrome (IBS) is supported by various lines of evidence, including differences in mucosal and faecal microbiota between patients with IBS and healthy individuals, development of post-infectious IBS, and the efficacy of some probiotics and nonsystemic antibiotics (e.g. rifaximin). To review the literature regarding the role of rifaximin in IBS and its potential mechanism(s) of action. A literature search was conducted using the terms 'rifaximin', 'irritable bowel syndrome' and 'mechanism of action'. Rifaximin was approved in 2015 for the treatment of IBS with diarrhoea. In contrast to other currently available IBS therapies that require daily administration to maintain efficacy, 2-week rifaximin treatment achieved symptom improvement that persisted ≥12 weeks post-treatment. The mechanisms of action of rifaximin, therefore, may extend beyond direct bactericidal effects. Data suggest that rifaximin may decrease host proinflammatory responses to bacterial products in patients with IBS. In some cases, small intestinal bacterial overgrowth (SIBO) may play a role in the clinical symptoms of IBS. Because of the high level of solubility of rifaximin in the small intestine, rifaximin may reset microbial diversity in this environment. Consistent with this hypothesis, rifaximin has antibiotic efficacy against isolates derived from patients with SIBO. Resetting microbial diversity via rifaximin use may lead to a decrease in bacterial fermentation and a reduction in the clinical symptoms of IBS. © 2015 John Wiley & Sons Ltd.

  11. The Characteristics of Fluid Potential in Mud Diapirs Associated with Gas Hydrates in the Okinawa Trough

    Directory of Open Access Journals (Sweden)

    Ning Xu


    Full Text Available Many mud diapirs have been identified in the southern Okinawa Trough from a seismic survey using R/V KEXUE I in 2001. The movement and accumulation of free gas related to mud diapirs are discussed in detail by an analysis of fluid potential which is based upon velocity data. It can be found that free gas moves from the higher fluid potential strata to the lower ones and the gas hydrate comes into being during free gas movement meeting the proper criteria of temperature and pressure. In fact, gas hydrates have been found in the upper layers above the mud diapirs and in host rocks exhibiting other geophysical characteristics. As the result of the formation of the gas hydrate, the free gas bearing strata are enclosed by the gas hydrate bearing strata. Due to the high pressure anomalies of the free gas bearing strata the fluid potential increases noticeably. It can then be concluded that the high fluid potential anomaly on the low fluid potential background may be caused by the presence of the free gas below the gas hydrate bearing strata.

  12. In situ vitrification - A potential remedial action technique for hazardous wastes

    International Nuclear Information System (INIS)

    Fitzpatrick, V.F.; Buelt, J.L.; Oma, K.H.; Timmerman, C.L.


    In situ vitrification (ISV) is an innovative technology being developed as a potential method for stabilizing transuranic (TRU) contaminated wastes in place. Although the process is being developed for TRU contaminated wastes, it is envisioned that the process could also be applied to hazardous chemical wastes. In situ vitrification (ISV) is the conversion of contaminated soil into a durable glass and crystalline wastes form through melting by joule heating. The technology for in situ vitrification is based upon electric melter technology developed at the Pacific Northwest Laboratory (PNL) for the immobilization of high-level nuclear waste. In situ vitrification was initially tested by researchers at PNL in August, 1980 (U.S. Patent 4,376,598). Since then, ISV has grown from a concept to an emerging technology through a series of 21 engineering-scale (laboratory) tests and 7 pilot-scale (field) tests. A large-scale system is currently being fabricated for testing. The program has been sponsored by the U.S. Department of Energy's (DOE) Richland Operations Office for potential application to Hanford TRU contaminated soil sites. A more detailed description outlining the power system design and the off-gas treatment system follows

  13. Methods for the numerical calculation of the plasma potential from measured Langmuir probe characteristics

    International Nuclear Information System (INIS)

    Seifert, W.; Johanning, D.; Bankov, N.


    In a previous paper the results of the Langmuir probe experiment carried out on board of two INTERKOSMOS satellites have been described. The experiences have shown that the usage of high quality algorithms for analyzing the current-voltage-characteristics is necessary to yield real physical parameters. The key problem is the determination of the plasma potential. This paper reviews the different methods to determine the plasma potential especially under the circumstances of computer application. The test of the well developed methods shows, that for the evaluation of the applied methods a number of different factors, discussed in the following sections of this paper, has to be taken into account. The used test data are model values or real measurements obtained by the satellite missions IK-10, IK-18 and BULGARIA-1300. The computer procedures have been realized as FORTRAN-subroutines for the BESM 6 and ES 1040. (author)

  14. An evaluation of the utility and limitations of counting motor unit action potentials in the surface electromyogram (United States)

    Zhou, Ping; Zev Rymer, William


    The number of motor unit action potentials (MUAPs) appearing in the surface electromyogram (EMG) signal is directly related to motor unit recruitment and firing rates and therefore offers potentially valuable information about the level of activation of the motoneuron pool. In this paper, based on morphological features of the surface MUAPs, we try to estimate the number of MUAPs present in the surface EMG by counting the negative peaks in the signal. Several signal processing procedures are applied to the surface EMG to facilitate this peak counting process. The MUAP number estimation performance by this approach is first illustrated using the surface EMG simulations. Then, by evaluating the peak counting results from the EMG records detected by a very selective surface electrode, at different contraction levels of the first dorsal interosseous (FDI) muscles, the utility and limitations of such direct peak counts for MUAP number estimation in surface EMG are further explored.

  15. Intraoperative observation of changes in cochlear nerve action potentials during exposure to electromagnetic fields generated by mobile phones. (United States)

    Colletti, Vittorio; Mandalà, Marco; Manganotti, Paolo; Ramat, Stefano; Sacchetto, Luca; Colletti, Liliana


    The rapid spread of devices generating electromagnetic fields (EMF) has raised concerns as to the possible effects of this technology on humans. The auditory system is the neural organ most frequently and directly exposed to electromagnetic activity owing to the daily use of mobile phones. In recent publications, a possible correlation between mobile phone usage and central nervous system tumours has been detected. Very recently a deterioration in otoacoustic emissions and in the auditory middle latency responses after intensive and long-term magnetic field exposure in humans has been demonstrated. To determine with objective observations if exposure to mobile phone EMF affects acoustically evoked cochlear nerve compound action potentials, seven patients suffering from Ménière's disease and undergoing retrosigmoid vestibular neurectomy were exposed to the effects of mobile phone placed over the craniotomy for 5 min. All patients showed a substantial decrease in amplitude and a significant increase in latency of cochlear nerve compound action potentials during the 5 min of exposure to EMF. These changes lasted for a period of around 5 min after exposure. The possibility that EMF can produce relatively long-lasting effects on cochlear nerve conduction is discussed and analysed in light of contrasting previous literature obtained under non-surgical conditions. Limitations of this novel approach, including the effects of the anaesthetics, craniotomy and surgical procedure, are presented in detail.

  16. Sensitivity of Rabbit Ventricular Action Potential and Ca2+ Dynamics to Small Variations in Membrane Currents and Ion Diffusion Coefficients

    Directory of Open Access Journals (Sweden)

    Yuan Hung Lo


    Full Text Available Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004 to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl− background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl−-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling.

  17. Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current. (United States)

    Liu, Pin W; Blair, Nathaniel T; Bean, Bruce P


    Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC 50 action potentials of small-diameter rat DRG neurons showed spike broadening at frequencies as low as 1 Hz and that spike broadening resulted predominantly from frequency-dependent inactivation of Kv3 channels. Spike width helps to control transmitter release, conduction velocity, and firing patterns and understanding the role of particular potassium channels can help to guide new pharmacological strategies for targeting pain-sensing neurons selectively. Copyright © 2017 the authors 0270-6474/17/379705-10$15.00/0.

  18. Period doubling cascades of limit cycles in cardiac action potential models as precursors to chaotic early Afterdepolarizations. (United States)

    Kügler, Philipp; Bulelzai, M A K; Erhardt, André H


    Early afterdepolarizations (EADs) are pathological voltage oscillations during the repolarization phase of cardiac action potentials (APs). EADs are caused by drugs, oxidative stress or ion channel disease, and they are considered as potential precursors to cardiac arrhythmias in recent attempts to redefine the cardiac drug safety paradigm. The irregular behaviour of EADs observed in experiments has been previously attributed to chaotic EAD dynamics under periodic pacing, made possible by a homoclinic bifurcation in the fast subsystem of the deterministic AP system of differential equations. In this article we demonstrate that a homoclinic bifurcation in the fast subsystem of the action potential model is neither a necessary nor a sufficient condition for the genesis of chaotic EADs. We rather argue that a cascade of period doubling (PD) bifurcations of limit cycles in the full AP system paves the way to chaotic EAD dynamics across a variety of models including a) periodically paced and spontaneously active cardiomyocytes, b) periodically paced and non-active cardiomyocytes as well as c) unpaced and spontaneously active cardiomyocytes. Furthermore, our bifurcation analysis reveals that chaotic EAD dynamics may coexist in a stable manner with fully regular AP dynamics, where only the initial conditions decide which type of dynamics is displayed. EADs are a potential source of cardiac arrhythmias and hence are of relevance both from the viewpoint of drug cardiotoxicity testing and the treatment of cardiomyopathies. The model-independent association of chaotic EADs with period doubling cascades of limit cycles introduced in this article opens novel opportunities to study chaotic EADs by means of bifurcation control theory and inverse bifurcation analysis. Furthermore, our results may shed new light on the synchronization and propagation of chaotic EADs in homogeneous and heterogeneous multicellular and cardiac tissue preparations.

  19. Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Cadavid, Diego; Steiner, Deborah


    progressive MS (SPMS), for which approved disease-modifying therapies are limited. In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS......Multiple sclerosis (MS) is a common and chronic central nervous system (CNS) demyelinating disease and a leading cause of permanent disability. Patients most often present with a relapsing-remitting disease course, typically progressing over time to a phase of relentless advancement in secondary......, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. In both forms of MS, active brain-tissue injury is associated with inflammation; but in SPMS, the inflammatory response occurs at least partly behind the blood-brain barrier and is followed by a cascade of events...

  20. Potential food applications of biobased materials. An EU- concerted action project

    DEFF Research Database (Denmark)

    Haugaard, V.K.; Udsen, A.M.; Mortensen, G.


    and coatings to food but novel commercial applications of these are scarce. Based on information currently available on the properties of biobased packaging materials the study identified products in the fresh meat, dairy, ready meal, beverage, fruit and vegetable, snack, frozen food and dry food categories......The objective of the study was to ascertain the state of the art with regard to the applicability of biobased packaging materials to foods and to identify potential food applications for biobased materials. The study revealed relatively few examples of biobased materials used as primary, secondary...... or tertiary packaging materials for foods. This is due to the fact that published investigations on the use of biobased materials are still scarce, and results obtained remain unpublished because of commercial pressures. The scientific literature contains numerous reports on applications of edible films...

  1. Analyzing the greenhouse gas impact potential of smallholder development actions across a global food security program (United States)

    Grewer, Uwe; Nash, Julie; Gurwick, Noel; Bockel, Louis; Galford, Gillian; Richards, Meryl; Costa Junior, Ciniro; White, Julianna; Pirolli, Gillian; Wollenberg, Eva


    This article analyses the greenhouse gas (GHG) impact potential of improved management practices and technologies for smallholder agriculture promoted under a global food security development program. Under ‘business-as-usual’ development, global studies on the future of agriculture to 2050 project considerable increases in total food production and cultivated area. Conventional cropland intensification and conversion of natural vegetation typically result in increased GHG emissions and loss of carbon stocks. There is a strong need to understand the potential greenhouse gas impacts of agricultural development programs intended to achieve large-scale change, and to identify pathways of smallholder agricultural development that can achieve food security and agricultural production growth without drastic increases in GHG emissions. In an analysis of 134 crop and livestock production systems in 15 countries with reported impacts on 4.8 million ha, improved management practices and technologies by smallholder farmers significantly reduce GHG emission intensity of agricultural production, increase yields and reduce post-harvest losses, while either decreasing or only moderately increasing net GHG emissions per area. Investments in both production and post-harvest stages meaningfully reduced GHG emission intensity, contributing to low emission development. We present average impacts on net GHG emissions per hectare and GHG emission intensity, while not providing detailed statistics of GHG impacts at scale that are associated to additional uncertainties. While reported improvements in smallholder systems effectively reduce future GHG emissions compared to business-as-usual development, these contributions are insufficient to significantly reduce net GHG emission in agriculture beyond current levels, particularly if future agricultural production grows at projected rates.

  2. Dipeptidyl peptidase IV as a potential target for selective prodrug activation and chemotherapeutic action in cancers. (United States)

    Dahan, Arik; Wolk, Omri; Yang, Peihua; Mittal, Sachin; Wu, Zhiqian; Landowski, Christopher P; Amidon, Gordon L


    The efficacy of chemotherapeutic drugs is often offset by severe side effects attributable to poor selectivity and toxicity to normal cells. Recently, the enzyme dipeptidyl peptidase IV (DPPIV) was considered as a potential target for the delivery of chemotherapeutic drugs. The purpose of this study was to investigate the feasibility of targeting chemotherapeutic drugs to DPPIV as a strategy to enhance their specificity. The expression profile of DPPIV was obtained for seven cancer cell lines using DNA microarray data from the DTP database, and was validated by RT-PCR. A prodrug was then synthesized by linking the cytotoxic drug melphalan to a proline-glycine dipeptide moiety, followed by hydrolysis studies in the seven cell lines with a standard substrate, as well as the glycyl-prolyl-melphalan (GP-Mel). Lastly, cell proliferation studies were carried out to demonstrate enzyme-dependent activation of the candidate prodrug. The relative RT-PCR expression levels of DPPIV in the cancer cell lines exhibited linear correlation with U95Av2 Affymetrix data (r(2) = 0.94), and with specific activity of a standard substrate, glycine-proline-p-nitroanilide (r(2) = 0.96). The significantly higher antiproliferative activity of GP-Mel in Caco-2 cells (GI₅₀ = 261 μM) compared to that in SK-MEL-5 cells (GI₅₀ = 807 μM) was consistent with the 9-fold higher specific activity of the prodrug in Caco-2 cells (5.14 pmol/min/μg protein) compared to SK-MEL-5 cells (0.68 pmol/min/μg protein) and with DPPIV expression levels in these cells. Our results demonstrate the great potential to exploit DPPIV as a prodrug activating enzyme for efficient chemotherapeutic drug targeting.

  3. On macroeconomic characteristics of pharmaceutical generics and the potential for manufacturing and consumption under fuzzy conditions. (United States)

    Gascón, Fernando; de la Fuente, David; Puente, Javier; Lozano, Jesús


    The aim of this paper is to develop a methodology that is useful for analyzing, from a macroeconomic perspective, the aggregate demand and the aggregate supply features of the market of pharmaceutical generics. In order to determine the potential consumption and the potential production of pharmaceutical generics in different countries, two fuzzy decision support systems are proposed. Two fuzzy decision support systems, both based on the Mamdani model, were applied in this paper. These systems, generated by Matlab Toolbox 'Fuzzy' (v. 2.0), are able to determine the potential of a country for the manufacturing or the consumption of pharmaceutical generics. The systems make use of three macroeconomic input variables. In an empirical application of our proposed methodology, the potential towards consumption and manufacturing in Holland, Sweden, Italy and Spain has been estimated from national indicators. Cross-country comparisons are made and graphical surfaces are analyzed in order to interpret the results. The main contribution of this work is the development of a methodology that is useful for analyzing aggregate demand and aggregate supply characteristics of pharmaceutical generics. The methodology is valid for carrying out a systematic analysis of the potential generics have at a macrolevel in different countries. The main advantages of the use of fuzzy decision support systems in the context of pharmaceutical generics are the flexibility in the construction of the system, the speed in interpreting the results offered by the inference and surface maps and the ease with which a sensitivity analysis of the potential behavior of a given country may be performed.

  4. Current Government Actions and Potential Policy Options for Reducing Obesity in Queensland Schools

    Directory of Open Access Journals (Sweden)

    Naser A. Alsharairi


    Full Text Available School nutrition policies provide promising avenues towards the improvement of children’s eating habits and the prevention of obesity. Childhood obesity rates and related chronic diseases are increasing in Queensland, in part as a result of unhealthy eating habits and lack of physical activity. There is a very high investment by the Queensland government in maintaining healthy weight and promoting nutrition and physical activity among schoolchildren through delivering a range of initiatives across the state. However, there is a lack of evidence concerning the effectiveness of nutrition/physical education and parental involvement programs addressing obesity delivered in Queensland schools. This paper can be used to guide government and policy-makers regarding the most effective policy options that will promote healthy eating and physical activity among Queensland schoolchildren. The aim of this paper is to: (i summarize current evidence on Queensland government responses to obesity; and (ii discuss potential policy options that could support healthy eating and regular physical activity, and examine the evidence base for each option and suggest new areas for future research.

  5. Potentials of Mangifera indica in the treatment of depressive-anxiety disorders: possible mechanisms of action. (United States)

    Ishola, Ismail O; Awodele, Olufunsho; Eluogu, Chinedum O


    Mangifera indica (Anacardiaceae) is an important herb in the traditional African and Ayurvedic medicines. The stem barks are used in the treatment of hypertension, insomnia, tumour, depression, rheumatism and as a tonic. This study was carried out to investigate antidepressant- and anxiolytic-like effect of the hydroethanol stem bark extract of M. indica (HeMI) in mice. HeMI (12.5-100 mg/kg, p.o.) was administered 1 h before subjecting the animal to the forced swim test (FST), tail suspension test (TST) and elevated plus maze tests (EPM). HeMI (12.5-100 mg/kg, p.o.) treatment produced significant reduction in immobility time [F(6.56)=8.35, pindica through interaction with 5-HT2 receptor, α2-adrenoceptor and dopamine D2-receptors. Also, an anxiolytic-like effect through its affinity for 5-HT2 and benzodiazepine receptors. Hence, M. indica could be a potential phytotherapeutic agent in the treatment of mixed anxiety-depressive illness.

