Signal propagation along the axon.

PubMed

Rama, Sylvain; Zbili, Mickaël; Debanne, Dominique

2018-03-08

Axons link distant brain regions and are usually considered as simple transmission cables in which reliable propagation occurs once an action potential has been generated. Safe propagation of action potentials relies on specific ion channel expression at strategic points of the axon such as nodes of Ranvier or axonal branch points. However, while action potentials are generally considered as the quantum of neuronal information, their signaling is not entirely digital. In fact, both their shape and their conduction speed have been shown to be modulated by activity, leading to regulations of synaptic latency and synaptic strength. We report here newly identified mechanisms of (1) safe spike propagation along the axon, (2) compartmentalization of action potential shape in the axon, (3) analog modulation of spike-evoked synaptic transmission and (4) alteration in conduction time after persistent regulation of axon morphology in central neurons. We discuss the contribution of these regulations in information processing. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Quantitative Comparison of the Behavior of Human Ventricular Cardiac Electrophysiology Models in Tissue

PubMed Central

Elshrif, Mohamed M.; Cherry, Elizabeth M.

2014-01-01

Numerical integration of mathematical models of heart cell electrophysiology provides an important computational tool for studying cardiac arrhythmias, but the abundance of available models complicates selecting an appropriate model. We study the behavior of two recently published models of human ventricular action potentials, the Grandi-Pasqualini-Bers (GPB) and the O'Hara-Virág-Varró-Rudy (OVVR) models, and compare the results with four previously published models and with available experimental and clinical data. We find the shapes and durations of action potentials and calcium transients differ between the GPB and OVVR models, as do the magnitudes and rate-dependent properties of transmembrane currents and the calcium transient. Differences also occur in the steady-state and S1–S2 action potential duration and conduction velocity restitution curves, including a maximum conduction velocity for the OVVR model roughly half that of the GPB model and well below clinical values. Between single cells and tissue, both models exhibit differences in properties, including maximum upstroke velocity, action potential amplitude, and minimum diastolic interval. Compared to experimental data, action potential durations for the GPB and OVVR models agree fairly well (although OVVR epicardial action potentials are shorter), but maximum slopes of steady-state restitution curves are smaller. Although studies show alternans in normal hearts, it occurs only in the OVVR model, and only for a narrow range of cycle lengths. We find initiated spiral waves do not progress to sustained breakup for either model. The dominant spiral wave period of the GPB model falls within clinically relevant values for ventricular tachycardia (VT), but for the OVVR model, the dominant period is longer than periods associated with VT. Our results should facilitate choosing a model to match properties of interest in human cardiac tissue and to replicate arrhythmia behavior more closely. Furthermore, by indicating areas where existing models disagree, our findings suggest avenues for further experimental work. PMID:24416228

The dependence of the action potential of the frog's heart on the external and intracellular sodium concentration

PubMed Central

Niedergerke, R.; Orkand, R. K.

1966-01-01

1. The overshoot of the action potential of the frog's heart was reduced when external sodium chloride was replaced by sucrose. However, the potential decrement was only 17·3 mV for a 10-fold reduction of sodium as compared with 58 mV expected on the basis of the sodium hypothesis of excitation. 2. Replacement of up to 75% of the external sodium by choline did not reduce the overshoot, provided atropine was present in sufficient concentrations to suppress any parasympathomimetic action. 3. The maximum rate of rise of the action potential markedly declined in low sodium fluids whether sucrose or choline chloride was used to replace sodium chloride. 4. The maximum rate of rise was reduced to only a small extent when external sodium was replaced by lithium. 5. Increasing the intracellular sodium concentration in exchange for lost potassium caused overshoots to decline. The effects resembled those obtained in similar experiments with skeletal muscle fibres (Desmedt, 1953). 6. Action potentials occurring under certain conditions even in the presence of very low external sodium concentrations (≤ 5% normal) also declined in height when the intracellular sodium concentration was increased. 7. The behaviour of the action potential in low external sodium concentrations may be explained by an action of calcium on the excitable membrane. PMID:5921833

Pro-arrhythmic effects of low plasma [K+] in human ventricle: An illustrated review.

PubMed

Trenor, Beatriz; Cardona, Karen; Romero, Lucia; Gomez, Juan F; Saiz, Javier; Rajamani, Sridharan; Belardinelli, Luiz; Giles, Wayne

2018-05-01

Potassium levels in the plasma, [K + ] o , are regulated precisely under physiological conditions. However, increases (from approx. 4.5 to 8.0mM) can occur as a consequence of, e.g., endurance exercise, ischemic insult or kidney failure. This hyperkalemic modulation of ventricular electrophysiology has been studied extensively. Hypokalemia is also common. It can occur in response to diuretic therapy, following renal dialysis, or during recovery from endurance exercise. In the human ventricle, clinical hypokalemia (e.g., [K + ] o levels of approx. 3.0mM) can cause marked changes in both the resting potential and the action potential waveform, and these may promote arrhythmias. Here, we provide essential background information concerning the main K + -sensitive ion channel mechanisms that act in concert to produce prominent short-term ventricular electrophysiological changes, and illustrate these by implementing recent mathematical models of the human ventricular action potential. Even small changes (~1mM) in [K + ] o result in significant alterations in two different K + currents, I K1 and HERG. These changes can markedly alter in resting membrane potential and/or action potential waveform in human ventricle. Specifically, a reduction in net outward transmembrane K + currents (repolarization reserve) and an increased substrate input resistance contribute to electrophysiological instability during the plateau of the action potential and may promote pro-arrhythmic early after-depolarizations (EADs). Translational settings where these insights apply include: optimal diuretic therapy, and the interpretation of data from Phase II and III trials for anti-arrhythmic drug candidates. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Na and Ca components of action potentials in amphioxus muscle cells

PubMed Central

Hagiwara, S.; Kidokoro, Y.

1971-01-01

1. The ionic mechanism of the action potential produced in lamella-like muscle cells of amphioxus, Branchiostoma californiense, was investigated with intracellular recording and polarization techniques. 2. The resting potential and action potential overshoot in normal saline are -53±5 mV (S.D.) and +29±10 mV (S.D.) respectively. 3. The action potential is eliminated by tetrodotoxin (3 μM) and by replacing NaCl in the saline with Tris-chloride but maintained by replacing Na with Li. 4. After elimination of the normal action potential by tetrodotoxin or replacing Na with Tris, the addition of procaine (7·3 mM) to the external saline makes the membrane capable of producing a regenerative potential change. 5. The peak potential of the regenerative response depends on external Ca concentration in a manner predicted by the Nernst equation with Ca concentrations close to normal. 6. The Ca dependent response is reversibly suppressed by Co or La ions. 7. Similar regenerative responses are obtained when Ca is substituted with Sr or Ba. 8. It is concluded that two independent mechanisms of ionic permeability increase occur in the membrane of amphioxus muscle cell, one to Na and the other to Ca. PMID:5158595

Visual-motor recalibration in geographical slant perception

NASA Technical Reports Server (NTRS)

Bhalla, M.; Proffitt, D. R.; Kaiser, M. K. (Principal Investigator)

1999-01-01

In 4 experiments, it was shown that hills appear steeper to people who are encumbered by wearing a heavy backpack (Experiment 1), are fatigued (Experiment 2), are of low physical fitness (Experiment 3), or are elderly and/or in declining health (Experiment 4). Visually guided actions are unaffected by these manipulations of physiological potential. Although dissociable, the awareness and action systems were also shown to be interconnected. Recalibration of the transformation relating awareness and actions was found to occur over long-term changes in physiological potential (fitness level, age, and health) but not with transitory changes (fatigue and load). Findings are discussed in terms of a time-dependent coordination between the separate systems that control explicit visual awareness and visually guided action.

Environmental Assessment: Clear Zone and Accident Potential Zone Selective Tree Removal

DTIC Science & Technology

2011-05-25

PROPOSED ACTION The Proposed Action would occur within the CZ and APZs north and south of the runway. The overall area is undeveloped wetland and...existing runway. Therefore, there is no practicable alternative to conducting the action in floodplain/ wetland areas. Three technical alternatives for...or removal would be required. Alternative 3 was eliminated because leaving woody debris in wetlands would not meet U.S. Army Corps of Engineers

Active signal conduction through the sensory dendrite of a spider mechanoreceptor neuron.

PubMed

Gingl, Ewald; French, Andrew S

2003-07-09

Rapid responses to sensory stimulation are crucial for survival. This must be especially true for mechanical stimuli containing temporal information, such as vibration. Sensory transduction occurs at the tips of relatively long sensory dendrites in many mechanoreceptors of both vertebrates and invertebrates, but little is known about the electrical properties of these crucial links between transduction and action potential generation. The VS-3 slit-sense organ of the spider Cupiennius salei contains bipolar mechanosensory neurons that allow voltage-clamp recording from the somata, whereas mechanotransduction occurs at the tips of 100- to 200-microm-long sensory dendrites. We studied the properties of VS-3 sensory dendrites using three approaches. Voltage-jump experiments measured the spread of voltage outward from the soma by observing total mechanically transduced charge recovered at the soma as a function of time after a voltage jump. Frequency-response measurements between pseudorandom mechanical stimulation and somatic membrane potential estimated the passive cable properties of the dendrite for voltage spread in the opposite direction. Both of these sets of data indicated that the dendritic cable would significantly attenuate and retard a passively propagated receptor potential. Finally, current-clamp observations of receptor potentials and action potentials indicated that action potentials normally start at the distal dendrites and propagate regeneratively to the soma, reducing the temporal delay of passive conduction.

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

PubMed

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

2012-01-01

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

The Direct Detection of a Single Evoked Action Potential with Magnetic Resonance Spectroscopy in Lumbricus Terrestris

PubMed Central

Poplawsky, Alexander J.; Dingledine, Raymond

2011-01-01

Functional MRI (fMRI) indirectly measures neural activity 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 the present study, we used magnetic resonance 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 due to 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 magnetic resonance. PMID:21728204

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

PubMed

Eickenscheidt, Max; Zeck, Günther

2014-06-01

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

Simulation of action potentials from metabolically impaired cardiac myocytes. Role of ATP-sensitive K+ current.

PubMed

Ferrero, J M; Sáiz, J; Ferrero, J M; Thakor, N V

1996-08-01

The role of the ATP-sensitive K+ current (IK-ATP) and its contribution to electrophysiological changes that occur during metabolic impairment in cardiac ventricular myocytes is still being discussed. The aim of this work was to quantitatively study this issue by using computer modeling. A model of IK-ATP is formulated and incorporated into the Luo-Rudy ionic model of the ventricular action potential. Action potentials under different degrees of activation of IK-ATP are simulated. Our results show that in normal ionic concentrations, only approximately 0.6% of the KATP channels, when open, should account for a 50% reduction in action potential duration. However, increased levels of intracellular Mg2+ counteract this shortening. Under conditions of high [K+]0, such as those found in early ischemia, the activation of only approximately 0.4% of the KATP channels could account for a 50% reduction in action potential duration. Thus, our results suggest that opening of IK-ATP channels should play a significant role in action potential shortening during hypoxic/ischemic episodes, with the fraction of open channels involved being very low ( < 1%). However, the results of the model suggest that activation of IK-ATP alone does not quantitatively account for the observed K+ efflux in metabolically impaired cardiac myocytes. Mechanisms other than KATP channel activation should be responsible for a significant part of the K+ efflux measured in hypoxic/ischemic situations.

ELECTRIC IMPEDANCE OF NITELLA DURING ACTIVITY

PubMed Central

Cole, Kenneth S.; Curtis, Howard J.

1938-01-01

The changes in the alternating current impedance which occur during activity of cells of the fresh water plant Nitella have been measured with the current flow normal to the cell axis, at eight frequencies from 0.05 to 20 kilocycles per second, and with simultaneous records of the action potential under the impedance electrodes. At each frequency the resting cell was balanced in a Wheatstone bridge with a cathode ray oscillograph, and after electrical stimulation at one end of the cell, the changes in the complex impedance were determined from the bridge unbalance recorded by motion pictures of the oscillograph figure. An extension of the previous technique of interpretation of the transverse impedance shows that the normal membrane capacity of 0.9 µf./cm.2 decreases about 15 per cent without change of phase angle, while the membrane resistance decreases from 105 ohm cm.2 to about 500 ohm cm.2 during the passage of the excitation wave. This membrane change occurs during the latter part of the rising phase of the action potential, and it is shown that the membrane electromotive force remains unchanged until nearly the same time. The part of the action potential preceding these membrane changes is probably a passive fall of potential ahead of a partial short circuit. PMID:19873091

Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance.

PubMed

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

2016-01-01

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.

Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance

PubMed Central

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

2016-01-01

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. PMID:27525414

Plant and Fungal Food Components with Potential Activity on the Development of Microbial Oral Diseases

PubMed Central

Daglia, Maria; Papetti, Adele; Mascherpa, Dora; Grisoli, Pietro; Giusto, Giovanni; Lingström, Peter; Pratten, Jonathan; Signoretto, Caterina; Spratt, David A.; Wilson, Michael; Zaura, Egija; Gazzani, Gabriella

2011-01-01

This paper reports the content in macronutrients, free sugars, polyphenols, and inorganic ions, known to exert any positive or negative action on microbial oral disease such as caries and gingivitis, of seven food/beverages (red chicory, mushroom, raspberry, green and black tea, cranberry juice, dark beer). Tea leaves resulted the richest material in all the detected ions, anyway tea beverages resulted the richest just in fluoride. The highest content in zinc was in chicory, raspberry and mushroom. Raspberry is the richest food in strontium and boron, beer in selenium, raspberry and mushroom in copper. Beer, cranberry juice and, especially green and black tea are very rich in polyphenols, confirming these beverages as important sources of such healthy substances. The fractionation, carried out on the basis of the molecular mass (MM), of the water soluble components occurring in raspberry, chicory, and mushroom extracts (which in microbiological assays revealed the highest potential action against oral pathogens), showed that both the high and low MM fractions are active, with the low MM fractions displaying the highest potential action for all the fractionated extracts. Our findings show that more compounds that can play a different active role occur in these foods. PMID:22013381

Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts

PubMed Central

Chou, Chung-Chuan; Zhou, Shengmei; Hayashi, Hideki; Nihei, Motoki; Liu, Yen-Bin; Wen, Ming-Shien; Yeh, San-Jou; Fishbein, Michael C; Weiss, James N; Lin, Shien-Fong; Wu, Delon; Chen, Peng-Sheng

2007-01-01

We hypothesize that remodelling of action potential and intracellular calcium (Cai) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Cai and membrane potential (Vm) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37% showed elevation of Cai prior to Vm depolarization, suggesting reverse excitation–contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Cai alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Cai. Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Cai dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Cai cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting. PMID:17272354

Motor resonance facilitates movement execution: an ERP and kinematic study

PubMed Central

Ménoret, Mathilde; Curie, Aurore; des Portes, Vincent; Nazir, Tatjana A.; Paulignan, Yves

2013-01-01

Action observation, simulation and execution share neural mechanisms that allow for a common motor representation. It is known that when these overlapping mechanisms are simultaneously activated by action observation and execution, motor performance is influenced by observation and vice versa. To understand the neural dynamics underlying this influence and to measure how variations in brain activity impact the precise kinematics of motor behavior, we coupled kinematics and electrophysiological recordings of participants while they performed and observed congruent or non-congruent actions or during action execution alone. We found that movement velocities and the trajectory deviations of the executed actions increased during the observation of congruent actions compared to the observation of non-congruent actions or action execution alone. This facilitation was also discernible in the motor-related potentials of the participants; the motor-related potentials were transiently more negative in the congruent condition around the onset of the executed movement, which occurred 300 ms after the onset of the observed movement. This facilitation seemed to depend not only on spatial congruency but also on the optimal temporal relationship of the observation and execution events. PMID:24133437

Auditory thresholds in the American cockroach (Orthoptera: Blattidae): estimates using single-unit and compound-action potential recordings.

PubMed

Decker, T N; Jones, T A; Gold, R E

1989-06-01

Recent commercial suggestions that insect populations can be controlled through the use of ultrasound raises the question of whether or not certain insects have receptors that are sensitive to high-frequency sound. Single neural unit discharges and compound-action potentials were recorded from the ventral nerve cord in the American cockroach, Periplaneta americana L., to constant rise time tone pulses from 100 to 40,000 hertz (Hz). Unit responses and compound-action potentials show that the cockroach is insensitive to sound above approximately 3,000 Hz. Data relating latency of the response to intensity of the stimulus suggest that the cockroach cercal system operates on the principle of energy envelope detection. Decreases in latency likely occur primarily as a result of increases in the rate of membrane depolarization in cercal dendrites.

The impact of short term synaptic depression and stochastic vesicle dynamics on neuronal variability

PubMed Central

Reich, Steven

2014-01-01

Neuronal variability plays a central role in neural coding and impacts the dynamics of neuronal networks. Unreliability of synaptic transmission is a major source of neural variability: synaptic neurotransmitter vesicles are released probabilistically in response to presynaptic action potentials and are recovered stochastically in time. The dynamics of this process of vesicle release and recovery interacts with variability in the arrival times of presynaptic spikes to shape the variability of the postsynaptic response. We use continuous time Markov chain methods to analyze a model of short term synaptic depression with stochastic vesicle dynamics coupled with three different models of presynaptic spiking: one model in which the timing of presynaptic action potentials are modeled as a Poisson process, one in which action potentials occur more regularly than a Poisson process (sub-Poisson) and one in which action potentials occur more irregularly (super-Poisson). We use this analysis to investigate how variability in a presynaptic spike train is transformed by short term depression and stochastic vesicle dynamics to determine the variability of the postsynaptic response. We find that sub-Poisson presynaptic spiking increases the average rate at which vesicles are released, that the number of vesicles released over a time window is more variable for smaller time windows than larger time windows and that fast presynaptic spiking gives rise to Poisson-like variability of the postsynaptic response even when presynaptic spike times are non-Poisson. Our results complement and extend previously reported theoretical results and provide possible explanations for some trends observed in recorded data. PMID:23354693

Public Response to the Risk from Geological Radon.

ERIC Educational Resources Information Center

Sandman, Peter M.; And Others

1987-01-01

Analyzes reactions to naturally occurring radon in New Jersey. Suggests that successful risk communication must bridge the gap between focusing on hazard information and using the potential for public "outrage" as an important motivation to action. (NKA)

Complete unconscious control: Using (in)action primes to demonstrate completely unconscious activation of inhibitory control mechanisms

PubMed Central

Hepler, Justin; Albarracin, Dolores

2018-01-01

Although robust evidence indicates that action initiation can occur unconsciously and unintentionally, the literature on action inhibition suggests that inhibition requires both conscious thought and intentionality. In prior research demonstrating automatic inhibition in response to unconsciously processed stimuli, the unconscious stimuli had previously been consciously associated with an inhibitory response within the context of the experiment, and participants had consciously formed a goal to activate inhibition processes when presented with the stimuli (because task instructions required participants to engage in inhibition when the stimuli occurred). Therefore, prior work suggests that some amount of conscious thought and intentionality are required for inhibitory control. In the present research, we recorded event-related potentials during two go/no-go experiments in which participants were subliminally primed with general action/inaction concepts that had never been consciously associated with task-specific responses. We provide the first demonstration that inhibitory control processes can be modulated completely unconsciously and unintentionally. PMID:23747649

[Medical safety management in the setting of a clinical reference laboratory--risk management efforts in clinical testing].

PubMed

Seki, Akira; Miya, Tetsumasa

2011-03-01

As a result of recurring medical accidents, risk management in the medical setting has been given much attention. The announcement in August, 2000 by the Ministry of Health committee for formulating a standard manual for risk management, of a "Risk management manual formulation guideline" has since been accompanied by the efforts of numerous medical testing facilities to develop such documents. In 2008, ISO/TS 22367:2008 on "Medical laboratories-Reduction of error through risk management and continual improvement" was published. However, at present, risk management within a medical testing facility stresses the implementation of provisional actions in response to a problem after it has occurred. Risk management is basically a planned process and includes "corrective actions" as well as "preventive actions." A corrective action is defined as identifying the root cause of the problem and removing it, and is conducted to prevent the problem from recurring. A preventive action is defined as identifying of the any potential problem and removing it, and is conducted to prevent a problem before it occurs. Presently, I shall report on the experiences of our laboratory regarding corrective and preventive actions taken in response to accidents and incidents, respectively.

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

PubMed

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

2018-04-11

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

Noninvasive Assessment of Attention State from Correlated Oscillations in Brain and Muscle

DTIC Science & Technology

2010-11-29

rhythms depend in part on activity in the thalamus. EMG is a composite of muscle fiber action potentials occurring in the muscle . The action...the subjects were asked to perform the isometric MVCs with the first dorsal interosseus muscle of the right hand. The MVC was determined using a...REPORT Noninvasive assessment of attention state from correlated oscillations in brain and muscle 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: In motor

Diuretic‐sensitive electroneutral Na+ movement and temperature effects on central axons

PubMed Central

Kanagaratnam, Meneka; Pendleton, Christopher; Souza, Danilo Almeida; Pettit, Joseph; Howells, James

2017-01-01

Key points Optic nerve axons get less excitable with warming.F‐fibre latency does not shorten at temperatures above 30°C.Action potential amplitude falls when the Na+‐pump is blocked, an effect speeded by warming.Diuretics reduce the rate of action potential fall in the presence of ouabain.Our data are consistent with electroneutral entry of Na+ occurring in axons and contributing to setting the resting potential. Abstract Raising the temperature of optic nerve from room temperature to near physiological has effects on the threshold, refractoriness and superexcitability of the shortest latency (fast, F) nerve fibres, consistent with hyperpolarization. The temperature dependence of peak impulse latency was weakened at temperatures above 30°C suggesting a temperature‐sensitive process that slows impulse propagation. The amplitude of the supramaximal compound action potential gets larger on warming, whereas in the presence of bumetanide and amiloride (blockers of electroneutral Na+ movement), the action potential amplitude consistently falls. This suggests a warming‐induced hyperpolarization that is reduced by blocking electroneutral Na+ movement. In the presence of ouabain, the action potential collapses. This collapse is speeded by warming, and exposure to bumetanide and amiloride slows the temperature‐dependent amplitude decline, consistent with a warming‐induced increase in electroneutral Na+ entry. Blocking electroneutral Na+ movement is predicted to be useful in the treatment of temperature‐dependent symptoms under conditions with reduced safety factor (Uhthoff's phenomenon) and provide a route to neuroprotection. PMID:28213919

Identity and collective action among European Kurds.

PubMed

Ufkes, Elze G; Dovidio, John F; Tel, Gulizar

2015-03-01

This research investigated the role of group-based anger and efficacy in explaining the effects of subgroup (ethnic) and common (European) identity on collective action among Kurds in Europe responding to different types of disadvantage. Whereas stronger Kurdish identity positively predicted intentions for collective action (mediated by anger and efficacy), stronger common ingroup identity was negatively related to collective action intentions. This effect occurred primarily when structural disadvantage was salient, not when attention was drawn to a specific incident of disadvantage, and was mediated by anger but not efficacy. The findings complement recent work demonstrating that intergroup harmony can undermine social change, suggesting that stronger common-group identification reduces collective action by reducing minority-group members' sensitivity to potential bias against them. © 2014 The British Psychological Society.

Patient safety in the care of mentally ill people in Switzerland: Action plan 2016

PubMed

Richard, Aline; Mascherek, Anna C; Schwappach, David L B

2017-01-01

Background: Patient safety in mental healthcare has not attracted great attention yet, although the burden and the prevalence of mental diseases are high. The risk of errors with potential for harm of patients, such as aggression against self and others or non-drug treatment errors is particularly high in this vulnerable group. Aim: To develop priority topics and strategies for action to foster patient safety in mental healthcare. Method: The Swiss patient safety foundation together with experts conducted round table discussions and a Delphi questionnaire to define topics along the treatment pathway, and to prioritise these topics. Finally, fields of action were developed. Results: An action plan was developed including the definition and prioritization of 9 topics where errors may occur. A global rating task revealed errors concerning diagnostics and structural errors as most important. This led to the development of 4 fields of action (awareness raising, research, implementation, and education and training) including practice-oriented potential starting points to enhance patient safety. Conclusions: The action plan highlights issues of high concern for patient safety in mental healthcare. It serves as a starting point for the development of strategies for action as well as of concrete activities.

Influence of asymmetric attenuation of single and paired dendritic inputs on summation of synaptic potentials and initiation of action potentials.

PubMed

Fortier, Pierre A; Bray, Chelsea

2013-04-16

Previous studies revealed mechanisms of dendritic inputs leading to action potential initiation at the axon initial segment and backpropagation into the dendritic tree. This interest has recently expanded toward the communication between different parts of the dendritic tree which could preprocess information before reaching the soma. This study tested for effects of asymmetric voltage attenuation between different sites in the dendritic tree on summation of synaptic inputs and action potential initiation using the NEURON simulation environment. Passive responses due to the electrical equivalent circuit of the three-dimensional neuron architecture with leak channels were examined first, followed by the responses after adding voltage-gated channels and finally synaptic noise. Asymmetric attenuation of voltage, which is a function of asymmetric input resistance, was seen between all pairs of dendritic sites but the transfer voltages (voltage recorded at the opposite site from stimulation among a pair of dendritic sites) were equal and also summed linearly with local voltage responses during simultaneous stimulation of both sites. In neurons with voltage-gated channels, we reproduced the observations where a brief stimulus to the proximal ascending dendritic branch of a pyramidal cell triggers a local action potential but a long stimulus triggers a somal action potential. Combined stimulation of a pair of sites in this proximal dendrite did not alter this pattern. The attraction of the action potential onset toward the soma with a long stimulus in the absence of noise was due to the higher density of voltage-gated sodium channels at the axon initial segment. This attraction was, however, negligible at the most remote distal dendritic sites and was replaced by an effect due to high input resistance. Action potential onset occurred at the dendritic site of higher input resistance among a pair of remote dendritic sites, irrespective of which of these two sites received the synaptic input. Exploration of the parameter space showed how the gradient of voltage-gated channel densities and input resistances along a dendrite could draw the action potential onset away from the stimulation site. The attraction of action potential onset toward the higher density of voltage-gated channels in the soma during stimulation of the proximal dendrite was, however, reduced after the addition of synaptic noise. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Birinyi-Strachan, Liesl C.; Gunning, Simon J.; Lewis, Richard J.

2005-04-15

The present study investigated the actions of the polyether marine toxin Pacific ciguatoxin-1 (P-CTX-1) on neuronal excitability in rat dorsal root ganglion (DRG) neurons using patch-clamp recording techniques. Under current-clamp conditions, bath application of 2-20 nM P-CTX-1 caused a rapid, concentration-dependent depolarization of the resting membrane potential in neurons expressing tetrodotoxin (TTX)-sensitive voltage-gated sodium (Na{sub v}) channels. This action was completely suppressed by the addition of 200 nM TTX to the external solution, indicating that this effect was mediated through TTX-sensitive Na{sub v} channels. In addition, P-CTX-1 also prolonged action potential and afterhyperpolarization (AHP) duration. In a subpopulation of neurons,more » P-CTX-1 also produced tonic action potential firing, an effect that was not accompanied by significant oscillation of the resting membrane potential. Conversely, in neurons expressing TTX-resistant Na{sub v} currents, P-CTX-1 failed to alter any parameter of neuronal excitability examined in this study. Under voltage-clamp conditions in rat DRG neurons, P-CTX-1 inhibited both delayed-rectifier and 'A-type' potassium currents in a dose-dependent manner, actions that occurred in the absence of alterations to the voltage dependence of activation. These actions appear to underlie the prolongation of the action potential and AHP, and contribute to repetitive firing. These data indicate that a block of potassium channels contributes to the increase in neuronal excitability, associated with a modulation of Na{sub v} channel gating, observed clinically in response to ciguatera poisoning.« less

A two-channel action-potential generator for testing neurophysiologic data acquisition/analysis systems.

PubMed

Lisiecki, R S; Voigt, H F

1995-08-01

A 2-channel action-potential generator system was designed for use in testing neurophysiologic data acquisition/analysis systems. The system consists of a personal computer controlling an external hardware unit. This system is capable of generating 2 channels of simulated action potential (AP) waveshapes. The AP waveforms are generated from the linear combination of 2 principal-component template functions. Each channel generates randomly occurring APs with a specified rate ranging from 1 to 200 events per second. The 2 trains may be independent of one another or the second channel may be made to be excited or inhibited by the events from the first channel with user-specified probabilities. A third internal channel may be made to excite or inhibit events in both of the 2 output channels with user-specified rate parameters and probabilities. The system produces voltage waveforms that may be used to test neurophysiologic data acquisition systems for recording from 2 spike trains simultaneously and for testing multispike-train analysis (e.g., cross-correlation) software.