  6. When syntax meets action: Brain potential evidence of overlapping between language and motor sequencing. (United States)

    Casado, Pilar; Martín-Loeches, Manuel; León, Inmaculada; Hernández-Gutiérrez, David; Espuny, Javier; Muñoz, Francisco; Jiménez-Ortega, Laura; Fondevila, Sabela; de Vega, Manuel


    This study aims to extend the embodied cognition approach to syntactic processing. The hypothesis is that the brain resources to plan and perform motor sequences are also involved in syntactic processing. To test this hypothesis, Event-Related brain Potentials (ERPs) were recorded while participants read sentences with embedded relative clauses, judging for their acceptability (half of the sentences contained a subject-verb morphosyntactic disagreement). The sentences, previously divided into three segments, were self-administered segment-by-segment in two different sequential manners: linear or non-linear. Linear self-administration consisted of successively pressing three buttons with three consecutive fingers in the right hand, while non-linear self-administration implied the substitution of the finger in the middle position by the right foot. Our aim was to test whether syntactic processing could be affected by the manner the sentences were self-administered. Main results revealed that the ERPs LAN component vanished whereas the P600 component increased in response to incorrect verbs, for non-linear relative to linear self-administration. The LAN and P600 components reflect early and late syntactic processing, respectively. Our results convey evidence that language syntactic processing and performing non-linguistic motor sequences may share resources in the human brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Phytochemistry and potential therapeutic actions of Boswellic acids: A mini-review

    Directory of Open Access Journals (Sweden)

    Farah Iram


    Full Text Available The pentacyclic triterpenic acids isolated from the oleo gum resin of various Boswellia species are collectively called as Boswellic acids (BA. The oleo gum resin obtained from Indian variety i.e. Boswellia serrata (Family – Burseraceae is commonly known as Salai guggal. The resin fraction of Salai guggal is rich in Boswellic acids and its essential oil is composed of a mixture of mono, di and sesquiterpenes while gum fraction chiefly contains pentose and hexose sugars. This oleo-gum resin is quite popular among traditional practitioners of traditional Chinese and Indian Systems of medicine owing to their wide range of useful biological properties such as anti-inflammatory, anti-arthritic, anti-rheumatic, anti-diarrheal, anti-hyperlipidemic, anti-asthmatic, anti-cancer, anti-microbial anti-fungal, anti-complementary and analgesic activity, etc. It has been used as a herbal medicine since the prehistoric time to cure acute and chronic ailments including inflammatory diseases. Phytochemical investigation of this herbal medicine lead to identification of Boswellic acids which are found to be novel, potent, specific anti-inflammatory agents due to non-redox inhibition of 5-lipoxygenase (5-LO enzyme. However, the other important targets of Boswellic acids also include topoisomerases, angiogenesis, and cytochrome p450 enzymes. This review is a sincere attempt to discuss and present the current status of therapeutic potential, phytochemical as well as pharmacological profile of Boswellic acids primarily obtained from B. serrata.

  8. Efficacy of Morin as a Potential Therapeutic Phytocomponent: Insights into the Mechanism of Action

    Directory of Open Access Journals (Sweden)

    Amarendranath Choudhury


    Full Text Available Morin (3,5,7,29,49-pentahydroxyflavone is a yellow colour natural bioflavonoid abundantly available in different species of Moraceae family. Besides this, Morin is also harvested from several other sources like tea, coffee, cereals, fruits and red wine. Anti-oxidant, anti-inflammatory, and antiproliferative potency of Morin is well established in both in vivo and in vitro experiments. Among all major sources of Morin, Almond (Prunus dulcis, Fig (Chlorophora tinctoria, and Indian guava (Psidium guajava contains high quantity of it. Easy availability, less side effects and robust functional properties have encouraged the use of these plants in the traditional herbal medicine. In last few decades, the studies on Morin have opened up a whole new era in the therapeutic medicine. Besides anti-oxidant, anti-inflammatory, and antiproliferative activity, Morin has also been reported as a potential neuroprotective agent against many neurological diseases including Alzheimer’s disease, Parkinson’s disease, and cerebral ischemia. According to published reports, the underlying neuroprotective mechanism of Morin is focused mainly on its capacity to inhibit oxidative stress in brain. However, recent data also supports its efficacy in neuroprotection by effectively interacting in the β‒amyloid pathways, inflammatory pathways, and apoptotic pathways. In the present review, we have accumulated all the protective contributions of Morin and intended to drag a mechanistic pathway containing the molecular events leading to the protection against various anomalies.

  9. Quantitative motor unit action potential analysis of supraspinatus, infraspinatus, deltoideus and biceps femoris muscles in adult Royal Dutch sport horses. (United States)

    Jose-Cunilleras, E; Wijnberg, I D


    Reference values for quantitative electromyography (QEMG) in shoulder and hindlimb muscles of horses are limited. To determine normative data on QEMG analysis of supraspinatus (SS), infraspinatus (IS), deltoideus (DT) and biceps femoris (BF) muscles. Experimental observational study and retrospective case series. Seven adult healthy Royal Dutch sport horses underwent quantitative motor unit action potential analysis of each muscle using commercial electromyography equipment. Measurements were made according to published methods. One-way ANOVA was used to compare quantitative motor unit action potential variables between muscles, with post hoc testing according to Bonferroni, with significance set at Paction potential were 8.7-10.4 ms, 651-867 μV, 3.2-3.7, 3.7-4.7, 1054-1457 μV·ms and 1.1-1.5 for SS, 9.6-11.0 ms, 779-1082 μV, 3.3-3.7, 3.8-4.7, 1349-2204 μV·ms and 1.4-1.9 for IS, 6.0-9.1 ms, 370-691 μV, 2.9-3.7, 2.8-4.5, 380-1374 μV·ms and 0.3-1.3 for DT and 5.7-7.8 ms, 265-385 μV, 2.7-3.2, 2.6-3.1, 296-484 μV·ms and 0.2-0.5 for BF, respectively. Mean duration, amplitude, number of phases and turns, area and size index were significantly (P15% polyphasic motor unit action potentials in SS and IS muscles. Differences between muscles should be taken into account when performing QEMG in order to be able to distinguish normal horses from horses with suspected neurogenic or myogenic disorders. These normal data provide the basis for objective QEMG assessment of shoulder and hindlimb muscles. Quantitative electromyography appears to be helpful in diagnosing neuropathies and discriminating these from myopathies. © 2015 EVJ Ltd.

  10. Physico-chemical characteristics and market potential of sawdust charcoal briquette

    Energy Technology Data Exchange (ETDEWEB)

    Akowuah, Joseph O.; Kemausuor, Francis [Kwame Nkrumah Univ. of Science and Technology, Kumasi (Ghana). Dept. of Agricultural Engineering; Mitchual, Stephen J. [Univ. of Education, Winneba, Kumasi (Ghana). Dept. of Design and Technology Education


    In the absence of the widespread distribution of modern cooking fuels in developing countries, efforts are being made to utilise biomass residues which abound in most of these countries. This is intended to replace portions of firewood and charcoal and thereby reduce the cutting down of forests for fuel purposes. Briquettes from agro-residues have therefore been promoted as a better replacement to firewood and charcoals for heating, cooking and other industrial applications in both urban and rural communities. This study sought to assess the physico-chemical properties of charcoal briquettes produced in Ghana and also establish demand for and willingness of potential users to substitute charcoal and firewood with a charcoal briquette. A laboratory experiment was conducted to determine the physicochemical characteristics of the briquettes. This was done prior to the distribution of the briquette to potential users to collaborate their views or otherwise on the handling and burning characteristics of the charcoal briquette. A survey was undertaken a week later using questionnaires to access the willingness of the potential users to use the briquettes. Sixty respondents were purposively selected from households and the hospitality industry for the survey. Results of the physico-chemical assessment of the briquettes were as follows: length (75 to 120 mm), moisture content (5.7% dry basis), density (1.1 g/cm{sup 3}), ash content (2.6%), fixed carbon (20.7%), volatile matter (71%) and calorific value (4,820 kcal/kg). Responses from the survey indicated that the briquette is easy to ignite, has a long burning time and has good heat output. Respondents also observed that the briquettes did not give off sparks and had less smoke and ash content as compared to the regular charcoal they often used. Finally, 93% of the respondents indicated their willingness to use the briquettes if the price was comparable to charcoal. (orig.)

  11. Simulations of the cardiac action potential based on the Hodgkin-Huxley kinetics with the use of Microsoft Excel spreadsheets. (United States)

    Wu, Sheng-Nan


    The purpose of this study was to develop a method to simulate the cardiac action potential using a Microsoft Excel spreadsheet. The mathematical model contained voltage-gated ionic currents that were modeled using either Beeler-Reuter (B-R) or Luo-Rudy (L-R) phase 1 kinetics. The simulation protocol involves the use of in-cell formulas directly typed into a spreadsheet. The capability of spreadsheet iteration was used in these simulations. It does not require any prior knowledge of computer programming, although the use of the macro language can speed up the calculation. The normal configuration of the cardiac ventricular action potential can be well simulated in the B-R model that is defined by four individual ionic currents, each representing the diffusion of ions through channels in the membrane. The contribution of Na+ inward current to the rate of depolarization is reproduced in this model. After removal of Na+ current from the model, a constant current stimulus elicits an oscillatory change in membrane potential. In the L-R phase 1 model where six types of ionic currents were defined, the effect of extracellular K+ concentration on changes both in the time course of repolarization and in the time-independent K+ current can be demonstrated, when the solutions are implemented in Excel. Using the simulation protocols described here, the users can readily study and graphically display the underlying properties of ionic currents to see how changes in these properties determine the behavior of the heart cell. The method employed in these simulation protocols may also be extended or modified to other biological simulation programs.

  12. Potassium conductances mediate bidirectional state-dependent modulation of action potential evoked dendritic calcium signals in dentate gyrus granule cells

    Directory of Open Access Journals (Sweden)

    János Brunner


    Full Text Available Backpropagating action potentials (bAPs and local calcium signals that they trigger are fundamental for dendritic functions. Here we addressed the question what extent the changes of local dendritic membrane properties can contribute to the shaping of the coupling between dendritic action potentials and the local calcium responses. Using a combination of in vitro electrophysiological and confocal imaging techniques we found that activation of dendritic GIRK channels via mGlu2 or GABAB receptors enhanced the bAP¬-triggered calcium signals in the dendrites of dentate gyrus granule cells (GCs. The enhancement of calcium signals was significant only in those dendritic regions, where these receptors are predominantly expressed. Similarly to GIRK channel activation, somatic hyperpolarization by DC current injection (from -64 mV to -77 mV, significantly increased bAP-associated calcium signals in the proximal dendrites. The hyperpolarization was associated with a decrease in the input resistance due to the rectification of the membrane potential of GCs. The effect of hyperpolarization on the calcium signals was maintained when T-type calcium currents were blocked but it decreased when GIRK channels were inhibited. Simultaneous dual somato-dendritic recordings from GCs showed that somatic hyperpolarization accelerated the repolarization phase of dendritic bAP in the proximal region whereas the rising phase and peak amplitude was not affected. We hypothesize that the larger driving force for calcium ions during the faster repolarization can contribute to the increasing in calcium signals. Employment of previously recorded dendritic bAP waveforms from hyperpolarized membrane potential as voltage command evoked larger calcium currents in nucleated patches compared to bAP waveform from the same recording at depolarized membrane potential. Furthermore, addition of native, high-voltage activated, inactivating potassium conductance by somatic dynamic clamp

  13. [Pollution Characteristics and Potential Ecological Risk of Heavy Metals in Urban Surface Water Sediments from Yongkang]. (United States)

    Qi, Peng; Yu, Shu-quan; Zhang, Chao; Liang, Li-cheng; Che, Ji-lu


    In order to understand the pollution characteristics of heavy metals in surface water sediments of Yongkang, we analyzed the concentrations of 10 heavy metals including Ti, Cr, Mn, Co, Ni, Cu, Zn, As, Pb and Fe in 122 sediment samples, explored the underlying source of heavy metals and then assessed the potential ecological risks of those metals by methods of the index of geo-accumulation and the potential ecological risk. The study results showed that: 10 heavy metal contents followed the order: Fe > Ti > Mn > Zn > Cr > Cu > Ph > Ni > As > Co, all heavy metals except for Ti were 1. 17 to 3.78 times higher than those of Zhejiang Jinhua- Quzhou basin natural soils background values; The concentrations of all heavy metals had a significantly correlation between each other, indicating that those heavy metals had similar sources of pollution, and it mainly came from industrial and vehicle pollutions; The pollution extent of heavy metals in sediments by geo-accumulation index (Igeo) followed the order: Cr > Zn > Ni > Cu > Fe > As > Pb >Mn > Ti, thereinto, Cr, Zn, Cu and Ni were moderately polluted or heavily polluted at some sampling sites; The potential ecological risk of 9 heavy metals in sediments were in the following order: Cu > As > Ni > Cr > Pb > Co > Zn > Mn > Ti, Cu and As contributed the most to the total potential ecological risk, accounting for 22.84% and 21. 62% , others had a total of 55.54% , through the ecological risk assessment, 89. 34% of the potential ecological risk indexes ( RI) were low and 10. 66% were higher. The contamination level of heavy metals in Yongkang was slight in total, but was heavy in local areas.

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

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


    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.

  15. A Comparison of Beliefs and Disbeliefs and Reference Category Characteristics as Directive Factors of Social Action in Five Cultures. (United States)

    Reeder, William W.; And Others

    In order to illustrate the cross-culture applicability of Reeder's Theory of Beliefs, Disbeliefs, and Social Action and its usefulness in predicting and explaining social actions, studies conducted in communities in India, Sudan, Lebanon, northeastern United States, and western United States are examined. Using this theory, beliefs and disbeliefs…

  16. Potential Causes of Significant Inventory Differences at Bulk Handling Facilities and the Importance of Inventory Difference Action Levels

    International Nuclear Information System (INIS)

    Homer, Alan; O’Hagan, Brendan


    Accountancy for nuclear material can be split into two categories. Firstly, where possible, accountancy should be in terms of items that can be transferred as discrete packages and their contents fixed at the time of their creation. All items must remain accounted for at all times, and a single missing item is considered significant. Secondly, where nuclear material is unconstrained, for example in a reprocessing plant where it can change form, there is an uncertainty that relates to the amount of material present in any location. Cumulatively, these uncertainties can be summed and provide a context for any estimate of material in a process. Any apparent loss or gain between what has been physically measured within a facility during its physical inventory take and what is reported within its nuclear material accounts is known as an inventory difference. The cumulative measurement uncertainties can be used to set an action level for the inventory difference so that if an inventory difference is observed outside of such action levels, the difference is classified as significant and an investigation to find the root cause(s) is required. The purpose of this paper is to explore the potential causes of significant inventory differences and to provide a framework within which an inventory difference investigation can be carried out.

  17. An update on potential molecular mechanisms underlying the actions of snake venom L-amino acid oxidases (LAAOs). (United States)

    Paloschi, Mauro Valentino; Pontes, Adriana Silva; Soares, Andreimar Martins; Zuliani, Juliana Pavan


    LAAOs (EC are found in concentrations that vary according to each species of snakes; Viperidae, Crotalidae and Elapidae contain 1-9% of this enzyme in their venoms. This review focuses on an update on molecular mechanisms, platelet activities, antimicrobial, antiprotozoal, induction of apoptosis and inflammatory potential underlying the actions of SV-LAAOs. Snake venom LAAOs (SV-LAAOs) have become an interesting subject for pharmacological, structural and molecular studies. Although the mechanisms of action of these enzymes are not well understood they are a subject of a variety of studies, because LAAOs are multifunctional enzymes exhibiting a wide range of pharmacological effects, including the inhibition or induction of platelet aggregation, hemolysis and hemorrhage, in addition to the stimulation of apoptosis, the activation of leukocytes and the formation of edema. Moreover, SV-LAAOs play an important role in bactericidal, cytotoxic, anti-parasitic, anti-tumor, and antiviral activities. Copyright© Bentham Science Publishers; For any queries, please email at

  18. Potential study of bed filtration characteristics in impressed boreholes by radon tracer technique

    International Nuclear Information System (INIS)

    Litvinov, A.A.; Pinkenzon, D.B.; Makarov, M.S.; Vinarskij, M.S.


    Potential study of bed filtration characteristics in impressed boreholes by radon tracer method is shown. Effects recorded by radon tracer result from gamma radiation of short-living radon decay daughter products. During filtration of tracer through punched holes, cement stone, and rocks the products are deposited and cause a local effect for 2-3 hours. There is a shortage of short-living products in filtrated radon liquid and for some time (which is necessary for production of notable quantity of new decay products) it is practically not a gamma emitter. It is shown that the feature of effect formation governs the technique for well logging as well as interpretation of the results obtained

  19. Investigation of wind characteristics and assessment of wind energy potential for Waterloo region, Canada

    International Nuclear Information System (INIS)

    Li Meishen; Li Xianguo


    Wind energy becomes more and more attractive as one of the clean renewable energy resources. Knowledge of the wind characteristics is of great importance in the exploitation of wind energy resources for a site. It is essential in designing or selecting a wind energy conversion system for any application. This study examines the wind characteristics for the Waterloo region in Canada based on a data source measured at an elevation 10 m above the ground level over a 5-year period (1999-2003) with the emphasis on the suitability for wind energy technology applications. Characteristics such as annual, seasonal, monthly and diurnal wind speed variations and wind direction variations are examined. Wind speed data reveal that the windy months in Waterloo are from November to April, defined as the Cold Season in this study, with February being the windiest month. It is helpful that the high heating demand in the Cold Season coincides with the windy season. Analysis shows that the day time is the windy time, with 2 p.m. in the afternoon being the windiest moment. Moreover, a model derived from the maximum entropy principle (MEP) is applied to determine the diurnal, monthly, seasonal and yearly wind speed frequency distributions, and the corresponding Lagrangian parameters are determined. Based on these wind speed distributions, this study quantifies the available wind energy potential to provide practical information for the application of wind energy in this area. The yearly average wind power density is 105 W/m 2 . The day and night time wind power density in the Cold Season is 180 and 111 W/m 2 , respectively

  20. Effect of DSPE-PEG on compound action potential, injury potential and ion concentration following compression in ex vivo spinal cord. (United States)

    Wang, Aihua; Huo, Xiaolin; Zhang, Guanghao; Wang, Xiaochen; Zhang, Cheng; Wu, Changzhe; Rong, Wei; Xu, Jing; Song, Tao


    It has been shown that polyethylene glycol (PEG) can reseal membrane disruption on the spinal cord, but only high concentrations of PEG have been shown to have this effect. Therefore, the effect of PEG is somewhat limited, and it is necessary to investigate a new approach to repair spinal cord injury. This study assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological function and attenuate the injury-induced influx of extracellular ions in ex vivo spinal cord injury. Isolated spinal cords were subjected to compression injury and treated with PEG or DSPE-PEG immediately after injury. The compound action potential (CAP) was recorded before and after injury to assess the functional recovery. Furthermore, injury potential, the difference in gap potentials before and after compression, and the concentration of intracellular ions were used to evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the injury potential and ion concentration of the untreated, PEG and DSPE-PEG group, without significant difference among them, are remarkably higher than those of the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated spinal cords was significantly greater than that of the untreated spinal cords. The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same, but the concentration of DSPE-PEG used was much lower than the concentration of PEG. These results suggest that instant application of DSPE-PEG could effectively repair functional disturbance in SCI at a much lower concentration than PEG. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Promoting HIV Vaccine Research in African American Communities: Does the Theory of Reasoned Action Explain Potential Outcomes of Involvement? (United States)

    Frew, Paula M; Archibald, Matthew; Martinez, Nina; del Rio, Carlos; Mulligan, Mark J


    The HIV/AIDS pandemic continues to challenge the African American community with disproportionate rates of infection, particularly among young women ages 25 to 34 years. Development of a preventive HIV vaccine may bring a substantial turning point in this health crisis. Engagement of the African American community is necessary to improve awareness of the effort and favorably influence attitudes and referent norms. The Theory of Reasoned Action (TRA) may be a useful framework for exploration of community engagement outcomes including future attendance, community mobilization, and study participation. Within the context of HIV vaccine outreach, we conducted a cross-sectional survey in early 2007 with 175 African-American adults (>/= 18 years). Confirmatory factor analysis and structural equation modeling were performed and the findings support the potential of the model in understanding behavioral intentions toward HIV vaccine research.

  2. [Value of condensation and rarefaction click evoked action potential latency difference in the diagnosis of Meniere's disease]. (United States)

    Wang, Z; Shao, X; Yan, W; Lin, H


    To study the value of condensation and rarefaction clicks evoked action potential (AP) latency difference (LD) in diagnosis of Meniere's disease. AP was recorded with ECochG in controls (50 ears) and patients with Meniere's disease(90 ears) and sensorineural hearing loss(SNHL) of other origins(60 ears). LD was calculated and analyzed. LD in patients with Meniere's disease was (0.30 +/- 0.15) ms, which was significantly larger than that of controls(0.18 +/- 0.07) ms and of patients with SNHL of other origins(0.20 +/- 0.10) ms (P curve was larger than those with flat auditory sensation curve(P rarefaction click evoked AP latency difference can be an objective parameter in diagnosis of Meniere's disease.

  3. Isolation of lactic acid bacteria with potential protective culture characteristics from fruits (United States)

    Hashim, Nurul Huda; Sani, Norrakiah Abdullah


    Lactic acid bacteria are also known as beneficial microorganisms abundantly found in fermented food products. In this study, lactic acid bacteria were isolated from fresh cut fruits obtained from local markets. Throughout the isolation process from 11 samples of fruits, 225 presumptive lactic acid bacteria were isolated on MRS agar medium. After catalase and oxidase tests, 149 resulted to fit the characteristics of lactic acid bacteria. Further identification using Gram staining was conducted to identify the Gram positive bacteria. After this confirmation, the fermentation characteristics of these isolates were identified. It was found that 87 (58.4%) isolates were heterofermentative, while the rest of 62 (41.6%) are homofermentative lactic acid bacteria. Later, all these isolates were investigated for the ability to inhibit growth of Staphylococcus aureus using agar spot assay method. Seven (4.7%) isolates showed strong antagonistic capacity, while 127 (85.2%) and 8 (5.4%) isolates have medium and weak antagonistic capacity, respectively. The other 7 (4.7%) isolates indicated to have no antagonistic effect on S. aureus. Results support the potential of LAB isolated in this study which showed strong antagonistic activity against S. aureus may be manipulated to become protective cultures in food products. While the homofermentative or heterofermentative LAB can be utilized in fermentation of food and non-food products depending on the by-products required during the fermentation.

  4. Basic characteristics of Sporolactobacillus inulinus BCRC 14647 for potential probiotic properties. (United States)

    Huang, Hui-Ying; Huang, Shih-Yi; Chen, Pei-Yu; King, V An-Erl; Lin, Yeu-Pyng; Tsen, Jen-Horng


    The basic characteristics of the spore-forming lactic acid bacterium, Sporolactobacillus inulinus BCRC 14647, was evaluated in vitro for its potential probiotic properties. Assessments including acid and bile salt tolerance, adhesiveness, and antagonistic effects on pathogenic Salmonella enteritidis BCRC 10744, as well as inhibition factors of spent culture supernatant (SCS) and an invasion assay, were conducted using Lactobacillus acidophilus BCRC 10695 and two bifidobacteria (Bifidobacterium bifidum BCRC 14615 and B. longum BCRC 11847) as a reference. In the results, S. inulinus spores presented significantly higher survival rates than the vegetative cell form in acidic conditions as well as the reference bifidobacteria. However, L. acidophilus showed the highest viability among all tested strains. Similar results were found in the bile tolerance test. Compared with the reference strains, the vegetative cell form of S. inulinus possessed a proper adhesive characteristic (71.7 bacteria/field for S. inulinus and 91.3 and 45.7 bacteria/field for B. bifidum and B. longum, respectively). In the adhesion assay, both the spore form of S. inulinus (17.1 bacteria/field) and the negative control, L. bulgaricus BCRC 14009 (5.9 bacteria/field), displayed nonadhesive traits. The vegetative cells of S. inulinus and its SCS both dramatically decrease the adhesion of S. enteritidis to Caco-2 cells; meanwhile, the SCS of S. inulinus vegetative cells inhibited the growth of S. enteritidis in the inhibition zone test. The existing inhibition factor could be assumed to be lactic acid in the SCS. From the results of the invasion assay, S. inulinus showed high safety properties. In conclusion, based on these in vitro evaluations, results suggest that S. inulinus presents probiotic features of great potential in the vegetative cell form.

  5. Resveratrol exhibits a strong cytotoxic activity in cultured cells and has an antiviral action against polyomavirus: potential clinical use

    Directory of Open Access Journals (Sweden)

    Galati Gaspare


    Full Text Available Abstract Background Resveratrol is a non flavonoid polyphenol compound present in many plants and fruits and, at especially high concentrations, in the grape berries of Vitis vinifera. This compound has a strong bioactivity and its cytoprotective action has been demonstrated, however at high concentrations the drug exhibits also an effective anti-proliferative action. We recently showed its ability to abolish the effects of oxidative stress in cultured cells. In this work we assayed the bioactivity of resveratrol as antiproliferative and antiviral drug in cultured fibroblasts. Studies by other Authors showed that this natural compound inhibits the proliferation of different viruses such as herpes simplex, varicella-zoster and influenza A. The results presented here show an evident toxic activity of the drug at high concentrations, on the other hand at sub-cytotoxic concentrations, resveratrol can effectively inhibit the synthesis of polyomavirus DNA. A possible interpretation is that, due to the damage caused by resveratrol to the plasma membrane, the transfer of the virus from the endoplasmic reticulum to the nucleus, may be hindered thus inhibiting the production of viral DNA. Methods The mouse fibroblast line 3T6 and the human tumor line HL60 were used throughout the work. Cell viability and vital cell count were assessed respectively, by the MTT assay and Trypan Blue staining. Cytotoxic properties and evaluation of viral DNA production by agarose gel electrophoresis were performed according to standard protocols. Results Our results show a clear dose dependent both cytotoxic and antiviral effect of resveratrol respectively at high and low concentrations. The cytotoxic action is exerted towards a stabilized cell-line (3T6 as well as a tumor-line (HL60. Furthermore the antiviral action is evident after the phase of virion entry, therefore data suggest that the drug acts during the synthesis of the viral progeny DNA. Conclusion Resveratrol is

  6. Changes in contractile properties and action potentials of motor units in the rat medial gastrocnemius muscle during maturation. (United States)

    Dobrzynska, Z; Celichowski, J


    The early phase of development of muscles stops following the disappearance of embryonic and neonatal myosin and the elimination of polyneuronal innervation of muscle fibres with the formation of motor units (MUs), but later the muscle mass still considerably increases. It is unknown whether the three types are visible among newly formed MUs soon after the early postnatal period and whether their proportion is similar to that in adult muscle. Moreover, the processes responsible for MU-force regulation by changes in motoneuronal firing rate as well as properties of motor unit action potentials (MUAPs) during maturation are unknown. Three groups of Wistar rats were investigated - 1 month old, 2 months old and the adult, 9 months old. The basic contractile properties and action potentials of MUs in the medial gastrocnemius (MG) muscle were analysed. The three types of MUs were distinguishable in all age groups, but higher proportion of slow MUs was noticed in young rats (29%, 18% and 11% in 1, 2 and 9 months rats, respectively). The fatigue index for fast fatigable MUs in 1 month old rats was about 2 times higher than in 9 months old rats. The twitch time parameters of fast MUs were shortened during the maturation; for these units, the force-frequency curves in young rats were shifted towards lower frequencies, which suggested that fast motoneurons of young animals generate lower firing rates. Higher twitch-to-tetanus ratios noted for the three MU types in young rats suggested the smaller role of rate coding in force regulation processes, and the higher role of MU recruitment in young rats. No significant differences in MUAP parameters between two groups of young and adult animals were observed. Concluding, the maturation process evokes deeper changes in fast MUs than in slow ones.

  7. Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy (United States)

    Meredith, Rhiannon M.; van Ooyen, Arjen


    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

  8. Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. (United States)

    De Petrocellis, L; Orlando, P; Moriello, A Schiano; Aviello, G; Stott, C; Izzo, A A; Di Marzo, V


    Plant cannabinoids, like Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), activate/desensitize thermosensitive transient receptor potential (TRP) channels of vanilloid type-1 or -2 (TRPV1 or TRPV2). We investigated whether cannabinoids also activate/desensitize two other 'thermo-TRP's', the TRP channels of vanilloid type-3 or -4 (TRPV3 or TRPV4), and if the TRPV-inactive cannabichromene (CBC) modifies the expression of TRPV1-4 channels in the gastrointestinal tract. TRP activity was assessed by evaluating elevation of [Ca(2+)](i) in rat recombinant TRPV3- and TRPV4-expressing HEK-293 cells. TRP channel mRNA expression was measured by quantitative RT-PCR in the jejunum and ileum of mice treated with vehicle or the pro-inflammatory agent croton oil. (i) CBD and tetrahydrocannabivarin (THCV) stimulated TRPV3-mediated [Ca(2+)](i) with high efficacy (50-70% of the effect of ionomycin) and potency (EC(50∼) 3.7 μm), whereas cannabigerovarin (CBGV) and cannabigerolic acid (CBGA) were significantly more efficacious at desensitizing this channel to the action of carvacrol than at activating it; (ii) cannabidivarin and THCV stimulated TRPV4-mediated [Ca(2+)](i) with moderate-high efficacy (30-60% of the effect of ionomycin) and potency (EC(50) 0.9-6.4 μm), whereas CBGA, CBGV, cannabinol and cannabigerol were significantly more efficacious at desensitizing this channel to the action of 4-α-phorbol 12,13-didecanoate (4α-PDD) than at activating it; (iii) CBC reduced TRPV1β, TRPV3 and TRPV4 mRNA in the jejunum, and TRPV3 and TRPV4 mRNA in the ileum of croton oil-treated mice. Cannabinoids can affect both the activity and the expression of TRPV1-4 channels, with various potential therapeutic applications, including in the gastrointestinal tract. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

  9. Effect of acute stretch injury on action potential and network activity of rat neocortical neurons in culture. (United States)

    Magou, George C; Pfister, Bryan J; Berlin, Joshua R


    The basis for acute seizures following traumatic brain injury (TBI) remains unclear. Animal models of TBI have revealed acute hyperexcitablility in cortical neurons that could underlie seizure activity, but studying initiating events causing hyperexcitability is difficult in these models. In vitro models of stretch injury with cultured cortical neurons, a surrogate for TBI, allow facile investigation of cellular changes after injury but they have only demonstrated post-injury hypoexcitability. The goal of this study was to determine if neuronal hyperexcitability could be triggered by in vitro stretch injury. Controlled uniaxial stretch injury was delivered to a spatially delimited region of a spontaneously active network of cultured rat cortical neurons, yielding a region of stretch-injured neurons and adjacent regions of non-stretched neurons that did not directly experience stretch injury. Spontaneous electrical activity was measured in non-stretched and stretch-injured neurons, and in control neuronal networks not subjected to stretch injury. Non-stretched neurons in stretch-injured cultures displayed a three-fold increase in action potential firing rate and bursting activity 30-60 min post-injury. Stretch-injured neurons, however, displayed dramatically lower rates of action potential firing and bursting. These results demonstrate that acute hyperexcitability can be observed in non-stretched neurons located in regions adjacent to the site of stretch injury, consistent with reports that seizure activity can arise from regions surrounding the site of localized brain injury. Thus, this in vitro procedure for localized neuronal stretch injury may provide a model to study the earliest cellular changes in neuronal function associated with acute post-traumatic seizures. Copyright © 2015. Published by Elsevier B.V.

  10. Effects of piezoelectric potential on the transport characteristics of metal-ZnO nanowire-metal field effect transistor

    KAUST Repository

    Gao, Zhiyuan; Zhou, Jun; Gu, Yudong; Fei, Peng; Hao, Yue; Bao, Gang; Wang, Zhong Lin


    We have investigated the effects of piezoelectric potential in a ZnO nanowire on the transport characteristics of the nanowire based field effect transistor through numerical calculations and experimental observations. Under different straining

  11. Across-site patterns of electrically evoked compound action potential amplitude-growth functions in multichannel cochlear implant recipients and the effects of the interphase gap. (United States)

    Schvartz-Leyzac, Kara C; Pfingst, Bryan E


    Electrically evoked compound action potential (ECAP) measures of peak amplitude, and amplitude-growth function (AGF) slope have been shown to reflect characteristics of cochlear health (primarily spiral ganglion density) in anesthetized cochlear-implanted guinea pigs. Likewise, the effect of increasing the interphase gap (IPG) in each of these measures also reflects SGN density in the implanted guinea pig. Based on these findings, we hypothesize that suprathreshold ECAP measures, and also how they change as the IPG is increased, have the potential to be clinically applicable in human subjects. However, further work is first needed in order to determine the characteristics of these measures in humans who use cochlear implants. The current study examined across-site patterns of suprathreshold ECAP measures in 10 bilaterally-implanted, adult cochlear implant users. Results showed that both peak amplitude and slope of the AGF varied significantly from electrode to electrode in ear-specific patterns across the subjects' electrode arrays. As expected, increasing the IPG on average increased the peak amplitude and slope. Across ears, there was a significant, negative correlation between the slope of the ECAP AGF and the duration of hearing loss. Across-site patterns of ECAP peak amplitude and AGF slopes were also compared with common ground impedance values and significant correlations were observed in some cases, depending on the subject and condition. The results of this study, coupled with previous studies in animals, suggest that it is feasible to measure the change in suprathreshold ECAP measures as the IPG increases on most electrodes. Further work is needed to investigate the relationship between these measures and cochlear implant outcomes, and determine how these measures might be used when programming a cochlear-implant processor. Published by Elsevier B.V.

  12. Emission characteristics of VOCs emitted from consumer and commercial products and their ozone formation potential. (United States)

    Dinh, Trieu-Vuong; Kim, Su-Yeon; Son, Youn-Suk; Choi, In-Young; Park, Seong-Ryong; Sunwoo, Young; Kim, Jo-Chun


    The characteristics of volatile organic compounds (VOCs) emitted from several consumer and commercial products (body wash, dishwashing detergent, air freshener, windshield washer fluid, lubricant, hair spray, and insecticide) were studied and compared. The spray products were found to emit the highest amount of VOCs (~96 wt%). In contrast, the body wash products showed the lowest VOC contents (~1.6 wt%). In the spray products, 21.6-96.4 % of the VOCs were propane, iso-butane, and n-butane, which are the components of liquefied petroleum gas. Monoterpene (C10H16) was the dominant component of the VOCs in the non-spray products (e.g., body wash, 53-88 %). In particular, methanol was present with the highest amount of VOCs in windshield washer fluid products. In terms of the number of carbon, the windshield washer fluids, lubricants, insecticides, and hair sprays comprised >95 % of the VOCs in the range C2-C5. The VOCs in the range C6-C10 were predominantly found in the body wash products. The dishwashing detergents and air fresheners contained diverse VOCs from C2 to C11. Besides comprising hazardous VOCs, VOCs from consumer products were also ozone precursors. The ozone formation potential of the consumer and commercial spray products was estimated to be higher than those of liquid and gel materials. In particular, the hair sprays showed the highest ozone formation potential.

  13. The activity of spontaneous action potentials in developing hair cells is regulated by Ca(2+-dependence of a transient K+ current.

    Directory of Open Access Journals (Sweden)

    Snezana Levic

    Full Text Available Spontaneous action potentials have been described in developing sensory systems. These rhythmic activities may have instructional roles for the functional development of synaptic connections. The importance of spontaneous action potentials in the developing auditory system is underpinned by the stark correlation between the time of auditory system functional maturity, and the cessation of spontaneous action potentials. A prominent K(+ current that regulates patterning of action potentials is I(A. This current undergoes marked changes in expression during chicken hair cell development. Although the properties of I(A are not normally classified as Ca(2+-dependent, we demonstrate that throughout the development of chicken hair cells, I(A is greatly reduced by acute alterations of intracellular Ca(2+. As determinants of spike timing and firing frequency, intracellular Ca(2+ buffers shift the activation and inactivation properties of the current to more positive potentials. Our findings provide evidence to demonstrate that the kinetics and functional expression of I(A are tightly regulated by intracellular Ca(2+. Such feedback mechanism between the functional expression of I(A and intracellular Ca(2+ may shape the activity of spontaneous action potentials, thus potentially sculpting synaptic connections in an activity-dependent manner in the developing cochlea.

  14. Planar Diamond-Based Multiarrays to Monitor Neurotransmitter Release and Action Potential Firing: New Perspectives in Cellular Neuroscience. (United States)

    Carabelli, Valentina; Marcantoni, Andrea; Picollo, Federico; Battiato, Alfio; Bernardi, Ettore; Pasquarelli, Alberto; Olivero, Paolo; Carbone, Emilio


    High biocompatibility, outstanding electrochemical responsiveness, inertness, and transparency make diamond-based multiarrays (DBMs) first-rate biosensors for in vitro detection of electrochemical and electrical signals from excitable cells together, with potential for in vivo applications as neural interfaces and prostheses. Here, we will review the electrochemical and physical properties of various DBMs and how these devices have been employed for recording released neurotransmitter molecules and all-or-none action potentials from living cells. Specifically, we will overview how DBMs can resolve localized exocytotic events from subcellular compartments using high-density microelectrode arrays (MEAs), or monitoring oxidizable neurotransmitter release from populations of cells in culture and tissue slices using low-density MEAs. Interfacing DBMs with excitable cells is currently leading to the promising opportunity of recording electrical signals as well as creating neuronal interfaces through the same device. Given the recent increasingly growing development of newly available DBMs of various geometries to monitor electrical activity and neurotransmitter release in a variety of excitable and neuronal tissues, the discussion will be limited to planar DBMs.

  15. Potential role of monkey inferior parietal neurons coding action semantic equivalences as precursors of parts of speech. (United States)

    Yamazaki, Yumiko; Yokochi, Hiroko; Tanaka, Michio; Okanoya, Kazuo; Iriki, Atsushi


    The anterior portion of the inferior parietal cortex possesses comprehensive representations of actions embedded in behavioural contexts. Mirror neurons, which respond to both self-executed and observed actions, exist in this brain region in addition to those originally found in the premotor cortex. We found that parietal mirror neurons responded differentially to identical actions embedded in different contexts. Another type of parietal mirror neuron represents an inverse and complementary property of responding equally to dissimilar actions made by itself and others for an identical purpose. Here, we propose a hypothesis that these sets of inferior parietal neurons constitute a neural basis for encoding the semantic equivalence of various actions across different agents and contexts. The neurons have mirror neuron properties, and they encoded generalization of agents, differentiation of outcomes, and categorization of actions that led to common functions. By integrating the activities of these mirror neurons with various codings, we further suggest that in the ancestral primates' brains, these various representations of meaningful action led to the gradual establishment of equivalence relations among the different types of actions, by sharing common action semantics. Such differential codings of the components of actions might represent precursors to the parts of protolanguage, such as gestural communication, which are shared among various members of a society. Finally, we suggest that the inferior parietal cortex serves as an interface between this action semantics system and other higher semantic systems, through common structures of action representation that mimic language syntax.