Computing by physical interaction in neurons.

PubMed

Aur, Dorian; Jog, Mandar; Poznanski, Roman R

2011-12-01

The electrodynamics of action potentials represents the fundamental level where information is integrated and processed in neurons. The Hodgkin-Huxley model cannot explain the non-stereotyped spatial charge density dynamics that occur during action potential propagation. Revealed in experiments as spike directivity, the non-uniform charge density dynamics within neurons carry meaningful information and suggest that fragments of information regarding our memories are endogenously stored in structural patterns at a molecular level and are revealed only during spiking activity. The main conceptual idea is that under the influence of electric fields, efficient computation by interaction occurs between charge densities embedded within molecular structures and the transient developed flow of electrical charges. This process of computation underlying electrical interactions and molecular mechanisms at the subcellular level is dissimilar from spiking neuron models that are completely devoid of physical interactions. Computation by interaction describes a more powerful continuous model of computation than the one that consists of discrete steps as represented in Turing machines.

Action Potentials Initiate in the Axon Initial Segment and Propagate Through Axon Collaterals Reliably in Cerebellar Purkinje Neurons

PubMed Central

Foust, Amanda; Popovic, Marko; Zecevic, Dejan; McCormick, David A.

2010-01-01

Purkinje neurons are the output cells of the cerebellar cortex and generate spikes in two distinct modes, known as simple and complex spikes. Revealing the point of origin of these action potentials, and how they conduct into local axon collaterals, is important for understanding local and distal neuronal processing and communication. By utilizing a recent improvement in voltage sensitive dye imaging technique that provided exceptional spatial and temporal resolution, we were able to resolve the region of spike initiation as well as follow spike propagation into axon collaterals for each action potential initiated on single trials. All fast action potentials, for both simple and complex spikes, whether occurring spontaneously or in response to a somatic current pulse or synaptic input, initiated in the axon initial segment. At discharge frequencies of less than approximately 250 Hz, spikes propagated faithfully through the axon and axon collaterals, in a saltatory manner. Propagation failures were only observed for very high frequencies or for the spikelets associated with complex spikes. These results demonstrate that the axon initial segment is a critical decision point in Purkinje cell processing and that the properties of axon branch points are adjusted to maintain faithful transmission. PMID:20484631

Isosteviol prevents the prolongation of action potential in hypertrophied cardiomyoctyes by regulating transient outward potassium and L-type calcium channels.

PubMed

Fan, Zhuo; Lv, Nanying; Luo, Xiao; Tan, Wen

2017-10-01

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.

Effects of redox and sulfhydryl reagents on the bioelectric properties of the giant axon of the squid.

PubMed

Huneeus-Cox, F; Fernandez, H L; Smith, B H

1966-09-01

The effects of internally and externally applied sulfhydryl reagents on the bioelectric properties of the giant axon of the squid Loligo pealeii and Dosidicus gigas were studied. Cysteine-HCl (400 mM, pH 7.3) was used to remove axoplasm from the perfusion channel. Oxidizing agents (1 to 60 mM) tended to increase the duration of the action potential and had a slow, irreversible blocking effect when perfused internally; the membrane potential was little affected. Reducing agents applied internally caused a decrease in the spike duration without affecting its height or the membrane potential, although at high concentrations there was reversible deterioration of the action potential. Both external and internal perfusion of mercaptide-forming reagents caused deterioration in the action and membrane potentials with conduction block occurring in 5 to 45 min. 2-mercaptoethanol reversed the effects. Thiol alkylating reagents, iodoacetate and iodoacetamide, were without effect. N-ethylmaleimide did, however, block. Tests with chelating agents for nonheme iron in the membrane brought about no change in the electrical parameters. The implications of the present findings with regard to the macromolecular mechanism of excitation are discussed.

Effects of Redox and Sulfhydryl Reagents on the Bioelectric Properties of the Giant Axon of the Squid

PubMed Central

Huneeus-Cox, F.; Fernandez, H. L.; Smith, B. H.

1966-01-01

The effects of internally and externally applied sulfhydryl reagents on the bioelectric properties of the giant axon of the squid Loligo pealeii and Dosidicus gigas were studied. Cysteine-HCl (400 mM, pH 7.3) was used to remove axoplasm from the perfusion channel. Oxidizing agents (1 to 60 mM) tended to increase the duration of the action potential and had a slow, irreversible blocking effect when perfused internally; the membrane potential was little affected. Reducing agents applied internally caused a decrease in the spike duration without affecting its height or the membrane potential, although at high concentrations there was reversible deterioration of the action potential. Both external and internal perfusion of mercaptide-forming reagents caused deterioration in the action and membrane potentials with conduction block occurring in 5 to 45 min. 2-mercaptoethanol reversed the effects. Thiol alkylating reagents, iodoacetate and iodoacetamide, were without effect. N-ethylmaleimide did, however, block. Tests with chelating agents for nonheme iron in the membrane brought about no change in the electrical parameters. The implications of the present findings with regard to the macromolecular mechanism of excitation are discussed. ImagesFigure 1 PMID:5970570

15 CFR 990.51 - Injury assessment-injury determination.

Code of Federal Regulations, 2011 CFR

2011-01-01

... natural resource service has occurred as a result of response actions or a substantial threat of a..., identify the nature of the injury. Potential categories of injury include, but are not limited to, adverse changes in: survival, growth, and reproduction; health, physiology and biological condition; behavior...

15 CFR 990.51 - Injury assessment-injury determination.

Code of Federal Regulations, 2010 CFR

2010-01-01

... natural resource service has occurred as a result of response actions or a substantial threat of a..., identify the nature of the injury. Potential categories of injury include, but are not limited to, adverse changes in: survival, growth, and reproduction; health, physiology and biological condition; behavior...

15 CFR 990.51 - Injury assessment-injury determination.

Code of Federal Regulations, 2013 CFR

2013-01-01

... natural resource service has occurred as a result of response actions or a substantial threat of a..., identify the nature of the injury. Potential categories of injury include, but are not limited to, adverse changes in: survival, growth, and reproduction; health, physiology and biological condition; behavior...

15 CFR 990.51 - Injury assessment-injury determination.

Code of Federal Regulations, 2014 CFR

2014-01-01

... natural resource service has occurred as a result of response actions or a substantial threat of a..., identify the nature of the injury. Potential categories of injury include, but are not limited to, adverse changes in: survival, growth, and reproduction; health, physiology and biological condition; behavior...

15 CFR 990.51 - Injury assessment-injury determination.

Code of Federal Regulations, 2012 CFR

2012-01-01

... natural resource service has occurred as a result of response actions or a substantial threat of a..., identify the nature of the injury. Potential categories of injury include, but are not limited to, adverse changes in: survival, growth, and reproduction; health, physiology and biological condition; behavior...

Electrochemical sensor for monitoring electrochemical potentials of fuel cell components

DOEpatents

Kunz, Harold R.; Breault, Richard D.

1993-01-01

An electrochemical sensor comprised of wires, a sheath, and a conduit can be utilized to monitor fuel cell component electric potentials during fuel cell shut down or steady state. The electrochemical sensor contacts an electrolyte reservoir plate such that the conduit wicks electrolyte through capillary action to the wires to provide water necessary for the electrolysis reaction which occurs thereon. A voltage is applied across the wires of the electrochemical sensor until hydrogen evolution occurs at the surface of one of the wires, thereby forming a hydrogen reference electrode. The voltage of the fuel cell component is then determined with relation to the hydrogen reference electrode.

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

PubMed

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

2017-05-06

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

Mechanical bioeffects of pulsed high intensity focused ultrasound on a simple neural model.

PubMed

Wahab, Radia Abdul; Choi, Mina; Liu, Yunbo; Krauthamer, Victor; Zderic, Vesna; Myers, Matthew R

2012-07-01

To study how pressure pulses affect nerves through mechanisms that are neither thermal nor cavitational, and investigate how the effects are related to cumulative radiation-force impulse (CRFI). Applications include traumatic brain injury and acoustic neuromodulation. A simple neural model consisting of the giant axon of a live earthworm was exposed to trains of pressure pulses produced by an 825 kHz focused ultrasound transducer. The peak negative pressure of the pulses and duty cycle of the pulse train were controlled so that neither cavitation nor significant temperature rise occurred. The amplitude and conduction velocity of action-potentials triggered in the worm were measured as the magnitude of the pulses and number of pulses in the pulse trains were varied. The functionality of the axons decreased when sufficient pulse energy was applied. The level of CRFI at which the observed effects occur is consistent with the lower levels of injury observed in this study relative to blast tubes. The relevant CRFI values are also comparable to CRFI values in other studies showing measureable changes in action-potential amplitudes and velocities. Plotting the measured action-potential amplitudes and conduction velocities from different experiments with widely varying exposure regimens against the single parameter of CRFI yielded values that agreed within 21% in terms of amplitude and 5% in velocity. A predictive model based on the assumption that the temporal rate of decay of action-potential amplitude and velocity is linearly proportional the radiation force experienced by the axon predicted the experimental amplitudes and conduction velocities to within about 20% agreement. The functionality of axons decreased due to noncavitational mechanical effects. The radiation force, possibly by inducing changes in ion-channel permeability, appears to be a possible mechanism for explaining the observed degradation. The CRFI is also a promising parameter for quantifying neural bioeffects during exposure to pressure waves, and for predicting axon functionality.

New insights into the acute actions from a high dosage of fluoxetine on neuronal and cardiac function: Drosophila, crayfish and rodent models.

PubMed

Majeed, Zana R; Ritter, Kyle; Robinson, Jonathan; Blümich, Sandra L E; Brailoiu, Eugen; Cooper, Robin L

2015-01-01

The commonly used mood altering drug fluoxetine (Prozac) in humans has a low occurrence in reports of harmful effects from overdose; however, individuals with altered metabolism of the drug and accidental overdose have led to critical conditions and even death. We addressed direct actions of high concentrations on synaptic transmission at neuromuscular junctions (NMJs), neural properties, and cardiac function unrelated to fluoxetine's action as a selective 5-HT reuptake inhibitor. There appears to be action in blocking action potentials in crayfish axons, enhanced occurrences of spontaneous synaptic vesicle fusion events in the presynaptic terminals at NMJs of both Drosophila and crayfish. In rodent neurons, cytoplasmic Ca(2+) rises by fluoxetine and is thapsigargin dependent. The Drosophila larval heart showed a dose dependent effect in cardiac arrest. Acute paralytic behavior in crayfish occurred at a systemic concentration of 2mM. A high percentage of death as well as slowed development occurred in Drosophila larvae consuming food containing 100μM fluoxetine. The release of Ca(2+) from the endoplasmic reticulum in neurons and the cardiac tissue as well as blockage of voltage-gated Na(+) channels in neurons could explain the effects on the whole animal as well as the isolated tissues. The use of various animal models in demonstrating the potential mechanisms for the toxic effects with high doses of fluoxetine maybe beneficial for acute treatments in humans. Future studies in determining how fluoxetine is internalized in cells and if there are subtle effects of these mentioned mechanisms presented with chronic therapeutic doses are of general interest. Copyright © 2015 Elsevier Inc. All rights reserved.

Insecticide solvents: interference with insecticidal action.

PubMed

Brattsten, L B; Wilkinson, C F

1977-06-10

Several commercial solvent mixtures commonly used as insecticide carriers in spray formulations increase by more than threefold the microsomal N-demethylation of p-chloro N-methylaniline in midgut preparations of southern army-worm (Spodoptera eridania) larvae exposed orally to the test solvents. Under laboratory conditions, the same solvent mixtures exhibit a protective action against the in vivo toxicity of the insecticide carbaryl to the larvae. The data are discussed with respect to possible solvent-insecticide interactions occurring under field conditions and, more broadly, to potential toxicological hazards of these solvents to humans.

BDNF mRNA abundance regulated by antidromic action potentials and AP-LTD in hippocampus.

PubMed

Bukalo, Olena; Lee, Philip R; Fields, R Douglas

2016-12-02

Action-potential-induced LTD (AP-LTD) is a form of synaptic plasticity that reduces synaptic strength in CA1 hippocampal neurons firing antidromically during sharp-wave ripples. This firing occurs during slow-wave sleep and quiet moments of wakefulness, which are periods of offline replay of neural sequences learned during encoding sensory information. Here we report that rapid and persistent down-regulation of different mRNA transcripts of the BDNF gene accompanies AP-LTD, and that AP-LTD is abolished in mice with the BDNF gene knocked out in CA1 hippocampal neurons. These findings increase understanding of the mechanism of AP-LTD and the cellular mechanisms of memory consolidation. Published by Elsevier Ireland Ltd.

Trial-Type Dependent Frames of Reference for Value Comparison

PubMed Central

Hunt, Laurence T.; Woolrich, Mark W.; Rushworth, Matthew F. S.; Behrens, Timothy E. J.

2013-01-01

A central question in cognitive neuroscience regards the means by which options are compared and decisions are resolved during value-guided choice. It is clear that several component processes are needed; these include identifying options, a value-based comparison, and implementation of actions to execute the decision. What is less clear is the temporal precedence and functional organisation of these component processes in the brain. Competing models of decision making have proposed that value comparison may occur in the space of alternative actions, or in the space of abstract goods. We hypothesized that the signals observed might in fact depend upon the framing of the decision. We recorded magnetoencephalographic data from humans performing value-guided choices in which two closely related trial types were interleaved. In the first trial type, each option was revealed separately, potentially causing subjects to estimate each action's value as it was revealed and perform comparison in action-space. In the second trial type, both options were presented simultaneously, potentially leading to comparison in abstract goods-space prior to commitment to a specific action. Distinct activity patterns (in distinct brain regions) on the two trial types demonstrated that the observed frame of reference used for decision making indeed differed, despite the information presented being formally identical, between the two trial types. This provides a potential reconciliation of conflicting accounts of value-guided choice. PMID:24068906

Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release.

PubMed Central

Debanne, D; Guérineau, N C; Gähwiler, B H; Thompson, S M

1996-01-01

1. Excitatory synaptic transmission between pairs of monosynaptically coupled pyramidal cells was examined in rat hippocampal slice cultures. Action potentials were elicited in single CA3 pyramidal cells impaled with microelectrodes and unitary excitatory postsynaptic currents (EPSCs) were recorded in whole-cell voltage-clamped CA1 or CA3 cells. 2. The amplitude of successive unitary EPSCs in response to single action potentials varied. The amplitude of EPSCs was altered by adenosine or changes in the [Mg2+]/[CA2+] ratio. We conclude that single action potentials triggered the release of multiple quanta of glutamate. 3. When two action potentials were elicited in the presynaptic cell, the amplitude of the second EPSC was inversely related to the amplitude of the first. Paired-pulse facilitation (PPF) was observed when the first EPSC was small, i.e. the second EPSC was larger than the first, whereas paired-pulse depression (PPD) was observed when the first EPSC was large. 4. The number of trials displaying PPD was greater when release probability was increased, and smaller when release probability was decreased. 5. PPD was not postsynaptically mediated because it was unaffected by decreasing ionic flux with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or receptor desensitization with aniracetam. 6. PPF was maximal at an interstimulus interval of 70 ms and recovered within 500 ms. Recovery from PPD occurred within 5 s. 7. We propose that multiple release sites are formed by the axon of a CA3 pyramidal cell and a single postsynaptic CA1 or CA3 cell. PPF is observed if the first action potential fails to release transmitter at most release sites. PPD is observed if the first action potential successfully triggers release at most release sites. 8. Our observations of PPF are consistent with the residual calcium hypothesis. We conclude that PPD results from a decrease in quantal content, perhaps due to short-term depletion of readily releasable vesicles. PMID:9011608

Drosophila TRPA1 channel is required to avoid the naturally occurring insect repellent citronellal.

PubMed

Kwon, Young; Kim, Sang Hoon; Ronderos, David S; Lee, Youngseok; Akitake, Bradley; Woodward, Owen M; Guggino, William B; Smith, Dean P; Montell, Craig

2010-09-28

Plants produce insect repellents, such as citronellal, which is the main component of citronellal oil. However, the molecular pathways through which insects sense botanical repellents are unknown. Here, we show that Drosophila use two pathways for direct avoidance of citronellal. The olfactory coreceptor OR83b contributes to citronellal repulsion and is essential for citronellal-evoked action potentials. Mutations affecting the Ca(2+)-permeable cation channel TRPA1 result in a comparable defect in avoiding citronellal vapor. The TRPA1-dependent aversion to citronellal relies on a G protein (Gq)/phospholipase C (PLC) signaling cascade rather than direct detection of citronellal by TRPA1. Loss of TRPA1, Gq, or PLC causes an increase in the frequency of citronellal-evoked action potentials in olfactory receptor neurons. Absence of the Ca(2+)-activated K(+) channel (BK channel) Slowpoke results in a similar impairment in citronellal avoidance and an increase in the frequency of action potentials. These results suggest that TRPA1 is required for activation of a BK channel to modulate citronellal-evoked action potentials and for aversion to citronellal. In contrast to Drosophila TRPA1, Anopheles gambiae TRPA1 is directly and potently activated by citronellal, thereby raising the possibility that mosquito TRPA1 may be a target for developing improved repellents to reduce insect-borne diseases such as malaria. Copyright © 2010 Elsevier Ltd. All rights reserved.

76 FR 58050 - Tennessee Valley Authority, Bellefonte Nuclear Power Plant, Unit 1; Environmental Assessment and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

...--federal candidate) were identified in the TVA Biological Assessment (BA) as occurring in areas potentially... major pumps, motors, heat exchangers, tanks, and piping; refurbish major equipment, such as reactor... actions with SIPs, amends 40 CFR part 51, Subpart W, and specifically identifies tribal agencies as...

The anti-cancer agent guttiferone-A permeabilizes mitochondrial membrane: Ensuing energetic and oxidative stress implications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pardo-Andreu, Gilberto L., E-mail: gilbertopardo@infomed.sld.cu; Departamento de Fisica e Quimica, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av. Cafe s/n, 14040-903 Ribeirao Preto, SP; Nunez-Figueredo, Yanier

Guttiferone-A (GA) is a natural occurring polyisoprenylated benzophenone with cytotoxic action in vitro and anti-tumor action in rodent models. We addressed a potential involvement of mitochondria in GA toxicity (1-25 {mu}M) toward cancer cells by employing both hepatic carcinoma (HepG2) cells and succinate-energized mitochondria, isolated from rat liver. In HepG2 cells GA decreased viability, dissipated mitochondrial membrane potential, depleted ATP and increased reactive oxygen species (ROS) levels. In isolated rat-liver mitochondria GA promoted membrane fluidity increase, cyclosporine A/EGTA-insensitive membrane permeabilization, uncoupling (membrane potential dissipation/state 4 respiration rate increase), Ca{sup 2+} efflux, ATP depletion, NAD(P)H depletion/oxidation and ROS levels increase. Allmore » effects in cells, except mitochondrial membrane potential dissipation, as well as NADPH depletion/oxidation and permeabilization in isolated mitochondria, were partly prevented by the a NAD(P)H regenerating substrate isocitrate. The results suggest the following sequence of events: 1) GA interaction with mitochondrial membrane promoting its permeabilization; 2) mitochondrial membrane potential dissipation; 3) NAD(P)H oxidation/depletion due to inability of membrane potential-sensitive NADP{sup +} transhydrogenase of sustaining its reduced state; 4) ROS accumulation inside mitochondria and cells; 5) additional mitochondrial membrane permeabilization due to ROS; and 6) ATP depletion. These GA actions are potentially implicated in the well-documented anti-cancer property of GA/structure related compounds. - Graphical abstract: Guttiferone-A permeabilizes mitochondrial membrane and induces cancer cell death Display Omitted Highlights: > We addressed the involvement of mitochondria in guttiferone (GA) toxicity toward cancer cells. > GA promoted membrane permeabilization, membrane potential dissipation, NAD(P)H depletion, ROS accumulation and ATP depletion. > These actions could be implicated in the well-documented anti-cancer property of GA/structure related compounds.« less

Asymmetrical electrically induced injury of rabbit ventricular myocytes.

PubMed

Knisley, S B; Grant, A O

1995-05-01

Strong defibrillation-type electric field stimulation may injure myocytes when transmembrane potentials during the pulse exceed the threshold for membrane permeabilization. The location of injury may depend on intrinsic transmembrane potential or influx of calcium by "electro-osmosis" during the stimulation pulse in addition to the transmembrane potential changes induced by the pulse. We have studied injury by examining contracture and changes in transmembrane potential-sensitive dye fluorescence induced by electric field stimulation (St) with a duration of 20 ms and strength of 16-400 V/cm in isolated rabbit ventricular myocytes. St of 100-150 V/cm produced injury in myocytes oriented parallel to the St field frequently without injuring myocytes oriented perpendicular to the field. Injury required calcium in the solution and was asymmetric, occurring first at the myocyte and facing the St anode in 100% of injured myocytes in normal Tyrode's solution. Injury depended significantly on whether the product of the electric field strength and myocyte length exceeded a threshold of 1.1 V (P < 0.05). Asymmetric injury at the end facing the anode was still present in 96% of injured myocytes for stimulation after depolarization by an action potential or 20 mM or 125 mM potassium, suggesting that intrinsic transmembrane potential is not responsible for asymmetry. In 125 mM potassium, eliminating calcium from the bathing solution during the St pulse and introducing calcium after the pulse decreased the fraction of injured myocytes in which injury occurred at the end facing the anode to 62%, suggesting that calcium influx by "electro-osmosis" at the myocyte end facing the anode contributes to asymmetry. Asymmetric injury at the end facing the anode was still present in 100% of injured myocytes after adding 1 mM tetraethylammonium chloride, indicating that asymmetry is not sensitive to the potassium channel blockade. For stimulation pulses stronger than 50 V/cm given after depolarization by an action potential, transmembrane potentials at both myocyte ends decayed after the initial deflection indicating that permeabilization occurred at both ends. In conclusion, injury depends on myocyte orientation and is asymmetric occurring first at the myocyte end facing the anode. Asymmetric injury is not explained by asymmetric permeabilization, is independent of the intrinsic transmembrane potential and may result from "electro-osmosis" during the stimulation pulse.

High-Bandwidth Atomic Force Microscopy Reveals A Mechanical spike Accompanying the Action Potential in mammalian Nerve Terminals

NASA Astrophysics Data System (ADS)

Salzberg, Brian M.

2008-03-01

Information transfer from neuron to neuron within nervous systems occurs when the action potential arrives at a nerve terminal and initiates the release of a chemical messenger (neurotransmitter). In the mammalian neurohypophysis (posterior pituitary), large and rapid changes in light scattering accompany secretion of transmitter-like neuropeptides. In the mouse, these intrinsic optical signals are intimately related to the arrival of the action potential (E-wave) and the release of arginine vasopressin and oxytocin (S-wave). We have used a high bandwidth (20 kHz) atomic force microscope (AFM) to demonstrate that these light scattering signals are associated with changes in nerve terminal volume, detected as nanometer-scale movements of a cantilever positioned on top of the neurohypophysis. The most rapid mechanical response, the ``spike'', has duration comparable to that of the action potential (˜2 ms) and probably reflects an increase in terminal volume due to H2O movement associated with Na^+-influx. Elementary calculations suggest that two H2O molecules accompanying each Na^+-ion could account for the ˜0.5-1.0 å increase in the diameter of each terminal during the action potential. Distinguishable from the mechanical ``spike'', a slower mechanical event, the ``dip'', represents a decrease in nerve terminal volume, depends upon Ca^2+-entry, as well as on intra-terminal Ca^2+-transients, and appears to monitor events associated with secretion. A simple hypothesis is that this ``dip'' reflects the extrusion of the dense core granule that comprises the secretory products. These dynamic high bandwidth AFM recordings are the first to monitor mechanical events in nervous systems and may provide novel insights into the mechanism(s) by which excitation is coupled to secretion at nerve terminals.

Harm avoiders suppress motor resonance to observed immoral actions

PubMed Central

Candidi, Matteo; Sforza, Anna Laura; Aglioti, Salvatore Maria

2015-01-01

Motor resonance (MR) contingent upon action observation is thought to occur largely automatically. Although recent studies suggest that this process is not completely impervious to top-down modulations, much less is known on the possible role of the moral connotation of observed action goal in modulating MR. Here, we explored whether observing actions with different moral connotations modulates MR and whether any modulation depends on the onlookers’ personality. To this aim, we recorded motor potentials evoked by single-pulse transcranial magnetic stimulation from hand muscles of participants who were watching images of a model performing hand actions with the same postures and low-level goals (i.e. grasping an object) but with different moral connotations (‘stealing a wallet’ vs ‘picking up a notepaper’). Participants’ personality traits were measured using the temperament and character inventory. Results show a selective suppression of corticospinal excitability during observation of immoral actions in individuals with high scores in harm avoidance, a personality trait characterized by excessive worrying and fearfulness. Thus, a combination of dispositional (personality traits) and situational (morality of an action) variables appears to influence MR with the observed actions. PMID:24526183

Space for action: How practitioners influence environmental assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kågström, Mari, E-mail: mari.kagstrom@slu.se; Richardson, Tim, E-mail: tim.richardson@nmbu.no

2015-09-15

Highlights: • The concept of ‘space for action’ offers an important new lens on EA practice. • Focuses on the relation between practitioner's understanding and their actions • Environmental assessment practice is decisively shaped by practitioners. • Practitioners may underestimate their potential to make a difference. • Contributes to understanding change in the environmental assessment field. This article contributes to understanding of how change occurs in the field of environmental assessment (EA). It argues that the integration of new issues in EA, such as human health, is significantly influenced by how practitioners' understandings shape their actions, and by what happensmore » when those, possibly different, interpretations of appropriate action are acted out. The concept of space for action is developed as a means of investigating this relation between understanding and action. Frame theory is also used, to develop a sharper focus on how ‘potential spaces for action’ are created, what these imply for (individuals') preferred choices and actions in certain situations, and what happens in practice when these are acted out and ‘actual spaces for action’ are created. This novel approach is then applied in a Swedish case study of transport planning. The analysis reveals the important work done by practitioners, revealing just how EA practice is decisively shaped by practitioners. Analysis of practice using the lens of spaces for action offers an important new perspective in understanding how the field adapts to new challenges.« less

Effects of action video game training on visual working memory.

PubMed

Blacker, Kara J; Curby, Kim M; Klobusicky, Elizabeth; Chein, Jason M

2014-10-01

The ability to hold visual information in mind over a brief delay is critical for acquiring information and navigating a complex visual world. Despite the ubiquitous nature of visual working memory (VWM) in our everyday lives, this system is fundamentally limited in capacity. Therefore, the potential to improve VWM through training is a growing area of research. An emerging body of literature suggests that extensive experience playing action video games yields a myriad of perceptual and attentional benefits. Several lines of converging work suggest that action video game play may influence VWM as well. The current study utilized a training paradigm to examine whether action video games cause improvements to the quantity and/or the quality of information stored in VWM. The results suggest that VWM capacity, as measured by a change detection task, is increased after action video game training, as compared with training on a control game, and that some improvement to VWM precision occurs with action game training as well. However, these findings do not appear to extend to a complex span measure of VWM, which is often thought to tap into higher-order executive skills. The VWM improvements seen in individuals trained on an action video game cannot be accounted for by differences in motivation or engagement, differential expectations, or baseline differences in demographics as compared with the control group used. In sum, action video game training represents a potentially unique and engaging platform by which this severely capacity-limited VWM system might be enhanced.

Longitudinal density modulation and energy conversion in intense beams.

PubMed

Harris, J R; Neumann, J G; Tian, K; O'Shea, P G

2007-08-01

Density modulation of charged particle beams may occur as a consequence of deliberate action, or may occur inadvertently because of imperfections in the particle source or acceleration method. In the case of intense beams, where space charge and external focusing govern the beam dynamics, density modulation may, under some circumstances, be converted to velocity modulation, with a corresponding conversion of potential energy to kinetic energy. Whether this will occur depends on the properties of the beam and the initial modulation. This paper describes the evolution of discrete and continuous density modulations on intense beams and discusses three recent experiments related to the dynamics of density-modulated electron beams.

The Relative Influences of Phosphometabolites and pH on Action Potential Morphology during Myocardial Reperfusion: A Simulation Study

PubMed Central

Roberts, Byron N.; Christini, David J.

2012-01-01

Myocardial ischemia-reperfusion (IR) injury represents a constellation of pathological processes that occur when ischemic myocardium experiences a restoration of perfusion. Reentrant arrhythmias, which represent a particularly lethal manifestation of IR injury, can result when ischemic tissue exhibits decreased excitability and/or changes of action potential duration (APD), conditions that precipitate unidirectional conduction block. Many of the cellular components that are involved with IR injury are modulated by pH and/or phosphometabolites such as ATP and phosphocreatine (PCr), all of which can be manipulated in vivo and potentially in the clinical setting. Using a mathematical model of the cardiomyocyte that we previously developed to study ischemia and reperfusion, we performed a series of simulations with the aim of determining whether pH- or phosphometabolite-related processes play a more significant role in generating changes in excitability and action potential morphology that are associated with the development of reentry. In our simulations, persistent shortening of APD, action potential amplitude (APA), and depolarization of the resting membrane potential were more severe when ATP and PCr availability were suppressed during reperfusion than when extracellular pH recovery was inhibited. Reduced phosphometabolite availability and pH recovery affected multiple ion channels and exchangers. Some of these effects were the result of direct modulation by phosphometabolites and/or acidosis, while others resulted from elevated sodium and calcium loads during reperfusion. In addition, increasing ATP and PCr availability during reperfusion was more beneficial in terms of increasing APD and APA than was increasing the amount of pH recovery. Together, these results suggest that therapies directed at increasing ATP and/or PCr availability during reperfusion may be more beneficial than perturbing pH recovery with regard to mitigating action potential changes that increase the likelihood of reentrant arrhythmias. PMID:23144801

Emulation as an Integrating Principle for Cognition

PubMed Central

Colder, Brian

2011-01-01

Emulations, defined as ongoing internal representations of potential actions and the futures those actions are expected to produce, play a critical role in directing human bodily activities. Studies of gross motor behavior, perception, allocation of attention, response to errors, interoception, and homeostatic activities, and higher cognitive reasoning suggest that the proper execution of all these functions relies on emulations. Further evidence supports the notion that reinforcement learning in humans is aimed at updating emulations, and that action selection occurs via the advancement of preferred emulations toward realization of their action and environmental prediction. Emulations are hypothesized to exist as distributed active networks of neurons in cortical and sub-cortical structures. This manuscript ties together previously unrelated theories of the role of prediction in different aspects of human information processing to create an integrated framework for cognition. PMID:21660288

REVIEW OF SIGNAL DISTORTION THROUGH METAL MICROELECTRODE RECORDING CIRCUITS AND FILTERS

PubMed Central

NELSON, Matthew J.; POUGET, Pierre; NILSEN, Erik A.; PATTEN, Craig D.; SCHALL, Jeffrey D.

2008-01-01

Interest in local field potentials (LFPs) and action potential shape has increased markedly. The present work describes distortions of these signals that occur for two reasons. First, the microelectrode recording circuit operates as a voltage divider producing frequency-dependent attenuation and phase-shifts when electrode impedance is not negligible relative to amplifier input impedance. Because of the much higher electrode impedance at low frequencies, this occurred over frequency ranges of LFPs measured by neurophysiologists for one head-stage tested. Second, frequency-dependent phase shifts are induced by subsequent filters. Thus, we report these effects and the resulting amplitude envelope delays and distortion of waveforms recorded through a commercial data acquisition system and a range of tungsten microelectrodes. These distortions can be corrected, but must be accounted for when interpreting field potential and spike shape data. PMID:18242715

Review of signal distortion through metal microelectrode recording circuits and filters.

PubMed

Nelson, Matthew J; Pouget, Pierre; Nilsen, Erik A; Patten, Craig D; Schall, Jeffrey D

2008-03-30

Interest in local field potentials (LFPs) and action potential shape has increased markedly. The present work describes distortions of these signals that occur for two reasons. First, the microelectrode recording circuit operates as a voltage divider producing frequency-dependent attenuation and phase shifts when electrode impedance is not negligible relative to amplifier input impedance. Because of the much higher electrode impedance at low frequencies, this occurred over frequency ranges of LFPs measured by neurophysiologists for one head-stage tested. Second, frequency-dependent phase shifts are induced by subsequent filters. Thus, we report these effects and the resulting amplitude envelope delays and distortion of waveforms recorded through a commercial data acquisition system and a range of tungsten microelectrodes. These distortions can be corrected, but must be accounted for when interpreting field potential and spike shape data.

Motor mapping of implied actions during perception of emotional body language.

PubMed

Borgomaneri, Sara; Gazzola, Valeria; Avenanti, Alessio

2012-04-01

Perceiving and understanding emotional cues is critical for survival. Using the International Affective Picture System (IAPS) previous TMS studies have found that watching humans in emotional pictures increases motor excitability relative to seeing landscapes or household objects, suggesting that emotional cues may prime the body for action. Here we tested whether motor facilitation to emotional pictures may reflect the simulation of the human motor behavior implied in the pictures occurring independently of its emotional valence. Motor-evoked potentials (MEPs) to single-pulse TMS of the left motor cortex were recorded from hand muscles during observation and categorization of emotional and neutral pictures. In experiment 1 participants watched neutral, positive and negative IAPS stimuli, while in experiment 2, they watched pictures depicting human emotional (joyful, fearful), neutral body movements and neutral static postures. Experiment 1 confirms the increase in excitability for emotional IAPS stimuli found in previous research and shows, however, that more implied motion is perceived in emotional relative to neutral scenes. Experiment 2 shows that motor excitability and implied motion scores for emotional and neutral body actions were comparable and greater than for static body postures. In keeping with embodied simulation theories, motor response to emotional pictures may reflect the simulation of the action implied in the emotional scenes. Action simulation may occur independently of whether the observed implied action carries emotional or neutral meanings. Our study suggests the need of controlling implied motion when exploring motor response to emotional pictures of humans. Copyright © 2012 Elsevier Inc. All rights reserved.

Predicting global population connectivity and targeting conservation action for snow leopard across its range

Treesearch

Philip Riordan; Samuel A. Cushman; David Mallon; Kun Shi; Joelene Hughes

2016-01-01

Movements of individuals within and among populations help to maintain genetic variability and population viability. Therefore, understanding landscape connectivity is vital for effective species conservation. The snow leopard is endemic to mountainous areas of central Asia and occurs within 12 countries. We assess potential connectivity across the species’...

'Long-Cell Action' Corrosion: A Basic Mechanism Hidden Behind Components Degradation Issues in Nuclear Power Plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Genn Saji

2006-07-01

In spite of industries' effort over the last 40 years, corrosion-related issues continue to be one of the largest unresolved problems for nuclear power plants worldwide. There are several types of strange corrosion phenomena from the point of view of our current understanding of corrosion science established in other fields. Some of these are IGSCC, PWSCC, AOA, and FAC (Erosion-Corrosion). Through studying and coping with diverse corrosion phenomena, the author believes that they share a common basis with respect to the assumed corrosion mechanism (e.g., 'local cell action' hypothesis). In general, local cell action is rarely severe since it producesmore » a fairly uniform corrosion. The 'long cell action' that transports electrons through structures far beyond the region of local cell corrosion activities has been identified as a basic mechanism in soil corrosion. If this mechanism is assumed in nuclear power plants, the structure becomes anodic in the area where the potential is less positive and cathodic where this potential is more positive. Metallic ions generated at anodic corrosion sites are transported to remote cathodic sites through the circulation of water and deposits as corrosion products. The SCC, FAC (E-C) and PWSCC occur in the anodic sites as the structure itself acts as a short-circuiting conductor between the two sites, the action is similar to a galvanic cell but in a very large scale. This situation is the same as a battery that has been short-circuited at the terminals. No apparent external potential difference exists between the two electrodes, but an electrochemical reaction is still taking place inside the battery cell with a large internal short current. In this example what is important is the potential difference between the local coolant and the surface of the structural material. Long cell action corrosion is likely enhancing the local cell action's anodic corrosion activities, such as SCC, FAC/E-C, and PWSCC. It tends to be more hazardous because of its localized nature compared with the local cell action corrosion. There exist various mechanisms (electrochemical cell configurations) that induce such potential differences, including: ionic concentration, aeration, temperature, flow velocity, radiation and corrosion potentials. In this paper, the author will discuss these potential differences and their relevance to the un-resolved corrosion issues in nuclear power plants. Due to the importance of this potential mechanism the author is calling for further verification experiments as a joint international project. (author)« less

Dorsal–Ventral Gradient for Neuronal Plasticity in the Embryonic Spinal Cord

PubMed Central

Pineda, Ricardo H.; Ribera, Angeles B.

2008-01-01

Within the developing Xenopus spinal cord, voltage-gated potassium (Kv) channel genes display different expression patterns, many of which occur in opposing dorsal–ventral gradients. Regional differences in Kv gene expression would predict different patterns of potassium current (IKv) regulation. However, during the first 24 h of postmitotic differentiation, all primary spinal neurons undergo a temporally coordinated upregulation of IKv density that shortens the duration of the action potential. Here, we tested whether spinal neurons demonstrate regional differences in IKv regulation subsequent to action potential maturation. We show that two types of neurons, I and II, can be identified in culture on the basis of biophysical and pharmacological properties of IKv and different firing patterns. Chronic increases in extracellular potassium, a signature of high neuronal activity, do not alter excitability properties of either neuron type. However, elevating extracellular potassium acutely after the period of action potential maturation leads to different changes in membrane properties of the two types of neurons. IKv of type I neurons gains sensitivity to the blocker XE991, whereas type II neurons increase IKv density and fire fewer action potentials. Moreover, by recording from neurons in vivo, we found that primary spinal neurons can be identified as either type I or type II. Type I neurons predominate in dorsal regions, whereas type II neurons localize to ventral regions. The findings reveal a dorsal–ventral gradient for IKv regulation and a novel form of neuronal plasticity in spinal cord neurons. PMID:18385340

Body posture modulates action perception.

PubMed

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

2013-04-03

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

Update on sideline and event preparation for management of sudden cardiac arrest in athletes.

PubMed

Harmon, Kimberly G; Drezner, Jonathan A

2007-06-01

Sudden death in athletes occurs approximately once every 3 days in the United States. Each school or venue should have an emergency action plan that is coordinated with local emergency medical services (EMS). Access to early defibrillation to treat sudden cardiac arrest (SCA) is critical. If EMS response times are greater than 3 to 5 minutes from collapse to first shock, an on-site automated external defibrillator (AED) should be available. Delays in recognition of SCA in athletes occur commonly. Any collapsed and unresponsive athlete should be considered to be in cardiac arrest and an AED should be applied for rhythm analysis as soon as possible. Cardiopulmonary resuscitation should be provided while waiting for an AED and interruptions in chest compressions should be minimized. Rehearsal of the emergency action plan with potential first responders is essential to ensuring an efficient response to SCA in athletics.

Andrographolide: antibacterial activity against common bacteria of human health concern and possible mechanism of action.

PubMed

Banerjee, Malabika; Parai, Debaprasad; Chattopadhyay, Subrata; Mukherjee, Samir Kumar

2017-05-01

Increasing bacterial resistance to common drugs is a major public health concern for the treatment of infectious diseases. Certain naturally occurring compounds of plant sources have long been reported to possess potential antimicrobial activity. This study was aimed to investigate the antibacterial activity and possible mechanism of action of andrographolide (Andro), a diterpenoid lactone from a traditional medicinal herb Andrographis paniculata. Extent of antibacterial action was assessed by minimal bactericidal concentration method. Radiolabeled N-acetyl glucosamine, leucine, thymidine, and uridine were used to determine the effect of Andro on the biosyntheses of cell wall, protein, DNA, and RNA, respectively. In addition, anti-biofilm potential of this compound was also tested. Andro showed potential antibacterial activity against most of the tested Gram-positive bacteria. Among those, Staphylococcus aureus was found to be most sensitive with a minimal inhibitory concentration value of 100 μg/mL. It was found to be bacteriostatic. Specific inhibition of intracellular DNA biosynthesis was observed in a dose-dependent manner in S. aureus. Andro mediated inhibition of biofilm formation by S. aureus was also found. Considering its antimicrobial potency, Andro might be accounted as a promising lead for new antibacterial drug development.

Health working with industry to promote fruit and vegetables: a case study of the Western Australian Fruit and Vegetable Campaign with reflection on effectiveness of inter-sectoral action.

PubMed

Miller, Margaret; Pollard, Christina

2005-04-01

In 1990, the Department of Health in Western Australia (DOH) initiated a five-year campaign to increase awareness of the need to eat more fruit and vegetables and to encourage increased consumption. This paper describes aspects of the campaign and reviews the strengths and weaknesses of health and fruit and vegetable industry alliances to extend and sustain the campaign. The fruit and vegetable industry was engaged through information sharing, consultation, working groups and joint promotions. The partnership was examined in terms of six inter-sectoral action dimensions (necessity; opportunity and capacity to work together; established relationships for goal achievement; degree of planning; potential for evaluation; and sustainability of action). There were both need and opportunity for each sector to work together. Health had commitment, expertise and resources to plan, implement and evaluate the campaign. Industry had established channels of communication within the supply chain. Sustained health sector presence provided incentive, endorsement and policy direction. Resources and infrastructure limited partnership sustainability. Greatest potential for success occurred when participants' contributions were closely aligned to their core business and there was a body responsible for co-ordinating action.

Relative Contributions of Goal Representation and Kinematic Information to Self-Monitoring by Chimpanzees and Humans

ERIC Educational Resources Information Center

Kaneko, Takaaki; Tomonaga, Masaki

2012-01-01

It is important to monitor feedback related to the intended result of an action while executing that action. This monitoring process occurs hierarchically; that is, sensorimotor processing occurs at a lower level, and conceptual representation of action goals occurs at a higher level. Although the hierarchical nature of self-monitoring may derive…

77 FR 55459 - Takes of Marine Mammals Incidental to Specified Activities; Piling and Fill Removal in Woodard...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-10

... and are expected to occur for approximately 20 days over the course of this work window. Other work... log boom haul-outs located in the action area. Other potential disturbance could result from the..., primarily by flushing seals off log booms, or by causing short-term avoidance of the area or similar short...

Nonvesicular inhibitory neurotransmission via reversal of the GABA transporter GAT-1

PubMed Central

Wu, Yuanming; Wang, Wengang; Díez-Sampedro, Ana; Richerson, George B.

2007-01-01

SUMMARY GABA transporters play an important but poorly understood role in neuronal inhibition. They can reverse, but this is widely thought to occur only under pathological conditions. Here we use a heterologous expression system to show that the reversal potential of GAT-1 under physiologically relevant conditions is near the normal resting potential of neurons, and that reversal can occur rapidly enough to release GABA during simulated action potentials. We then use paired recordings from cultured hippocampal neurons, and show that GABAergic transmission is not prevented by four methods widely used to block vesicular release. This nonvesicular neurotransmission was potently blocked by GAT-1 antagonists, and was enhanced as predicted by agents that increase cytosolic [GABA] or [Na+]. The results indicate that GAT-1 regulates tonic inhibition by clamping ambient [GABA] at a level high enough to activate high affinity GABAA receptors, and that transporter-mediated GABA release can contribute to phasic inhibition. PMID:18054861

Weighing costs and losses: A decision making game using probabilistic forecasts

NASA Astrophysics Data System (ADS)

Werner, Micha; Ramos, Maria-Helena; Wetterhall, Frederik; Cranston, Michael; van Andel, Schalk-Jan; Pappenberger, Florian; Verkade, Jan

2017-04-01

Probabilistic forecasts are increasingly recognised as an effective and reliable tool to communicate uncertainties. The economic value of probabilistic forecasts has been demonstrated by several authors, showing the benefit to using probabilistic forecasts over deterministic forecasts in several sectors, including flood and drought warning, hydropower, and agriculture. Probabilistic forecasting is also central to the emerging concept of risk-based decision making, and underlies emerging paradigms such as impact-based forecasting. Although the economic value of probabilistic forecasts is easily demonstrated in academic works, its evaluation in practice is more complex. The practical use of probabilistic forecasts requires decision makers to weigh the cost of an appropriate response to a probabilistic warning against the projected loss that would occur if the event forecast becomes reality. In this paper, we present the results of a simple game that aims to explore how decision makers are influenced by the costs required for taking a response and the potential losses they face in case the forecast flood event occurs. Participants play the role of one of three possible different shop owners. Each type of shop has losses of quite different magnitude, should a flood event occur. The shop owners are presented with several forecasts, each with a probability of a flood event occurring, which would inundate their shop and lead to those losses. In response, they have to decide if they want to do nothing, raise temporary defences, or relocate their inventory. Each action comes at a cost; and the different shop owners therefore have quite different cost/loss ratios. The game was played on four occasions. Players were attendees of the ensemble hydro-meteorological forecasting session of the 2016 EGU Assembly, professionals participating at two other conferences related to hydrometeorology, and a group of students. All audiences were familiar with the principles of forecasting and water-related risks, and one of the audiences comprised a group of experts in probabilistic forecasting. Results show that the different shop owners do take the costs of taking action and the potential losses into account in their decisions. Shop owners with a low cost/loss ratio were found to be more inclined to take actions based on the forecasts, though the absolute value of the losses also increased the willingness to take action. Little differentiation was found between the different groups of players.

Corrective Action Decision Document/Closure Report for Corrective Action Unit 252: Area 25 Engine Test Stand 1 Decontamination Pad, Nevada Test Site, Nevada

DOE Office of Scientific and Technical Information (OSTI.GOV)

DOE /NV

This Corrective Action Decision Document/Closure Report (CADD/CR) has been prepared for Corrective Action Unit (CAU) 252: Area 25 Engine Test Stand-1 Decontamination Pad, in accordance with the Federal Facility Agreement and Consent Order (FFACO). Located at the Nevada Test Site in Nevada, CAU 252 consists of only one Corrective Action Site (25-07-04, Decontamination Pad). This CADD/CR identifies and rationalizes the U.S. Department of Energy, Nevada Operations Office's (DOE/NV's) recommendation that no corrective action is deemed necessary at CAU 252. The Corrective Action Decision Document and Closure Report have been combined into one report because the potential contaminants of concern weremore » either not detected during the corrective action investigation or were only present at naturally occurring concentrations. Based on the field results, neither corrective action or a corrective action plan is required at this site. A Notice of Completion to DOE/NV is being requested from the Nevada Division of Environmental Protection for closure of CAU 252, as well as a request that this site be moved from Appendix III to Appendix IV of the FFACO. Further, no use restrictions are required to be placed on this CAU.« less

A non-inactivating high-voltage-activated two-pore Na+ channel that supports ultra-long action potentials and membrane bistability

NASA Astrophysics Data System (ADS)

Cang, Chunlei; Aranda, Kimberly; Ren, Dejian

2014-09-01

Action potentials (APs) are fundamental cellular electrical signals. The genesis of short APs lasting milliseconds is well understood. Ultra-long APs (ulAPs) lasting seconds to minutes also occur in eukaryotic organisms, but their biological functions and mechanisms of generation are largely unknown. Here, we identify TPC3, a previously uncharacterized member of the two-pore channel protein family, as a new voltage-gated Na+ channel (NaV) that generates ulAPs, and that establishes membrane potential bistability. Unlike the rapidly inactivating NaVs that generate short APs in neurons, TPC3 has a high activation threshold, activates slowly and does not inactivate—three properties that help generate long-lasting APs and guard the membrane against unintended perturbation. In amphibian oocytes, TPC3 forms a channel similar to channels induced by depolarization and sperm entry into eggs. TPC3 homologues are present in plants and animals, and they may be important for cellular processes and behaviours associated with prolonged membrane depolarization.

A model for the transfer of perceptual-motor skill learning in human behaviors.

PubMed

Rosalie, Simon M; Müller, Sean

2012-09-01

This paper presents a preliminary model that outlines the mechanisms underlying the transfer of perceptual-motor skill learning in sport and everyday tasks. Perceptual-motor behavior is motivated by performance demands and evolves over time to increase the probability of success through adaptation. Performance demands at the time of an event create a unique transfer domain that specifies a range of potentially successful actions. Transfer comprises anticipatory subconscious and conscious mechanisms. The model also outlines how transfer occurs across a continuum, which depends on the individual's expertise and contextual variables occurring at the incidence of transfer

An Investigation of Student Involvement in IEP Meetings in Suffolk County, New York

ERIC Educational Resources Information Center

Jurgens, Matthew A.

2016-01-01

The purpose of this study was to identify the possible barriers as to why student involvement in IEP meetings has not been occurring in the past and to subsequently suggest further action and research as to how to potentially combat these barriers so students with disabilities in Suffolk County, Long Island can begin to be offered these kinds of…

Role of cyclophilins in somatolactogenic action.

PubMed

Rycyzyn, M A; Clevenger, C V

2000-01-01

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

A strong protective action of guttiferone-A, a naturally occurring prenylated benzophenone, against iron-induced neuronal cell damage.

PubMed

Figueredo, Yanier Núñez; García-Pupo, Laura; Cuesta Rubio, Osmany; Delgado Hernández, René; Naal, Zeki; Curti, Carlos; Pardo Andreu, Gilberto L

2011-01-01

Guttiferone-A (GA) is a natural occurring polyisoprenylated benzophenone with several reported pharmacological actions. We have assessed the protective action of GA on iron-induced neuronal cell damage by employing the PC12 cell line and primary culture of rat cortical neurons (PCRCN). A strong protection by GA, assessed by the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carbox-anilide (XTT) assay, was revealed, with IC(50) values <1 µM. GA also inhibited Fe(3+)-ascorbate reduction, iron-induced oxidative degradation of 2-deoxiribose, and iron-induced lipid peroxidation in rat brain homogenate, as well as stimulated oxygen consumption by Fe(2+) autoxidation. Absorption spectra and cyclic voltammograms of GA-Fe(2+)/Fe(3+) complexes suggest the formation of a transient charge transfer complex between Fe(2+) and GA, accelerating Fe(2+) oxidation. The more stable Fe(3+) complex with GA would be unable to participate in Fenton-Haber Weiss-type reactions and the propagation phase of lipid peroxidation. The results show a potential of GA against neuronal diseases associated with iron-induced oxidative stress.

Early oestrogens in shaping reproductive networks: evidence for a potential organisational role of oestradiol in female brain development.

PubMed

Bakker, J; Brock, O

2010-07-01

A central tenet of contemporary theories on mammalian brain and behavioural sexual differentiation is that an organisational action of testosterone, secreted by the male's testes, controls male-typical aspects of brain and behavioural development, whereas no active perinatal sex hormone signalling is required for female-typical sexual differentiation. Furthermore, the available evidence suggests that many, although not all, of the perinatal organisational actions of testosterone on the development of the male brain result from the cellular effects of oestradiol formed via neural aromatisation of testosterone. However, a default developmental programme for the female brain has been criticised. Indeed, we review new results obtained in aromatase knockout mice indicating that oestradiol actively contributes to the differentiation of female-typical aspects of brain and behavioural sexual differentiation. Furthermore, we propose that male-typical neural and behavioural differentiation occurs prenatally in genetic males under the influence of oestradiol, which is avoided in foetal genetic females by the neuroprotective actions of alpha-fetoprotein, whereas female-typical neural and behavioural differentiation normally occurs postnatally in genetic females under the influence of oestradiol that is presumably produced by the ovaries.

Novel ecosystems: Theoretical and management aspects of the new ecological world order

USGS Publications Warehouse

Hobbs, R.J.; Arico, S.; Aronson, J.; Baron, Jill S.; Bridgewater, P.; Cramer, V.A.; Epstein, P.R.; Ewel, J.J.; Klink, C.A.; Lugo, A.E.; Norton, D.; Ojima, D.; Richardson, D.M.; Sanderson, E.W.; Valladares, F.; Vila, M.; Zamora, R.; Zobel, M.

2006-01-01

We explore the issues relevant to those types of ecosystems containing new combinations of species that arise through human action, environmental change, and the impacts of the deliberate and inadvertent introduction of species from other regions. Novel ecosystems (also termed ‘emerging ecosystems’) result when species occur in combinations and relative abundances that have not occurred previously within a given biome. Key characteristics are novelty, in the form of new species combinations and the potential for changes in ecosystem functioning, and human agency, in that these ecosystems are the result of deliberate or inadvertent human action. As more of the Earth becomes transformed by human actions, novel ecosystems increase in importance, but are relatively little studied. Either the degradation or invasion of native or ‘wild’ ecosystems or the abandonment of intensively managed systems can result in the formation of these novel systems. Important considerations are whether these new systems are persistent and what values they may have. It is likely that it may be very difficult or costly to return such systems to their previous state, and hence consideration needs to be given to developing appropriate management goals and approaches.

Closing the Loop in ICU Decision Support: Physiologic Event Detection, Alerts, and Documentation

PubMed Central

Norris, Patrick R.; Dawant, Benoit M.

2002-01-01

Automated physiologic event detection and alerting is a challenging task in the ICU. Ideally care providers should be alerted only when events are clinically significant and there is opportunity for corrective action. However, the concepts of clinical significance and opportunity are difficult to define in automated systems, and effectiveness of alerting algorithms is difficult to measure. This paper describes recent efforts on the Simon project to capture information from ICU care providers about patient state and therapy in response to alerts, in order to assess the value of event definitions and progressively refine alerting algorithms. Event definitions for intracranial pressure and cerebral perfusion pressure were studied by implementing a reliable system to automatically deliver alerts to clinical users’ alphanumeric pagers, and to capture associated documentation about patient state and therapy when the alerts occurred. During a 6-month test period in the trauma ICU at Vanderbilt University Medical Center, 530 alerts were detected in 2280 hours of data spanning 14 patients. Clinical users electronically documented 81% of these alerts as they occurred. Retrospectively classifying documentation based on therapeutic actions taken, or reasons why actions were not taken, provided useful information about ways to potentially improve event definitions and enhance system utility.

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

PubMed

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

2014-03-01

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

Compound muscle action potential duration in critical illness neuromyopathy.

PubMed

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

2018-03-01

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.

Melatonin and mitochondrial function during ischemia/reperfusion injury.

PubMed

Ma, Zhiqiang; Xin, Zhenlong; Di, Wencheng; Yan, Xiaolong; Li, Xiaofei; Reiter, Russel J; Yang, Yang

2017-11-01

Ischemia/reperfusion (IR) injury occurs in many organs and tissues, and contributes to morbidity and mortality worldwide. Melatonin, an endogenously produced indolamine, provides a strong defense against IR injury. Mitochondrion, an organelle for ATP production and a decider for cell fate, has been validated to be a crucial target for melatonin to exert its protection against IR injury. In this review, we first clarify the mechanisms underlying mitochondrial dysfunction during IR and melatonin's protection of mitochondria under this condition. Thereafter, special focus is placed on the protective actions of melatonin against IR injury in brain, heart, liver, and others. Finally, we explore several potential future directions of research in this area. Collectively, the information compiled here will serve as a comprehensive reference for the actions of melatonin in IR injury identified to date and will hopefully aid in the design of future research and increase the potential of melatonin as a therapeutic agent.

[Neuromuscular blocking and respiratory depressing actions of sodium ammonium dimethyl-2-(propano-1,3-dithiosulfate) monohydrate].

PubMed

Cao, B J; Chen, Z K; Chi, Z Q

1990-05-01

The neuromuscular blocking and respiratory depressing actions of the new insecticide sodium ammonium dimethyl-2-(propano-1,3-dithiosulfate) monohydrate (SCD) were investigated. In peroneal-tibialis anterior nerve-muscle preparations of urethane anesthetized rabbit, SCD 6.5 mg/kg iv completely depressed the indirectly elicited twitch tension but not the directly elicited one. This compound also caused initial potentiation of the indirectly elicited twitch tension. In the partially paralyzed preparations, potentiation of contractions occurred following a brief period of indirectly tetanic stimulation. Nereistoxin but not SCD blocked the indirectly elicited twitch tension of isolated rat diaphragm. The neuromuscular blockade induced by SCD and nereistoxin was antagonized by neostigmine and 4-aminopyridine. SCD and nereistoxin had little or no effect on arterial blood pressure and phrenic nerve discharge of rabbits. The results indicated that SCD-poisoned rabbits died of respiratory paralysis following the neuromuscular blockade.

Long Duration Responses in Squid Giant Axons Injected with 134Cesium Sulfate Solutions

PubMed Central

Sjodin, R. A.