  16. Nanoelectronics-biology frontier: From nanoscopic probes for action potential recording in live cells to three-dimensional cyborg tissues. (United States)

    Duan, Xiaojie; Fu, Tian-Ming; Liu, Jia; Lieber, Charles M


    Semiconductor nanowires configured as the active channels of field-effect transistors (FETs) have been used as detectors for high-resolution electrical recording from single live cells, cell networks, tissues and organs. Extracellular measurements with substrate supported silicon nanowire (SiNW) FETs, which have projected active areas orders of magnitude smaller than conventional microfabricated multielectrode arrays (MEAs) and planar FETs, recorded action potential and field potential signals with high signal-to-noise ratio and temporal resolution from cultured neurons, cultured cardiomyocytes, acute brain slices and whole animal hearts. Measurements made with modulation-doped nanoscale active channel SiNW FETs demonstrate that signals recorded from cardiomyocytes are highly localized and have improved time resolution compared to larger planar detectors. In addition, several novel three-dimensional (3D) transistor probes, which were realized using advanced nanowire synthesis methods, have been implemented for intracellular recording. These novel probes include (i) flexible 3D kinked nanowire FETs, (ii) branched intracellular nanotube SiNW FETs, and (iii) active silicon nanotube FETs. Following phospholipid modification of the probes to mimic the cell membrane, the kinked nanowire, branched intracellular nanotube and active silicon nanotube FET probes recorded full-amplitude intracellular action potentials from spontaneously firing cardiomyocytes. Moreover, these probes demonstrated the capability of reversible, stable, and long-term intracellular recording, thus indicating the minimal invasiveness of the new nanoscale structures and suggesting biomimetic internalization via the phospholipid modification. Simultaneous, multi-site intracellular recording from both single cells and cell networks were also readily achieved by interfacing independently addressable nanoprobe devices with cells. Finally, electronic and biological systems have been seamlessly merged in 3D

  17. Characteristics of special-case wastes potentially destined for disposal at the Nevada Test Site

    International Nuclear Information System (INIS)

    Price, L.L.; Duran, F.A.


    The U.S. Department of Energy (DOE) is responsible for disposing of a variety of radioactive and mixed wastes, some of which are considered special-case waste because they do not currently have a clear disposal option. It may be possible to dispose of some of the DOE's special-case waste using greater confinement disposal techniques at the Nevada Test Site (NTS). The DOE asked Sandia National Laboratories to investigate this possibility by performing system configuration analyses. The first step in performing system configuration analyses is to estimate the characteristics of special-case waste that might be destined for disposal at the NTS. The objective of this report is to characterize this special-case waste based upon information available in the literature. No waste was sampled and analyzed specifically for this report. The waste compositions given are not highly detailed, consisting of grains and curies of specific radionuclides per cubic meter. However, such vague waste characterization is adequate for the purposes of the system configuration task. In some previous work done on this subject, Kudera et al. [1990] identified nine categories of special-case radioactive waste and estimated volumes and activities for these categories. It would have been difficult to develop waste compositions based on the categories proposed by Kudera et al. [1990], so we created five groups of waste on which to base the waste compositions. These groups are (1) transuranic waste, (2) fission product waste, (3) activation product waste, (4) mobile/volatile waste, and (5) sealed sources. The radionuclides within a given group share common characteristics (e.g., alpha-emitters, heat generators), and we believe that these groups adequately represent the DOE's special-case waste potentially destined for greater confinement disposal at the NTS

  18. Predictors of response to a nasal expiratory resistor device and its potential mechanisms of action for treatment of obstructive sleep apnea. (United States)

    Patel, Amit V; Hwang, Dennis; Masdeu, Maria J; Chen, Guo-Ming; Rapoport, David M; Ayappa, Indu


    A one-way nasal resistor has recently been shown to reduce sleep disordered breathing (SDB) in a subset of patients with Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS). The purpose of this study was to examine characteristics predictive of therapeutic response to the device and provide pilot data as to its potential mechanisms of action. PATIENTS, INTERVENTIONS, AND MEASUREMENTS: 20 subjects (15M/5F, age 54 ± 12 years, BMI 33.5 ± 5.6 kg/m²) with OSAHS underwent 3 nocturnal polysomnograms (NPSG) including diagnostic, therapeutic (with a Provent® nasal valve device), and CPAP. Additional measurements included intranasal pressures and PCO₂, closing pressures (Pcrit), and awake lung volumes in different body positions. In 19/20 patients who slept with the device, RDI was significantly reduced with the nasal valve device compared to the diagnostic NPSG (27 ± 29/h vs 49 ± 28/h), with 50% of patients having an acceptable therapeutic response. Among demographic, lung volume, or diagnostic NPSG measures or markers of collapsibility, no significant predictors of therapeutic response were found. There was a suggestion that patients with position-dependent SDB (supine RDI > lateral RDI) were more likely to have an acceptable therapeutic response to the device. Successful elimination of SDB was associated with generation and maintenance of an elevated end expiratory pressure. No single definitive mechanism of action was elucidated. The present study shows that the nasal valve device can alter SDB across the full spectrum of SDB severity. There was a suggestion that subjects with positional or milder SDB in the lateral position were those most likely to respond.

  19. Assessing the Electrode-Neuron Interface with the Electrically Evoked Compound Action Potential, Electrode Position, and Behavioral Thresholds. (United States)

    DeVries, Lindsay; Scheperle, Rachel; Bierer, Julie Arenberg


    Variability in speech perception scores among cochlear implant listeners may largely reflect the variable efficacy of implant electrodes to convey stimulus information to the auditory nerve. In the present study, three metrics were applied to assess the quality of the electrode-neuron interface of individual cochlear implant channels: the electrically evoked compound action potential (ECAP), the estimation of electrode position using computerized tomography (CT), and behavioral thresholds using focused stimulation. The primary motivation of this approach is to evaluate the ECAP as a site-specific measure of the electrode-neuron interface in the context of two peripheral factors that likely contribute to degraded perception: large electrode-to-modiolus distance and reduced neural density. Ten unilaterally implanted adults with Advanced Bionics HiRes90k devices participated. ECAPs were elicited with monopolar stimulation within a forward-masking paradigm to construct channel interaction functions (CIF), behavioral thresholds were obtained with quadrupolar (sQP) stimulation, and data from imaging provided estimates of electrode-to-modiolus distance and scalar location (scala tympani (ST), intermediate, or scala vestibuli (SV)) for each electrode. The width of the ECAP CIF was positively correlated with electrode-to-modiolus distance; both of these measures were also influenced by scalar position. The ECAP peak amplitude was negatively correlated with behavioral thresholds. Moreover, subjects with low behavioral thresholds and large ECAP amplitudes, averaged across electrodes, tended to have higher speech perception scores. These results suggest a potential clinical role for the ECAP in the objective assessment of individual cochlear implant channels, with the potential to improve speech perception outcomes.

  20. Failure of action potential propagation in sensory neurons: mechanisms and loss of afferent filtering in C-type units after painful nerve injury

    NARCIS (Netherlands)

    Gemes, Geza; Koopmeiners, Andrew; Rigaud, Marcel; Lirk, Philipp; Sapunar, Damir; Bangaru, Madhavi Latha; Vilceanu, Daniel; Garrison, Sheldon R.; Ljubkovic, Marko; Mueller, Samantha J.; Stucky, Cheryl L.; Hogan, Quinn H.


    The T-junction of sensory neurons in the dorsal root ganglion (DRG) is a potential impediment to action potential (AP) propagation towards the CNS. Using intracellular recordings from rat DRG neuronal somata during stimulation of the dorsal root, we determined that the maximal rate at which all of

  1. Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis–a new potential diagnostic biomarker

    International Nuclear Information System (INIS)

    Allen, John; Murray, Alan; Di Maria, Costanzo; Newton, Julia L


    Autonomic nervous system dysfunction is frequently reported in chronic fatigue syndrome (CFS) with orthostatic intolerance, a common symptom that can be objectively assessed. The frequent finding of autonomic dysfunction and symptoms on standing has the potential to provide a diagnostic biomarker in chronic fatigue. In this study we explored the clinical value of non-invasive optical multi-site photoplethysmography (PPG) technology to assess cardiovascular responses to standing. Multi-site PPG pulses were collected from tissue pads of the ears, fingers and toes of 14 patients with CFS and 14 age-matched sedentary subjects using a measurement protocol of a 10 min baseline (subject supine) followed by 3 min of tilting on a tilt table (head-up to 70°). Percentage change in pulse timing (pulse transit time, PTTf) and pulse amplitude (AMP) at each site were calculated using beat-to-beat pulse wave analysis. A significant reduction in the overall pulse timing response to controlled standing was found for the CFS group (using summed absolute percentage change in PTTf for ear, finger and toe sites, median change of 26% for CFS and 37% for control with p = 0.002). There were no significant differences between subject groups for the AMP measure at any site. Changes in AMP with tilt were, however, weakly significantly and negatively correlated with fatigue severity (p < 0.05). Receiver operating characteristic (ROC) analysis of timing measures produced an area under the curve of 0.81. Experimental linear discriminant classification analysis comparing both timing and amplitude measures produced an overall diagnostic accuracy of 82%. Pulse wave abnormalities have been observed in CFS and represent a potential objective measure to help differentiate between CFS patients and healthy controls. (paper)

  2. Contribution of two-pore K+ channels to cardiac ventricular action potential revealed using human iPSC-derived cardiomyocytes. (United States)

    Chai, Sam; Wan, Xiaoping; Nassal, Drew M; Liu, Haiyan; Moravec, Christine S; Ramirez-Navarro, Angelina; Deschênes, Isabelle


    Two-pore K + (K 2p ) channels have been described in modulating background conductance as leak channels in different physiological systems. In the heart, the expression of K 2p channels is heterogeneous with equivocation regarding their functional role. Our objective was to determine the K 2p expression profile and their physiological and pathophysiological contribution to cardiac electrophysiology. Induced pluripotent stem cells (iPSCs) generated from humans were differentiated into cardiomyocytes (iPSC-CMs). mRNA was isolated from these cells, commercial iPSC-CM (iCells), control human heart ventricular tissue (cHVT), and ischemic (iHF) and nonischemic heart failure tissues (niHF). We detected 10 K 2p channels in the heart. Comparing quantitative PCR expression of K 2p channels between human heart tissue and iPSC-CMs revealed K 2p 1.1, K 2p 2.1, K 2p 5.1, and K 2p 17.1 to be higher expressed in cHVT, whereas K 2p 3.1 and K 2p 13.1 were higher in iPSC-CMs. Notably, K 2p 17.1 was significantly lower in niHF tissues compared with cHVT. Action potential recordings in iCells after K 2p small interfering RNA knockdown revealed prolongations in action potential depolarization at 90% repolarization for K 2p 2.1, K 2p 3.1, K 2p 6.1, and K 2p 17.1. Here, we report the expression level of 10 human K 2p channels in iPSC-CMs and how they compared with cHVT. Importantly, our functional electrophysiological data in human iPSC-CMs revealed a prominent role in cardiac ventricular repolarization for four of these channels. Finally, we also identified K 2p 17.1 as significantly reduced in niHF tissues and K 2p 4.1 as reduced in niHF compared with iHF. Thus, we advance the notion that K 2p channels are emerging as novel players in cardiac ventricular electrophysiology that could also be remodeled in cardiac pathology and therefore contribute to arrhythmias. NEW & NOTEWORTHY Two-pore K + (K 2p ) channels are traditionally regarded as merely background leak channels in myriad

  3. Changes in the action potential and transient outward potassium current in cardiomyocytes during acute cardiac rejection in rats. (United States)

    Luo, Wenqi; Jia, Yixin; Zheng, Shuai; Li, Yan; Han, Jie; Meng, Xu


    Acute cardiac rejection contributes to the changes in the electrophysiological properties of grafted hearts. However, the electrophysiological changes of cardiomyocytes during acute cardiac rejection are still unknown. An understanding of the electrophysiological mechanisms of cardiomyocytes could improve the diagnosis and treatment of acute cardiac rejection. So it is important to characterize the changes in the action potential ( AP ) and the transient outward potassium current ( I to ) in cardiomyocytes during acute cardiac rejection. Heterotopic heart transplantation was performed in allogeneic [Brown Norway (BN)-to-Lewis] and isogeneic (BN-to-BN) rats. Twenty models were established in each group. Ten recipients were sacrificed at the 2nd day and the other ten recipients were sacrificed at the 4 th day after the operation in each group. Histopathological examinations of the grafted hearts were performed in half of the recipients in each group randomly. The other half of the grafted hearts were excised rapidly and enzymatically dissociated to obtain single cardiomyocytes. The AP and I to current were recorded using the whole cell patch-clamp technique. Forty grafted hearts were successfully harvested and used in experiments. Histologic examination showed mild rejection at the 2 nd day and moderate rejection at the 4 th day in the allogeneic group after cardiac transplantation, while no evidence of histologic lesions of rejection were observed in the isogeneic group. Compared with the isogeneic group, the action potential duration ( APD ) of cardiomyocytes in the allogeneic group was significantly prolonged ( APD 90 was 49.28±5.621 mV in the isogeneic group and 88.08±6.445 mV in the allogeneic group at the 2 nd day, P=0.0016; APD 90 was 59.34±5.183 mV in the isogeneic group and 104.0±9.523 mV in the allogeneic group at the 4 th day, P=0.0064). The current density of I to was significantly decreased at the 4 th day after cardiac transplantation. The APD of

  4. Corrosion potential detection method, potential characteristic simulation method for reaction rate and plant monitoring system using the same

    International Nuclear Information System (INIS)

    Sakai, Masanori; Onaka, Noriyuki; Takahashi, Tatsuya; Yamanaka, Hiroshi.


    In a calculation controlling device for a plant monitoring system, concentrations of materials concerning reaction materials in a certain state of a reaction process, and an actually measured value for the potential of a material in this state are substituted into a reaction rate equation obtained in accordance with a reaction process model. With such procedures, a relation between the reaction rate (current value) and the potential of the material can be obtained. A potential at which the reaction rates of an anode reaction and a cathode reaction contained in a corrosion reaction are made equal is determined by a numerical value calculation, based on an electrochemical hybrid potential logic by using the reaction rate equation, the reaction rate information relative to the corrosion reaction of the material and the concentration of the material concerning the corrosion reaction is obtained by a numerical value calculation. Then, simulation for the corrosion potential is enabled based on the handling corresponding to the actual reaction. Further, even for a portion which can not be measured actually, the corrosion potential can be recognized by simulation. (N.H.)


    Matsumoto, Kensaku; Okada, Takashi; Takeuchi, Atsuo; Yazawa, Masato; Uchibori, Sumio; Shimizu, Yoshihiko

    Field Measurement of Self Potential Method using Copper Sulfate Electrode was performed in base of riverbank in WATARASE River, where has leakage problem to examine leakage characteristics. Measurement results showed typical S-shape what indicates existence of flow groundwater. The results agreed with measurement results by Ministry of Land, Infrastructure and Transport with good accuracy. Results of 1m depth ground temperature detection and Chain-Array detection showed good agreement with results of the Self Potential Method. Correlation between Self Potential value and groundwater velocity was examined model experiment. The result showed apparent correlation. These results indicate that the Self Potential Method was effective method to examine the characteristics of ground water of base of riverbank in leakage problem.

  6. Action Learning: Avoiding Conflict or Enabling Action (United States)

    Corley, Aileen; Thorne, Ann


    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…

  7. Perspectives on the production, structural characteristics and potential applications of bioplastics derived from polyhydroxyalkanoates. (United States)

    Albuquerque, Priscilla B S; Malafaia, Carolina B


    Since the last two decades, the use of synthetic materials has increased and become more frequent in this capitalist system. Polymers used as raw materials are usually disposed very rapidly and considered serious damages when they return to the environment. Because of this behaviour, there was an increasing in the global awareness by minimizing the waste generated, in addition to the scientific community concern for technological alternatives to solve this problem. Alternatively, biodegradable polymers are attracting special interest due to their inherent properties, which are similar to the ones of the conventional plastics. Bioplastics covers plastics made from renewable resources, including plastics that biodegrade under controlled conditions at the end of their use phase. Polyhydroxyalkanoates (PHAs) are polyesters composed of hydroxy acids, synthesized by a variety of microorganisms as intracellular carbon and energy storage. These environmentally friendly biopolymers have excellent potential in domestic, agricultural, industrial and medical field, however their production on a large scale is still limited. This review considered the most recent scientific publications on the production of bioplastics based on PHAs, their structural characteristics and the exploitation of different renewable sources of raw materials. In addition, there were also considered the main biotechnological applications of these biopolymers. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Cadmium tolerance and accumulation characteristics of Bidens pilosa L. as a potential Cd-hyperaccumulator

    International Nuclear Information System (INIS)

    Sun Yuebing; Zhou Qixing; Wang Lin; Liu Weitao


    Recently, researchers are becoming interested in using hyperaccumulators for decontamination of heavy metal polluted soils, whereas few species that hyperaccumulate cadmium (Cd) has been identified in the plant kingdom. In this study, the physiological mechanisms at the seedling stage and growth responses and Cd uptake and accumulation at flowering and mature stages of Bidens pilosa L. under Cd treatments were investigated. At the seedling stage, when soil Cd was lower than 16 mg kg -1 , the plant did not show obvious symptom of phytoxicity, and the alterations of chlorophyll (CHL), superoxide dismutase (SOD), peroxidase (POD), malondialdehyde (MDA), and soluble protein (SP) did not have significant differences when compared with the control. At the flowering and mature stages, under low Cd treatments (≤16 mg kg -1 ), the application of Cd could facilitate plant growth, resulting in 3.9-11.0% and 5.9-13.8%, respectively, increase in shoots dry biomass compared with the control. The Cd concentrations in stems, leaves and shoots exceeded 100 mg kg -1 when soil Cd was at 8 mg kg -1 , and they were positively correlated with Cd concentration in soils, the bioaccumulation factor (BF) and translocation factor (TF) values were all greater than 1.0. Thus, it is clear that B. pilosa has the basic characteristics of a Cd-hyperaccumulator. All the results elementarily indicated that B. pilosa is a potential Cd-hyperaccumulating plant

  9. Evaluation of soil characteristics potentially affecting arsenic concentration in paddy rice (Oryza sativa L.)

    International Nuclear Information System (INIS)

    Bogdan, Katja; Schenk, Manfred K.


    Paddy rice may contribute considerably to the human intake of As. The knowledge of soil characteristics affecting the As content of the rice plant enables the development of agricultural measures for controlling As uptake. During field surveys in 2004 and 2006, plant samples from 68 fields (Italy, Po-area) revealed markedly differing As concentration in polished rice. The soil factors total As (aquaregia) , pH, grain size fractions, total C, plant available P (CAL) , poorly crystalline Fe (oxal.) and plant available Si (Na-acetate) content that potentially affect As content of rice were determined. A multiple linear regression analysis showed a significant positive influence of the total As (aquaregia) and plant available P (CAL) content and a negative influence of the poorly crystalline Fe (oxal.) content of the soil on the As content in polished rice and rice straw. Si concentration in rice straw varied widely and was negatively related to As content in straw and polished rice. - Field selection for total As, poorly crystalline Fe and plant available P in soil might contribute to control As content of paddy rice.

  10. Characteristics of electron cyclotron waves creating field-aligned and transverse plasma-potential structures

    International Nuclear Information System (INIS)

    Takahashi, K; Kaneko, T; Hatakeyama, R; Fukuyama, A


    Characteristics of electromagnetic waves of azimuthal mode number m = ±1 are investigated experimentally, analytically and numerically when the waves triggering the field-aligned and transverse plasma-potential structure modification near an electron cyclotron resonance (ECR) point are injected into an inhomogeneously magnetized plasma with high-speed ion flow. The waves of m = +1 and -1 modes generate an electric double layer near the ECR point at the radially central and peripheral areas of the plasma column, respectively, and the transverse electric fields are consequently formed. At these areas the waves have a right-handed polarization and are absorbed through the ECR mechanism, where the experimental and analytical results do show the polarization reversal along the radial axis. The numerical results by plasma analysis by finite element method (FEM)/wave analysis by FEM (PAF/WF) code show that the wave-absorption area is localized at the radially central and peripheral areas for m = +1 and -1 mode waves, respectively, being consistent with the experimental and analytical ones.