1966-01-01

Giant axons from the squid were injected with 1.5 M cesium sulfate solutions containing the radioactive isotopes 42K and 134Cs. These axons, when stimulated, gave characteristic long duration action potentials lasting between 5 and 45 msec. The effluxes of 42K and 134Cs were measured both under resting conditions and during periods of repetitive stimulation. During the lengthened responses there were considerable increases in potassium efflux but only small increases in cesium efflux. The selectivity of the delayed rectification process was about 9 times greater for potassium ions than for cesium ions. The data suggest that internal cesium ions inhibit the outward potassium movement occurring during an action potential. The extra potassium effluxes taking place during excitation appear to be reduced in the presence of cesium ions to values between 7 and 22% of those expected in the absence of cesium inhibition. PMID:11526828

Health Impacts of Climate Change in Vanuatu: An Assessment and Adaptation Action Plan

PubMed Central

Spickett, Jeffery T; Katscherian, Dianne; McIver, Lachlan

2013-01-01

Climate change is one of the greatest global challenges and Pacific island countries are particularly vulnerable due to, among other factors, their geography, demography and level of economic development. A Health Impact Assessment (HIA) framework was used as a basis for the consideration of the potential health impacts of changes in the climate on the population of Vanuatu, to assess the risks and propose a range of potential adaptive responses appropriate for Vanuatu. The HIA process involved the participation of a broad range of stakeholders including expert sector representatives in the areas of bio-physical, socio-economic, infrastructure, environmental diseases and food, who provided informed comment and input into the understanding of the potential health impacts and development of adaptation strategies. The risk associated with each of these impacts was assessed with the application of a qualitative process that considered both the consequences and the likelihood of each of the potential health impacts occurring. Potential adaptation strategies and actions were developed which could be used to mitigate the identified health impacts and provide responses which could be used by the various sectors in Vanuatu to contribute to future decision making processes associated with the health impacts of climate change. PMID:23618474

Inhibition of the reverse mode of the Na+/Ca2+ exchange by KB-R7943 augments arrhythmogenicity in the canine heart during rapid heart rates.

PubMed

Shinada, Takuro; Hirayama, Yoshiyuki; Maruyama, Mitsunori; Ohara, Toshihiko; Yashima, Masaaki; Kobayashi, Yoshinori; Atarashi, Hirotsugu; Takano, Teruo

2005-07-01

To test the hypothesis that the reverse mode of the Na+/Ca2+ exchange augmented by a rapid heart rate has an antiarrhythmic effect by shortening the action potential duration, we examined the effects of KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl] isothiourea methanesulfonate), a selective inhibitor of the reverse mode of the Na+/Ca2+ exchange, to attenuate this effect. We recorded the electrocardiogram, monophasic action potential (MAP), and left ventricular pressure in canine beating hearts. In comparison to the control, KB-R7943 significantly increased the QTc value and MAP duration. MAP alternans and left ventricular pressure alternans were observed after changing the cycle length to 300 milliseconds in the control studies. KB-R7943 magnified both types of alternans and produced spatially discordant alternans between right and left ventricles. Early after-depolarizations and nonsustained ventricular tachycardia occurred in the presence of KB-R7943. Our data suggest that the reverse mode of the Na+/Ca2+ exchange may contribute to suppression of arrhythmias by abbreviating action potential duration under pathophysiological conditions. This conclusion is based on further confirmation by future studies of the specificity of KB-R7943 for block of the reverse mode of the Na+/Ca2+ exchange.

Cysteine analogues potentiate glucose-induced insulin release in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ammon, H.P.; Hehl, K.H.; Enz, G.

1986-12-01

In rat pancreatic islets, cysteine analogues, including glutathione, acetylcysteine, cysteamine, D-penicillamine, L-cysteine ethyl ester, and cysteine-potentiated glucose (11.1 mM) induced insulin secretion in a concentration-dependent manner. Their maximal effects were similar and occurred at approximately 0.05, 0.05, 0.1, 0.5, 1.0, 1.0 mM, respectively. At substimulatory glucose levels (2.8 mM), insulin release was not affected by these compounds. In contrast, thiol compounds, structurally different from cysteine and its analogues, such as mesna, tiopronin, meso-2,3-dimercaptosuccinic acid (DMSA), dimercaprol (BAL), beta-thio-D-glucose, as well as those cysteine analogues that lack a free-thiol group, including L-cystine, cystamine, D-penicillamine disulfide, S-carbocysteine, and S-carbamoyl-L-cysteine, did not enhancemore » insulin release at stimulatory glucose levels (11.1 mM); cystine (5 mM) was inhibitory. These in vitro data indicate that among the thiols tested here, only cysteine and its analogues potentiate glucose-induced insulin secretion, whereas thiols that are structurally not related to cysteine do not. This suggests that a cysteine moiety in the molecule is necessary for the insulinotropic effect. For their synergistic action to glucose, the availability of a sulfhydryl group is also a prerequisite. The maximal synergistic action is similar for all cysteine analogues tested, whereas the potency of action is different, suggesting similarity in the mechanism of action but differences in the affinity to the secretory system.« less

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

PubMed

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

2016-02-01

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.

Beat-to-Beat Variation in Periodicity of Local Calcium Releases Contributes to Intrinsic Variations of Spontaneous Cycle Length in Isolated Single Sinoatrial Node Cells

PubMed Central

Monfredi, Oliver; Maltseva, Larissa A.; Spurgeon, Harold A.; Boyett, Mark R.; Lakatta, Edward G.; Maltsev, Victor A.

2013-01-01

Spontaneous, submembrane local Ca2+ releases (LCRs) generated by the sarcoplasmic reticulum in sinoatrial nodal cells, the cells of the primary cardiac pacemaker, activate inward Na+/Ca2+-exchange current to accelerate the diastolic depolarization rate, and therefore to impact on cycle length. Since LCRs are generated by Ca2+ release channel (i.e. ryanodine receptor) openings, they exhibit a degree of stochastic behavior, manifested as notable cycle-to-cycle variations in the time of their occurrence. Aim The present study tested whether variation in LCR periodicity contributes to intrinsic (beat-to-beat) cycle length variability in single sinoatrial nodal cells. Methods We imaged single rabbit sinoatrial nodal cells using a 2D-camera to capture LCRs over the entire cell, and, in selected cells, simultaneously measured action potentials by perforated patch clamp. Results LCRs begin to occur on the descending part of the action potential-induced whole-cell Ca2+ transient, at about the time of the maximum diastolic potential. Shortly after the maximum diastolic potential (mean 54±7.7 ms, n = 14), the ensemble of waxing LCR activity converts the decay of the global Ca2+ transient into a rise, resulting in a late, whole-cell diastolic Ca2+ elevation, accompanied by a notable acceleration in diastolic depolarization rate. On average, cells (n = 9) generate 13.2±3.7 LCRs per cycle (mean±SEM), varying in size (7.1±4.2 µm) and duration (44.2±27.1 ms), with both size and duration being greater for later-occurring LCRs. While the timing of each LCR occurrence also varies, the LCR period (i.e. the time from the preceding Ca2+ transient peak to an LCR’s subsequent occurrence) averaged for all LCRs in a given cycle closely predicts the time of occurrence of the next action potential, i.e. the cycle length. Conclusion Intrinsic cycle length variability in single sinoatrial nodal cells is linked to beat-to-beat variations in the average period of individual LCRs each cycle. PMID:23826247

The role of health promotion: between global thinking and local action.

PubMed

King, Lesley

2006-12-01

The persistence of health inequities provides an ongoing challenge for health promotion. The dictum 'think globally, act locally' fails to recognise the significance of infrastructure and policy in linking global issues and local practices as a means of addressing health inequities. Commentary and opinion. Through analytic tools and methods, health promotion has much to contribute to facilitating health-improving changes in social, economic and physical environments. Local actions provide excellent illustrations of organisational change and intersectoral action, and present the possibility that such actions could be widely implemented. While this has occurred on some issues, this is not usually the case. Political support, policy and infrastructure are required to link global ideas and local actions and overcome the impasse. Media advocacy is one example of an approach with potential to make these links and mobilise political support. Reframing media and political discussion, away from the dichotomy of individual responsibility and government intervention and towards acknowledging the social context of human behaviour, could contribute to policy and social environments with greater capacity to address inequities.

Infrared Sensor Readout Design

DTIC Science & Technology

1975-11-01

Line Replaceable Unit LT Level Translator MRT Minimum Resolvable Temperature MTF Modulation Transfer Function PC Printed Circuit SCCCD Surface...reduced, not only will the aliased noise increase, but signal aliasing will also start to occur. Atlbe display level this means that sharp edges could...converted from a quantity ol charge to a voltage- level shift by the action ol the precharge pulse that presets the potential on the output diode node to

The Brazilian Air Force Health System: Workforce-Needs Estimation Using System Dynamics

DTIC Science & Technology

2009-03-01

workforce in the system. 3. Non- intervention This forecast provides a potential scenario of workforce numbers, based solely on actual numbers derived from...present knowledge and actions taken under the assumption that no unexpected interventions will occur. It is a red flag that guides future decisions...represented as a distribution. Bartholomew (1974) establishes a stochastic model of manpower systems as a probabilistic description of the

Additive effect of combined application of magnesium and MK-801 on analgesic action of morphine.

PubMed

Bujalska-Zadrożny, Magdalena; Duda, Kamila

2014-01-01

As previously reported, magnesium ions (Mg(2+)) administered in relatively low doses markedly potentiated opioid analgesia in neuropathic pain, in which the effectiveness of opioids is limited. Considering that Mg(2+) behaves like an N-methyl-D-aspartate receptor antagonist, the effect of this ion on the analgesic action of morphine was compared with that of MK-801. Acute pain was evoked by mechanical or thermal stimuli, whereas neuropathic hyperalgesia was induced by streptozotocin (STZ) administration. Magnesium sulphate (40 mg/kg i.p.) or MK-801 (0.05 mg/kg s.c.) administered alone did not modify the nociceptive threshold to acute stimuli or the streptozotocin hyperalgesia but significantly augmented the analgesic action of morphine (5 mg/kg i.p.). Furthermore, if these drugs (i.e. magnesium sulphate and MK-801) were applied concomitantly, a clear additive effect on the analgesic action of morphine occurred in both models of pain. Possible explanations of these observations are discussed. © 2014 S. Karger AG, Basel.

The faces of pain: a cluster analysis of individual differences in facial activity patterns of pain.

PubMed

Kunz, M; Lautenbacher, S

2014-07-01

There is general agreement that facial activity during pain conveys pain-specific information but is nevertheless characterized by substantial inter-individual differences. With the present study we aim to investigate whether these differences represent idiosyncratic variations or whether they can be clustered into distinct facial activity patterns. Facial actions during heat pain were assessed in two samples of pain-free individuals (n = 128; n = 112) and were later analysed using the Facial Action Coding System. Hierarchical cluster analyses were used to look for combinations of single facial actions in episodes of pain. The stability/replicability of facial activity patterns was determined across samples as well as across different basic social situations. Cluster analyses revealed four distinct activity patterns during pain, which stably occurred across samples and situations: (I) narrowed eyes with furrowed brows and wrinkled nose; (II) opened mouth with narrowed eyes; (III) raised eyebrows; and (IV) furrowed brows with narrowed eyes. In addition, a considerable number of participants were facially completely unresponsive during pain induction (stoic cluster). These activity patterns seem to be reaction stereotypies in the majority of individuals (in nearly two-thirds), whereas a minority displayed varying clusters across situations. These findings suggest that there is no uniform set of facial actions but instead there are at least four different facial activity patterns occurring during pain that are composed of different configurations of facial actions. Raising awareness about these different 'faces of pain' might hold the potential of improving the detection and, thereby, the communication of pain. © 2013 European Pain Federation - EFIC®

Lateralization of motor excitability during observation of bimanual signs.

PubMed

Möttönen, Riikka; Farmer, Harry; Watkins, Kate E

2010-08-01

Viewing another person's hand actions enhances excitability in an observer's left and right primary motor (M1) cortex. We aimed to determine whether viewing communicative hand actions alters this bilateral sensorimotor resonance. Using single-pulse transcranial magnetic stimulation (TMS), we measured excitability in the left and right M1 while right-handed non-signing participants observed bimanual communicative hand actions, i.e., meaningful signs in British Sign Language. TMS-induced motor evoked potentials were recorded from hand muscles during sign observation before and after teaching the participants to associate meanings with half of the signs. Before this teaching, when participants did not know that the presented hand actions were signs, excitability of left and right M1 was modulated equally. After learning the meanings of half the signs, excitability of the left, but not right, M1 was significantly enhanced. This left-lateralized enhancement of M1 excitability occurred during observation of signs with known and unknown meanings. The findings suggest that awareness of the communicative nature of another person's hand actions strengthens sensorimotor resonance in the left M1 cortex and alters hemispheric balance during action observation. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Action potentials and amphetamine release antipsychotic drug from dopamine neuron synaptic VMAT vesicles.

PubMed

Tucker, Kristal R; Block, Ethan R; Levitan, Edwin S

2015-08-11

Based on lysotracker red imaging in cultured hippocampal neurons, antipsychotic drugs (APDs) were proposed to accumulate in synaptic vesicles by acidic trapping and to be released in response to action potentials. Because many APDs are dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be particularly interesting if it operated in midbrain DA neurons. Here, the APD cyamemazine (CYAM) is visualized directly by two-photon microscopy in substantia nigra and striatum brain slices. CYAM accumulated slowly into puncta based on vacuolar H(+)-ATPase activity and dispersed rapidly upon dissipating organelle pH gradients. Thus, CYAM is subject to acidic trapping and released upon deprotonation. In the striatum, Ca(2+)-dependent reduction of the CYAM punctate signal was induced by depolarization or action potentials. Striatal CYAM overlapped with the dopamine transporter (DAT). Furthermore, parachloroamphetamine (pCA), acting via vesicular monoamine transporter (VMAT), and a charged VMAT, substrate 1-methyl-4-phenylpyridinium (MPP(+)), reduced striatal CYAM. In vivo CYAM administration and in vitro experiments confirmed that clinically relevant CYAM concentrations result in vesicular accumulation and pCA-dependent release. These results show that some CYAM is in DA neuron VMAT vesicles and suggests a new drug interaction in which amphetamine induces CYAM deprotonation and release as a consequence of the H(+) countertransport by VMAT that accompanies vesicular uptake, but not by inducing exchange or acting as a weak base. Therefore, in the striatum, APDs are released with DA in response to action potentials and an amphetamine. This synaptic corelease is expected to enhance APD antagonism of D2Rs where and when dopaminergic transmission occurs.

Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells.

PubMed

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

2018-07-14

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.

Properties of Ca2+ sparks evoked by action potentials in mouse ventricular myocytes

PubMed Central

Bridge, John H B; Ershler, Philip R; Cannell, Mark B

1999-01-01

Calcium sparks were examined in enzymatically dissociated mouse cardiac ventricular cells using the calcium indicator fluo-3 and confocal microscopy. The properties of the mouse cardiac calcium spark are generally similar to those reported for other species.Examination of the temporal relationship between the action potential and the time course of calcium spark production showed that calcium sparks are more likely to occur during the initial repolarization phase of the action potential. The latency of their occurrence varied by less than 1·4 ms (s.d.) and this low variability may be explained by the interaction of the gating of L-type calcium channels with the changes in driving force for calcium entry during the action potential.When fixed sites within the cell are examined, calcium sparks have relatively constant amplitude but the amplitude of the sparks was variable among sites. The low variability of the amplitude of the calcium sparks suggests that more than one sarcoplasmic reticulum (SR) release channel must be involved in their genesis. Noise analysis (with the assumption of independent gating) suggests that > 18 SR calcium release channels may be involved in the generation of the calcium spark. At a fixed site, the response is close to ‘all-or-none’ behaviour which suggests that calcium sparks are indeed elementary events underlying cardiac excitation-contraction coupling.A method for selecting spark sites for signal averaging is presented which allows the time course of the spark to be examined with high temporal and spatial resolution. Using this method we show the development of the calcium spark at high signal-to-noise levels. PMID:10381593

Engineering evaluation/cost analysis for the proposed management of 15 nonprocess buildings (15 series) at the Weldon Spring Site Chemical Plant, Weldon Spring, Missouri. Environmental assessment: Weldon Spring Site Remedial Action Project, Weldon Spring, Missouri

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacDonell, M.M.; Peterson, J.M.

1991-11-01

The US Department of Energy, under its Surplus Facilities Management Program (SFMP), is responsible for cleanup activities at the Weldon Spring site, located near Weldon Spring, Missouri. The site consists of two noncontiguous areas: (1) a raffinate pits and chemical plant area and (2) a quarry. This engineering evaluation/cost analysis (EE/CA) report has been prepared to support a proposed removal action to manage 15 nonprocess buildings, identified as the 15 Series buildings, at the chemical plant on the Weldon Spring site. These buildings have been nonoperational for more than 20 years, and the deterioration that has occurred during this timemore » has resulted in a potential threat to site workers, the general public, and the environment. The EE/CA documentation of this proposed action is consistent with guidance from the US Environmental Protection Agency (EPA) that addresses removal actions at sites subject to the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) of 1980, as amended by the Superfund Amendments and Reauthorization Act of 1986. Actions at the Weldon Spring site are subject to CERCLA requirements because the site is on the EPA`s National Priorities List. The objectives of this report are to (1) identify alternatives for management of the nonprocess buildings; (2) document the selection of response activities that will mitigate the potential threat to workers, the public, and the environment associated with these buildings; and (3) address environmental impact associated with the proposed action.« less

The potential of expert systems for remote sensing application

NASA Technical Reports Server (NTRS)

Mooneyhan, D. W.

1983-01-01

An overview of the status and potential of artificial intelligence-driven expert systems in the role of image data analysis is presented. An expert system is defined and its structure is summarized. Three such systems designed for image interpretation are outlined. The use of an expert system to detect changes on the earth's surface is discussed, and the components of a knowledge-based image interpretation system and their make-up are outlined. An example of how such a system should work for an area in the tropics where deforestation has occurred is presented as a sequence of situation/action decisions.

Effects of carbon fibers on consumer products

NASA Technical Reports Server (NTRS)

Wise, R. A.; Lovett, C. D.

1980-01-01

The potential effects of carbon fibers on consumer products such as dishwashers, microwave ovens, and smoke detectors were investigated. The investigation was divided into two categories to determine the potential faults and hazards that could occur if fibers should enter the electrical circuits of the selected appliances. The categories were a fault analysis and a hazard analysis. Hazards considered were fire, flood, physical harm, explosion, and electrical shock. Electrical shock was found to be a possible occurrence related to carbon fibers. Faults were considered to be any effect on the performance of an appliance which would result in complaint or require service action.

Obesity-related hypertension: is there a role for selective leptin resistance?

PubMed

Correia, Marcelo L G; Haynes, William G

2004-06-01

Obesity is a risk factor for cardiovascular diseases, in particular for hypertension. Serum leptin levels and sympathetic nerve activity are both increased in obesity. Leptin has been demonstrated to increase sympathetic nerve activity. Thus, leptin-dependent sympathoactivation might contribute to obesity-related hypertension. However, leptin resistance occurs in obesity. One possibility is that leptin resistance is selective to the metabolic effects of leptin, sparing its sympathoexcitatory actions. In this article, we review experimental evidence supporting the novel concept of selective leptin resistance. We also discuss the sympathetic actions of leptin that are relevant to blood pressure modulation and potential mechanisms of leptin resistance. Disruption of leptin intracellular signaling pathways and resistance of specific leptin-responsive neural networks provide theoretic models of selective leptin resistance. However, most information about leptin-sympathetic actions and leptin-resistance mechanisms derive from in vitro and animal studies. Future research in humans is widely awaited.

Molecular motions that shape the cardiac action potential: Insights from voltage clamp fluorometry.

PubMed

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

2016-01-01

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.

Empowering potential: a theory of wellness motivation.

PubMed

Fleury, J D

1991-01-01

Data were collected from 29 individuals who were attempting to initiate and sustain programs of cardiac risk factor modification. Data were analyzed through the technique of constant comparative analysis. Empowering potential, the basic social process identified from the data, explained individual motivation to initiate and sustain cardiovascular health behavior. Empowering potential was a continuous process of individual growth and development which facilitated the emergence of new and positive health patterns. Within the process of empowering potential, individuals use a variety of strategies which guide the initiation and maintenance of health-related change. The process of empowering potential consists of three stages: appraising readiness, changing, and integrating change. Two categories occurred throughout the process of empowering potential: imaging and social support systems. These findings provide a better understanding of how motivated action is initiated and reinitiated over time.

49 CFR 27.11 - Remedial action, voluntary action and compliance planning.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 1 2011-10-01 2011-10-01 false Remedial action, voluntary action and compliance....11 Remedial action, voluntary action and compliance planning. (a) Remedial action. (1) If the... discrimination not occurred. (b) Voluntary action. A recipient may take steps, in addition to any action that is...

Critical Defense Materials: Government Collected Data Are Sufficiently Reliable to Assess Tantalum Availability

DTIC Science & Technology

2016-03-01

conflict in the Democratic Republic of the Congo or an adjoining country. Pub. L. No. 111- 203 §1502( e )(4). Columbite-tantalite (coltan), cassiterite, and...departments—the Securities and Exchange Commission, the Department of State, and the Department of Commerce —to take certain actions to implement the...USGS and Department of Commerce , and performing analyses to determine if shortfalls for materials will occur during potential conflict scenarios

Environmental Assessment, Glide Slope/Clear Zone Obstructions, Wright-Patterson Air Force Base, Ohio

DTIC Science & Technology

2013-06-01

would be implemented. The Proposed Action would not pose any new risks; however, minor adverse effects on groundwater would continue to occur as a...consulted regarding potential effects on biological resources in the project areas. According to information obtained from the ODNR, the only federally...designated treatment sites. The USFWS concurred with the USAF determination that no adverse effects are likely and that consultation under Section 7(a

Vortex transmutation.

PubMed

Ferrando, Albert; Zacarés, Mario; García-March, Miguel-Angel; Monsoriu, Juan A; de Córdoba, Pedro Fernández

2005-09-16

Using group theory arguments and numerical simulations, we demonstrate the possibility of changing the vorticity or topological charge of an individual vortex by means of the action of a system possessing a discrete rotational symmetry of finite order. We establish on theoretical grounds a "transmutation pass" determining the conditions for this phenomenon to occur and numerically analyze it in the context of two-dimensional optical lattices. An analogous approach is applicable to the problems of Bose-Einstein condensates in periodic potentials.

The late posterior negativity in ERP studies of episodic memory: action monitoring and retrieval of attribute conjunctions.

PubMed

Johansson, Mikael; Mecklinger, Axel

2003-10-01

The focus of the present paper is a late posterior negative slow wave (LPN) that has frequently been reported in event-related potential (ERP) studies of memory. An overview of these studies suggests that two broad classes of experimental conditions tend to elicit this component: (a) item recognition tasks associated with enhanced action monitoring demands arising from response conflict and (b) memory tasks that require the binding of items with contextual information specifying the study episode. A combined stimulus- and response-locked analysis of data from two studies mapping onto these classes allowed a temporal and functional decomposition of the LPN. While only the LPN observed in the item recognition task could be attributed to the involvement of a posteriorly distributed response-locked error-related negativity (or error negativity; ERN/Ne) occurring immediately after the response, the source-memory task was associated with a stimulus-locked negative slow wave occurring prior and during response execution that was evident when data were matched for response latencies. We argue that the presence of the former reflects action monitoring due to high levels of response conflict, whereas the latter reflects retrieval processes that may act to reconstruct the prior study episode when task-relevant attribute conjunctions are not readily recovered or need continued evaluation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hutchinson, Kenneth

To perform remedial vegetation management for keeping vegetation a safe distance away from electric power facilities and controlling noxious weeds within a section of BPA's Big Eddy-Ostrander Transmission Corridor. During a site review conducted in late fall of 2001, the inspector observed various species of hardwood trees resprouted from stumps. The new vegetative growth encroached on the required “Minimum Safe Distance” between the top of vegetation and the conductor cables. The management action is necessary to reduce the current and potential future hazards that tall-growing vegetation poses to transmission conductors. In addition, BPA will include weed control as part ofmore » their remedial vegetation management action. Noxious weeds occur within the corridor. Under a 1999 Executive Order, all federal agencies are required to detect and control noxious weeds. In addition, BPA is required under the 1990 amendment to the Noxious Weed Act (7 USC 2801-2814) to manage undesirable plants on federal land. Also, the Bonneville Power Administration (BPA) has responsibility to manage noxious weeds under the Transmission System Vegetation Management Program Final Environmental Impact Statement (FEIS).1 State statutes and regulations also mandate action by BPA and the USFS to control noxious weeds. The Oregon Department of Agriculture (ODA) has requested that agencies aggressively control these weeds before additional spread occurs.« less

Closing the loop in ICU decision support: physiologic event detection, alerts, and documentation.

PubMed Central

Norris, P. R.; Dawant, B. M.

2001-01-01

Automated physiologic event detection and alerting is a challenging task in the ICU. Ideally care providers should be alerted only when events are clinically significant and there is opportunity for corrective action. However, the concepts of clinical significance and opportunity are difficult to define in automated systems, and effectiveness of alerting algorithms is difficult to measure. This paper describes recent efforts on the Simon project to capture information from ICU care providers about patient state and therapy in response to alerts, in order to assess the value of event definitions and progressively refine alerting algorithms. Event definitions for intracranial pressure and cerebral perfusion pressure were studied by implementing a reliable system to automatically deliver alerts to clinical users alphanumeric pagers, and to capture associated documentation about patient state and therapy when the alerts occurred. During a 6-month test period in the trauma ICU at Vanderbilt University Medical Center, 530 alerts were detected in 2280 hours of data spanning 14 patients. Clinical users electronically documented 81% of these alerts as they occurred. Retrospectively classifying documentation based on therapeutic actions taken, or reasons why actions were not taken, provided useful information about ways to potentially improve event definitions and enhance system utility. PMID:11825238

Implications of movement-related cortical potential for understanding neural adaptations in muscle strength tasks

PubMed Central

2014-01-01

This systematic review aims to provide information about the implications of the movement-related cortical potential (MRCP) in acute and chronic responses to the counter resistance training. The structuring of the methods of this study followed the proposals of the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses). It was performed an electronically search in Pubmed/Medline and ISI Web of Knowledge data bases, from 1987 to 2013, besides the manual search in the selected references. The following terms were used: Bereitschaftspotential, MRCP, strength and force. The logical operator “AND” was used to combine descriptors and terms used to search publications. At the end, 11 studies attended all the eligibility criteria and the results demonstrated that the behavior of MRCP is altered because of different factors such as: force level, rate of force development, fatigue induced by exercise, and the specific phase of muscular action, leading to an increase in the amplitude in eccentric actions compared to concentric actions, in acute effects. The long-term adaptations demonstrated that the counter resistance training provokes an attenuation in the amplitude in areas related to the movement, which may be caused by neural adaptation occurred in the motor cortex. PMID:24602228

Removal of sodium inactivation and block of sodium channels by chloramine-T in crayfish and squid giant axons.

PubMed Central

Huang, J. M.; Tanguy, J.; Yeh, J. Z.

1987-01-01

Modification of sodium channels by chloramine-T was examined in voltage clamped internally perfused crayfish and squid giant axons using the double sucrose gap and axial wire technique, respectively. Freshly prepared chloramine-T solution exerted two major actions on sodium channels: (a) an irreversible removal of the fast Na inactivation, and (b) a reversible block of the Na current. Both effects were observed when chloramine-T was applied internally or externally (5-10 mM) to axons. The first effect was studied in crayfish axons. We found that the removal of the fast Na inactivation did not depend on the states of the channel since the channel could be modified by chloramine-T at holding potential (from -80 to -100 mV) or at depolarized potential of -30 mV. After removal of fast Na inactivation, the slow inactivation mechanism was still present, and more channels could undergo slow inactivation. This result indicates that in crayfish axons the transition through the fast inactivated state is not a prerequisite for the slow inactivation to occur. During chloramine-T treatment, a distinct blocking phase occurred, which recovered upon washing out the drug. This second effect of chloramine-T was studied in detail in squid axons. After 24 h, chloramine-T solution lost its ability to remove fast inactivation but retained its blocking action. After removal of the fast Na inactivation, both fresh and aged chloramine-T solutions blocked the Na currents with a similar potency and in a voltage-dependent manner, being more pronounced at lower depolarizing potentials. A similar voltage-dependent block was observed with aged chloramine-T solution in an axon with intact inactivation. In contrast to the action of the fresh solution, the aged chloramine-T solution was found to accelerate the decay of Na currents.These results suggest that chloramine-T solution contains at least two active molecular forms that act at different sites in the Na channel. PMID:2444276

Anticipation of delayed action-effects: learning when an effect occurs, without knowing what this effect will be.

PubMed

Dignath, David; Janczyk, Markus

2017-09-01

According to the ideomotor principle, behavior is controlled via a retrieval of the sensory consequences that will follow from the respective movement ("action-effects"). These consequences include not only what will happen, but also when something will happen. In fact, recollecting the temporal duration between response and effect takes time and prolongs the initiation of the response. We investigated the associative structure of action-effect learning with delayed effects and asked whether participants acquire integrated action-time-effect episodes that comprise a compound of all three elements or whether they acquire separate traces that connect actions to the time until an effect occurs and actions to the effects that follow them. In three experiments, results showed that participants retrieve temporal intervals that follow from their actions even when the identity of the effect could not be learned. Furthermore, retrieval of temporal intervals in isolation was not inferior to retrieval of temporal intervals that were consistently followed by predictable action-effects. More specifically, when tested under extinction, retrieval of action-time and action-identity associations seems to compete against each other, similar to overshadowing effects reported for stimulus-response conditioning. Together, these results suggest that people anticipate when the consequences of their action will occur, independently from what the consequences will be.

Action potentials reliably invade axonal arbors of rat neocortical neurons

PubMed Central

Cox, Charles L.; Denk, Winfried; Tank, David W.; Svoboda, Karel

2000-01-01

Neocortical pyramidal neurons have extensive axonal arborizations that make thousands of synapses. Action potentials can invade these arbors and cause calcium influx that is required for neurotransmitter release and excitation of postsynaptic targets. Thus, the regulation of action potential invasion in axonal branches might shape the spread of excitation in cortical neural networks. To measure the reliability and extent of action potential invasion into axonal arbors, we have used two-photon excitation laser scanning microscopy to directly image action-potential-mediated calcium influx in single varicosities of layer 2/3 pyramidal neurons in acute brain slices. Our data show that single action potentials or bursts of action potentials reliably invade axonal arbors over a range of developmental ages (postnatal 10–24 days) and temperatures (24°C-30°C). Hyperpolarizing current steps preceding action potential initiation, protocols that had previously been observed to produce failures of action potential propagation in cultured preparations, were ineffective in modulating the spread of action potentials in acute slices. Our data show that action potentials reliably invade the axonal arbors of neocortical pyramidal neurons. Failures in synaptic transmission must therefore originate downstream of action potential invasion. We also explored the function of modulators that inhibit presynaptic calcium influx. Consistent with previous studies, we find that adenosine reduces action-potential-mediated calcium influx in presynaptic terminals. This reduction was observed in all terminals tested, suggesting that some modulatory systems are expressed homogeneously in most terminals of the same neuron. PMID:10931955

[Mechanism of action of neurotoxins acting on the inactivation of voltage-gated sodium channels].

PubMed

Benoit, E

1998-01-01

This review focuses on the mechanism(s) of action of neurotoxins acting on the inactivation of voltage-gated Na channels. Na channels are transmembrane proteins which are fundamental for cellular communication. These proteins form pores in the plasma membrane allowing passive ionic movements to occur. Their opening and closing are controlled by gating systems which depend on both membrane potential and time. Na channels have three functional properties, mainly studied using electrophysiological and biochemical techniques, to ensure their role in the generation and propagation of action potentials: 1) a highly selectivity for Na ions, 2) a rapid opening ("activation"), responsible for the depolarizing phase of the action potential, and 3) a late closing ("inactivation") involved in the repolarizing phase of the action potential. As an essential protein for membrane excitability, the Na channel is the specific target of a number of vegetal and animal toxins which, by binding to the channel, alter its activity by affecting one or more of its properties. At least six toxin receptor sites have been identified on the neuronal Na channel on the basis of binding studies. However, only toxins interacting with four of these sites (sites 2, 3, 5 et 6) produce alterations of channel inactivation. The maximal percentage of Na channels modified by the binding of neurotoxins to sites 2 (batrachotoxin and some alkaloids), 3 (alpha-scorpion and sea anemone toxins), 5 (brevetoxins and ciguatoxins) et 6 (delta-conotoxins) is different according to the site considered. However, in all cases, these channels do not inactivate. Moreover, Na channels modified by toxins which bind to sites 2, 5 and 6 activate at membrane potentials more negative than do unmodified channels. The physiological consequences of Na channel modifications, induced by the binding of neurotoxins to sites 2, 3, 5 and 6, are (i) an inhibition of cellular excitability due to an important membrane depolarization (site 2), (ii) a decrease of cellular excitability due to an important increase in the action potential duration (site 3) and (iii) an increase in cellular excitability which results in spontaneous and repetitive firing of action potentials (sites 5 and 6). The biochemical and electrophysiological studies performed with these toxins, as well as the determination of their molecular structure, have given basic information on the function and structure of the Na channel protein. Therefore, various models representing the different states of Na channels have been proposed to account for the neurotoxin-induced modifications of Na inactivation. Moreover, the localization of receptor binding sites 2, 3, 5 et 6 for these toxins on the neuronal Na channel has been deduced and the molecular identification of the recognition site(s) for some of them has been established on the alpha sub-unit forming the Na channel protein.

The effects of an action video game on visual and affective information processing.

PubMed

Bailey, Kira; West, Robert

2013-04-04

Playing action video games can have beneficial effects on visuospatial cognition and negative effects on social information processing. However, these two effects have not been demonstrated in the same individuals in a single study. The current study used event-related brain potentials (ERPs) to examine the effects of playing an action or non-action video game on the processing of emotion in facial expression. The data revealed that 10h of playing an action or non-action video game had differential effects on the ERPs relative to a no-contact control group. Playing an action game resulted in two effects: one that reflected an increase in the amplitude of the ERPs following training over the right frontal and posterior regions that was similar for angry, happy, and neutral faces; and one that reflected a reduction in the allocation of attention to happy faces. In contrast, playing a non-action game resulted in changes in slow wave activity over the central-parietal and frontal regions that were greater for targets (i.e., angry and happy faces) than for non-targets (i.e., neutral faces). These data demonstrate that the contrasting effects of action video games on visuospatial and emotion processing occur in the same individuals following the same level of gaming experience. This observation leads to the suggestion that caution should be exercised when using action video games to modify visual processing, as this experience could also have unintended effects on emotion processing. Published by Elsevier B.V.

Landscape Suitability in Botswana for the Conservation of Its Six Large African Carnivores

PubMed Central

Winterbach, Hanlie E. K.; Winterbach, Christiaan W.; Somers, Michael J.

2014-01-01

Wide-ranging large carnivores often range beyond the boundaries of protected areas into human-dominated areas. Mapping out potentially suitable habitats on a country-wide scale and identifying areas with potentially high levels of threats to large carnivore survival is necessary to develop national conservation action plans. We used a novel approach to map and identify these areas in Botswana for its large carnivore guild consisting of lion (Panthera leo), leopard (Panthera pardus), spotted hyaena (Crocuta crocuta), brown hyaena (Hyaena brunnea), cheetah (Acinonyx jubatus) and African wild dog (Lycaon pictus). The habitat suitability for large carnivores depends primarily on prey availability, interspecific competition, and conflict with humans. Prey availability is most likely the strongest natural determinant. We used the distribution of biomass of typical wild ungulate species occurring in Botswana which is preyed upon by the six large carnivores to evaluate the potential suitability of the different management zones in the country to sustain large carnivore populations. In areas where a high biomass of large prey species occurred, we assumed interspecific competition between dominant and subordinated competitors to be high. This reduced the suitability of these areas for conservation of subordinate competitors, and vice versa. We used the percentage of prey biomass of the total prey and livestock biomass to identify areas with potentially high levels of conflict in agricultural areas. High to medium biomass of large prey was mostly confined to conservation zones, while small prey biomass was more evenly spread across large parts of the country. This necessitates different conservation strategies for carnivores with a preference for large prey, and those that can persist in the agricultural areas. To ensure connectivity between populations inside Botswana and also with its neighbours, a number of critical areas for priority management actions exist in the agricultural zones. PMID:24949735

Landscape suitability in Botswana for the conservation of its six large African carnivores.

PubMed

Winterbach, Hanlie E K; Winterbach, Christiaan W; Somers, Michael J

2014-01-01

Wide-ranging large carnivores often range beyond the boundaries of protected areas into human-dominated areas. Mapping out potentially suitable habitats on a country-wide scale and identifying areas with potentially high levels of threats to large carnivore survival is necessary to develop national conservation action plans. We used a novel approach to map and identify these areas in Botswana for its large carnivore guild consisting of lion (Panthera leo), leopard (Panthera pardus), spotted hyaena (Crocuta crocuta), brown hyaena (Hyaena brunnea), cheetah (Acinonyx jubatus) and African wild dog (Lycaon pictus). The habitat suitability for large carnivores depends primarily on prey availability, interspecific competition, and conflict with humans. Prey availability is most likely the strongest natural determinant. We used the distribution of biomass of typical wild ungulate species occurring in Botswana which is preyed upon by the six large carnivores to evaluate the potential suitability of the different management zones in the country to sustain large carnivore populations. In areas where a high biomass of large prey species occurred, we assumed interspecific competition between dominant and subordinated competitors to be high. This reduced the suitability of these areas for conservation of subordinate competitors, and vice versa. We used the percentage of prey biomass of the total prey and livestock biomass to identify areas with potentially high levels of conflict in agricultural areas. High to medium biomass of large prey was mostly confined to conservation zones, while small prey biomass was more evenly spread across large parts of the country. This necessitates different conservation strategies for carnivores with a preference for large prey, and those that can persist in the agricultural areas. To ensure connectivity between populations inside Botswana and also with its neighbours, a number of critical areas for priority management actions exist in the agricultural zones.

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

PubMed

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

2015-07-01

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

The sense of agency is action-effect causality perception based on cross-modal grouping.

PubMed

Kawabe, Takahiro; Roseboom, Warrick; Nishida, Shin'ya

2013-07-22

Sense of agency, the experience of controlling external events through one's actions, stems from contiguity between action- and effect-related signals. Here we show that human observers link their action- and effect-related signals using a computational principle common to cross-modal sensory grouping. We first report that the detection of a delay between tactile and visual stimuli is enhanced when both stimuli are synchronized with separate auditory stimuli (experiment 1). This occurs because the synchronized auditory stimuli hinder the potential grouping between tactile and visual stimuli. We subsequently demonstrate an analogous effect on observers' key press as an action and a sensory event. This change is associated with a modulation in sense of agency; namely, sense of agency, as evaluated by apparent compressions of action-effect intervals (intentional binding) or subjective causality ratings, is impaired when both participant's action and its putative visual effect events are synchronized with auditory tones (experiments 2 and 3). Moreover, a similar role of action-effect grouping in determining sense of agency is demonstrated when the additional signal is presented in the modality identical to an effect event (experiment 4). These results are consistent with the view that sense of agency is the result of general processes of causal perception and that cross-modal grouping plays a central role in these processes.

Differential facilitation of N- and P/Q-type calcium channels during trains of action potential-like waveforms

PubMed Central

Currie, Kevin P M; Fox, Aaron P

2002-01-01

Inhibition of presynaptic voltage-gated calcium channels by direct G-protein βγ subunit binding is a widespread mechanism that regulates neurotransmitter release. Voltage-dependent relief of this inhibition (facilitation), most likely to be due to dissociation of the G-protein from the channel, may occur during bursts of action potentials. In this paper we compare the facilitation of N- and P/Q-type Ca2+ channels during short trains of action potential-like waveforms (APWs) using both native channels in adrenal chromaffin cells and heterologously expressed channels in tsA201 cells. While both N- and P/Q-type Ca2+ channels exhibit facilitation that is dependent on the frequency of the APW train, there are important quantitative differences. Approximately 20 % of the voltage-dependent inhibition of N-type ICa was reversed during a train while greater than 40 % of the inhibition of P/Q-type ICa was relieved. Changing the duration or amplitude of the APW dramatically affected the facilitation of N-type channels but had little effect on the facilitation of P/Q-type channels. Since the ratio of N-type to P/Q-type Ca2+ channels varies widely between synapses, differential facilitation may contribute to the fine tuning of synaptic transmission, thereby increasing the computational repertoire of neurons. PMID:11882675

AMELIORATING TREATMENT-REFRACTORY DEPRESSION WITH INTRANASAL KETAMINE: POTENTIAL NMDA RECEPTOR ACTIONS IN THE PAIN CIRCUITRY REPRESENTING MENTAL ANGUISH

PubMed Central

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

2014-01-01

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

Monitoring is not enough: on the need for a model-based approach to migratory bird management

USGS Publications Warehouse

Nichols, J.D.; Bonney, Rick; Pashley, David N.; Cooper, Robert; Niles, Larry

2000-01-01

Informed management requires information about system state and about effects of potential management actions on system state. Population monitoring can provide the needed information about system state, as well as information that can be used to investigate effects of management actions. Three methods for investigating effects of management on bird populations are (1) retrospective analysis, (2) formal experimentation and constrained-design studies, and (3) adaptive management. Retrospective analyses provide weak inferences, regardless of the quality of the monitoring data. The active use of monitoring data in experimental or constrained-design studies or in adaptive management is recommended. Under both approaches, learning occurs via the comparison of estimates from the monitoring program with predictions from competing management models.

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

PubMed

Furong, Liu; Shengtian, L I

2016-05-25

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

Temporal distortion in the perception of actions and events.

PubMed

Yabe, Yoshiko; Dave, Hemangi; Goodale, Melvyn A

2017-01-01

In everyday life, actions and sensory events occur in complex sequences, with events triggering actions that in turn give rise to additional events and so on. Earlier work has shown that a sensory event that is triggered by a voluntary action is perceived to have occurred earlier in time than an identical event that is not triggered by an action. In other words, events that are believed to be caused by our actions are drawn forward in time towards our actions. Similarly, when a sensory event triggers an action, that event is again drawn in time towards the action and is thus perceived to have occurred later than it really did. This alteration in time perception serves to bind together events and actions that are causally linked. It is not clear, however, whether or not the perceived timing of a sensory event embedded within a longer series of actions and sensory events is also temporally bound to the actions in that sequence. In the current study, we measured the temporal binding in sequences consisting of two simple dyads of event-action and action-event in a series of manual action tasks: an event-action-event triad (Experiment 1) and an action-event-action triad (Experiment 2). Auditory tones either triggered an action or were presented 250ms after an action was performed. To reduce the influence of sensory events other than the tone, such as a noise associated with pressing a key on a keyboard, we used an optical sensor to detect hand movements where no contact was made with a surface. In Experiment 1, there appeared to be no change in the perceived onset of an auditory tone when the onset of that tone followed a hand movement and then the tone triggered a second hand movement. It was as if the temporal binding between the action and the tone and then the tone and the subsequent action summed algebraically and cancelled each other out. In Experiment 2, both the perceived onset of an initial tone which triggered an action and the perceived onset of a second tone which was presented 250ms after the action were temporally bound to the action. Taken together, the present study suggests that the temporal binding between our actions and sensory events occur separately in each dyad within a longer sequence of actions and events. Copyright © 2016 Elsevier B.V. All rights reserved.

Stimfit: quantifying electrophysiological data with Python

PubMed Central

Guzman, Segundo J.; Schlögl, Alois; Schmidt-Hieber, Christoph

2013-01-01

Intracellular electrophysiological recordings provide crucial insights into elementary neuronal signals such as action potentials and synaptic currents. Analyzing and interpreting these signals is essential for a quantitative understanding of neuronal information processing, and requires both fast data visualization and ready access to complex analysis routines. To achieve this goal, we have developed Stimfit, a free software package for cellular neurophysiology with a Python scripting interface and a built-in Python shell. The program supports most standard file formats for cellular neurophysiology and other biomedical signals through the Biosig library. To quantify and interpret the activity of single neurons and communication between neurons, the program includes algorithms to characterize the kinetics of presynaptic action potentials and postsynaptic currents, estimate latencies between pre- and postsynaptic events, and detect spontaneously occurring events. We validate and benchmark these algorithms, give estimation errors, and provide sample use cases, showing that Stimfit represents an efficient, accessible and extensible way to accurately analyze and interpret neuronal signals. PMID:24600389

Dopamine modulates an intrinsic mGluR5-mediated depolarization underlying prefrontal persistent activity

PubMed Central

Sidiropoulou, Kyriaki; Lu, Fang-Min; Fowler, Melissa A.; Xiao, Rui; Phillips, Christopher; Ozkan, Emin D.; Zhu, Michael X.; White, Francis J.; Cooper, Donald C.

2009-01-01

Intrinsic properties of neurons that enable them to maintain depolarized, persistently activated states in the absence of sustained input are poorly understood. In short-term memory tasks, individual prefrontal cortical (PFC) neurons are capable of maintaining persistent action potential output during delay periods between informative cues and behavioral responses. Dopamine and drugs of abuse alter PFC function and working memory possibly by modulating intrinsic neuronal properties. Here we use patch-clamp recording of layer 5 PFC pyramidal neurons to identify an action potential burst-evoked intrinsic mGluR5-mediated postsynaptic depolarization that initiates an activated state. Depolarization occurs in the absence of recurrent synaptic activity and is reduced by a postsynaptic dopamine D1/5 receptor pathway. The depolarization is substantially diminished following behavioral sensitization to cocaine; moreover the D1/5 receptor modulation is lost. We propose the burst-evoked intrinsic depolarization to be a novel form of short-term cellular memory that is modulated by dopamine and cocaine experience. PMID:19169252

[Effect of gamma-aminobutyric acid on peripheral mechanisms regulating autonomic functions].

PubMed

Godovalova, L A

1976-01-01

Experiments with cats ascertained the potentiating action of GABA (100,300,500 mg/kg) on the pressor reactions of the small intestine vessels, the systemic arterial pressure, depressing (100 mg/kg) and facilitating (500 mg/kg) effect upon the reactions of inhibition of the small intestine motor activity evoked by the efferent stimulation of the celiac nerve. Adrenolytics (dihydroergotoxin, inderal) abolished the facilitating effects of GABA. The latter (0.01 solution) inhibited spontaneous contractions of isolated small intestine lengths. As proved histochemically GABA (500 mg/kg) reduces the catecholamines content in the suprarenals, in the solar plexus ganglia and in vessles "in vivo". It also increases the catecholamines content in the small intestine wall in experiments in vivo and reduces in vitro tests. The potentiating action of GABA on the vegetative reactions in efferent stimulation of the ciliac nerve occurs, apparently, due to an increased ejection of catecholamines by suprarenals and lowered the content of catecholamines in the solar plexus ganglia, which causes facilitated conduction of excitation in the ganglia.

Improvements in Metabolic Health with Consumption of Ellagic Acid and Subsequent Conversion into Urolithins: Evidence and Mechanisms12

PubMed Central

Kang, Inhae; Buckner, Teresa; Gu, Liwei

2016-01-01

Ellagic acid (EA) is a naturally occurring polyphenol found in some fruits and nuts, including berries, pomegranates, grapes, and walnuts. EA has been investigated extensively because of its antiproliferative action in some cancers, along with its anti-inflammatory effects. A growing body of evidence suggests that the intake of EA is effective in attenuating obesity and ameliorating obesity-mediated metabolic complications, such as insulin resistance, type 2 diabetes, nonalcoholic fatty liver disease, and atherosclerosis. In this review, we summarize how intake of EA regulates lipid metabolism in vitro and in vivo, and delineate the potential mechanisms of action of EA on obesity-mediated metabolic complications. We also discuss EA as an epigenetic effector, as well as a modulator of the gut microbiome, suggesting that EA may exert a broader spectrum of health benefits than has been demonstrated to date. Therefore, this review aims to suggest the potential metabolic benefits of consumption of EA-containing fruits and nuts against obesity-associated health conditions. PMID:27633111

A distributed real-time model of degradation in a solid oxide fuel cell, part II: Analysis of fuel cell performance and potential failures

NASA Astrophysics Data System (ADS)

Zaccaria, V.; Tucker, D.; Traverso, A.

2016-09-01

Solid oxide fuel cells are characterized by very high efficiency, low emissions level, and large fuel flexibility. Unfortunately, their elevated costs and relatively short lifetimes reduce the economic feasibility of these technologies at the present time. Several mechanisms contribute to degrade fuel cell performance during time, and the study of these degradation modes and potential mitigation actions is critical to ensure the durability of the fuel cell and their long-term stability. In this work, localized degradation of a solid oxide fuel cell is modeled in real-time and its effects on various cell parameters are analyzed. Profile distributions of overpotential, temperature, heat generation, and temperature gradients in the stack are investigated during degradation. Several causes of failure could occur in the fuel cell if no proper control actions are applied. A local analysis of critical parameters conducted shows where the issues are and how they could be mitigated in order to extend the life of the cell.

Précis of the illusion of conscious will.

PubMed

Wegner, Daniel M

2004-10-01

The experience of conscious will is the feeling that we are doing things. This feeling occurs for many things we do, conveying to us again and again the sense that we consciously cause our actions. But the feeling may not be a true reading of what is happening in our minds, brains, and bodies as our actions are produced. The feeling of conscious will can be fooled. This happens in clinical disorders such as alien hand syndrome, dissociative identity disorder, and schizophrenic auditory hallucinations. And in people without disorders, phenomena such as hypnosis, automatic writing, Ouija board spelling, water dowsing, facilitated communication, speaking in tongues, spirit possession, and trance channeling also illustrate anomalies of will--cases when actions occur without will or will occurs without action. This book brings these cases together with research evidence from laboratories in psychology to explore a theory of apparent mental causation. According to this theory, when a thought appears in consciousness just prior to an action, is consistent with the action, and appears exclusive of salient alternative causes of the action, we experience conscious will and ascribe authorship to ourselves for the action. Experiences of conscious will thus arise from processes whereby the mind interprets itself--not from processes whereby mind creates action. Conscious will, in this view, is an indication that we think we have caused an action, not a revelation of the causal sequence by which the action was produced.

Optical transmembrane potential measurements during defibrillation-strength shocks in perfused rabbit hearts.

PubMed

Zhou, X; Ideker, R E; Blitchington, T F; Smith, W M; Knisley, S B

1995-09-01

To study the optical transmembrane potential change (delta F) induced during shocks, optical recordings were obtained in 15 isolated perfused rabbit hearts treated with the potentiometric dye di-4-ANEPPS and diacetyl monoxime. Shock electrodes were sutured on the right and left ventricles. A laser beam 30 microns in diameter was used to optically excite di-4-ANEPPS. Fluorescence from a region 150 microns in diameter was recorded during a shock. In the macroscopic study (six animals), there were nine recording spots that were 3 mm apart between the two shock electrodes. In the microscopic study, there were three recording regions that were 3 mm away from either shock electrode and midway between them, with nine recording spots that were 30 microns (three animals), 100 microns (three animals), and 300 microns (three animals) apart in each region. After 20 S1 stimuli, a 10-ms truncated exponential S2 shock of defibrillation-threshold strength was given during the plateau of the last S1 action potential. In the microscopic study, shocks were also given during diastole, with delta F recordings at the three recording regions. Shocks of both polarities were tested. delta F during the shock was expressed as a percentage of the fluorescence change during the S1 upstroke action potential amplitude (the S1 Fapa), ie, delta F/Fapa%. In the macroscopic study, the magnitudes of delta F/Fapa% from recording spots 1 to 9, numbered from the left to the right ventricular electrodes, were 77 +/- 41%, 46 +/- 32%, 32 +/- 27%, 28 +/- 20%, 37 +/- 25%, 24 +/- 20%, 33 +/- 22%, 37 +/- 25%, and 59 +/- 29%, respectively (P < .05 among the nine spots). Depolarization or hyperpolarization could occur near either shock electrode with both shock polarities, but the magnitude of hyperpolarization was 1.8 +/- 0.9 times that of depolarization at the same recording spot when the shock polarity was reversed (P < .01). In the microscopic study, the change in delta F/Fapa% varied significantly over the microscopic regions examined. The maximum values of delta F/Fapa% for hyperpolarizing shocks during diastole reached only 7 +/- 10% of those for shocks during the plateau (P < .01). During diastole, the time until a new action potential occurred after the beginning of the shock was shorter when the membrane was depolarized (1.1 +/- 0.5 ms) than when it was hyperpolarized (12.8 +/- 9.1 ms, P < .01). Conclusions are as follows: (1) A shock can induce either hyperpolarization or depolarization. (2) Hyperpolarization or depolarization during a shock can occur near either the anodal or cathodal shock electrode. (3) Variation of delta F/Fapa% exists within a microscopic region.(ABSTRACT TRUNCATED AT 400 WORDS)

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2012-10-01

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

Short- and medium-term plasticity associated with augmenting responses in cortical slabs and spindles in intact cortex of cats in vivo

PubMed Central

Timofeev, Igor; Grenier, François; Bazhenov, Maxim; Houweling, Arthur R; Sejnowski, Terrence J; Steriade, Mircea

2002-01-01

Plastic changes in the synaptic responsiveness of neocortical neurones, which occur after rhythmic stimuli within the frequency range of sleep spindles (10 Hz), were investigated in isolated neocortical slabs and intact cortex of anaesthetized cats by means of single, dual and triple simultaneous intracellular recordings in conjunction with recordings of local field potential responses. In isolated cortical slabs (10 mm long, 6 mm wide and 4–5 mm deep), augmenting responses to pulse-trains at 10 Hz (responses with growing amplitudes from the second stimulus in a train) were elicited only by relatively high-intensity stimuli. At low intensities, responses were decremental. The largest augmenting responses were evoked in neurones located close to the stimulation site. Quantitative analyses of the number of action potentials and the amplitude and area of depolarization during augmenting responses in a population of neurones recorded from slabs showed that the most dramatic increases in the number of spikes with successive stimuli, and the greatest increase in depolarization amplitude, were found in conventional fast-spiking (FS) neurones. The largest increase in the area of depolarization was found in regular-spiking (RS) neurones. Dual intracellular recordings from a pair of FS and RS neurones in the slab revealed more action potentials in the FS neurone during augmenting responses and a significant increase in the depolarization area of the RS neurone that was dependent on the firing of the FS neurone. Self-sustained seizures could occur in the slab after rhythmic stimuli at 10 Hz. In the intact cortex, repeated sequences of stimuli generating augmenting responses or spontaneous spindles could induce an increased synaptic responsiveness to single stimuli, which lasted for several minutes. A similar time course of increased responsiveness was obtained with induction of cellular plasticity. These data suggest that augmenting responses elicited by stimulation, as well as spontaneously occurring spindles, may induce short- and medium-term plasticity of neuronal responses. PMID:12122155

Action of certain tropine esters on voltage-clamped lobster axon.

PubMed

Blaustein, M P

1968-03-01

Tropine p-tolylacetate (TPTA) and its quaternary analogue, tropine p-tolylacetate methiodide (TPTA MeI) decrease the early transient (Na) and late (K) currents in the voltage-clamped lobster giant axon. These agents, which block the nerve action potential, reduce the maximum Na and K conductance increases associated with membrane depolarization. They also slow the rate at which the sodium conductance is increased and shift the (normalized) membrane conductance vs. voltage curves in the direction of depolarization along the voltage axis. All these effects are qualitatively similar to those resulting from the action of procaine on the voltage-clamped axon. One unusual effect of the tropine esters, noticeable particularly at large depolarization steps, is that they cause the late, K current to reach a peak and then fall off with increasing pulse duration. This effect has not been reported to occur as a result of procaine action. Tropine p-chlorophenyl acetate (TPClphiA), which differs from TPTA only by the substitution of a p-Cl for a p-CH(3) group on the benzene ring, had a negligible effect on axonal excitability.

Action of Certain Tropine Esters on Voltage-Clamped Lobster Axon

PubMed Central

Blaustein, M. P.

1968-01-01

Tropine p-tolylacetate (TPTA) and its quaternary analogue, tropine p-tolylacetate methiodide (TPTA MeI) decrease the early transient (Na) and late (K) currents in the voltage-clamped lobster giant axon. These agents, which block the nerve action potential, reduce the maximum Na and K conductance increases associated with membrane depolarization. They also slow the rate at which the sodium conductance is increased and shift the (normalized) membrane conductance vs. voltage curves in the direction of depolarization along the voltage axis. All these effects are qualitatively similar to those resulting from the action of procaine on the voltage-clamped axon. One unusual effect of the tropine esters, noticeable particularly at large depolarization steps, is that they cause the late, K current to reach a peak and then fall off with increasing pulse duration. This effect has not been reported to occur as a result of procaine action. Tropine p-chlorophenyl acetate (TPClφA), which differs from TPTA only by the substitution of a p-Cl for a p-CH3 group on the benzene ring, had a negligible effect on axonal excitability. PMID:5648830

Botulinum neurotoxin type A: Actions beyond SNAP-25?