  11. Peri-urban dairy production systems in developing countries: Characteristics, potential and opportunities for improvement

    International Nuclear Information System (INIS)

    Devendra, C.


    Full text: Peri-urban dairy production systems in developing countries are discussed with reference to type of systems, their characteristics, potential, and opportunities for improvement. Three types of dairy systems are identified and described: smallholder systems, smallholder co-perative dairy production systems, and intensive dairy production systems. The first two systems are by far the most important, and are associated with increasing intensification. Buffaloes are especially important in South Asia, but elsewhere dairy production mainly involves Holstein-Friesian cross-bred cattle. Dairy goats are important in some countries, but are generally neglected in development programmes. The expansion and intensification of peri-urban dairy production is fuelled by increased demand for milk with associated problems of milk handling and distribution, hygiene and environmental pollution. The major constraints to production are inter alia, choice of species, breeds and availability of animals; feed resources and improved feeding systems; improved breeding, reproduction, and animal health care; management of animal manure, and organised marketing, and market outlets. These constraints provide major opportunities and challenges for research and development to increase dairy production, efficient management of natural resources, and improved livelihoods of poor farmers. Specific areas for research are identified, as also the need of a holistic focus involving interdisciplinary research and integrated natural resource management, in a shared partnership between farmers and scientists that can demonstrate increased productivity and sustainable production systems. Suggestions for performance indicators for such systems are indicated. (author)

  12. Quantitative determination of biological activity of botulinum toxins utilizing compound muscle action potentials (CMAP), and comparison of neuromuscular transmission blockage and muscle flaccidity among toxins. (United States)

    Torii, Yasushi; Goto, Yoshitaka; Takahashi, Motohide; Ishida, Setsuji; Harakawa, Tetsuhiro; Sakamoto, Takashi; Kaji, Ryuji; Kozaki, Shunji; Ginnaga, Akihiro


    The biological activity of various types of botulinum toxin has been evaluated using the mouse intraperitoneal LD(50) test (ip LD(50)). This method requires a large number of mice to precisely determine toxin activity, and so has posed a problem with regard to animal welfare. We have used a direct measure of neuromuscular transmission, the compound muscle action potential (CMAP), to evaluate the effect of different types of botulinum neurotoxin (NTX), and we compared the effects of these toxins to evaluate muscle relaxation by employing the digit abduction scoring (DAS) assay. This method can be used to measure a broad range of toxin activities the day after administration. Types A, C, C/D, and E NTX reduced the CMAP amplitude one day after administration at below 1 ip LD(50), an effect that cannot be detected using the mouse ip LD(50) assay. The method is useful not only for measuring toxin activity, but also for evaluating the characteristics of different types of NTX. The rat CMAP test is straightforward, highly reproducible, and can directly determine the efficacy of toxin preparations through their inhibition of neuromuscular transmission. Thus, this method may be suitable for pharmacology studies and the quality control of toxin preparations. Copyright 2009 Elsevier Ltd. All rights reserved.

  13. Interactive Methods for Teaching Action Potentials, an Example of Teaching Innovation from Neuroscience Postdoctoral Fellows in the Fellowships in Research and Science Teaching (FIRST) Program (United States)

    Keen-Rhinehart, E.; Eisen, A.; Eaton, D.; McCormack, K.


    Acquiring a faculty position in academia is extremely competitive and now typically requires more than just solid research skills and knowledge of one’s field. Recruiting institutions currently desire new faculty that can teach effectively, but few postdoctoral positions provide any training in teaching methods. Fellowships in Research and Science Teaching (FIRST) is a successful postdoctoral training program funded by the National Institutes of Health (NIH) providing training in both research and teaching methodology. The FIRST program provides fellows with outstanding interdisciplinary biomedical research training in fields such as neuroscience. The postdoctoral research experience is integrated with a teaching program which includes a How to Teach course, instruction in classroom technology and course development and mentored teaching. During their mentored teaching experiences, fellows are encouraged to explore innovative teaching methodologies and to perform science teaching research to improve classroom learning. FIRST fellows teaching neuroscience to undergraduates have observed that many of these students have difficulty with the topic of neuroscience. Therefore, we investigated the effects of interactive teaching methods for this topic. We tested two interactive teaching methodologies to determine if they would improve learning and retention of this information when compared with standard lectures. The interactive methods for teaching action potentials increased understanding and retention. Therefore, FIRST provides excellent teaching training, partly by enhancing the ability of fellows to integrate innovative teaching methods into their instruction. This training in turn provides fellows that matriculate from this program more of the characteristics that hiring institutions desire in their new faculty. PMID:23493377

  14. Anticancer potential and mechanism of action of mango ginger (Curcuma amada Roxb.) supercritical CO₂ extract in human glioblastoma cells. (United States)

    Ramachandran, Cheppail; Lollett, Ivonne V; Escalon, Enrique; Quirin, Karl-Werner; Melnick, Steven J


    Mango ginger (Curcuma amada Roxb.) is among the less-investigated species of Curcuma for anticancer properties. We have investigated the anticancer potential and the mechanism of action of a supercritical CO2 extract of mango ginger (CA) in the U-87MG human glioblastoma cell line. CA demonstrated higher cytotoxicity than temozolomide, etoposide, curcumin, and turmeric force with IC50, IC75, and IC90 values of 4.92 μg/mL, 12.87 μg/mL, and 21.30 μg/mL, respectively. Inhibitory concentration values of CA for normal embryonic mouse hypothalamus cell line (mHypoE-N1) is significantly higher than glioblastoma cell line, indicating the specificity of CA against brain tumor cells. CompuSyn analysis indicates that CA acts synergistically with temozolomide and etoposide for the cytotoxicity with combination index values of <1. CA treatment also induces apoptosis in glioblastoma cells in a dose-dependent manner and downregulates genes associated with apoptosis, cell proliferation, telomerase activity, oncogenesis, and drug resistance in glioblastoma cells. © The Author(s) 2014.

  15. Acute Elevated Glucose Promotes Abnormal Action Potential-Induced Ca2+ Transients in Cultured Skeletal Muscle Fibers

    Directory of Open Access Journals (Sweden)

    Erick O. Hernández-Ochoa


    Full Text Available A common comorbidity of diabetes is skeletal muscle dysfunction, which leads to compromised physical function. Previous studies of diabetes in skeletal muscle have shown alterations in excitation-contraction coupling (ECC—the sequential link between action potentials (AP, intracellular Ca2+ release, and the contractile machinery. Yet, little is known about the impact of acute elevated glucose on the temporal properties of AP-induced Ca2+ transients and ionic underlying mechanisms that lead to muscle dysfunction. Here, we used high-speed confocal Ca2+ imaging to investigate the temporal properties of AP-induced Ca2+ transients, an intermediate step of ECC, using an acute in cellulo model of uncontrolled hyperglycemia (25 mM, 48 h.. Control and elevated glucose-exposed muscle fibers cultured for five days displayed four distinct patterns of AP-induced Ca2+ transients (phasic, biphasic, phasic-delayed, and phasic-slow decay; most control muscle fibers show phasic AP-induced Ca2+ transients, while most fibers exposed to elevated D-glucose displayed biphasic Ca2+ transients upon single field stimulation. We hypothesize that these changes in the temporal profile of the AP-induced Ca2+ transients are due to changes in the intrinsic excitable properties of the muscle fibers. We propose that these changes accompany early stages of diabetic myopathy.

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

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


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

  17. Establishment of alternative potency test for botulinum toxin type A using compound muscle action potential (CMAP) in rats. (United States)

    Torii, Yasushi; Goto, Yoshitaka; Nakahira, Shinji; Ginnaga, Akihiro


    The biological activity of botulinum toxin type A has been evaluated using the mouse intraperitoneal (ip) LD50 test. This method requires a large number of mice to precisely determine toxin activity, and, as such, poses problems with regard to animal welfare. We previously developed a compound muscle action potential (CMAP) assay using rats as an alternative method to the mouse ip LD50 test. In this study, to evaluate this quantitative method of measuring toxin activity using CMAP, we assessed the parameters necessary for quantitative tests according to ICH Q2 (R1). This assay could be used to evaluate the activity of the toxin, even when inactive toxin was mixed with the sample. To reduce the number of animals needed, this assay was set to measure two samples per animal. Linearity was detected over a range of 0.1-12.8 U/mL, and the measurement range was set at 0.4-6.4 U/mL. The results for accuracy and precision showed low variability. The body weight was selected as a variable factor, but it showed no effect on the CMAP amplitude. In this study, potency tests using the rat CMAP assay of botulinum toxin type A demonstrated that it met the criteria for a quantitative analysis method. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels

    International Nuclear Information System (INIS)

    Franzellitti, Silvia; Buratti, Sara; Capolupo, Marco; Du, Bowen; Haddad, Samuel P.; Chambliss, C. Kevin; Brooks, Bryan W.; Fabbri, Elena


    Highlights: • Mode of action (MOA) related endpoints and biomarkers of toxicity were assessed in mussels exposed to fluoxetine (FX). • Significant FX bioaccumulation was observed in tissues of mussels exposed to 30 and 300 ng/L FX. • Alterations of cAMP-related cell signaling were observed in exposed mussels as part of the MOA of FX. • FX reduced the health status of mussels inducing lysosomal effects in digestive gland and antioxidant responses in gills. • The importance of considering additional MOAs and adverse outcome pathways for FX impacts on mussels is highlighted. - Abstract: The present study investigated possible adverse outcome pathways (AOPs) of the antidepressant fluoxetine (FX) in the marine mussel Mytilus galloprovincialis. An evaluation of molecular endpoints involved in modes of action (MOAs) of FX and biomarkers for sub-lethal toxicity were explored in mussels after a 7-day administration of nominal FX concentrations encompassing a range of environmentally relevant values (0.03–300 ng/L). FX bioaccumulated in mussel tissues after treatment with 30 and 300 ng/L FX, resulting in bioconcentration factor (BCF) values ranging from 200 to 800, which were higher than expected based solely on hydrophobic partitioning models. Because FX acts as a selective serotonin (5-HT) re-uptake inhibitor increasing serotonergic neurotransmission at mammalian synapses, cell signaling alterations triggered by 5-HT receptor occupations were assessed. cAMP levels and PKA activities were decreased in digestive gland and mantle/gonads of FX-treated mussels, consistent with an increased occupation of 5-HT1 receptors negatively coupled to the cAMP/PKA pathway. mRNA levels of a ABCB gene encoding the P-glycoprotein were also significantly down-regulated. This membrane transporter acts in detoxification towards xenobiotics and in altering pharmacokinetics of antidepressants; moreover, it is under a cAMP/PKA transcriptional regulation in mussels. Potential stress

  19. An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels

    Energy Technology Data Exchange (ETDEWEB)

    Franzellitti, Silvia, E-mail: [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy); Buratti, Sara; Capolupo, Marco [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); Du, Bowen; Haddad, Samuel P. [Department of Environmental Science, Baylor University, Waco, TX 76798 (United States); Chambliss, C. Kevin [Department of Chemistry and Biochemistry, Baylor University, Waco, TX 76798 (United States); Brooks, Bryan W. [Department of Environmental Science, Baylor University, Waco, TX 76798 (United States); Fabbri, Elena [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy)


    Highlights: • Mode of action (MOA) related endpoints and biomarkers of toxicity were assessed in mussels exposed to fluoxetine (FX). • Significant FX bioaccumulation was observed in tissues of mussels exposed to 30 and 300 ng/L FX. • Alterations of cAMP-related cell signaling were observed in exposed mussels as part of the MOA of FX. • FX reduced the health status of mussels inducing lysosomal effects in digestive gland and antioxidant responses in gills. • The importance of considering additional MOAs and adverse outcome pathways for FX impacts on mussels is highlighted. - Abstract: The present study investigated possible adverse outcome pathways (AOPs) of the antidepressant fluoxetine (FX) in the marine mussel Mytilus galloprovincialis. An evaluation of molecular endpoints involved in modes of action (MOAs) of FX and biomarkers for sub-lethal toxicity were explored in mussels after a 7-day administration of nominal FX concentrations encompassing a range of environmentally relevant values (0.03–300 ng/L). FX bioaccumulated in mussel tissues after treatment with 30 and 300 ng/L FX, resulting in bioconcentration factor (BCF) values ranging from 200 to 800, which were higher than expected based solely on hydrophobic partitioning models. Because FX acts as a selective serotonin (5-HT) re-uptake inhibitor increasing serotonergic neurotransmission at mammalian synapses, cell signaling alterations triggered by 5-HT receptor occupations were assessed. cAMP levels and PKA activities were decreased in digestive gland and mantle/gonads of FX-treated mussels, consistent with an increased occupation of 5-HT1 receptors negatively coupled to the cAMP/PKA pathway. mRNA levels of a ABCB gene encoding the P-glycoprotein were also significantly down-regulated. This membrane transporter acts in detoxification towards xenobiotics and in altering pharmacokinetics of antidepressants; moreover, it is under a cAMP/PKA transcriptional regulation in mussels. Potential stress

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

    Directory of Open Access Journals (Sweden)

    Erum Malik


    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

  1. Molecular characteristics and virulence potential of Listeria monocytogenes isolates from Chinese food systems. (United States)

    Chen, Jianshun; Luo, Xiaokai; Jiang, Lingli; Jin, Peijie; Wei, Wei; Liu, Dongyou; Fang, Weihuan


    In this study, we examined Listeria monocytogenes isolates from Chinese food sources in an attempt to gain further insights on the molecular characteristics and virulence potential of this important foodborne pathogen. Of the 88 L. monocytogenes food isolates recovered, 42 (47.7%) were of serovars 1/2a or 3a; 23 (26.1%) of serovars 1/2b or 3b; 15 (17.0%) of 1/2c or 3c; 6 (6.8%) of serovars 4b, 4d or 4e; and 2 (2.2%) of serovars 4a or 4c. In contrast to inlAB locus conserved in all serovars, internalin cluster between ascB and dapE varies with different serovars, with inlC2DE, inlGC2DE and inlGHE predominantly in serovars 1/2b or 4b, serovar 1/2a and serovar 1/2c. While inlF existed in all the inlGHE- and inlGC2DE-containing isolates but 17.4% of those having inlC2DE, lmo2026 existed in all the inlGHE-containing isolates but 20.0% of those bearing inlGC2DE, suggesting that inlF might have co-evolved with inlGC2DE and inlGHE while lmo2026 with inlGHE only. With the exception of serovar 4a isolate, most serovar isolates demonstrated remarkable ability to form plaques on L929 cells and produced significant mouse mortality irrespective of the internalin gene organization and whether an intact actA gene is present or not. These results indicate that majority of these food isolates may have the potential to cause human diseases if ingested via contaminated foods. Given that serovar 4b accounts for nearly half of human clinical listeriosis cases documented, the relative low proportion of serovar 4b food isolates suggests that this serovar is probably more tolerant of the adverse conditions in the host's stomach and/or more efficient in entering host cells than serovars 1/2a, 1/2b and 1/2c.

  2. Time-response characteristic and potential biomarker identification of heavy metal induced toxicity in zebrafish. (United States)

    Yin, Jian; Wang, Ai-Ping; Li, Wan-Fang; Shi, Rui; Jin, Hong-Tao; Wei, Jin-Feng


    The present work aims to explore the time-response (from 24 h to 96 h) characteristic and identify early potential sensitive biomarkers of copper (Cu) (as copper chloride dihydrate), cadmium (Cd) (as cadmium acetate), lead (Pb) (as lead nitrate) and chromium (Cr) (as potassium dichromate) exposure in adult zebrafish, focusing on reactive oxygen species (ROS), SOD activity, lipid peroxidation and gene expression related to oxidative stress and inflammatory response. Furthermore, the survival rate decreased apparently by a concentration-dependent manner after Cu, Cr, Cd and Pb exposure, and we selected non-lethal concentrations 0.05 mg/L for Cu, 15 mg/L for Cr, 3 mg/L for Cd and 93.75μg/L for Pb to test the effect on the following biological indicators. Under non-lethal concentration, the four heavy metals have no apparent histological change in adult zebrafish gills. Similar trends in ROS production, MDA level and SOD activity were up-regulated by the four heavy metals, while MDA level responded more sensitive to Pb by time-dependent manner than the other three heavy metals. In addition, mRNA levels related to antioxidant system (SOD1, SOD2 and Nrf2) were up-regulated by non-lethal concentration Cu, Cr, Cd and Pb exposure. MDA level and SOD1 gene have a more delayed response to heavy metals. Genes related to immunotoxicity were increased significantly after heavy metals exposure at non-lethal concentrations. TNF-α and IL-1β gene have similar sensibility to the four heavy metals, while IL-8 gene was more responsive to Cr, Cd and Pb exposure at 48 h groups and IFN-γ gene showed more sensitivity to Cu at 48 h groups than the other heavy metals. In conclusion, the present works have suggested that the IFN-γ gene may applied as early sensitive biomarker to identify Cu-induced toxicity, while MDA content and IL-8 gene may use as early sensitive biomarkers for evaluating the risk of Pb exposure. Moreover, IL-8 and IFN-γ gene were more responsive to heavy

  3. Similar simulation study on the characteristics of the electric potential response to coal mining (United States)

    Niu, Yue; Li, Zhonghui; Kong, Biao; Wang, Enyuan; Lou, Quan; Qiu, Liming; Kong, Xiangguo; Wang, Jiali; Dong, Mingfu; Li, Baolin


    An electric potential (EP) can be generated during the failure process of coal and rock. In this article, a similar physical model of coal rock was built and the characteristics of the EP responding to the process of coal mining were studied. The results showed that, at the early mining stage, the structure of coal rock strata were stable in the simulation model, the support stress of overlying coal rock strata was low and the maximum subsidence was little, while the EP change was less. With the advancement of the working face, the support stress of the overlying coal rock strata in the mined-out area changed dramatically, the maximum subsidence increased constantly, the deformation and destruction were aggravated, and cracks expanded continuously. Meanwhile, the EP response was significant with fluctuation. When significant macro damage appeared in coal rock strata, the EP signal fluctuation was violent. The overlying coal rock strata were influenced by gravity and mining activity. During the mining process, the crack growth and the friction, together with slip between coal and rock particles, resulted in the response of EP. The change in EP was closely related to the damage state and stress distribution of the coal rock strata. EP monitoring has the advantages of accurate reflection and strong anti-interference in the field. Therefore, with further study, an EP monitoring method could be applied for monitoring and early warning of coal and rock dynamic disaster, and risk evaluation in the future. The strength of the EP and its fluctuation degree could serve as the key discrimination indexes.

  4. Land characteristics, run-off and potential for rainwater harvesting in ...

    African Journals Online (AJOL)

    Effective utilization of rainfall in semi-arid areas is very much dependent on land characteristics land use, and management practices. Important land characteristics include soil, type, soil hydraulic properties down the profile, soil valiation along-the catena, slope and vegetation cover. In most semi-mid areas of Tanzania, ...