PubMed

Matak, Ivica; Lacković, Zdravko

2015-09-01

Botulinum neurotoxin type A (BoNT/A), the most potent toxin known in nature which causes botulism, is a commonly used therapeutic protein. It prevents synaptic vesicle neuroexocytosis by proteolytic cleavage of synaptosomal-associated protein of 25 kDa (SNAP-25). It is widely believed that BoNT/A therapeutic or toxic actions are exclusively mediated by SNAP-25 cleavage. On the other hand, in vitro and in vivo findings suggest that several BoNT/A actions related to neuroexocytosis, cell cycle and apoptosis, neuritogenesis and gene expression are not necessarily mediated by this widely accepted mechanism of action. In present review we summarize the literature evidence which point to the existence of unknown BoNT/A molecular target(s) and modulation of unknown signaling pathways. The effects of BoNT/A apparently independent of SNAP-25 occur at similar doses/concentrations known to induce SNAP-25 cleavage and prevention of neurotransmitter release. Accordingly, these effects might be pharmacologically significant. Potentially the most interesting are observations of antimitotic and antitumor activity of BoNT/A. However, the exact mechanisms require further studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Piracetam interactions with neuroleptics in psychopharmacological tests.

PubMed

Bourin, M; Poisson, L; Larousse, C

1986-01-01

Two psychopharmacological tests which usually predict neuroleptic activity were conducted after joint administration of piracetam and three neuroleptics (haloperidol, fluphenazine and sulpiride) chosen for their different chemical classes and dopaminergic affinities. In these tests, specific doses of the neuroleptics were used to determine whether piracetam induced potentiation or antagonism of their action. Overall, piracetam increased neuroleptic action regardless of the administration timetable used, but the interaction of fluphenazine differed from that of the other two substances, because piracetam did not modify its action in a specific test of the presynaptic DA-2 dopaminergic receptors. This variation for fluphenazine may be explained by the fact that its pKa value is closer to that of piracetam, thus preventing better bioavailability of the neuroleptic, or its better affinity for DA-1 dopaminergic receptors. Nevertheless, the variation may have been due to a differing affinity for dopaminergic receptors, although this hypothesis is not completely satisfactory because it does not account for differences due to the administration timetable. It is thus suggested that action occurs on nonspecific sites and has the effect of increasing overall neuroleptic bioavailability.

Potential Health Impacts of Bauxite Mining in Kuantan

PubMed Central

Abdullah, Noor Hisham; Mohamed, Norlen; Sulaiman, Lokman Hakim; Zakaria, Thahirahtul Asma; Rahim, Daud Abdul

2016-01-01

Bauxite mining is not known to most Malaysian except recently due to environmental pollution issues in Kuantan, Pahang. Potential impacts are expected to go beyond physical environment and physical illness if the situation is not controlled. Loss of economic potentials, and the presence of unpleasant red dust causing mental distress, anger and community outrage. More studies are needed to associate it with chronic physical illness. While evidences are vital for action, merely waiting for a disease to occur is a sign of failure in prevention. All responsible agencies should focus on a wider aspect of health determinants rather than merely on the occurrence of diseases to act and the need to emphasize on sustainable mining to ensure health of people is not compromised. PMID:27418864

Potential Health Impacts of Bauxite Mining in Kuantan.

PubMed

Abdullah, Noor Hisham; Mohamed, Norlen; Sulaiman, Lokman Hakim; Zakaria, Thahirahtul Asma; Rahim, Daud Abdul

2016-05-01

Bauxite mining is not known to most Malaysian except recently due to environmental pollution issues in Kuantan, Pahang. Potential impacts are expected to go beyond physical environment and physical illness if the situation is not controlled. Loss of economic potentials, and the presence of unpleasant red dust causing mental distress, anger and community outrage. More studies are needed to associate it with chronic physical illness. While evidences are vital for action, merely waiting for a disease to occur is a sign of failure in prevention. All responsible agencies should focus on a wider aspect of health determinants rather than merely on the occurrence of diseases to act and the need to emphasize on sustainable mining to ensure health of people is not compromised.

Pharmacological properties of Datura stramonium L. as a potential medicinal tree: An overview

PubMed Central

Soni, Priyanka; Siddiqui, Anees Ahmad; Dwivedi, Jaya; Soni, Vishal

2012-01-01

India has a great wealth of various naturally occurring plant drugs which have great potential pharmacological activities. Datura stramonium (D. stramonium) is one of the widely well known folklore medicinal herbs. The troublesome weed, D. stramonium is a plant with both poisonous and medicinal properties and has been proven to have great pharmacological potential with a great utility and usage in folklore medicine. D. stromonium has been scientifically proven to contain alkaloids, tannins, carbohydrates and proteins. This plant has contributed various pharmacological actions in the scientific field of Indian systems of medicines like analgesic and antiasthmatic activities. The present paper presents an exclusive review work on the ethnomedical, phytochemical, pharmacological activities of this plant. PMID:23593583

Suppressing memories of words and familiar objects results in their affective devaluation: Evidence from Think/No-think tasks.

PubMed

De Vito, David; Fenske, Mark J

2017-05-01

Potentially distracting or otherwise-inappropriate stimuli, thoughts, or actions often must be inhibited to prevent interference with goal-directed behaviour. Growing evidence suggests that the impact of inhibition is not limited to reduced neurocognitive processing, but also includes negative affective consequences for any associated stimuli. The link between inhibition and aversive response has primarily been studied using tasks involving attentional- or response-related inhibition of external sensory stimuli. Here we show that affective devaluation also occurs when inhibition is applied to fully-encoded stimulus representations in memory. We first replicated prior findings of increased forgetting of words whose memories were suppressed in a Think/No-think procedure (Experiment 1). Incorporating a stimulus-evaluation task within this procedure revealed that suppressing memories of words (Experiment 2) and visual objects (Experiment 3) also results in their affective devaluation. Given the critical role of memory for guiding thoughts and actions, these results suggest that the affective consequences of inhibition may occur across a far broader range of situations than previously understood. Copyright © 2017 Elsevier B.V. All rights reserved.

Plant Essential Oils Synergize and Antagonize Toxicity of Different Conventional Insecticides against Myzus persicae (Hemiptera: Aphididae)

PubMed Central

Faraone, Nicoletta; Hillier, N. Kirk; Cutler, G. Christopher

2015-01-01

Plant-derived products can play an important role in pest management programs. Essential oils from Lavandula angustifolia (lavender) and Thymus vulgaris (thyme) and their main constituents, linalool and thymol, respectively, were evaluated for insecticidal activity and synergistic action in combination with insecticides against green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae). The essential oils and their main constituents exerted similar insecticidal activity when aphids were exposed by direct sprays, but were non-toxic by exposure to treated leaf discs. In synergism experiments, the toxicity of imidacloprid was synergized 16- to 20-fold by L. angustifolia and T. vulgaris essential oils, but far less synergism occurred with linalool and thymol, indicating that secondary constituents of the oils were probably responsible for the observed synergism. In contrast to results with imidacloprid, the insecticidal activity of spirotetramat was antagonized by L. angustifolia and T. vulgaris essential oils, and linalool and thymol. Our results demonstrate the potential of plant essential oils as synergists of insecticides, but show that antagonistic action against certain insecticides may occur. PMID:26010088

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

PubMed

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

2012-06-03

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.

Social Transmission of Experience of Agency: An Experimental Study.

PubMed

Khalighinejad, Nima; Bahrami, Bahador; Caspar, Emilie A; Haggard, Patrick

2016-01-01

The sense of controlling one's own actions is fundamental to normal human mental function, and also underlies concepts of social responsibility for action. However, it remains unclear how the wider social context of human action influences sense of agency. Using a simple experimental design, we investigated, for the first time, how observing the action of another person or a robot could potentially influence one's own sense of agency. We assessed how observing another's action might change the perceived temporal relationship between one's own voluntary actions and their outcomes, which has been proposed as an implicit measure of sense of agency. Working in pairs, participants chose between two action alternatives, one rewarded more frequently than the other, while watching a rotating clock hand. They judged, in separate blocks, either the time of their own action, or the time of a tone that followed the action. These were compared to baseline judgements of actions alone, or tones alone, to calculate the perceptual shift of action toward outcome and vice versa. Our design focused on how these two dependent variables, which jointly provide an implicit measure of sense of agency, might be influenced by observing another's action. In the observational group, each participant could see the other's actions. Multivariate analysis showed that the perceived time of action and tone shifted progressively toward the actual time of outcome with repeated experience of this social situation. No such progressive change occurred in other groups for whom a barrier hid participants' actions from each other. However, a similar effect was observed in the group that viewed movements of a human-like robotic hand, rather than actions of another person. This finding suggests that observing the actions of others increases the salience of the external outcomes of action and this effect is not unique to observing human agents. Social contexts in which we see others controlling external events may play an important role in mentally representing the impact of our own actions on the external world.

Voltage-gated sodium channel expression and action potential generation in differentiated NG108-15 cells.

PubMed

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

2012-10-25

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.

Safety analysis of occupational exposure of healthcare workers to residual contaminations of cytotoxic drugs using FMECA security approach.

PubMed

Le, Laetitia Minh Mai; Reitter, Delphine; He, Sophie; Bonle, Franck Té; Launois, Amélie; Martinez, Diane; Prognon, Patrice; Caudron, Eric

2017-12-01

Handling cytotoxic drugs is associated with chemical contamination of workplace surfaces. The potential mutagenic, teratogenic and oncogenic properties of those drugs create a risk of occupational exposure for healthcare workers, from reception of starting materials to the preparation and administration of cytotoxic therapies. The Security Failure Mode Effects and Criticality Analysis (FMECA) was used as a proactive method to assess the risks involved in the chemotherapy compounding process. FMECA was carried out by a multidisciplinary team from 2011 to 2016. Potential failure modes of the process were identified based on the Risk Priority Number (RPN) that prioritizes corrective actions. Twenty-five potential failure modes were identified. Based on RPN results, the corrective actions plan was revised annually to reduce the risk of exposure and improve practices. Since 2011, 16 specific measures were implemented successively. In six years, a cumulative RPN reduction of 626 was observed, with a decrease from 912 to 286 (-69%) despite an increase of cytotoxic compounding activity of around 23.2%. In order to anticipate and prevent occupational exposure, FMECA is a valuable tool to identify, prioritize and eliminate potential failure modes for operators involved in the cytotoxic drug preparation process before the failures occur. Copyright © 2017 Elsevier B.V. All rights reserved.

African Flora Has the Potential to Fight Multidrug Resistance of Cancer

PubMed Central

Kuete, Victor; Efferth, Thomas

2015-01-01

Background. Continuous efforts from scientists of diverse fields are necessary not only to better understand the mechanism by which multidrug-resistant (MDR) cancer cells occur, but also to boost the discovery of new cytotoxic compounds to fight MDR phenotypes. Objectives. The present review reports on the contribution of African flora in the discovery of potential cytotoxic phytochemicals against MDR cancer cells. Methodology. Scientific databases such as PubMed, ScienceDirect, Scopus, Google Scholar, and Web of Knowledge were used to retrieve publications related to African plants, isolated compounds, and drug resistant cancer cells. The data were analyzed to highlight cytotoxicity and the modes of actions of extracts and compounds of the most prominent African plants. Also, thresholds and cutoff points for the cytotoxicity and modes of action of phytochemicals have been provided. Results. Most published data related to the antiproliferative potential of African medicinal plants were from Cameroon, Egypt, Nigeria, or Madagascar. The cytotoxicity of phenolic compounds isolated in African plants was generally much better documented than that of terpenoids and alkaloids. Conclusion. African flora represents an enormous resource for novel cytotoxic compounds. To unravel the full potential, efforts should be strengthened throughout the continent, to meet the challenge of a successful fight against MDR cancers. PMID:25961047

Sensory predictions during action support perception of imitative reactions across suprasecond delays.

PubMed

Yon, Daniel; Press, Clare

2018-04-01

Perception during action is optimized by sensory predictions about the likely consequences of our movements. Influential theories in social cognition propose that we use the same predictions during interaction, supporting perception of similar reactions in our social partners. However, while our own action outcomes typically occur at short, predictable delays after movement execution, the reactions of others occur at longer, variable delays in the order of seconds. To examine whether we use sensorimotor predictions to support perception of imitative reactions, we therefore investigated the temporal profile of sensory prediction during action in two psychophysical experiments. We took advantage of an influence of prediction on apparent intensity, whereby predicted visual stimuli appear brighter (more intense). Participants performed actions (e.g., index finger lift) and rated the brightness of observed outcomes congruent (index finger lift) or incongruent (middle finger lift) with their movements. Observed action outcomes could occur immediately after execution, or at longer delays likely reflective of those in natural social interaction (1800 or 3600 ms). Consistent with the previous literature, Experiment 1 revealed that congruent action outcomes were rated as brighter than incongruent outcomes. Importantly, this facilitatory perceptual effect was found irrespective of whether outcomes occurred immediately or at delay. Experiment 2 replicated this finding and demonstrated that it was not the result of response bias. These findings therefore suggest that visual predictions generated during action are sufficiently general across time to support our perception of imitative reactions in others, likely generating a range of benefits during social interaction. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanisms of Hormone Action

PubMed Central

Abeles, F. B.; Ruth, J. M.; Forrence, L. E.; Leather, G. R.

1972-01-01

We observed no exchange between deuterated ethylene (C2D4) and the hydrogen of pea seedlings (Pisum sativum L. cv. Alaska). This suggests that bonding forces in which exchange could readily occur are not important in the physiological action of ethylene. Deuterated ethylene was just as effective as normal ethylene in inhibiting the growth of pea root sections. These results indicate that splitting carbon to hydrogen bonds did not occur during ethylene action. PMID:16658026

Blink and you’ll miss it: the role of blinking in the perception of magic tricks

PubMed Central

Nakano, Tamami

2016-01-01

Magicians use several techniques to deceive their audiences, including, for example, the misdirection of attention and verbal suggestion. We explored another potential stratagem, namely the relaxation of attention. Participants watched a video of a highly skilled magician whilst having their eye-blinks recorded. The timing of spontaneous eye-blinks was highly synchronized across participants. In addition, the synchronized blinks frequency occurred immediately after a seemingly impossible feat, and often coincided with actions that the magician wanted to conceal from the audience. Given that blinking is associated with the relaxation of attention, these findings suggest that blinking plays an important role in the perception of magic, and that magicians may utilize blinking and the relaxation of attention to hide certain secret actions. PMID:27069808

Blink and you'll miss it: the role of blinking in the perception of magic tricks.

PubMed

Wiseman, Richard J; Nakano, Tamami

2016-01-01

Magicians use several techniques to deceive their audiences, including, for example, the misdirection of attention and verbal suggestion. We explored another potential stratagem, namely the relaxation of attention. Participants watched a video of a highly skilled magician whilst having their eye-blinks recorded. The timing of spontaneous eye-blinks was highly synchronized across participants. In addition, the synchronized blinks frequency occurred immediately after a seemingly impossible feat, and often coincided with actions that the magician wanted to conceal from the audience. Given that blinking is associated with the relaxation of attention, these findings suggest that blinking plays an important role in the perception of magic, and that magicians may utilize blinking and the relaxation of attention to hide certain secret actions.

Controlling Attention through Action: Observing Actions Primes Action-Related Stimulus Dimensions

ERIC Educational Resources Information Center

Fagioli, Sabrina; Ferlazzo, Fabio; Hommel, Bernhard

2007-01-01

Previous findings suggest that planning an action "backward-primes" perceptual dimension related to this action: planning a grasp facilitates the processing of visual size information, while planning a reach facilitates the processing of location information. Here we show that dimensional priming of perception through action occurs even in the…

Vestibular short latency responses to pulsed linear acceleration in unanesthetized animals

NASA Technical Reports Server (NTRS)

Jones, T. A.

1992-01-01

Linear acceleration transients were used to elicit vestibular compound action potentials in non-invasively prepared, unanesthetized animals for the first time (chicks, Gallus domesticus, n = 33). Responses were composed of a series of up to 8 dominant peaks occurring within 8 msec of the stimulus. Response amplitudes for 1.0 g stimulus ranged from 1 to 10 microV. A late, slow, triphasic, anesthesia-labile component was identified as a dominant response feature in unanesthetized animals. Amplitudes increased and latencies decreased as stimulus intensity was increased (MANOVA P less than 0.05). Linear regression slope ranges were: amplitudes = 1.0-5.0 microV/g; latencies = -300 to -1100 microseconds/g. Thresholds for single polarity stimuli (0.035 +/- 0.022 g, n = 11) were significantly lower than those of alternating polarity (0.074 +/- 0.028 g, n = 18, P less than 0.001). Bilateral labyrinthectomy eliminated responses whereas bilateral extirpation of cochleae did not significantly change response thresholds. Intense acoustic masking (100/104 dB SL) produced no effect in 2 animals, but did produce small to moderate effects on response amplitudes in 7 others. Changes were attributed to effects on vestibular end organs. Results of unilateral labyrinth blockade (tetrodotoxin) suggest that P1 and N1 preferentially reflect ipsilateral eighth nerve compound action potentials whereas components beyond approximately 2 msec reflect activity from vestibular neurons that depend on both labyrinths. The results demonstrate that short latency vestibular compound action potentials can be measured in unanesthetized, non-invasively prepared animals.

A mathematical model of action potential heterogeneity in adult rat left ventricular myocytes.

PubMed Central

Pandit, S V; Clark, R B; Giles, W R; Demir, S S

2001-01-01

Mathematical models were developed to reconstruct the action potentials (AP) recorded in epicardial and endocardial myocytes isolated from the adult rat left ventricle. The main goal was to obtain additional insight into the ionic mechanisms responsible for the transmural AP heterogeneity. The simulation results support the hypothesis that the smaller density and the slower reactivation kinetics of the Ca(2+)-independent transient outward K(+) current (I(t)) in the endocardial myocytes can account for the longer action potential duration (APD), and more prominent rate dependence in that cell type. The larger density of the Na(+) current (I(Na)) in the endocardial myocytes results in a faster upstroke (dV/dt(max)). This, in addition to the smaller magnitude of I(t), is responsible for the larger peak overshoot of the simulated endocardial AP. The prolonged APD in the endocardial cell also leads to an enhanced amplitude of the sustained K(+) current (I(ss)), and a larger influx of Ca(2+) ions via the L-type Ca(2+) current (I(CaL)). The latter results in an increased sarcoplasmic reticulum (SR) load, which is mainly responsible for the higher peak systolic value of the Ca(2+) transient [Ca(2+)](i), and the resultant increase in the Na(+)-Ca(2+) exchanger (I(NaCa)) activity, associated with the simulated endocardial AP. In combination, these calculations provide novel, quantitative insights into the repolarization process and its naturally occurring transmural variations in the rat left ventricle. PMID:11720973

Factors associated with regulatory action involving investigation of illnesses associated with Shiga toxin-producing Escherichia coli in products regulated by the Food Safety and Inspection Service.

PubMed

Green, Alice L; Seys, Scott; Douris, Aphrodite; Levine, Jeoff; Robertson, Kis

2014-07-01

We described characteristics of the Escherichia coli O157 and Escherichia coli non-O157 illness investigations conducted by the United States Department of Agriculture's Food Safety and Inspection Service (FSIS) during the 5-year period from 2006 through 2010. We created a multivariable logistic regression model to determine characteristics of these investigations that were associated with FSIS regulatory action, which was defined as having occurred if a product recall occurred or if FSIS personnel performed an environmental health assessment (Food Safety Assessment) at the implicated establishment. During this period, FSIS took regulatory action in 38 of 88 (43%) investigations. Illness investigations in which FoodNet states were involved were more likely to result in regulatory action. Illness investigations in which state and local traceback, or FSIS traceback occurred were more likely to result in regulatory action. Reasons for lack of action included evidence of cross-contamination after the product left a regulated establishment, delayed notification, lack of epidemiological information, and insufficient product information.

Caffeine affects the biological responses of human hematopoietic cells of myeloid lineage via downregulation of the mTOR pathway and xanthine oxidase activity

PubMed Central

Abooali, Maryam; Yasinska, Inna M.; Casely-Hayford, Maxwell A.; Berger, Steffen M.; Fasler-Kan, Elizaveta; Sumbayev, Vadim V.

2015-01-01

Correction of human myeloid cell function is crucial for the prevention of inflammatory and allergic reactions as well as leukaemia progression. Caffeine, a naturally occurring food component, is known to display anti-inflammatory effects which have previously been ascribed largely to its inhibitory actions on phosphodiesterase. However, more recent studies suggest an additional role in affecting the activity of the mammalian target of rapamycin (mTOR), a master regulator of myeloid cell translational pathways, although detailed molecular events underlying its mode of action have not been elucidated. Here, we report the cellular uptake of caffeine, without metabolisation, by healthy and malignant hematopoietic myeloid cells including monocytes, basophils and primary acute myeloid leukaemia mononuclear blasts. Unmodified caffeine downregulated mTOR signalling, which affected glycolysis and the release of pro-inflammatory/pro-angiogenic cytokines as well as other inflammatory mediators. In monocytes, the effects of caffeine were potentiated by its ability to inhibit xanthine oxidase, an enzyme which plays a central role in human purine catabolism by generating uric acid. In basophils, caffeine also increased intracellular cyclic adenosine monophosphate (cAMP) levels which further enhanced its inhibitory action on mTOR. These results demonstrate an important mode of pharmacological action of caffeine with potentially wide-ranging therapeutic impact for treating non-infectious disorders of the human immune system, where it could be applied directly to inflammatory cells. PMID:26384306

The modulatory action of harmane on serotonergic neurotransmission in rat brain.

PubMed

Abu Ghazaleh, Haya; Lalies, Maggie D; Nutt, David J; Hudson, Alan L

2015-02-09

The naturally occurring β-carboline, harmane, has been implicated in various physiological and psychological conditions. Some of these effects are attributed to its interaction with monoaminergic systems. Previous literature indicates that certain β-carbolines including harmane modulate central monoamine levels partly through monoamine oxidase (MAO) inhibition. However, this is not always the case and thus additional mechanisms may be involved. This study set to assess the potential modulatory role of harmane on the basal or K(+) stimulated release of preloaded radiolabelled noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in rat brain cortex in vitro in the presence of the MAO inhibitor pargyline. Harmane displayed an overt elevation in K(+) -evoked [(3)H]5-HT release; whilst little and no effect was reported with [(3)H]DA and [(3)H]NA respectively. The effect of harmane on [(3)H]5-HT efflux was partially compensated in K(+)-free medium. Further analyses demonstrated that removal of Ca(2+) ions and addition of 1.2mM EGTA did not alter the action of harmane on [(3)H]5-HT release from rat brain cortex. The precise mechanism of action however remains unclear but is unlikely to reflect an involvement of MAO inhibition. The current finding aids our understanding on the modulatory action of harmane on monoamine levels and could potentially be of therapeutic use in psychiatric conditions such as depression and anxiety. Copyright © 2014 Elsevier B.V. All rights reserved.

Near-Term Actions to Address Long-Term Climate Risk

NASA Astrophysics Data System (ADS)

Lempert, R. J.

2014-12-01

Addressing climate change requires effective long-term policy making, which occurs when reflecting on potential events decades or more in the future causes policy makers to choose near-term actions different than those they would otherwise pursue. Contrary to some expectations, policy makers do sometimes make such long-term decisions, but not as commonly and successfully as climate change may require. In recent years however, the new capabilities of analytic decision support tools, combined with improved understanding of cognitive and organizational behaviors, has significantly improved the methods available for organizations to manage longer-term climate risks. In particular, these tools allow decision makers to understand what near-term actions consistently contribute to achieving both short- and long-term societal goals, even in the face of deep uncertainty regarding the long-term future. This talk will describe applications of these approaches for infrastructure, water, and flood risk management planning, as well as studies of how near-term choices about policy architectures can affect long-term greenhouse gas emission reduction pathways.

Discovery and Characterization of ACT-451840: an Antimalarial Drug with a Novel Mechanism of Action.

PubMed

Boss, Christoph; Aissaoui, Hamed; Amaral, Nathalie; Bauer, Aude; Bazire, Stephanie; Binkert, Christoph; Brun, Reto; Bürki, Cédric; Ciana, Claire-Lise; Corminboeuf, Olivier; Delahaye, Stephane; Dollinger, Claire; Fischli, Christoph; Fischli, Walter; Flock, Alexandre; Frantz, Marie-Céline; Girault, Malory; Grisostomi, Corinna; Friedli, Astrid; Heidmann, Bibia; Hinder, Claire; Jacob, Gael; Le Bihan, Amelie; Malrieu, Sophie; Mamzed, Saskia; Merot, Aurelien; Meyer, Solange; Peixoto, Sabrina; Petit, Nolwenn; Siegrist, Romain; Trollux, Julien; Weller, Thomas; Wittlin, Sergio

2016-09-20

More than 40 % of the world's population is at risk of being infected with malaria. Most malaria cases occur in the countries of sub-Saharan Africa, Central and South America, and Asia. Resistance to standard therapy, including artemisinin combinations, is increasing. There is an urgent need for novel antimalarials with new mechanisms of action. In a phenotypic screen, we identified a series of phenylalanine-based compounds that exhibit antimalarial activity via a new and yet unknown mechanism of action. Our optimization efforts culminated in the selection of ACT-451840 [(S,E)-N-(4-(4-acetylpiperazin-1-yl)benzyl)-3-(4-(tert-butyl)phenyl)-N-(1-(4-(4-cyanobenzyl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl)acrylamide] for clinical development. Herein we describe our optimization efforts from the screening hit to the potential drug candidate with respect to antiparasitic activity, drug metabolism and pharmacokinetics (DMPK) properties, and in vivo pharmacological efficacy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electrophysiology of neurones of the inferior mesenteric ganglion of the cat.

PubMed Central

Julé, Y; Szurszewski, J H

1983-01-01

Intracellular recordings were obtained from cells in vitro in the inferior mesenteric ganglia of the cat. Neurones could be classified into three types: non-spontaneous, irregular discharging and regular discharging neurones. Non-spontaneous neurones had a stable resting membrane potential and responded with action potentials to indirect preganglionic nerve stimulation and to intracellular injection of depolarizing current. Irregular discharging neurones were characterized by a discharge of excitatory post-synaptic potentials (e.p.s.p.s.) which sometimes gave rise to action potentials. This activity was abolished by hexamethonium bromide, chlorisondamine and d-tubocurarine chloride. Tetrodotoxin and a low Ca2+ -high Mg2+ solution also blocked on-going activity in irregular discharging neurones. Regular discharging neurones were characterized by a rhythmic discharge of action potentials. Each action potential was preceded by a gradual depolarization of the intracellularly recorded membrane potential. Intracellular injection of hyperpolarizing current abolished the regular discharge of action potential. No synaptic potentials were observed during hyperpolarization of the membrane potential. Nicotinic, muscarinic and adrenergic receptor blocking drugs did not modify the discharge of action potentials in regular discharging neurones. A low Ca2+ -high Mg2+ solution also had no effect on the regular discharge of action potentials. Interpolation of an action potential between spontaneous action potentials in regular discharging neurones reset the rhythm of discharge. It is suggested that regular discharging neurones were endogenously active and that these neurones provided synaptic input to irregular discharging neurones. PMID:6140310

Electrophysiology of neurones of the inferior mesenteric ganglion of the cat.

PubMed

Julé, Y; Szurszewski, J H

1983-11-01

Intracellular recordings were obtained from cells in vitro in the inferior mesenteric ganglia of the cat. Neurones could be classified into three types: non-spontaneous, irregular discharging and regular discharging neurones. Non-spontaneous neurones had a stable resting membrane potential and responded with action potentials to indirect preganglionic nerve stimulation and to intracellular injection of depolarizing current. Irregular discharging neurones were characterized by a discharge of excitatory post-synaptic potentials (e.p.s.p.s.) which sometimes gave rise to action potentials. This activity was abolished by hexamethonium bromide, chlorisondamine and d-tubocurarine chloride. Tetrodotoxin and a low Ca2+ -high Mg2+ solution also blocked on-going activity in irregular discharging neurones. Regular discharging neurones were characterized by a rhythmic discharge of action potentials. Each action potential was preceded by a gradual depolarization of the intracellularly recorded membrane potential. Intracellular injection of hyperpolarizing current abolished the regular discharge of action potential. No synaptic potentials were observed during hyperpolarization of the membrane potential. Nicotinic, muscarinic and adrenergic receptor blocking drugs did not modify the discharge of action potentials in regular discharging neurones. A low Ca2+ -high Mg2+ solution also had no effect on the regular discharge of action potentials. Interpolation of an action potential between spontaneous action potentials in regular discharging neurones reset the rhythm of discharge. It is suggested that regular discharging neurones were endogenously active and that these neurones provided synaptic input to irregular discharging neurones.

Occupational safety and health criteria for responsible development of nanotechnology

NASA Astrophysics Data System (ADS)

Schulte, P. A.; Geraci, C. L.; Murashov, V.; Kuempel, E. D.; Zumwalde, R. D.; Castranova, V.; Hoover, M. D.; Hodson, L.; Martinez, K. F.

2014-01-01

Organizations around the world have called for the responsible development of nanotechnology. The goals of this approach are to emphasize the importance of considering and controlling the potential adverse impacts of nanotechnology in order to develop its capabilities and benefits. A primary area of concern is the potential adverse impact on workers, since they are the first people in society who are exposed to the potential hazards of nanotechnology. Occupational safety and health criteria for defining what constitutes responsible development of nanotechnology are needed. This article presents five criterion actions that should be practiced by decision-makers at the business and societal levels—if nanotechnology is to be developed responsibly. These include (1) anticipate, identify, and track potentially hazardous nanomaterials in the workplace; (2) assess workers' exposures to nanomaterials; (3) assess and communicate hazards and risks to workers; (4) manage occupational safety and health risks; and (5) foster the safe development of nanotechnology and realization of its societal and commercial benefits. All these criteria are necessary for responsible development to occur. Since it is early in the commercialization of nanotechnology, there are still many unknowns and concerns about nanomaterials. Therefore, it is prudent to treat them as potentially hazardous until sufficient toxicology, and exposure data are gathered for nanomaterial-specific hazard and risk assessments. In this emergent period, it is necessary to be clear about the extent of uncertainty and the need for prudent actions.

Discordant U waves in the setting of hyperkalaemia.

PubMed

Chhabra, Lovely; Spodick, David H

2013-07-04

Physiological U wave genesis occurs likely secondary to either late repolarisation of Purkinje fibres, or late repolarisation of some myocardial cells and/or delayed after depolarisation of the ventricular wall occurring during ventricular filling. Hypokalaemia has a well-known association with pathological 'U wave' which actually combines with the T wave (TU complex) and results from slowing of phase 3 of the action potential with resultant electrical interaction between the three myocardial layers. U waves usually tend to disappear in the setting of hyperkalaemia. We report an unusual case where hyperkalaemia and discordant U waves coexisted. We believe that this may have occurred as a result of partial clinical adaptation of cardiac myocytes to the long-standing effects of hyperkalaemia as the patient had underlying history of chronic kidney disease. We also discuss the possible mechanisms of the U wave genesis and the importance of different U wave morphologies encountered in the real clinical practice.

Accidents on hospital wards.

PubMed Central

Levene, S; Bonfield, G

1991-01-01

Eight hospitals reported 781 non-iatrogenic accidents occurring to patients and visitors under 16 years of age during an 18 month period up to October 1989. Accidents more often involved boys and children aged 3 to 5 years old. Falls from a height, slips, and striking accidents were common by day and falls by night. A total of 41% of accidents to inpatients occurred when parents were present. Only three accidents were serious. Altogether 27% involved beds and cots, and only one consequent injury was more than minor. Data collected routinely in case of medicolegal action can be presented in a form that may facilitate preventative work. Potentially remediable causes for concern include falls from beds and cots and the use of makeshift equipment. PMID:1929510

Mechanisms and consequences of action potential burst firing in rat neocortical pyramidal neurons

PubMed Central

Williams, Stephen R; Stuart, Greg J

1999-01-01

Electrophysiological recordings and pharmacological manipulations were used to investigate the mechanisms underlying the generation of action potential burst firing and its postsynaptic consequences in visually identified rat layer 5 pyramidal neurons in vitro.Based upon repetitive firing properties and subthreshold membrane characteristics, layer 5 pyramidal neurons were separated into three classes: regular firing and weak and strong intrinsically burst firing.High frequency (330 ± 10 Hz) action potential burst firing was abolished or greatly weakened by the removal of Ca2+ (n = 5) from, or by the addition of the Ca2+ channel antagonist Ni2+ (250–500 μm; n = 8) to, the perfusion medium.The blockade of apical dendritic sodium channels by the local dendritic application of TTX (100 nm; n = 5) abolished or greatly weakened action potential burst firing, as did the local apical dendritic application of Ni2+ (1 mm; n = 5).Apical dendritic depolarisation resulted in low frequency (157 ± 26 Hz; n = 6) action potential burst firing in regular firing neurons, as classified by somatic current injection. The intensity of action potential burst discharges in intrinsically burst firing neurons was facilitated by dendritic depolarisation (n = 11).Action potential amplitude decreased throughout a burst when recorded somatically, suggesting that later action potentials may fail to propagate axonally. Axonal recordings demonstrated that each action potential in a burst is axonally initiated and that no decrement in action potential amplitude is apparent in the axon > 30 μm from the soma.Paired recordings (n = 16) from synaptically coupled neurons indicated that each action potential in a burst could cause transmitter release. EPSPs or EPSCs evoked by a presynaptic burst of action potentials showed use-dependent synaptic depression.A postsynaptic, TTX-sensitive voltage-dependent amplification process ensured that later EPSPs in a burst were amplified when generated from membrane potentials positive to -60 mV, providing a postsynaptic mechanism that counteracts use-dependent depression at synapses between layer 5 pyramidal neurons. PMID:10581316

A challenge to chaotic itinerancy from brain dynamics

NASA Astrophysics Data System (ADS)

Kay, Leslie M.

2003-09-01

Brain hermeneutics and chaotic itinerancy proposed by Tsuda are attractive characterizations of perceptual dynamics in the mammalian olfactory system. This theory proposes that perception occurs at the interface between itinerant neural representation and interaction with the environment. Quantifiable application of these dynamics has been hampered by the lack of definable history and action processes which characterize the changes induced by behavioral state, attention, and learning. Local field potentials measured from several brain areas were used to characterize dynamic activity patterns for their use as representations of history and action processes. The signals were recorded from olfactory areas (olfactory bulb, OB, and pyriform cortex) and hippocampal areas (entorhinal cortex and dentate gyrus, DG) in the brains of rats. During odor-guided behavior the system shows dynamics at three temporal scales. Short time-scale changes are system-wide and can occur in the space of a single sniff. They are predictable, associated with learned shifts in behavioral state and occur periodically on the scale of the intertrial interval. These changes occupy the theta (2-12 Hz), beta (15-30 Hz), and gamma (40-100 Hz) frequency bands within and between all areas. Medium time-scale changes occur relatively unpredictably, manifesting in these data as alterations in connection strength between the OB and DG. These changes are strongly correlated with performance in associated trial blocks (5-10 min) and may be due to fluctuations in attention, mood, or amount of reward received. Long time-scale changes are likely related to learning or decline due to aging or disease. These may be modeled as slow monotonic processes that occur within or across days or even weeks or years. The folding of different time scales is proposed as a mechanism for chaotic itinerancy, represented by dynamic processes instead of static connection strengths. Thus, the individual maintains continuity of experience within the stability of fast periodic and slow monotonic processes, while medium scale events alter experience and performance dramatically but temporarily. These processes together with as yet to be determined action effects from motor system feedback are proposed as an instantiation of brain hermeneutics and chaotic itinerancy.

Action of caffeine on x-irradiated HeLa cells. V. Identity of the sector of cells that expresses potentially lethal damage in G/sub 1/ and G/sub 2/

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1982-07-01

When HeLa S3 cells are irradiated in early G/sub 1/ with 4 Gy of 220-kV x rays and are then incubated in growth medium containing up to 5 mM caffeine, survival is reduced (as reported previously), reaching a concentration-dependent plateau. Cell killing presumably occurs as a result of the fixation of a portion of the potentially lethal damage the cells contain. These cells respond to continued treatment with caffeine at concentrations greater than 2 mM during S, but less so than during G/sub 1/. When they reach G/sub 2/ arrest, however, extensive cell killing again occurs (reported previously), presumably alsomore » the result of potentially lethal damage fixation. G/sub 1/-irradiated cultures that are treated with caffeine either continuously at a concentration in the range 1 to 5 mM, or at 10 mM for 8 hr and subsequently with the low concentration, achieve the same survival level in G/sub 2/, provided that the potentially lethal damage is not repaired during G/sub 1/ and S. Repair seems to be completely inhibited in the presence of 3 to 4 mM caffeine. The results indicate that fixation of potentially lethal damage occurs in the same sector of cells in G/sub 1/ and G/sub 2/, suggesting that the same cellular lesion gives rise to cell killing in the two phases.« less

Representing the Hyphen in Action-Effect Associations: Automatic Acquisition and Bidirectional Retrieval of Action-Effect Intervals

ERIC Educational Resources Information Center

Dignath, David; Pfister, Roland; Eder, Andreas B.; Kiesel, Andrea; Kunde, Wilfried

2014-01-01

We examined whether a temporal interval between an action and its sensory effect is integrated in the cognitive action structure in a bidirectional fashion. In 3 experiments, participants first experienced that actions produced specific acoustic effects (high and low tones) that occurred temporally delayed after their actions. In a following test…

Reduction of radiation-induced cell cycle blocks by caffeine does not necessarily lead to increased cell killing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Musk, S.R.

1991-03-01

The effect of caffeine upon the radiosensitivities of three human tumor lines was examined and correlated with its action upon the radiation-induced S-phase and G2-phase blocks. Caffeine was found to reduce at least partially the S-phase and G2-phase blocks in all the cell lines examined but potentiated cytotoxicity in only one of the three tumor lines. That reductions have been demonstrated to occur in the absence of increased cell killing provides supporting evidence for the hypothesis that reductions may not be causal in those cases when potentiation of radiation-induced cytotoxicity is observed in the presence of caffeine.

Ensuring that consumers receive appropriate information from drug ads: what is the FDA's role?

PubMed

Waxman, Henry A

2004-01-01

The promise of direct-to-consumer (DTC) prescription drug advertisements lies in their potential to educate consumers about medical conditions and the possibility of treatment. But this promise can only be fulfilled if consumers are given clear and accurate information. The responsibility for ensuring that this occurs falls on the Food and Drug Administration (FDA). Recent congressional investigations have indicated that the agency is failing at this task, as FDA enforcement actions against false and misleading ads have declined precipitously in recent years. Other FDA efforts, such as its recently released guidelines on prescription drugs, do not appear to be helpful, potentially confusing consumers more than helping them.

Short latency compound action potentials from mammalian gravity receptor organs

NASA Technical Reports Server (NTRS)

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

1999-01-01

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.

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

PubMed

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

2015-08-01

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

PREDICTING ABUSE POTENTIAL OF STIMULANTS AND OTHER DOPAMINERGIC DRUGS: OVERVIEW AND RECOMMENDATIONS

PubMed Central

Huskinson, Sally L.; Naylor, Jennifer E.; Rowlett, James K.; Freeman, Kevin B.

2014-01-01

Examination of a drug’s abuse potential at multiple levels of analysis (molecular/cellular action, whole-organism behavior, epidemiological data) is an essential component to regulating controlled substances under the Controlled Substances Act (CSA). We reviewed studies that examined several central nervous system (CNS) stimulants, focusing on those with primarily dopaminergic actions, in drug self-administration, drug discrimination, and physical dependence. For drug self-administration and drug discrimination, we distinguished between experiments conducted with rats and nonhuman primates (NHP) to highlight the common and unique attributes of each model in the assessment of abuse potential. Our review of drug self-administration studies suggests that this procedure is important in predicting abuse potential of dopaminergic compounds, but there were many false positives. We recommended that tests to determine how reinforcing a drug is relative to a known drug of abuse may be more predictive of abuse potential than tests that yield a binary, yes-or-no classification. Several false positives also occurred with drug discrimination. With this procedure, we recommended that future research follow a standard decision-tree approach that may require examining the drug being tested for abuse potential as the training stimulus. This approach would also allow several known drugs of abuse to be tested for substitution, and this may reduce false positives. Finally, we reviewed evidence of physical dependence with stimulants and discussed the feasibility of modeling these phenomena in nonhuman animals in a rational and practical fashion. PMID:24662599

Elimination of Potential Electrical Stress During EMC (CS01) Testing

NASA Technical Reports Server (NTRS)

Erickson, Kenneth P.; Whittlesey, Albert C.; Vorperian, Vatche

2006-01-01

This viewgraph presentation reviews possible ways to eliminate electrical stress during Electromagneticic Compatibility (EMC) testing. The presentation reviews tests that have had problems due to electrical stress. On December 5, 1995 Cassini Radar instrument failed a functional test in preparation for EMC conducted susceptibility (CSO 1 ) testing. The instrument power supply did not turn on as required, and failure occurred prior to injection of CS test stimulus. A investigation of the failure was conducted. A PSPICE simulation of Cassini Radar 30V line using the EMC test setup was performed; the result of the simulation was an oscillation on the 30V input of the power supply. In another case: on December 28, 1999 an oscillation occurred on the input power line of the SlRTF Infrared Array Camera (IRAC) while preparing to perform CSOI testing, Resulted in damage to flight hardware. Subsequent to failure, JPL provided GSFC history and corrective action from Cassini Radar CSOI test failure GSFC implemented the same corrective action as JPL, except that the value of the resistor connected across the isolation transformer primary winding is 2.5 ohms instead of 50 ohms. Three recommendations are made: (1) Make EMC test community aware of the problem and potential solutions by presenting papers at major environmental test conferences (2) Include warnings and safeguards in EMC test requirements and procedures (3) Try to convince EMC test equipment suppliers to design a CSOl test fixture similar to fixture shown in the diagram

Neuroprotective action and free radical scavenging activity of Guttiferone-A, a naturally occurring prenylated benzophenone.

PubMed

Nuñez-Figueredo, Y; García-Pupo, L; Ramírez-Sánchez, J; Alcántara-Isaac, Y; Cuesta-Rubio, O; Hernández, R D; Naal, Z; Curti, C; Pardo-Andreu, G L

2012-12-01

Reactive oxygen species (ROS) are important mediators in a number of neurodegenerative diseases and molecules capable of scavenging ROS may be a feasible strategy for protecting neuronal cells. We previously demonstrated a powerful iron-chelating action of Guttiferone-A (GA), a naturally occurring polyphenol, on oxidative stress injuries initiated by iron overload. Here we addressed the neuroprotective potential of GA in hydrogen peroxide and glutamate-induced injury on rat's primary culture of cortical neurons and PC12 cells, respectively, and antioxidant properties concerning scavenging and anti-lipoperoxidative activities in cell-free models. The decrease in cell viability induced by each of the toxins, assessed by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay, was significantly attenuated by GA. In addition, GA was found to be a potent antioxidant, as shown by (i) inhibition of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical reduction (EC50=20.0 μM), (ii) prevention against chemically or electrochemically generated superoxide radicals, (iii) inhibition of spontaneous brain lipid peroxidation and (iv) interference with the Fenton reaction. These results indicate that GA exerts neuroprotective effects against H2O2 or glutamate toxicity and its antioxidant activity, demonstrated in vitro, could be at least partly involved. They also suggest a promising potential for GA as a therapeutic agent against neurodegenerative diseases involving ROS and oxidative damage. © Georg Thieme Verlag KG Stuttgart · New York.

Decision making and action implementation: evidence for an early visually triggered motor activation specific to potential actions.

PubMed

Tandonnet, Christophe; Garry, Michael I; Summers, Jeffery J

2013-07-01

To make a decision may rely on accumulating evidence in favor of one alternative until a threshold is reached. Sequential-sampling models differ by the way of accumulating evidence and the link with action implementation. Here, we tested a model's prediction of an early action implementation specific to potential actions. We assessed the dynamics of action implementation in go/no-go and between-hand choice tasks by transcranial magnetic stimulation of the motor cortex (single- or paired-pulse TMS; 3-ms interstimulus interval). Prior to implementation of the selected action, the amplitude of the motor evoked potential first increased whatever the visual stimulus but only for the hand potentially involved in the to-be-produced action. These findings suggest that visual stimuli can trigger an early motor activation specific to potential actions, consistent with race-like models with continuous transmission between decision making and action implementation. Copyright © 2013 Society for Psychophysiological Research.

Potential Exposures to Australian Bat Lyssavirus Notified in Queensland, Australia, 2009-2014.

PubMed

Si, Damin; Marquess, John; Donnan, Ellen; Harrower, Bruce; McCall, Bradley; Bennett, Sonya; Lambert, Stephen

2016-12-01

Australian bat lyssavirus (ABLV) belongs to the genus Lyssavirus which also includes classic rabies virus and the European lyssaviruses. To date, the only three known human ABLV cases, all fatal, have been reported from Queensland, Australia. ABLV is widely distributed in Australian bats, and any bite or scratch from an Australian bat is considered a potential exposure to ABLV. Potential exposure to ABLV has been a notifiable condition in Queensland since 2005. We analysed notification data for potential exposures occurring between 2009 and 2014. There were 1,515 potential exposures to ABLV notified in Queensland, with an average annual notification rate of 5.6 per 100,000 population per year. The majority of notified individuals (96%) were potentially exposed to ABLV via bats, with a small number of cases potentially exposed via two ABLV infected horses and an ABLV infected human. The most common routes of potential exposure were through bat scratches (47%) or bites (37%), with less common routes being mucous membrane/broken skin exposure to bat saliva/brain tissue (2.2%). Intentional handling of bats by the general public was the major cause of potential exposures (56% of notifications). Examples of these potential exposures included people attempting to rescue bats caught in barbed wire fences/fruit tree netting, or attempting to remove bats from a home. Following potential exposures, 1,399 cases (92%) were recorded as having appropriate post-exposure prophylaxis (PEP) as defined in national guidelines, with the remainder having documentation of refusal or incomplete PEP. Up to a quarter of notifications occurred after two days from the potential exposure, but with some delays being more than three weeks. Of 393 bats available for testing during the reporting period, 20 (5.1%) had ABLV detected, including four species of megabats (all flying foxes) and one species of microbats (yellow-bellied sheathtail bat). Public health strategies should address the strong motivation of some members of the public to help injured bats or bats in distress, by emphasising that their action may harm the bat and put themselves at risk of the fatal ABLV infection. Alternative messaging should include seeking advice from professional animal rescue groups, or in the event of human contact, public health units. Further efforts are required to ensure that when potential exposure occurs, timely reporting and appropriate post-exposure prophylaxis occur.

Potential Exposures to Australian Bat Lyssavirus Notified in Queensland, Australia, 2009−2014

PubMed Central

Si, Damin; Marquess, John; Donnan, Ellen; Harrower, Bruce; McCall, Bradley; Bennett, Sonya; Lambert, Stephen

2016-01-01

Background Australian bat lyssavirus (ABLV) belongs to the genus Lyssavirus which also includes classic rabies virus and the European lyssaviruses. To date, the only three known human ABLV cases, all fatal, have been reported from Queensland, Australia. ABLV is widely distributed in Australian bats, and any bite or scratch from an Australian bat is considered a potential exposure to ABLV. Methodology/Principal Findings Potential exposure to ABLV has been a notifiable condition in Queensland since 2005. We analysed notification data for potential exposures occurring between 2009 and 2014. There were 1,515 potential exposures to ABLV notified in Queensland, with an average annual notification rate of 5.6 per 100,000 population per year. The majority of notified individuals (96%) were potentially exposed to ABLV via bats, with a small number of cases potentially exposed via two ABLV infected horses and an ABLV infected human. The most common routes of potential exposure were through bat scratches (47%) or bites (37%), with less common routes being mucous membrane/broken skin exposure to bat saliva/brain tissue (2.2%). Intentional handling of bats by the general public was the major cause of potential exposures (56% of notifications). Examples of these potential exposures included people attempting to rescue bats caught in barbed wire fences/fruit tree netting, or attempting to remove bats from a home. Following potential exposures, 1,399 cases (92%) were recorded as having appropriate post-exposure prophylaxis (PEP) as defined in national guidelines, with the remainder having documentation of refusal or incomplete PEP. Up to a quarter of notifications occurred after two days from the potential exposure, but with some delays being more than three weeks. Of 393 bats available for testing during the reporting period, 20 (5.1%) had ABLV detected, including four species of megabats (all flying foxes) and one species of microbats (yellow-bellied sheathtail bat). Conclusions/Significance Public health strategies should address the strong motivation of some members of the public to help injured bats or bats in distress, by emphasising that their action may harm the bat and put themselves at risk of the fatal ABLV infection. Alternative messaging should include seeking advice from professional animal rescue groups, or in the event of human contact, public health units. Further efforts are required to ensure that when potential exposure occurs, timely reporting and appropriate post-exposure prophylaxis occur. PMID:28033365

The effects of saxitoxin and tetrodotoxin on nerve conduction in the presence of lithium ions and of magnesium ions

PubMed Central

Evans, M. H.

1969-01-01

1. It has been shown that nerve fibres from rat cauda equina will conduct action potentials after immersion in saline in which lithium chloride is substituted for sodium chloride. 2. Both saxitoxin and tetrodotoxin inhibit lithium-generated action potentials. The concentration of toxin needed to inhibit the lithium-generated action potentials is similar to that needed to inhibit sodium-generated action potentials. 3. If magnesium chloride is added to the saline to give a concentration of 10-15 mM there is usually a slight fall in amplitude of the compound action potential. Saxitoxin and tetrodotoxin now inhibit the action potential to a greater degree than in the absence of magnesium ions. PMID:5789802

21 CFR 120.10 - Corrective actions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Corrective actions. 120.10 Section 120.10 Food and... actions. Whenever a deviation from a critical limit occurs, a processor shall take corrective action by... develop written corrective action plans, which become part of their HACCP plans in accordance with § 120.8...

Developmental axon stretch stimulates neuron growth while maintaining normal electrical activity, intracellular calcium flux, and somatic morphology

PubMed Central

Loverde, Joseph R.; Pfister, Bryan J.

2015-01-01

Elongation of nerve fibers intuitively occurs throughout mammalian development, and is synchronized with expansion of the growing body. While most tissue systems enlarge through mitosis and differentiation, elongation of nerve fibers is remarkably unique. The emerging paradigm suggests that axons undergo stretch as contiguous tissues enlarge between the proximal and distal segments of spanning nerve fibers. While stretch is distinct from growth, tension is a known stimulus which regulates the growth of axons. Here, we hypothesized that the axon stretch-growth process may be a natural form of injury, whereby regenerative processes fortify elongating axons in order to prevent disconnection. Harnessing the live imaging capability of our axon stretch-growth bioreactors, we assessed neurons both during and following stretch for biomarkers associated with injury. Utilizing whole-cell patch clamp recording, we found no evidence of changes in spontaneous action potential activity or degradation of elicited action potentials during real-time axon stretch at strains of up to 18% applied over 5 min. Unlike traumatic axonal injury, functional calcium imaging of the soma revealed no shifts in free intracellular calcium during axon stretch. Finally, the cross-sectional areas of nuclei and cytoplasms were normal, with no evidence of chromatolysis following week-long stretch-growth limited to the lower of 25% strain or 3 mm total daily stretch. The neuronal growth cascade coupled to stretch was concluded to be independent of the changes in membrane potential, action potential generation, or calcium flux associated with traumatic injury. While axon stretch-growth is likely to share overlap with regenerative processes, we conclude that developmental stretch is a distinct stimulus from traumatic axon injury. PMID:26379492

75 FR 6157 - Airworthiness Directives; Gulfstream Aerospace LP Model Gulfstream 100 Airplanes, and Model Astra...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-08

... objects may also occur. The proposed AD would require actions that are intended to address the unsafe... flying debris and objects may also occur. Required actions include modifying the warning and caution lights panel (WACLP), changing the WACLP and MED wiring, changing the wiring harness connecting the MED...

EEG beta-power changes reflect motor involvement in abstract action language processing.

PubMed

Schaller, Franziska; Weiss, Sabine; Müller, Horst M

2017-05-01

Brain oscillations in the α- and β-range become suppressed during motor processing and motor imagery. It has recently been discussed that such power changes also occur during action language processing. In our study, we compared β 2 -oscillations (16-25Hz) during the observation of prototypical arm movements (revealed via motion tracking) as well as during semantic processing of concrete and abstract sentences containing arm-related action verbs. Whereas we did find a strong desynchronization in the β 2 -range during action observation, the processing of action sentences evoked a rather weak desynchronization. However, this desynchronization occurred for action verbs in both concrete and abstract contexts. These results might indicate a tendency for abstract action language to be processed similar to concrete action language rather than abstract sentences. The oscillation patterns reflect the close relationship between language comprehension and motor functions - one of the core claims of current theories on embodied cognition. Copyright © 2017 Elsevier Inc. All rights reserved.

Proactive action preparation: seeing action preparation as a continuous and proactive process.

PubMed

Pezzulo, Giovanni; Ognibene, Dimitri

2012-07-01

In this paper, we aim to elucidate the processes that occur during action preparation from both a conceptual and a computational point of view. We first introduce the traditional, serial model of goal-directed action and discuss from a computational viewpoint its subprocesses occurring during the two phases of covert action preparation and overt motor control. Then, we discuss recent evidence indicating that these subprocesses are highly intertwined at representational and neural levels, which undermines the validity of the serial model and points instead to a parallel model of action specification and selection. Within the parallel view, we analyze the case of delayed choice, arguing that action preparation can be proactive, and preparatory processes can take place even before decisions are made. Specifically, we discuss how prior knowledge and prospective abilities can be used to maximize utility even before deciding what to do. To support our view, we present a computational implementation of (an approximated version of) proactive action preparation, showing its advantages in a simulated tennis-like scenario.

Cortical pyramidal cells as non-linear oscillators: experiment and spike-generation theory.

PubMed

Brumberg, Joshua C; Gutkin, Boris S

2007-09-26

Cortical neurons are capable of generating trains of action potentials in response to current injections. These discharges can take different forms, e.g., repetitive firing that adapts during the period of current injection or bursting behaviors. We have used a combined experimental and computational approach to characterize the dynamics leading to action potential responses in single neurons. Specifically we investigated the origin of complex firing patterns in response to sinusoidal current injections. Using a reduced model, the theta-neuron, alongside recordings from cortical pyramidal cells we show that both real and simulated neurons show phase-locking to sine wave stimuli up to a critical frequency, above which period skipping and 1-to-x phase-locking occurs. The locking behavior follows a complex "devil's staircase" phenomena, where locked modes are interleaved with irregular firing. We further show that the critical frequency depends on the time scale of spike generation and on the level of spike frequency adaptation. These results suggest that phase-locking of neuronal responses to complex input patterns can be explained by basic properties of the spike-generating machinery.

Chronological changes in the eighth cranial nerve compound action potential (CAP) in experimental endolymphatic hydrops: the effects of altering the polarity of click sounds.

PubMed

Morizono, Tetsuo; Kondo, Tsuyoshi; Yamano, Takafumi; Miyagi, Morimichi; Shiraishi, Kimio

2009-02-01

Using a guinea pig model of experimental endolymphatic hydrops, click sounds of altered polarity showed different latencies and amplitudes in hydropic compared with normal cochleae. Latency changes appeared as early as 1 week after endolymphatic obstruction. This method can help diagnose endolymphatic hydrops. The goal of the study was to develop an objective electrophysiological diagnosis of endolymphatic hydrops. Endolymphatic hydrops were created surgically in guinea pigs. The latency and the amplitude of the eighth cranial nerve compound action potential (CAP) for click sounds of altered polarity were measured up to 8 weeks after the surgery. At early stages after surgery, the latency for condensation clicks became longer, and at later stages the latencies for both condensation and rarefaction became longer. The discrepancy in the latencies for rarefaction and condensation click sounds (rarefaction minus condensation) became larger by the first week after surgery, but no further discrepancy occurred thereafter. Compared with latency changes, amplitude changes in the CAP were rapid and progressive following surgery, suggesting ongoing damage to hair cells.

A regenerative microchannel device for recording multiple single-unit action potentials in awake, ambulatory animals.