  5. Real-time relationship between PKA biochemical signal network dynamics and increased action potential firing rate in heart pacemaker cells (United States)

    Yaniv, Yael; Ganesan, Ambhighainath; Yang, Dongmei; Ziman, Bruce D.; Lyashkov, Alexey E.; Levchenko, Andre; Zhang, Jin; Lakatta, Edward G.


    cAMP-PKA protein kinase is a key nodal signaling pathway that regulates a wide range of heart pacemaker cell functions. These functions are predicted to be involved in regulation of spontaneous action potential (AP) generation of these cells. Here we investigate if the kinetics and stoichiometry of increase in PKA activity match the increase in AP firing rate in response to β-adrenergic receptor (β-AR) stimulation or phosphodiesterase (PDE) inhibition, that alter the AP firing rate of heart sinoatrial pacemaker cells. In cultured adult rabbit pacemaker cells infected with an adenovirous expressing the FRET sensor AKAR3, the EC50 in response to graded increases in the intensity of β-AR stimulation (by Isoproterenol) the magnitude of the increases in PKA activity and the spontaneous AP firing rate were similar (0.4±0.1nM vs. 0.6±0.15nM, respectively). Moreover, the kinetics (t1/2) of the increases in PKA activity and spontaneous AP firing rate in response to β-AR stimulation or PDE inhibition were tightly linked. We characterized the system rate-limiting biochemical reactions by integrating these experimentally derived data into mechanistic-computational model. Model simulations predicted that phospholamban phosphorylation is a potent target of the increase in PKA activity that links to increase in spontaneous AP firing rate. In summary, the kinetics and stoichiometry of increases in PKA activity in response to a physiological (β-AR stimulation) or pharmacological (PDE inhibitor) stimuli match those of changes in the AP firing rate. Thus Ca2+-cAMP/PKA-dependent phosphorylation limits the rate and magnitude of increase in spontaneous AP firing rate. PMID:26241846

  6. Intraoperative cochlear nerve mapping with the mobile cochlear nerve compound action potential tracer in vestibular schwannoma surgery. (United States)

    Watanabe, Nobuyuki; Ishii, Takuya; Fujitsu, Kazuhiko; Kaku, Shogo; Ichikawa, Teruo; Miyahara, Kosuke; Okada, Tomu; Tanino, Shin; Uriu, Yasuhiro; Murayama, Yuichi


    OBJECTIVE The authors describe the usefulness and limitations of the cochlear nerve compound action potential (CNAP) mobile tracer (MCT) that they developed to aid in cochlear nerve mapping during vestibular schwannoma surgery (VSS) for hearing preservation. METHODS This MCT device requires no more than 2 seconds for stable placement on the nerve to obtain the CNAP and thus is able to trace the cochlear nerve instantaneously. Simultaneous bipolar and monopolar recording is possible. The authors present the outcomes of 18 consecutive patients who underwent preoperative useful hearing (defined as class I or II of the Gardner-Robertson classification system) and underwent hearing-preservation VSS with the use of the MCT. Mapping was considered successful when it was possible to detect and trace the cochlear nerve. RESULTS Mapping of the cochlear nerve was successful in 13 of 18 patients (72.2%), and useful hearing was preserved in 11 patients (61.1%). Among 8 patients with large tumors (Koos grade 3 or 4), the rate of successful mapping was 62.5% (5 patients). The rate of hearing preservation in patients with large tumors was 50% (4 patients). CONCLUSIONS In addition to microsurgical presumption of the arrangement of each nerve, frequent probing on and around an unidentified nerve and comparison of each waveform are advisable with the use of both more sensitive monopolar and more location-specific bipolar MCT. MCT proved to be useful in cochlear nerve mapping and may consequently be helpful in hearing preservation. The authors discuss some limitations and problems with this device.

  7. Action potential-evoked calcium release is impaired in single skeletal muscle fibers from heart failure patients.

    Directory of Open Access Journals (Sweden)

    Marino DiFranco

    Full Text Available Exercise intolerance in chronic heart failure (HF has been attributed to abnormalities of the skeletal muscles. Muscle function depends on intact excitation-contraction coupling (ECC, but ECC studies in HF models have been inconclusive, due to deficiencies in the animal models and tools used to measure calcium (Ca2+ release, mandating investigations in skeletal muscle from HF patients. The purpose of this study was to test the hypothesis that Ca2+ release is significantly impaired in the skeletal muscle of HF patients in whom exercise capacity is severely diminished compared to age-matched healthy volunteers.Using state-of-the-art electrophysiological and optical techniques in single muscle fibers from biopsies of the locomotive vastus lateralis muscle, we measured the action potential (AP-evoked Ca2+ release in 4 HF patients and 4 age-matched healthy controls. The mean peak Ca2+ release flux in fibers obtained from HF patients (10±1.2 µM/ms was markedly (2.6-fold and significantly (p<0.05 smaller than in fibers from healthy volunteers (28±3.3 µM/ms. This impairment in AP-evoked Ca2+ release was ubiquitous and was not explained by differences in the excitability mechanisms since single APs were indistinguishable between HF patients and healthy volunteers.These findings prove the feasibility of performing electrophysiological experiments in single fibers from human skeletal muscle, and offer a new approach for investigations of myopathies due to HF and other diseases. Importantly, we have demonstrated that one step in the ECC process, AP-evoked Ca2+ release, is impaired in single muscle fibers in HF patients.

  8. Role of glycolysis in maintenance of the action potential duration and contractile activity in isolated perfused rat heart. (United States)

    Opie, L H; Tuschmidt, R; Bricknell, O; Girardier, L


    1. Changing substrates from glucose to pyruvate in paced isolated rat hearts, perfused by the Langendorff technique at 65 cm H2O with a Krebs-Henseleit bicarbonate buffer, produced effects which are opposite to those of ouabain treatment: negative inotropy, decreased work efficiency, hyperpolarization, increased maximum rate of rise and amplitude of the action potential, increased conduction velocity. 2. All the effects resulting from perfusion with pyruvate can be reversed by adding ouabain at a concentration of 100 microM. 3. The correlation between various tissue metabolises and change in contractile force (delta F), rate of tension development [maximum + (dF/dt)] and rate of relaxation [maximum -(dF/dt)] was studied by multiple linear regression. No significant correlation was found with either glycogen content and tissue lactate or with cAMP and cGMP. A weak negative correlation was found with ATP and phosphocreatine. The strongest correlation was found 76 to 807 nM/g in passing from glucose- to pyruvate-containing perfusion solution. 4. In vitro tests performed with a solution containing high energy phosphates and magnesium at concentrations equal to their calculated values in the cytosol (pH 7.0) showed that a significant negative correlation exists between citrate concentration (range: 1 and 1500 M) and free calcium concentration in the micromole range. 5. It is concluded that the effects of pyruvate (non glucose substrate) perfusion could be mediated by a decrease in cytosolic-free calcium resulting from an increase in intracellular citrate. The observation that all these effects can be reversed by ouabain is taken as a circumstantial evidence of a common mechanism.

  9. Role of suppression of the inward rectifier current in terminal action potential repolarization in the failing heart. (United States)

    Klein, Michael G; Shou, Matie; Stohlman, Jayna; Solhjoo, Soroosh; Haigney, Myles; Tidwell, Richard R; Goldstein, Robert E; Flagg, Thomas P; Haigney, Mark C


    The failing heart exhibits an increased arrhythmia susceptibility that is often attributed to action potential (AP) prolongation due to significant ion channel remodeling. The inwardly rectifying K + current (I K1 ) has been reported to be reduced, but its contribution to shaping the AP waveform and cell excitability in the failing heart remains unclear. The purpose of this study was to define the effect of I K1 suppression on the cardiac AP and excitability in the normal and failing hearts. We used electrophysiological and pharmacological approaches to investigate I K1 function in a swine tachy-pacing model of heart failure (HF). Terminal repolarization of the AP (TRAP; the time constant of the exponential fit to terminal repolarization) was markedly prolonged in both myocytes and arterially perfused wedges from animals with HF. TRAP was increased by 54.1% in HF myocytes (P < .001) and 26.2% in HF wedges (P = .014). The increase in TRAP was recapitulated by the potent and specific I K1 inhibitor, PA-6 (pentamidine analog 6), indicating that I K1 is the primary determinant of the final phase of repolarization. Moreover, we find that I K1 suppression reduced the ratio of effective refractory period to AP duration at 90% of repolarization, permitting re-excitation before full repolarization, reduction of AP upstroke velocity, and likely promotion of slow conduction. Using an objective measure of terminal repolarization, we conclude that I K1 is the major determinant of the terminal repolarization time course. Moreover, suppression of I K1 prolongs repolarization and reduces postrepolarization refractoriness without marked effects on the overall AP duration. Collectively, these findings demonstrate how I K1 suppression may contribute to arrhythmogenesis in the failing heart. Published by Elsevier Inc.

  10. A Parsimonious Model of the Rabbit Action Potential Elucidates the Minimal Physiological Requirements for Alternans and Spiral Wave Breakup. (United States)

    Gray, Richard A; Pathmanathan, Pras


    Elucidating the underlying mechanisms of fatal cardiac arrhythmias requires a tight integration of electrophysiological experiments, models, and theory. Existing models of transmembrane action potential (AP) are complex (resulting in over parameterization) and varied (leading to dissimilar predictions). Thus, simpler models are needed to elucidate the "minimal physiological requirements" to reproduce significant observable phenomena using as few parameters as possible. Moreover, models have been derived from experimental studies from a variety of species under a range of environmental conditions (for example, all existing rabbit AP models incorporate a formulation of the rapid sodium current, INa, based on 30 year old data from chick embryo cell aggregates). Here we develop a simple "parsimonious" rabbit AP model that is mathematically identifiable (i.e., not over parameterized) by combining a novel Hodgkin-Huxley formulation of INa with a phenomenological model of repolarization similar to the voltage dependent, time-independent rectifying outward potassium current (IK). The model was calibrated using the following experimental data sets measured from the same species (rabbit) under physiological conditions: dynamic current-voltage (I-V) relationships during the AP upstroke; rapid recovery of AP excitability during the relative refractory period; and steady-state INa inactivation via voltage clamp. Simulations reproduced several important "emergent" phenomena including cellular alternans at rates > 250 bpm as observed in rabbit myocytes, reentrant spiral waves as observed on the surface of the rabbit heart, and spiral wave breakup. Model variants were studied which elucidated the minimal requirements for alternans and spiral wave break up, namely the kinetics of INa inactivation and the non-linear rectification of IK.The simplicity of the model, and the fact that its parameters have physiological meaning, make it ideal for engendering generalizable mechanistic

  11. Effect of mental challenge induced by movie clips on action potential duration in normal human subjects independent of heart rate. (United States)

    Child, Nicholas; Hanson, Ben; Bishop, Martin; Rinaldi, Christopher A; Bostock, Julian; Western, David; Cooklin, Michael; O'Neil, Mark; Wright, Matthew; Razavi, Reza; Gill, Jaswinder; Taggart, Peter


    Mental stress and emotion have long been associated with ventricular arrhythmias and sudden death in animal models and humans. The effect of mental challenge on ventricular action potential duration (APD) in conscious healthy humans has not been reported. Activation recovery intervals measured from unipolar electrograms as a surrogate for APD (n=19) were recorded from right and left ventricular endocardium during steady-state pacing, whilst subjects watched an emotionally charged film clip. To assess the possible modulating role of altered respiration on APD, the subjects then repeated the same breathing pattern they had during the stress, but without the movie clip. Hemodynamic parameters (mean, systolic, and diastolic blood pressure, and rate of pressure increase) and respiration rate increased during the stressful part of the film clip (P=0.001). APD decreased during the stressful parts of the film clip, for example, for global right ventricular activation recovery interval at end of film clip 193.8 ms (SD, 14) versus 198.0 ms (SD, 13) during the matched breathing control (end film left ventricle 199.8 ms [SD, 16] versus control 201.6 ms [SD, 15]; P=0.004). Respiration rate increased during the stressful part of the film clip (by 2 breaths per minute) and was well matched in the respective control period without any hemodynamic or activation recovery interval changes. Our results document for the first time direct recordings of the effect of a mental challenge protocol on ventricular APD in conscious humans. The effect of mental challenge on APD was not secondary to emotionally induced altered respiration or heart rate. © 2014 American Heart Association, Inc.

  12. Evaluation of Nystatin Containing Chitosan Hydrogels as Potential Dual Action Bio-Active Restorative Materials: in Vitro Approach

    Directory of Open Access Journals (Sweden)

    V. Tamara Perchyonok


    Full Text Available Healing is a specific biological process related to the general phenomenon of growth and tissue regeneration and is a process generally affected by several systemic conditions or as detrimental side-effects of chemotherapy- and radiotherapy-induced inflammation of the oral mucosa. The objectives of this study is to evaluate the novel chitosan based functional drug delivery systems, which can be successfully incorporated into “dual action bioactive restorative materials”, capable of inducing in vitro improved wound healing prototype and containing an antibiotic, such as nystatin, krill oil as an antioxidant and hydroxyapatite as a molecular bone scaffold, which is naturally present in bone and is reported to be successfully used in promoting bone integration when implanted as well as promoting healing. The hydrogels were prepared using a protocol as previously reported by us. The physico-chemical features, including surface morphology (SEM, release behaviors, stability of the therapeutic agent-antioxidant-chitosan, were measured and compared to the earlier reported chitosan-antioxidant containing hydrogels. Structural investigations of the reactive surface of the hydrogel are reported. Release of nystatin was investigated for all newly prepared hydrogels. Bio-adhesive studies were performed in order to assess the suitability of these designer materials. Free radical defense capacity of the biomaterials was evaluated using established in vitro model. The bio-adhesive capacity of the materials in the in vitro system was tested and quantified. It was found that the favorable synergistic effect of free radical built-in defense mechanism of the new functional materials increased sustainable bio-adhesion and therefore acted as a functional multi-dimensional restorative material with potential application in wound healing in vitro.

  13. New evidence for primordial action site of Fluazifop-P-butyl on Acanthospermum hispidum seedlings: From the effects on chlorophyll fluorescence characteristics and histological observation. (United States)

    Shang, Yuhong; Yang, Congjun; Liu, Zhihang; Song, Jiqing; Li, Pingliang; Li, Lingxu; Zhou, Fei; Xin, Hua; Wan, Fanghao; Matsumoto, Hiroshi; Luo, Xiaoyong


    Acanthospermum hispidum DC, an Asteraceae weed species, was very susceptible to fluazifop-P-butyl, but tolerant to other aryloxyphenoxypropionate herbicides, such as haloxyfop-P-methyl. However, other Asteraceae weeds including Bidens pilosa were all tolerant to fluazifop-P-butyl. Membrane lipid peroxidation by increasing the levels of reactive oxygen species (ROS) was proposed as an action mechanism of fluazifop-P-butyl in A. hispidum. To further clarify the primordial action site of fluazifop-P-butyl in this species, the effects on chlorophyll fluorescence characteristics and cytohistology of apical meristems were studied. Chlorophyll fluorescence characteristics (CFC) in sensitive A. hispidum seedlings were markedly affected by 10μM fluazifop-P-butyl, with the dark fluorescence yield (Fo), maximal fluorescence yield (Fm), maximal PS II quantum yield (Fv/Fm), effective photosystem II (PS II) quantum yield [Y(II)], and quantum yield of regulated energy dissipation [Y(NPQ)] declining, quantum yield of nonregulated energy dissipation [Y(NO)] rising, but these measures were not affected in Bidens pilosa. The effects of fluazifop-P-butyl on chlorophyll fluorescence properties were observed on the growing point before the mature leaves by about 4-6h. Haloxyfop-P-methyl, a control herbicide, had no effects on CFC of either A. hispidum or B. pilosa. In addition, damage to apical meristem cells of A. hispidum was observed at 6 HAT prior to changes in chlorophyll fluorescence parameters suggesting that the primary action site of fluazifop-P-butyl in this species is in the apical meristem and the effects on CFC may be the results of secondary action. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Florida long-distance travel characteristics and their potential impacts on the transportation system. (United States)


    The overall goal of this project is to enhance the fundamental understanding of Florida long-distance travel characteristics, and to provide policy implications for long-distance transportation planning in the future. To achieve the research goal, th...

  15. Normative findings of electrically evoked compound action potential measurements using the neural response telemetry of the Nucleus CI24M cochlear implant system.

    NARCIS (Netherlands)

    Cafarelli-Dees, D.; Dillier, N.; Lai, W.K.; Wallenberg, E. von; Dijk, B. van; Akdas, F.; Aksit, M.; Batman, C.; Beynon, A.J.; Burdo, S.; Chanal, J.M.; Collet, L.; Conway, M.; Coudert, C.; Craddock, L.; Cullington, H.; Deggouj, N.; Fraysse, B.; Grabel, S.; Kiefer, J.; Kiss, J.G.; Lenarz, T.; Mair, A.; Maune, S.; Muller-Deile, J.; Piron, J.P.; Razza, S.; Tasche, C.; Thai-Van, H.; Toth, F.; Truy, E.; Uziel, A.; Smoorenburg, G.F.


    One hundred and forty-seven adult recipients of the Nucleus 24 cochlear implant system, from 13 different European countries, were tested using neural response telemetry to measure the electrically evoked compound action potential (ECAP), according to a standardised postoperative measurement

  16. Subtype-specific promoter-driven action potential imaging for precise disease modelling and drug testing in hiPSC-derived cardiomyocytes

    NARCIS (Netherlands)

    Chen, Zhifen; Xian, Wenying; Bellin, Milena; Dorn, Tatjana; Tian, Qinghai; Goedel, Alexander; Dreizehnter, Lisa; Schneider, Christine M.; Ward-van Oostwaard, Dorien; Ng, Judy King Man; Hinkel, Rabea; Pane, Luna Simona; Mummery, Christine L.; Lipp, Peter; Moretti, Alessandra; Laugwitz, Karl-Ludwig; Sinnecker, Daniel


    AIMS: Cardiomyocytes (CMs) generated from human induced pluripotent stem cells (hiPSCs) are increasingly used in disease modelling and drug evaluation. However, they are typically a heterogeneous mix of ventricular-, atrial-, and nodal-like cells based on action potentials (APs) and gene expression.

  17. High frequency action potential bursts (≥ 100 Hz) in L2/3 and L5B thick tufted neurons in anaesthetized and awake rat primary somatosensory cortex

    NARCIS (Netherlands)

    C.P.J. de Kock (Christiaan); B. Sakmann (Bert)


    textabstractHigh frequency (≥ 100 Hz) bursts of action potentials (APs) generated by neocortical neurons are thought to increase information content and, through back-propagation, to influence synaptic integration and efficacy in distal dendritic compartments. It was recently shown in acute slice

  18. Energy resources of the Denver and Cheyenne Basins, Colorado - resource characteristics, development potential, and environmental problems. Environmental Geology 12

    International Nuclear Information System (INIS)

    Kirkham, R.M.; Ladwig, L.R.


    The geological characteristics, development potential, and environmental problems related to the exploration for and development of energy resources in the Denver and Cheyenne Basins of Colorado were investigated. Coal, lignite, uranium, oil and natural gas were evaluated. Emphasis is placed on environmental problems that may develop from the exploration for an extraction of these energy resources

  19. Increased transient Na+ conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1-/y mouse. (United States)

    Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H


    Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 -/y mice. In fmr1 -/y L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na + conductance density is higher in fmr1 -/y L2/3 neurons. Measurements of three biophysically distinct K + currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K + conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1 -/y mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1 -/y mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1 -/y neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na + current was significantly larger in fmr1 -/y neurons. Furthermore, the activation curve of somatic A-type K + current was depolarized. Realistic conductance-based simulations revealed that these biophysical changes in Na

  20. Sexual Assault Perpetrators’ Justifications for Their Actions: Relationships to Rape Supportive Attitudes, Incident Characteristics, and Future Perpetration (United States)

    Wegner, Rhiana; Abbey, Antonia; Pierce, Jennifer; Pegram, Sheri E.; Woerner, Jacqueline


    Perpetrators use rape supportive attitudes and sexual assault incident characteristics to justify forcing sex on their victims. Perpetrators who can justify their behaviors are at increased risk for future perpetration. This study examined the relationships between rape supportive attitudes, sexual assault incident characteristics, and the post-assault justifications of 183 men sampled from the community who self-reported committing at least one act of sexual aggression. Hierarchical multiple regression analyses indicated that rape supportive attitudes, expectations for having sex, misperceptions of sexual intent, victims’ alcohol consumption, attempts to be alone with her, and the number of consensual sexual activities prior to the unwanted sex were significant predictors of perpetrators’ post-assault use of justifications. Greater use of justifications was a significant predictor of sexual aggression over a 1-year follow-up interval. These findings demonstrate the need for further research exploring when and why perpetrators use post-assault justifications and whether they are amenable to change. PMID:26056162

  1. Energy material transport, now through 2000, system characteristics and potential problems. Task 3. Final report - petroleum transportation

    Energy Technology Data Exchange (ETDEWEB)

    DeSteese, J.G.


    This report contains a summary characterization of the petroleum transportation system and an assessment of some potential problems that may impact petroleum transportation in the United States during the balance of the century. A primary purpose of this task is to provide information and perspective that contribute to the evaluation of research and development needs and priorities in future programs. The system characterization in Section 3 includes a review of petroleum product movements, modal operations and comparisons, and transportation regulations and safety. This system overview summarizes domestic production and consumption scenarios to the year 2000. A median scenario based on published projections shows that the US will probably rely on foreign oil to supply between 40 and 50 percent of domestic petroleum needs throughout the balance of the century. Potential problems in petroleum transportation were identified by the analysis and prioritization of current issues. The relative priorities of problem concerns were judged on the basis of their overall impact on the system and the immediacy of this potential impact. Two classes of concern are distinguished: 1. Potential problems that appear to require new programmatic action, in addition to effort already committed, to minimize the possible future impact of these concerns. 2. Latent concerns that may increase or decrease in priority or entirely change in nature as they develop. While the trend of these concerns should be monitored, new program action does not appear necessary at this time.

  2. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    International Nuclear Information System (INIS)

    Fischer, L.; Deppert, W.R.; Pfeifer, D.; Stanzel, S.; Weimer, M.; Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P.; Schaefer, W.R.


    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  3. A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.

    Directory of Open Access Journals (Sweden)

    Wing-Chiu Tong


    Full Text Available Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C coupling of uterine smooth muscle cells (USMC. Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: Ca2+ currents (L- and T-type, Na+ current, an hyperpolarization-activated current, three voltage-gated K+ currents, two Ca2+-activated K+ current, Ca2+-activated Cl current, non-specific cation current, Na+-Ca2+ exchanger, Na+-K+ pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area:volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/inactivation gating variables and temporal changes in intracellular Ca2+ computed from known Ca2+ fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltage-clamp. Phasic contraction is modeled in relation to the time constant of changing [Ca2+]i. This integrated model is validated by its reconstruction of the different USMC AP configurations (spikes, plateau and bursts of spikes, the change from bursting to plateau type AP produced by estradiol and of simultaneous experimental recordings of spontaneous AP, [Ca2+]i and phasic force. In summary, our advanced mathematical model provides a powerful tool to

  4. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, L.; Deppert, W.R. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Pfeifer, D. [Department of Hematology and Oncology, University Hospital Freiburg (Germany); Stanzel, S.; Weimer, M. [Department of Biostatistics, German Cancer Research Center, Heidelberg (Germany); Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Schaefer, W.R., E-mail: [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany)


    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  5. Detrended fluctuation analysis of compound action potentials re-corded in the cutaneous nerves of diabetic rats

    International Nuclear Information System (INIS)

    Quiroz-González, Salvador; Rodríguez-Torres, Erika Elizabeth; Segura-Alegría, Bertha; Pereira-Venegas, Javier; Lopez-Gomez, Rosa Estela; Jiménez-Estrada, Ismael


    Highlights: • Fractal analysis of compound action potentials (CAP) evoked in diabetic nerves. • Diabetic rats showed an increment in the chaotic behavior of CAP responses. • Diabetes provokes impaired transmission of sensory information in rats. - Abstract: The electrophysiological alterations in nerves due to diabetes are classically studied in relation to their instantaneous frequency, conduction velocity and amplitude. However, analysis of amplitude variability may reflect the occurrence of feedback loop mechanisms that adjust the output as a function of its previous activity could indicate fractal dynamics. We assume that a peripheral neuropathy, such as that evoked by diabetes, the inability to maintain a steady flow of sensory information is reflected as a breakdown of the long range power-law correlation of CAP area fluctuation from cutaneous nerves. To test this, we first explored in normal rats whether fluctuations in the trial-to-trial CAP area showed a self-similar behavior or fractal structure by means of detrended fluctuations analysis (DFA), and Poincare plots. In addition, we determine whether such CAP fluctuations varied by diabetes induction. Results showed that CAP area fluctuation of SU nerves evoked in normal rats present a long term correlation and self-similar organization (fractal behavior) from trial to trial stimulation as evidenced by DFA of CAP areas. However, CAPs recorded in diabetic nerves exhibited significant reductions in area, larger duration and increased area variability and different Poincare plots than control nerves. The Hurst exponent value determined with the DFA method from a series of 2000 CAPs evoked in diabetic SU nerves was smaller than in control nerves. It is proposed that in cutaneous nerves of normal rats variability of the CAP area present a long term correlation and self-similar organization (fractal behavior), and reflect the ability to maintain a steady flow of sensory information through cutaneous nerves

  6. A Comparative Study On The Action Potential Simulation (APS Therapy And The Routine Physiotherapy Protocol In Knee Osteoarthritisin Elderly People

    Directory of Open Access Journals (Sweden)

    Abbas Rahimi


    Full Text Available Background and Aim: Knee osteoarthritis is the most common cause for which the elderly people refere to physiotherapy outpatient clinics. This study aimed to investigate the effects of the Action Potential Stimulation (APS Therapy and the routine physiotherapy (PT protocol on relieving pain and swelling as well as the duration of the relief period in patients with knee osteoarthritis. Materials and Methods: 69 patients (62 females & 7 males with knee osteoarthritis were recruited in this study. The subjects were divided into two groups including APS Therapy (n=37, mean age: 55±13 years old and the routine PT protocol (n=32, mean age: 61±14 years old groups. A 10-session treatment period was carried out for each group; and their pain and swelling were measured at the first, fifth and tenth sessions and also one-month after the last session (follow up. The swelling was measured using measuring the circumference of the knee on the patella, 5 Cm above and 5 Cm below the patella. The routine PT protocol consisted of hot pack, ultrasound, TENS and exercise; and the APS therapy protocol included hot pack, APS Therapy and the same exercise. During the follow up, 50 out of 61 subjects were called on the phone and any pain changes were recorded.Results: In terms of swelling, the results showed significant reduction just on the patella only in the APS Therapy group (P<0.05. Visual Analogue Pain Scale (VAPS indicated a significant pain reduction in both groups. However, the APS Therapy group showed significantly pain reduction at the end of sessions five, ten and the follow up session (P<0.05. It was also revealed that while routine PT subjects showed no significant pain changes between the tenth and the follow up session, a gradual pain reduction was seen in the APS therapy group during this period (P<0.05. A gradual dosage reduction was recorded only in the APS therapy group, indicating a slight correlation with pain reduction (r=0.4.Conclusion: The

  7. Spatial correlation of action potential duration and diastolic dysfunction in transgenic and drug-induced LQT2 rabbits. (United States)

    Odening, Katja E; Jung, Bernd A; Lang, Corinna N; Cabrera Lozoya, Rocio; Ziupa, David; Menza, Marius; Relan, Jatin; Franke, Gerlind; Perez Feliz, Stefanie; Koren, Gideon; Zehender, Manfred; Bode, Christoph; Brunner, Michael; Sermesant, Maxime; Föll, Daniela


    Enhanced dispersion of action potential duration (APD) is a major contributor to long QT syndrome (LQTS)-related arrhythmias. To investigate spatial correlations of regional heterogeneities in cardiac repolarization and mechanical function in LQTS. Female transgenic LQTS type 2 (LQT2; n = 11) and wild-type littermate control (LMC) rabbits (n = 9 without E4031 and n = 10 with E4031) were subjected to phase contrast magnetic resonance imaging to assess regional myocardial velocities. In the same rabbits' hearts, monophasic APDs were assessed in corresponding segments. In LQT2 and E4031-treated rabbits, APD was longer in all left ventricular segments (P < .01) and APD dispersion was greater than that in LMC rabbits (P < .01). In diastole, peak radial velocities (Vr) were reduced in LQT2 and E4031-treated compared to LMC rabbits in LV base and mid (LQT2: -3.36 ± 0.4 cm/s, P < .01; E4031-treated: -3.24 ± 0.6 cm/s, P < .0001; LMC: -4.42 ± 0.5 cm/s), indicating an impaired diastolic function. Regionally heterogeneous diastolic Vr correlated with APD (LQT2: correlation coefficient [CC] 0.38, P = .01; E4031-treated: CC 0.42, P < .05). Time-to-diastolic peak Vr were prolonged in LQT2 rabbits (LQT2: 196.8 ± 2.9 ms, P < .001; E4031-treated: 199.5 ± 2.2 ms, P < .0001, LMC 183.1 ± 1.5), indicating a prolonged contraction duration. Moreover, in transgenic LQT2 rabbits, diastolic time-to-diastolic peak Vr correlated with APD (CC 0.47, P = .001). In systole, peak Vr were reduced in LQT2 and E4031-treated rabbits (P < .01) but longitudinal velocities or ejection fraction did not differ. Finally, random forest machine learning algorithms enabled a differentiation between LQT2, E4031-treated, and LMC rabbits solely based on "mechanical" magnetic resonance imaging data. The prolongation of APD led to impaired diastolic and systolic function in transgenic and drug-induced LQT2 rabbits. APD correlated with regional diastolic dysfunction, indicating that LQTS is not purely an

  8. Action of gamma radiation in the physico-chemical and sensorial characteristics of minimally processed cassava (Manihot esculenta CRANTZ)

    International Nuclear Information System (INIS)

    Simioni, Karime Raya


    Nowadays irradiation has been the most studied method of food conservation. The publication of thousand of papers, not just scientific but also technological, economical and social, have proved the technical validity of the irradiation method and showed the ways of how to introduce it in commercial facilities in ali countries of the modem world. Cassava is cultivated almost ali over the world and it is considered one of the most important nutritious sources of calories in human diet. Cassava is a viable food against starving in several poor areas of the world because it is an extremely resistant culture and may reach satisfactory economical yield. Cassava is a quite perishable root, characterized by fast post harvest deterioration. Because of the lack of researches about the effects of radiations in this root, the objective of the present work was to examine the gamma radiation coming from 60 Cobalt as a treatment to prolong the shelflife of the root after harvesting, aiming to increase its period of commercialization and to conserve its sensorial characteristics for a longer period. Samples were washed, peeled, cleaned and diced cassava roots packed in polyethylene bags. The treatments were: control; freezing and storage at 18 deg C for 21 days; and irradiation with the doses of 8 and 10 kGy. The control and the irradiated samples were stored under ambient temperature during 21 days. All samples were analyzed at each 7 days for alterations in the physicochemical and sensorial characteristics. The samples were analyzed for pH, acidity, weight, humidity, texture and color. The irradiation did not affect the chemical characteristics of the cassava. Neither the pH nor the acidity, the most relevant variables to verify deterioration in cassava, presented significant alterations during the period of storage. Comparing the irradiated treatments, the dose of 8 kGy was that less affected the physic-chemical characteristics of the cassava and scored the highest notes in the

  9. The Profiles of Creative Potential and Personality Characteristics of Adult Professionals (United States)

    Lee, Seon-Young; Min, Jiyeon


    Using 5 divergent thinking indices of the Torrance Tests of Creative Thinking and the Myers-Briggs Type Indicator, this study examined the creative profiles of 236 adult professionals and relationships between their creative characteristics and personality types. All these adults were in their middle or late stage of professional development in…

  10. Children of mothers being released from incarceration : Characteristics and potential targets for intervention

    NARCIS (Netherlands)

    Menting, Ankie T A; Orobio de Castro, Bram; Matthys, Walter


    Incarcerated mothers and their children may face a multitude of problems. To identify possible targets for intervention, more clarity is needed about characteristics of these children and their mothers. This study examined children’s life events, behaviour problems and social cognitions and mothers’

  11. Action video game training for cognitive enhancement


    Green, C. Shawn; Bavelier, Daphné


    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...

  12. Sexual Assault Perpetrators' Justifications for Their Actions: Relationships to Rape Supportive Attitudes, Incident Characteristics, and Future Perpetration. (United States)

    Wegner, Rhiana; Abbey, Antonia; Pierce, Jennifer; Pegram, Sheri E; Woerner, Jacqueline


    Perpetrators use rape supportive attitudes and sexual assault incident characteristics to justify forcing sex on their victims. Perpetrators who can justify their behaviors are at increased risk for future perpetration. This study examined the relationships between rape supportive attitudes, sexual assault incident characteristics, and the post-assault justifications of 183 men sampled from the community who self-reported committing at least one act of sexual aggression. Hierarchical multiple regression analyses indicated that rape supportive attitudes, expectations for having sex, misperceptions of sexual intent, victims' alcohol consumption, attempts to be alone with her, and the number of consensual sexual activities prior to the unwanted sex were significant predictors of perpetrators' post-assault use of justifications. Greater use of justifications was a significant predictor of sexual aggression over a 1-year follow-up interval. These findings demonstrate the need for further research exploring when and why perpetrators use post-assault justifications and whether they are amenable to change. © The Author(s) 2015.

  13. Determination of thermodynamic potentials and the aggregation number for micelles with the mass-action model by isothermal titration calorimetry

    DEFF Research Database (Denmark)

    Olesen, Niels Erik; Westh, Peter; Holm, René


    of micelles with ITC were compared to a mass-action model (MAM) of reaction type: n⋅S⇌Mn. This analysis can provide guidelines for future ITC studies of systems behaving in accordance with this model such as micelles and proteins that undergo self-association to oligomers. Micelles with small aggregation...

  14. V-amylose structural characteristics, methods of preparation, significance, and potential applications

    CSIR Research Space (South Africa)

    Obiro, WC


    Full Text Available , and postprandial hyperglycaemia in diabetics. Various aspects of V-amylose structure, methods of preparation, factors that affect its formation, and the significance and potential applications of the V-amylose complexes are reviewed....

  15. Investigation Characteristics Of Pulp Fibers AS Green Potential Polymer Reinforcing Agents


    Masruchin, Nanang; Subyakto


    Three kinds of pulp fiber (i.e. kenaf, pineapple and coconut fiber)were characterized as reinforcing agents in compositematerials to be applied at automotive interior industry.Abetter understanding on characteristics of fiber will lead to enhance interface adhesion between fiber and matrices. Furthermore, it will improve the properties of polymer significantly. Chemical, surface compositions as well as morphology of pulp fiber were investigated using TAPPI standard test method, Fourier Transf...

  16. NS5806 partially restores action potential duration but fails to ameliorate calcium transient dysfunction in a computational model of canine heart failure. (United States)

    Maleckar, Mary M; Lines, Glenn T; Koivumäki, Jussi T; Cordeiro, Jonathan M; Calloe, Kirstine


    The study investigates how increased Ito, as mediated by the activator NS5806, affects excitation-contraction coupling in chronic heart failure (HF). We hypothesized that restoring spike-and-dome morphology of the action potential (AP) to a healthy phenotype would be insufficient to restore the intracellular Ca(2) (+) transient (CaT), due to HF-induced remodelling of Ca(2+) handling. An existing mathematical model of the canine ventricular myocyte was modified to incorporate recent experimental data from healthy and failing myocytes, resulting in models of both healthy and HF epicardial, midmyocardial, and endocardial cell variants. Affects of NS5806 were also included in HF models through its direct interaction with Kv4.3 and Kv1.4. Single-cell simulations performed in all models (control, HF, and HF + drug) and variants (epi, mid, and endo) assessed AP morphology and underlying ionic processes with a focus on calcium transients (CaT), how these were altered in HF across the ventricular wall, and the subsequent effects of varying compound concentration in HF. Heart failure model variants recapitulated a characteristic increase in AP duration (APD) in the disease. The qualitative effects of application of half-maximal effective concentration (EC50) of NS5806 on APs and CaT are heterogeneous and non-linear. Deepening in the AP notch with drug is a direct effect of the activation of Ito; both Ito and consequent alteration of IK1 kinetics cause decrease in AP plateau potential. Decreased APD50 and APD90 are both due to altered IK1. Analysis revealed that drug effects depend on transmurality. Ca(2+) transient morphology changes-increased amplitude and shorter time to peak-are due to direct increase in ICa,L and indirect larger SR Ca(2+) release subsequent to Ito activation. Downstream effects of a compound acting exclusively on sarcolemmal ion channels are difficult to predict. Remediation of APD to pre-failing state does not ameliorate dysfunction in CaT; however

  17. Impaired action potential initiation in GABAergic interneurons causes hyperexcitable networks in an epileptic mouse model carrying a human Na(V)1.1 mutation. (United States)

    Hedrich, Ulrike B S; Liautard, Camille; Kirschenbaum, Daniel; Pofahl, Martin; Lavigne, Jennifer; Liu, Yuanyuan; Theiss, Stephan; Slotta, Johannes; Escayg, Andrew; Dihné, Marcel; Beck, Heinz; Mantegazza, Massimo; Lerche, Holger


    Mutations in SCN1A and other ion channel genes can cause different epileptic phenotypes, but the precise mechanisms underlying the development of hyperexcitable networks are largely unknown. Here, we present a multisystem analysis of an SCN1A mouse model carrying the NaV1.1-R1648H mutation, which causes febrile seizures and epilepsy in humans. We found a ubiquitous hypoexcitability of interneurons in thalamus, cortex, and hippocampus, without detectable changes in excitatory neurons. Interestingly, somatic Na(+) channels in interneurons and persistent Na(+) currents were not significantly changed. Instead, the key mechanism of interneuron dysfunction was a deficit of action potential initiation at the axon initial segment that was identified by analyzing action potential firing. This deficit increased with the duration of firing periods, suggesting that increased slow inactivation, as recorded for recombinant mutated channels, could play an important role. The deficit in interneuron firing caused reduced action potential-driven inhibition of excitatory neurons as revealed by less frequent spontaneous but not miniature IPSCs. Multiple approaches indicated increased spontaneous thalamocortical and hippocampal network activity in mutant mice, as follows: (1) more synchronous and higher-frequency firing was recorded in primary neuronal cultures plated on multielectrode arrays; (2) thalamocortical slices examined by field potential recordings revealed spontaneous activities and pathological high-frequency oscillations; and (3) multineuron Ca(2+) imaging in hippocampal slices showed increased spontaneous neuronal activity. Thus, an interneuron-specific generalized defect in action potential initiation causes multisystem disinhibition and network hyperexcitability, which can well explain the occurrence of seizures in the studied mouse model and in patients carrying this mutation. Copyright © 2014 the authors 0270-6474/14/3414874-16$15.00/0.

  18. A novel method for beef potentiator preparation and identification of its characteristic aroma compounds. (United States)

    Gao, Xianli; Yan, Shuang; Yang, Bao; Lu, Jian; Jin, Zhao


    Beef potentiator (BP) is the most popular savoury flavour and regarded as the soul of the modern food industry. In this work, BP was prepared by a novel method with Aspergillus oryzae and Aspergillus niger (BPSF). Three other BPs prepared using commercial enzymes (Protamex, Flavourzyme and papain; BPCEs) were used as controls to investigate its aroma characteristics and related compounds. Sensory evaluation showed that BPSF possessed more favourable and distinctive sauce-like, meat-like, roast and alcoholic attributes when compared with BPCEs. Significantly higher contents (peak areas) and proportions of pyrazines, pyrroles, sulfurous compounds and alcohols in BPSF were responsible for its sensory characteristics, and most of these aroma compounds were derived from microbial metabolism during beef koji preparation and the Maillard reaction. BP prepared by synergistic fermentation with A. oryzae and A. niger is a potential alternative for BP preparation. © 2013 Society of Chemical Industry.

  19. Correlation between mammographic findings and corresponding histopathology. Potential predictors for biological characteristics of breast diseases

    International Nuclear Information System (INIS)

    Tamaki, Kentaro; Ishida, Takanori; Miyashita, Minoru; Amari, Masakazu; Ohuchi, Noriaki; Tamaki, Nobumitsu; Sasano, Hironobu


    The present study retrospectively evaluated the mammographic findings of 606 Japanese women with breast cancer (median age 50 years; range 27-89 years) and correlated them with histopathological characteristics. Mammographic findings were evaluated with an emphasis on mass shape, margin, density, calcification, and the presence of architectural distortion; these findings were correlated with histopathological characteristics such as intrinsic subtype, histological grade, lymphovascular invasion, and the Ki-67 labeling index. An irregular mass shape and masses with a spiculated margin were significantly higher in the group of patients with luminal A breast cancer than in patients with masses that were lobular or round, or in tumors with an indistinct or microlobulated periphery (P=0.017, P=0.024, P<0.001, and P=0.001, respectively). Irregular mass shape and spiculated periphery were significantly lower in patients with Grade 3 cancer (P<0.001 for both). In terms of lymphovascular invasion, there were significant differences between oval and irregular or round mass shape (P=0.008 and P=0.034), between tumors with a microlobulated and indistinct periphery (P=0.014), between tumors with a punctate and amorphous or pleomorphic calcification shape (P=0.030 and 0.038), and between the presence and absence of architectural distortion (P=0.027). Equivalent or low-density masses were also higher in Grade 1 breast cancers (P=0.007). There were significant differences in the Ki-67 labeling index between irregular and lobular or round tumors (P<0.001 and P=0.014), as well as between spiculated and indistinct or microlobulated tumors (P<0.001 for both). Significant differences were noted in the mammographic features of different primary breast cancer subtypes. These proposed mammographic diagnostic criteria based on biological characteristics may contribute to a more accurate prediction of biological behavior of breast malignancies. (author)

  20. [Study on pharmacologic action characteristics of traditional Chinese medicines distributed along liver meridian based on medicinal properties combinations]. (United States)

    Guo, Hong-Ling; Gu, Hao; Wang, Yun; Qiao, Yan-Jiang


    To establish a characterization system of traditional Chinese medicinal properties in line with modern scientific cognition regularity, in order to reveal properties of traditional Chinese medicines distributed along liver meridian and relations of effects of medicinal properties. By collecting data about traditional Chinese medicinal properties recorded in the Pharmacopoeia of the People's Republic of China (2005 Edition), literature and data about pharmacological effects of traditional Chinese medicines recorded in the Chinese Materia Medica, by using the method of association rules, the authors dug pharmacological effect rules corresponds to relevant medicinal property combinations, with the medicinal property combination of traditional Chinese medicines distributed along liver meridian as the target. It was found that either obvious different pharmacological effects or identical pharmacological characteristics existed in traditional Chinese medicines distributed along liver meridian. With the aim to explore the correlations between traditional Chinese medicine medicinal properties and pharmacological effects, the authors linked the traditional Chinese medicine theory with modern research achievements, in order to provide the ideas and methods for interpreting mechanisms of medicinal properties.

  1. Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action

    International Nuclear Information System (INIS)

    Kampa, Marilena; Boskou, Dimitrios; Gravanis, Achille; Castanas, Elias; Alexaki, Vassilia-Ismini; Notas, George; Nifli, Artemissia-Phoebe; Nistikaki, Anastassia; Hatzoglou, Anastassia; Bakogeorgou, Efstathia; Kouimtzoglou, Elena; Blekas, George


    The oncoprotective role of food-derived polyphenol antioxidants has been described but the implicated mechanisms are not yet clear. In addition to polyphenols, phenolic acids, found at high concentrations in a number of plants, possess antioxidant action. The main phenolic acids found in foods are derivatives of 4-hydroxybenzoic acid and 4-hydroxycinnamic acid. This work concentrates on the antiproliferative action of caffeic acid, syringic acid, sinapic acid, protocatechuic acid, ferulic acid and 3,4-dihydroxy-phenylacetic acid (PAA) on T47D human breast cancer cells, testing their antioxidant activity and a number of possible mechanisms involved (interaction with membrane and intracellular receptors, nitric oxide production). The tested compounds showed a time-dependent and dose-dependent inhibitory effect on cell growth with the following potency: caffeic acid > ferulic acid = protocatechuic acid = PAA > sinapic acid = syringic acid. Caffeic acid and PAA were chosen for further analysis. The antioxidative activity of these phenolic acids in T47D cells does not coincide with their inhibitory effect on tumoral proliferation. No interaction was found with steroid and adrenergic receptors. PAA induced an inhibition of nitric oxide synthase, while caffeic acid competes for binding and results in an inhibition of aryl hydrocarbon receptor-induced CYP1A1 enzyme. Both agents induce apoptosis via the Fas/FasL system. Phenolic acids exert a direct antiproliferative action, evident at low concentrations, comparable with those found in biological fluids after ingestion of foods rich in phenolic acids. Furthermore, the direct interaction with the aryl hydrocarbon receptor, the nitric oxide synthase inhibition and their pro-apoptotic effect provide some insights into their biological mode of action

  2. Electrocardiographic Characteristics of Potential Organ Donors and Associations with Cardiac Allograft Utilization (United States)

    Khush, Kiran K.; Menza, Rebecca; Nguyen, John; Goldstein, Benjamin A.; Zaroff, Jonathan G.; Drew, Barbara J.


    Background Current regulations require that all cardiac allograft offers for transplantation must include an interpreted 12-lead electrocardiogram (ECG). However, little is known about the expected ECG findings in potential organ donors, or the clinical significance of any identified abnormalities in terms of cardiac allograft function and suitability for transplantation. Methods and Results A single experienced reviewer interpreted the first ECG obtained after brainstem herniation in 980 potential organ donors managed by the California Transplant Donor Network from 2002-2007. ECG abnormalities were summarized, and associations between specific ECG findings and cardiac allograft utilization for transplantation were studied. ECG abnormalities were present in 51% of all cases reviewed. The most common abnormalities included voltage criteria for left ventricular hypertrophy (LVH), prolongation of the corrected QT interval (QTc), and repolarization changes (ST/T wave abnormalities). Fifty seven percent of potential cardiac allografts in this cohort were accepted for transplantation. LVH on ECG was a strong predictor of allograft non-utilization. No significant associations were seen between QTc prolongation, repolarization changes and allograft utilization for transplantation, after adjusting for donor clinical variables and echocardiographic findings. Conclusions We have performed the first comprehensive study of ECG findings in potential donors for cardiac transplantation. Many of the common ECG abnormalities seen in organ donors may result from the heightened state of sympathetic activation that occurs after brainstem herniation, and are not associated with allograft utilization for transplantation. PMID:22615333

  3. Contrasts in oxidative potential and other particulate matter characteristics collected near major streets and background locations

    NARCIS (Netherlands)

    Boogaard, H.; Janssen, N.A.H.; Fischer, P.H.; Kos, G.P.A.; Weijers, E.P.; Cassee, F.R.; van der Zee, S.C.; Hartog, J. de; Brunekreef, B.; Hoek, G.


    BACKGROUND: Measuring the oxidative potential of airborne particulate matter (PM) may provide a more health-based exposure measure by integrating various biologically relevant properties of PM into a single predictor of biological activity. OBJECTIVES: We aimed to assess the contrast in oxidative

  4. Contrasts in oxidative potential and other particulate matter characteristics collected near major streets and background locations.

    NARCIS (Netherlands)

    Boogaard, H.; Janssen, N.A.; Fischer, P.H.; Kos, G.P.; Weijers, E.P.; Cassee, F.R.; Zee, S.C. van der; Hartog, J.J. de; Brunekreef, B.; Hoek, G.


    BACKGROUND: Measuring the oxidative potential of airborne particulate matter (PM) may provide a more health-based exposure measure by integrating various biologically relevant properties of PM into a single predictor of biological activity. OBJECTIVES: We aimed to assess the contrast in oxidative

  5. Determination of Smuggled Cigarette Characteristics in Brazil and Their Potential Risk to the Human Health

    Directory of Open Access Journals (Sweden)

    Cleber Pinto da Silva


    Full Text Available The objective of this study was to determine the different characteristics of tobacco found in thirty brands of smuggled cigarettes in Brazil. Determination of arsenic through atomic absorption spectrometry in graphite oven was carried out and classical methodologies were employed to determine dirtiness, total ash, insoluble ash, humidity, tobacco pH and sidestream smoke pH. The methodology used to quantify arsenic presented quantification limit of 15.0 ng g-1 and detection limit of 4.0 ng g-1 in dry tobacco mass. The recovery of arsenic for the method purpose was 98.2% and relative standard deviation 6.0%. About 56% of the brands were observed to have arsenic concentrations above 20.0 ng g-1, which means nearly twice as much as the arsenic found in cigarettes sold legally in Brazil. Levels above the recommended value for humidity were found in 53% of brands. About 96% of the brands presented total ash content above that indicated by the Brazilian Pharmacopoeia. About 53% of the samples contained levels of insoluble ash above the limit. In 90% of the samples, the smoke was alkaline. In dirtiness tests, 81.2% of the brands presented some kind of contaminant, such as fungi, insect fragments, grass or mites. The characteristics revealed that the consumption of this kind of cigarette can increase risks to consumer health. DOI: 

  6. Abuse potential of propofol used for sedation in gastric endoscopy and its correlation with subject characteristics. (United States)

    Kim, Ja Hyun; Byun, Heewon; Kim, Jun Hyun


    Propofol has been widely used for an induction and/or maintenance of general anesthesia, or for sedation for various procedures. Although it has many ideal aspects, there have been several cases of drug abuse and addiction. The authors investigated whether there are abuse liable groups among the general population. We surveyed 169 patients after gastric endoscopic examination, which used propofol as a sedative, with the Addiction Research Center Inventory (ARCI) questionnaire. Other characteristics of the patients, such as past history, smoking habits, depression, anxiety, alcohol abuse liability and sleep disturbance, were recorded by history taking and several questionnaires before the exam. Propofol had a high Morphine-Benzedrine Group (MBG) score (representative value for euphoria) of 6.3, which is higher than marijuana, and a Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) score (representative value of sedation) of 8.1, which is lower than most opioids. The MBG score showed no statistically significant correlation between any of the characteristics of the groups. In females, the PCAG score showed a correlation with age, and in males, it showed a correlation with a sleeping problem. Propofol had relatively high euphoria and low residual sedative effects. It had a more potent sedative effect in the female group who were young, and in the male group who had a low sleep quality index. There were differences in the abuse liability from a single exposure to propofol in the general population. Further study is needed to evaluate the abuse liability of repeated exposure.

  7. DoD Officials did Not Take Appropriate Action When Notified of Potential Travel Card Misuse at Casinos and Adult Entertainment Establishments (United States)


    develop or derogatory information is discovered that could have an adverse impact on an individual’s clearance eligibility, the potentially derogatory...the 45-day requirement impacted management’s ability to take action now against the cardholder for travel card misuse at casinos, and no disciplinary... delinquency and misuse at the first command. However, no information about the cardholder’s travel card delinquency or misuse was sent to his next

  8. Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons (United States)

    Liu, Pin W.


    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

  9. [Effects of 2-(p-dimethylaminostyryl) pyridine methycholide (DSPM-Ci) on ECG, left atrium contractivity and on papillary muscle action potentials]. (United States)

    Jiang, X Y; Zhou, C M; Li, D M; Zhang, K J


    The effects of DSPM-Cl on ECG in rats, on the dose-effect curve in guinea pig left atria and on the fast action potential (AP), high-K+ depolarized slow action potential (SAP) in guinea pigs papillary muscle were examined electrophysiologically. DSPM-Cl (2 showed significant nagative frequency, negative conductivity effect, and prolonged the PP and PR interval. DSPM-CI (30-50 mumol.L-1) was shown to inhibit left atria contractility and shift the concentration-response curve of Iso and CaCl2 to the right with PD2' values of 4.60 and 4.13, respectively. In addition, DSPM-Cl was found to prolong the duration of action potential 90 (APD90) and effective refractory period (ERP), and decrease the maximal upstroke velocity (Vmax) in K(+)-depolarized guinea pigs papillary muscles. The results suggest that, like verpamil, DSPM-Cl might be a calcium antagonist.

  10. Isosteviol prevents the prolongation of action potential in hypertrophied cardiomyoctyes by regulating transient outward potassium and L-type calcium channels. (United States)

    Fan, Zhuo; Lv, Nanying; Luo, Xiao; Tan, Wen


    Cardiac hypertrophy is a thickening of the heart muscle that is associated with cardiovascular diseases such as hypertension and myocardial infarction. It occurs initially as an adaptive process against increased workloads and often leads to sudden arrhythmic deaths. Studies suggest that the lethal arrhythmia is attributed to hypertrophy-induced destabilization of cardiac electrical activity, especially the prolongation of the action potential. The reduced activity of I to is demonstrated to be responsible for the ionic mechanism of prolonged action potential duration and arrhythmogeneity. Isosteviol (STV), a derivative of stevioside, plays a protective role in a variety of stress-induced cardiac diseases. Here we report effects of STV on rat ISO-induced hypertrophic cardiomyocytes. STV alleviated ISO-induced hypertrophy of cardiomyocytes by decreasing cell area of hypertrophied cardiomyocytes. STV application prevented the prolongation of action potential which was prominent in hypertrophied cells. The decrease and increase of current densities for I to and I CaL observed in hypertrophied myocytes were both prevented by STV application. In addition, the results of qRT-PCR suggested that the changes of electrophysiological activity of I to and I CaL are correlated to the alterations of the mRNA transcription level. Copyright © 2017. Published by Elsevier B.V.

  11. Physicochemical Characteristics of the Seed and Seed Oil of the Potentially Medicinal Plant Ziziphus oenoplia. (United States)

    Murthy, Hosakatte Niranjana; Joseph, Kadanthottu Sebastian; Madiwal, Abhishek; Gerald, Dinesh Rajen; Badiger, Mahananda; Kolkar, Lakshmi; Hiremath, Reshma


    The proximate composition of seeds, physicochemical characteristics, and fatty acid profiles of Ziziphus oenoplia seed oil were determined in this study. The seeds possessed low moisture (4.54%) and high carbohydrate (42.96%) and protein content (40%), making the seed oil suitable for storage and consumption. The saponification value (197.80) of the seed oil makes it a promising source for the soap and shampoo industry. The iodine and saponification values are comparable to those of major edible seed oils such as groundnut and soybean. The high amount of monounsaturated fatty acids (53.41%), especially oleic acid (53.38%), present in the oil makes it a better source for a low-fat diet and may reduce the risk of various heart-related diseases.

  12. The Ignimbritic tertiary volcanism of the Andes (Peru, Bolivia, Argentina): its characteristics and uraniferous potentiality

    International Nuclear Information System (INIS)

    Leroy, J.L.; George-Aniel, B.


    The petrographic and geochemical characteristics of the volcanism and the primary U distribution at the magmatic stage: alkali-rich volcanic rocks (Peru) appear to be fertile source-rocks, whereas sub alkaline and calc-alkaline rocks (Bolivia and Argentina) are less favorable. Uranium can only be leached from the matrix, due to the stability of the accessory minerals during all the following events. The fertility of a volcanic rock is thus directly controlled by the volume proportion of the matrix and the U fractionation between glass and accessory minerals. The preconcentration and concentration stages: the existence of mineralizations in relation with a fertile rock will depend on other events which must occur successively at the same place: the cooling type and rate of the volcanic pile (pre-concentration stage), the intensity and the duration of the hydrothermal circulations, the presence of reducing agents and trapps. (author)

  13. Influence of wastewater characteristics on methane potential in food-processing industry wastewaters

    DEFF Research Database (Denmark)

    Maya Altamira, Larisa; Baun, Anders; Angelidaki, Irini


    ) were compared to the theoretical methane yields (Bo,th) in order to evaluate the biodegradability of the tested wastewaters and the influence of their physico-chemical characteristics. The analytical method applied to quantify the wastewaters’ organic content proved to influence the estimation...... of their theoretical yields. The substrate:inoculum ratio as well as the dilution factor of the wastewaters influenced the ultimate practical methane yields differently in each of the wastewaters assessed. Substrate chemical oxygen demand (COD) concentrations did not present any influence on ultimate practical methane...... yields; on the other hand, it was found that they were affected positively by concentrations of total inorganic carbon when wastewaters were 25% and 50% diluted and affected negatively by concentrations of total acetate when wastewaters were undiluted. Carbohydrate and protein concentrations affected...

  14. Activated sewage sludge, a potential animal foodstuff. Part I. Nutritional characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Tacon, A.G.J.


    The nutritive value of activated sewage sludge is discussed in terms of its amino acid N, non-amino acid N, carbohydrate, fat, mineral, vitamin and microbial content. Processed activated sewage sludge is described as a stable dark brown material of relatively uniform quality, having a nutritive value broadly equivalent to brewers yeast or a protein-rich cereal. The potential hazards associated with the use of activated sewage sludge as a feed ingredient are discussed. 29 references

  15. A statistical investigation of wind characteristics and wind energy potential based on the Weibull and Rayleigh models in Rwanda

    Energy Technology Data Exchange (ETDEWEB)

    Safari, Bonfils; Gasore, Jimmy [Department of Physics, National University of Rwanda, P.O. Box 117, Huye, South Province (Rwanda)


    A wind energy system converts the kinetic energy of the wind into mechanical or electrical energy that can be harnessed for practical uses and transform the economy of rural areas where access to water and electricity is very restricted and industry is almost nonexistent in most of the developing countries like Rwanda. Assessing wind power potential for a location is an imperative requirement before making a decision for the installation of windmills or a wind electric generator and evaluating plans for relating projects. The aim of the present study