PubMed

Srinivasan, Akhil; Tipton, John; Tahilramani, Mayank; Kharbouch, Adel; Gaupp, Eric; Song, Chao; Venkataraman, Poornima; Falcone, Jessica; Lacour, Stéphanie P; Stanley, Garrett B; English, Arthur W; Bellamkonda, Ravi V

2016-02-01

Despite significant advances in robotics, commercially advanced prosthetics provide only a small fraction of the functionality of the amputated limb that they are meant to replace. Peripheral nerve interfacing could provide a rich controlling link between the body and these advanced prosthetics in order to increase their overall utility. Here, we report on the development of a fully integrated regenerative microchannel interface with 30 microelectrodes and signal extraction capabilities enabling evaluation in an awake and ambulatory rat animal model. In vitro functional testing validated the capability of the microelectrodes to record neural signals similar in size and nature to those that occur in vivo. In vitro dorsal root ganglia cultures revealed striking cytocompatibility of the microchannel interface. Finally, in vivo, the microchannel interface was successfully used to record a multitude of single-unit action potentials through 63% of the integrated microelectrodes at the early time point of 3 weeks. This marks a significant advance in microchannel interfacing, demonstrating the capability of microchannels to be used for peripheral nerve interfacing. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Decision-making under surprise and uncertainty: Arsenic contamination of water supplies

NASA Astrophysics Data System (ADS)

Randhir, Timothy O.; Mozumder, Pallab; Halim, Nafisa

2018-05-01

With ignorance and potential surprise dominating decision making in water resources, a framework for dealing with such uncertainty is a critical need in hydrology. We operationalize the 'potential surprise' criterion proposed by Shackle, Vickers, and Katzner (SVK) to derive decision rules to manage water resources under uncertainty and ignorance. We apply this framework to managing water supply systems in Bangladesh that face severe, naturally occurring arsenic contamination. The uncertainty involved with arsenic in water supplies makes the application of conventional analysis of decision-making ineffective. Given the uncertainty and surprise involved in such cases, we find that optimal decisions tend to favor actions that avoid irreversible outcomes instead of conventional cost-effective actions. We observe that a diversification of the water supply system also emerges as a robust strategy to avert unintended outcomes of water contamination. Shallow wells had a slight higher optimal level (36%) compare to deep wells and surface treatment which had allocation levels of roughly 32% under each. The approach can be applied in a variety of other cases that involve decision making under uncertainty and surprise, a frequent situation in natural resources management.

Tagatose: from a sweetener to a new diabetic medication?

PubMed

Espinosa, Ikna; Fogelfeld, Leon

2010-02-01

Tagatose is a naturally occurring simple sugar that is a more palatable bulk low-calorie (1.5 kcal/g) sweetener. It was approved as a food additive by the FDA in 2003. Tagatose has been studied as a potential antidiabetic and antiobesity medication. In preliminary studies in humans, tagatose has shown a low postprandial blood glucose and insulin response. Its proposed mechanism of action may involve interference in the absorption of carbohydrates by inhibiting intestinal disaccharidases and glucose transport. It may also act through hepatic inhibition of glycogenolysis. This article summarizes tagatose Phase I and II diabetes trials. It describes the pharmacodynamics and possible mechanism of action of this agent. Literature from 1974 to 2009 is reviewed. Better understanding of the implications of postprandial hyperglycemia. An appreciation of the liver as a target of glucose control. Increased awareness of tagatose, a sweetener, as a potential new medication that operates through improvement of postprandial hyperglycemia. Tagatose is currently being studied as a postprandial antihyperglycemic agent that may be safer with regard to hypoglycemia. Ongoing Phase III clinical trials will provide more definitive answers.

Post-error action control is neurobehaviorally modulated under conditions of constant speeded response.

PubMed

Soshi, Takahiro; Ando, Kumiko; Noda, Takamasa; Nakazawa, Kanako; Tsumura, Hideki; Okada, Takayuki

2014-01-01

Post-error slowing (PES) is an error recovery strategy that contributes to action control, and occurs after errors in order to prevent future behavioral flaws. Error recovery often malfunctions in clinical populations, but the relationship between behavioral traits and recovery from error is unclear in healthy populations. The present study investigated the relationship between impulsivity and error recovery by simulating a speeded response situation using a Go/No-go paradigm that forced the participants to constantly make accelerated responses prior to stimuli disappearance (stimulus duration: 250 ms). Neural correlates of post-error processing were examined using event-related potentials (ERPs). Impulsivity traits were measured with self-report questionnaires (BIS-11, BIS/BAS). Behavioral results demonstrated that the commission error for No-go trials was 15%, but PES did not take place immediately. Delayed PES was negatively correlated with error rates and impulsivity traits, showing that response slowing was associated with reduced error rates and changed with impulsivity. Response-locked error ERPs were clearly observed for the error trials. Contrary to previous studies, error ERPs were not significantly related to PES. Stimulus-locked N2 was negatively correlated with PES and positively correlated with impulsivity traits at the second post-error Go trial: larger N2 activity was associated with greater PES and less impulsivity. In summary, under constant speeded conditions, error monitoring was dissociated from post-error action control, and PES did not occur quickly. Furthermore, PES and its neural correlate (N2) were modulated by impulsivity traits. These findings suggest that there may be clinical and practical efficacy of maintaining cognitive control of actions during error recovery under common daily environments that frequently evoke impulsive behaviors.

Post-error action control is neurobehaviorally modulated under conditions of constant speeded response

PubMed Central

Soshi, Takahiro; Ando, Kumiko; Noda, Takamasa; Nakazawa, Kanako; Tsumura, Hideki; Okada, Takayuki

2015-01-01

Post-error slowing (PES) is an error recovery strategy that contributes to action control, and occurs after errors in order to prevent future behavioral flaws. Error recovery often malfunctions in clinical populations, but the relationship between behavioral traits and recovery from error is unclear in healthy populations. The present study investigated the relationship between impulsivity and error recovery by simulating a speeded response situation using a Go/No-go paradigm that forced the participants to constantly make accelerated responses prior to stimuli disappearance (stimulus duration: 250 ms). Neural correlates of post-error processing were examined using event-related potentials (ERPs). Impulsivity traits were measured with self-report questionnaires (BIS-11, BIS/BAS). Behavioral results demonstrated that the commission error for No-go trials was 15%, but PES did not take place immediately. Delayed PES was negatively correlated with error rates and impulsivity traits, showing that response slowing was associated with reduced error rates and changed with impulsivity. Response-locked error ERPs were clearly observed for the error trials. Contrary to previous studies, error ERPs were not significantly related to PES. Stimulus-locked N2 was negatively correlated with PES and positively correlated with impulsivity traits at the second post-error Go trial: larger N2 activity was associated with greater PES and less impulsivity. In summary, under constant speeded conditions, error monitoring was dissociated from post-error action control, and PES did not occur quickly. Furthermore, PES and its neural correlate (N2) were modulated by impulsivity traits. These findings suggest that there may be clinical and practical efficacy of maintaining cognitive control of actions during error recovery under common daily environments that frequently evoke impulsive behaviors. PMID:25674058

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

PubMed

Crago, Patrick E; Makowski, Nathaniel S

2014-10-01

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

The role of Na-Ca exchange current in the cardiac action potential.

PubMed

Janvier, N C; Boyett, M R

1996-07-01

Since 1981, when Mullins published his provocative book proposing that the Na-Ca exchanger is electrogenic, it has been shown, first by computer simulation by Noble and later by experiment by various investigators, that inward iNaCa triggered by the Ca2+ transient is responsible for the low plateau of the atrial action potential and contributes to the high plateau of the ventricular action potential. Reduction or complete block of inward iNaCa by buffering intracellular Ca2+ with EGTA or BAPTA, by blocking SR Ca2+ release or by substituting extracellular Na+ with Li+ can result in a shortening of the action potential. The effect of block of outward iNaCa or complete block of both inward and outward iNaCa on the action potential has not been investigated experimentally, because of the lack of a suitable blocker, and remains a goal for the future. An increase in the intracellular Na+ concentration (after the application of cardiac glycoside or an increase in heart rate) or an increase in extracellular Ca2+ are believed to lead to an outward shift in iNaCa at plateau potentials and a shortening of the action potential. Changes in the Ca2+ transient are expected to result in changes in inward iNaCa and thus the action potential. This may explain the shortening of the premature action potential as well as the prolongation of the action potential when a muscle is allowed to shorten during the action potential. Inward iNaCa may play an important role in both normal and abnormal pacemaker activity in the heart.

Auditory reafferences: the influence of real-time feedback on movement control.

PubMed

Kennel, Christian; Streese, Lukas; Pizzera, Alexandra; Justen, Christoph; Hohmann, Tanja; Raab, Markus

2015-01-01

Auditory reafferences are real-time auditory products created by a person's own movements. Whereas the interdependency of action and perception is generally well studied, the auditory feedback channel and the influence of perceptual processes during movement execution remain largely unconsidered. We argue that movements have a rhythmic character that is closely connected to sound, making it possible to manipulate auditory reafferences online to understand their role in motor control. We examined if step sounds, occurring as a by-product of running, have an influence on the performance of a complex movement task. Twenty participants completed a hurdling task in three auditory feedback conditions: a control condition with normal auditory feedback, a white noise condition in which sound was masked, and a delayed auditory feedback condition. Overall time and kinematic data were collected. Results show that delayed auditory feedback led to a significantly slower overall time and changed kinematic parameters. Our findings complement previous investigations in a natural movement situation with non-artificial auditory cues. Our results support the existing theoretical understanding of action-perception coupling and hold potential for applied work, where naturally occurring movement sounds can be implemented in the motor learning processes.

Opioids and the immune system: what is their mechanism of action?

PubMed

Eisenstein, Toby K

2011-12-01

There is a significant amount of literature showing that morphine and other opioids modulate immune responses. The findings support many mechanisms by which this may occur. In vitro experiments provide evidence for direct actions of opioids on immune cells using a variety of functional end points. When these drugs are given in vivo, a plethora of immune parameters are also altered. The paper in this issue of the journal by Zhang et al. provides new information on morphine alteration of immune cell subsets in the spleen and thymus of mice and the potential role of glucocorticoids in these observed phenomena. This Commentary reviews the in vitro activities of morphine on leucocytes, as well as other documented mechanisms by which morphine can alter immune function in vivo. © 2011 The Author. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Insights into defibrotide: an updated review.

PubMed

Morabito, F; Gentile, M; Gay, F; Bringhen, S; Mazzone, C; Vigna, E; Musto, P; Di Raimondo, F; Palumbo, A

2009-06-01

Defibrotide is a polydisperse oligonucleotide with antiatherosclerotic, anti-inflammatory, anti-ischaemic, pro-fibrinolytic and antithrombotic actions without significant systemic anticoagulant effects. It has been used in the treatment of various cardiovascular disorders, and especially in endothelial complications of allogeneic stem-cell transplantation. We reviewed the published work for the mechanism of action and clinical use of defibrotide to consolidate data and to describe new applications of this drug. We reviewed the most relevant papers on defibrotide published from November 1982 to January 2008. (selected through PubMed), and used recent meeting abstracts as sources for this review. Reports have suggested that defibrotide has clinical efficacy for treatment and prophylaxis of hepatic sinusoidal obstruction syndrome occurring after stem-cell transplantation. Animal models have clearly shown the potential antineoplastic effect of this drug. Further clinical investigations are needed to clarify this new application.

Saliency Detection as a Reactive Process: Unexpected Sensory Events Evoke Corticomuscular Coupling

PubMed Central

Kilintari, Marina; Srinivasan, Mandayam; Haggard, Patrick

2018-01-01

Survival in a fast-changing environment requires animals not only to detect unexpected sensory events, but also to react. In humans, these salient sensory events generate large electrocortical responses, which have been traditionally interpreted within the sensory domain. Here we describe a basic physiological mechanism coupling saliency-related cortical responses with motor output. In four experiments conducted on 70 healthy participants, we show that salient substartle sensory stimuli modulate isometric force exertion by human participants, and that this modulation is tightly coupled with electrocortical activity elicited by the same stimuli. We obtained four main results. First, the force modulation follows a complex triphasic pattern consisting of alternating decreases and increases of force, time-locked to stimulus onset. Second, this modulation occurs regardless of the sensory modality of the eliciting stimulus. Third, the magnitude of the force modulation is predicted by the amplitude of the electrocortical activity elicited by the same stimuli. Fourth, both neural and motor effects are not reflexive but depend on contextual factors. Together, these results indicate that sudden environmental stimuli have an immediate effect on motor processing, through a tight corticomuscular coupling. These observations suggest that saliency detection is not merely perceptive but reactive, preparing the animal for subsequent appropriate actions. SIGNIFICANCE STATEMENT Salient events occurring in the environment, regardless of their modalities, elicit large electrical brain responses, dominated by a widespread “vertex” negative-positive potential. This response is the largest synchronization of neural activity that can be recorded from a healthy human being. Current interpretations assume that this vertex potential reflects sensory processes. Contrary to this general assumption, we show that the vertex potential is strongly coupled with a modulation of muscular activity that follows the same pattern. Both the vertex potential and its motor effects are not reflexive but strongly depend on contextual factors. These results reconceptualize the significance of these evoked electrocortical responses, suggesting that saliency detection is not merely perceptive but reactive, preparing the animal for subsequent appropriate actions. PMID:29378865

Simulation of action potential propagation in plants.

PubMed

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

2011-12-21

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

FURTHER STUDY OF SOMA, DENDRITE, AND AXON EXCITATION IN SINGLE NEURONS

PubMed Central

Eyzaguirre, Carlos; Kuffler, Stephen W.

1955-01-01

The present investigation continues a previous study in which the soma-dendrite system of sensory neurons was excited by stretch deformation of the peripheral dendrite portions. Recording was done with intracellular leads which were inserted into the cell soma while the neuron was activated orthodromically or antidromically. The analysis was also extended to axon conduction. Crayfish, Procambarus alleni (Faxon) and Orconectes virilis (Hagen), were used. 1. The size and time course of action potentials recorded from the soma-dendrite complex vary greatly with the level of the cell's membrane potential. The latter can be changed over a wide range by stretch deformation which sets up a "generator potential" in the distal portions of the dendrites. If a cell is at its resting unstretched equilibrium potential, antidromic stimulation through the axon causes an impulse which normally overshoots the resting potential and decays into an afternegativity of 15 to 20 msec. duration. The postspike negativity is not followed by an appreciable hyperpolarization (positive) phase. If the membrane potential is reduced to a new steady level a postspike positivity appears and increases linearly over a depolarization range of 12 to 20 mv. in various cells. At those levels the firing threshold of the cell for orthodromic discharges is generally reached. 2. The safety factor for conduction between axon and cell soma is reduced under three unrelated conditions, (a) During the recovery period (2 to 3 msec.) immediately following an impulse which has conducted fully over the cell soma, a second impulse may be delayed, may invade the soma partially, or may be blocked completely. (b) If progressive depolarization is produced by stretch, it leads to a reduction of impulse height and eventually to complete block of antidromic soma invasion, resembling cathodal block, (c) In some cells, when the normal membrane potential is within several millivolts of the relaxed resting state, an antidromic impulse may be blocked and may set up within the soma a local potential only. The local potential can sum with a second one or it may sum with potential changes set up in the dendrites, leading to complete invasion of the soma. Such antidromic invasion block can always be relieved by appropriate stretch which shifts the membrane potential out of the "blocking range" nearer to the soma firing level. During the afterpositivity of an impulse in a stretched cell the membrane potential may fall below or near the blocking range. During that period another impulse may be delayed or blocked. 3. Information regarding activity and conduction in dendrites has been obtained indirectly, mainly by analyzing the generator action under various conditions of stretch. The following conclusions have been reached: The large dendrite branches have similar properties to the cell body from which they arise and carry the same kind of impulses. In the finer distal filaments of even lightly depolarized dendrites, however, no axon type all-or-none conduction occurs since the generator potential persists to a varying degree during antidromic invasion of the cell. With the membrane potential at its resting level the dendrite terminals contribute to the prolonged impulse afternegativity of the soma. 4. Action potentials in impaled axons and in cell bodies have been compared. It is thought that normally the over-all duration of axon impulses is shorter. Local activity during reduction of the safety margin for conduction was studied. 5. An analysis was made of high frequency grouped discharges which occasionally arise in cells. They differ in many essential aspects from the regular discharges set up by the generator action. It is proposed that grouped discharges occur only when invasion of dendrites is not synchronous, due to a delay in excitation spread between soma and dendrites. Each impulse in a group is assumed to be caused by an impulse in at least one of the large dendrite branches. Depolarization of dendrites abolishes the grouped activity by facilitating invasion of the large dendrite branches. PMID:13252238

Social Transmission of Experience of Agency: An Experimental Study

PubMed Central

Khalighinejad, Nima; Bahrami, Bahador; Caspar, Emilie A.; Haggard, Patrick

2016-01-01

The sense of controlling one’s own actions is fundamental to normal human mental function, and also underlies concepts of social responsibility for action. However, it remains unclear how the wider social context of human action influences sense of agency. Using a simple experimental design, we investigated, for the first time, how observing the action of another person or a robot could potentially influence one’s own sense of agency. We assessed how observing another’s action might change the perceived temporal relationship between one’s own voluntary actions and their outcomes, which has been proposed as an implicit measure of sense of agency. Working in pairs, participants chose between two action alternatives, one rewarded more frequently than the other, while watching a rotating clock hand. They judged, in separate blocks, either the time of their own action, or the time of a tone that followed the action. These were compared to baseline judgements of actions alone, or tones alone, to calculate the perceptual shift of action toward outcome and vice versa. Our design focused on how these two dependent variables, which jointly provide an implicit measure of sense of agency, might be influenced by observing another’s action. In the observational group, each participant could see the other’s actions. Multivariate analysis showed that the perceived time of action and tone shifted progressively toward the actual time of outcome with repeated experience of this social situation. No such progressive change occurred in other groups for whom a barrier hid participants’ actions from each other. However, a similar effect was observed in the group that viewed movements of a human-like robotic hand, rather than actions of another person. This finding suggests that observing the actions of others increases the salience of the external outcomes of action and this effect is not unique to observing human agents. Social contexts in which we see others controlling external events may play an important role in mentally representing the impact of our own actions on the external world. PMID:27625626

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

PubMed

Berger, Klaus; Hocke, Thomas; Hessel, Horst

2017-11-01

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

Genetic dissection of ion currents underlying all-or-none action potentials in C. elegans body-wall muscle cells

PubMed Central

Liu, Ping; Ge, Qian; Chen, Bojun; Salkoff, Lawrence; Kotlikoff, Michael I; Wang, Zhao-Wen

2011-01-01

Although the neuromuscular system of C. elegans has been studied intensively, little is known about the properties of muscle action potentials (APs). By combining mutant analyses with in vivo electrophysiological recording techniques and Ca2+ imaging, we have established the fundamental properties and molecular determinants of body-wall muscle APs. We show that, unlike mammalian skeletal muscle APs, C. elegans muscle APs occur in spontaneous trains, do not require the function of postsynaptic receptors, and are all-or-none overshooting events, rather than graded potentials as has been previously reported. Furthermore, we show that muscle APs depend on Ca2+ entry through the L-type Ca2+ channel EGL-19 with a contribution from the T-type Ca2+ channel CCA-1. Both the Shaker K+ channel SHK-1 and the Ca2+/Cl−-gated K+ channel SLO-2 play important roles in controlling the speed of membrane repolarization, the amplitude of afterhyperpolarization (AHP) and the pattern of AP firing; SLO-2 is also important in setting the resting membrane potential. Finally, AP-elicited elevations of [Ca2+]i require both EGL-19 and the ryanodine receptor UNC-68. Thus, like mammalian skeletal muscle, C. elegans body-wall myocytes generate all-or-none APs, which evoke Ca2+ release from the sarcoplasmic reticulum (SR), although the specific ion channels used for AP upstroke and repolarization differ. PMID:21059759

Learning from near misses: from quick fixes to closing off the Swiss-cheese holes.

PubMed

Jeffs, Lianne; Berta, Whitney; Lingard, Lorelei; Baker, G Ross

2012-04-01

The extent to which individuals in healthcare use near misses as learning opportunities remains poorly understood. Thus, an exploratory study was conducted to gain insight into the nature of, and contributing factors to, organisational learning from near misses in clinical practice. A constructivist grounded theory approach was employed which included semi-structured interviews with 24 participants (16 clinicians and 8 administrators) from a large teaching hospital in Canada. This study revealed three scenarios for the responses to near misses, the most common involved 'doing a quick fix' where clinicians recognised and corrected an error with no further action. The second scenario consisted of reporting near misses but not hearing back from management, which some participants characterised as 'going into a black hole'. The third scenario was 'closing off the Swiss-cheese holes', in which a reported near miss generated corrective action at an organisational level. Explanations for 'doing a quick fix' included the pervasiveness of near misses that cause no harm and fear associated with reporting the near miss. 'Going into a black hole' reflected managers' focus on operational duties and events that harmed patients. 'Closing off the Swiss-cheese holes' occurred when managers perceived substantial potential for harm and preventability. Where learning was perceived to occur, leaders played a pivotal role in encouraging near-miss reporting. To optimise learning, organisations will need to determine which near misses are appropriate to be responded to as 'quick fixes' and which ones require further action at the unit and corporate levels.

Zinc-Substituted Myoglobin Is a Naturally Occurring Photo-antimicrobial Agent with Potential Applications in Food Decontamination.

PubMed

Delcanale, Pietro; Montali, Chiara; Rodríguez-Amigo, Beatriz; Abbruzzetti, Stefania; Bruno, Stefano; Bianchini, Paolo; Diaspro, Alberto; Agut, Montserrat; Nonell, Santi; Viappiani, Cristiano

2016-11-16

Zinc-substituted myoglobin (ZnMb) is a naturally occurring photosensitizer that generates singlet oxygen with a high quantum yield. Using a combination of photophysical and fluorescence imaging techniques, we demonstrate the interaction of ZnMb with Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. An efficient antibacterial action against S. aureus was observed, with a reduction up to 99.9999% in the number of colony-forming units, whereas no sizable effect was detected against E. coli. Because ZnMb is known to form during the maturation of additive-free not-cooked cured ham, the use of this protein as a built-in photodynamic agent may constitute a viable method for the decontamination of these food products from Gram-positive bacteria.

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

PubMed

Lu, Siyuan; Madhukar, Anupam

2013-02-01

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

Recent Advances in Root Canal Disinfection: A Review

PubMed Central

Mohammadi, Zahed; Jafarzadeh, Hamid; Shalavi, Sousan; Palazzi, Flavio

2017-01-01

The microbial biofilm is an important factor for human infection. Finding effective antimicrobial strategies should be considered for decreasing antimicrobial resistance and controlling the infectious diseases. Treatment of infected canal systems may not be able to remove all bacteria and so bacterial persistence after treatment may occur. Application of antibacterial nanoparticles may be a potential strategy to improve the elimination of bacteria from the canal. Furthermore, mechanism of action and applications of photodynamic therapy and Photon-induced photoacoustic streaming (PIPS) and GentleWave system was reviewed. PMID:29225632

Botulism as a food poisoning: what is it?

PubMed

El-Bahnasawy, Mamdouh M; Aly, Nagwa Zein-El-Abdeen; Abdel-Fattah, Magda Abdel Hameed; Morsy, Tosson A

2014-04-01

Botulism is a rare but potentially life-threatening neuroparalytic syndrome resulting from the action of a neurotoxin elaborated by the microorganism Clostridium botulinum. This disease has a lengthy history; the first investigation of botulism occurred in the 1820s with a case report on hundreds of patients with "sausage poisoning" in a southern German town. Several decades later in Belgium, the association was demonstrated between a neuromuscular paralysis and ham infected by a spore forming bacillus that was isolated from the ham. The organism was named Bacillus botulinus after the Latin word for sausage, botulus.

A pilot rating scale for evaluating failure transients in electronic flight control systems

NASA Technical Reports Server (NTRS)

Hindson, William S.; Schroeder, Jeffery A.; Eshow, Michelle M.

1990-01-01

A pilot rating scale was developed to describe the effects of transients in helicopter flight-control systems on safety-of-flight and on pilot recovery action. The scale was applied to the evaluation of hardovers that could potentially occur in the digital flight-control system being designed for a variable-stability UH-60A research helicopter. Tests were conducted in a large moving-base simulator and in flight. The results of the investigation were combined with existing airworthiness criteria to determine quantitative reliability design goals for the control system.

Grounded and embodied mathematical cognition: Promoting mathematical insight and proof using action and language.

PubMed

Nathan, Mitchell J; Walkington, Candace

2017-01-01

We develop a theory of grounded and embodied mathematical cognition (GEMC) that draws on action-cognition transduction for advancing understanding of how the body can support mathematical reasoning. GEMC proposes that participants' actions serve as inputs capable of driving the cognition-action system toward associated cognitive states. This occurs through a process of transduction that promotes valuable mathematical insights by eliciting dynamic depictive gestures that enact spatio-temporal properties of mathematical entities. Our focus here is on pre-college geometry proof production. GEMC suggests that action alone can foster insight but is insufficient for valid proof production if action is not coordinated with language systems for propositionalizing general properties of objects and space. GEMC guides the design of a video game-based learning environment intended to promote students' mathematical insights and informal proofs by eliciting dynamic gestures through in-game directed actions. GEMC generates several hypotheses that contribute to theories of embodied cognition and to the design of science, technology, engineering, and mathematics (STEM) education interventions. Pilot study results with a prototype video game tentatively support theory-based predictions regarding the role of dynamic gestures for fostering insight and proof-with-insight, and for the role of action coupled with language to promote proof-with-insight. But the pilot yields mixed results for deriving in-game interventions intended to elicit dynamic gesture production. Although our central purpose is an explication of GEMC theory and the role of action-cognition transduction, the theory-based video game design reveals the potential of GEMC to improve STEM education, and highlights the complex challenges of connecting embodiment research to education practices and learning environment design.

Impacts on the seagrass, Zostera nigricaulis, from the herbicide Fusilade Forte® used in the management of Spartina anglica infestations.

PubMed

Carve, Megan; Coggan, Timothy L; Myers, Jackie H; Clarke, Bradley; Nugegoda, Dayanthi; Shimeta, Jeff

2018-02-01

The herbicide Fusilade Forte ® (FF) is widely applied in agricultural weed management and in the management of the invasive saltmarsh grass, Spartina anglica (ricegrass or cordgrass). FF (active ingredient fluazifop-P acid, FPA) is selective for poaceous grasses. Its primary mode of action is inhibition of the acetyl coenzyme-A carboxylase (ACCase) specific to this taxonomic group, and its secondary mode is by promotion of oxidative stress. FF is applied to S. anglica infestations in the intertidal zone, in proximity to seagrass meadows. Despite the potential for vital seagrass ecosystems to be exposed to FF, there is limited knowledge of any potential impacts. We investigated impacts of FPA on the endemic Australian seagrass, Zostera nigricaulis, measuring ACCase activity and parameters that reflect oxidative stress: photosynthetic performance, lipid peroxidation and photosynthetic pigment content. Seagrass was exposed to FF (0.01-10mgL -1 FPA and a control) for 7d, followed by a 7-d recovery in uncontaminated seawater. An enzyme assay demonstrated that FPA ≤10mgL -1 did not inhibit the activity of ACCase isolated from Z. nigricaulis, demonstrating that this seagrass is resistant to FF's primary mode of action. However, physiological impacts occurred following 7 days exposure to ≥0.1mgL -1 FPA, including up to a 72% reduction in photosynthetic pigment concentration. After 7-d recovery, photosynthetic pigment content improved in treatment plants; however, treated plants exhibited higher levels of lipid peroxidation. This study demonstrates that while Z. nigricaulis is resistant to FF's primary mode of action, significant physiological impacts occur following 7 days exposure to ≥0.1mgL -1 FPA. This study provides valuable information on the effects of FF on a non-target species that can better inform approaches to Spartina management in coastal seagrass ecosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

Wildlife habitat management on college and university campuses

USGS Publications Warehouse

Bosci, Tierney; Warren, Paige S.; Harper, Rick W.; DeStefano, Stephen

2018-01-01

With the increasing involvement of higher education institutions in sustainability movements, it remains unclear to what extent college and university campuses address wildlife habitat. Many campuses encompass significant areas of green space with potential to support diverse wildlife taxa. However, sustainability rating systems generally emphasize efforts like recycling and energy conservation over green landscaping and grounds maintenance. We sought to examine the types of wildlife habitat projects occurring at schools across the United States and whether or not factors like school type (public or private), size (number of students), urban vs. rural setting, and funding played roles in the implementation of such initiatives. Using case studies compiled by the National Wildlife Federation’s Campus Ecology program, we documented wildlife habitat-related projects at 60 campuses. Ten management actions derived from nationwide guidelines were used to describe the projects carried out by these institutions, and we recorded data about cost, funding, and outreach and education methods. We explored potential relationships among management actions and with school characteristics. We extracted themes in project types, along with challenges and responses to those challenges. Native plant species selection and sustainable lawn maintenance and landscaping were the most common management actions among the 60 campuses. According to the case studies we examined, we found that factors like school type, size, and location did not affect the engagement of a campus in wildlife habitat initiatives, nor did they influence the project expenditures or funding received by a campus. Our results suggest that many wildlife habitat initiatives are feasible for higher education institutions and may be successfully implemented at relatively low costs through simple, but deliberate management actions.

Understanding the impact of accreditation on quality in healthcare: A grounded theory approach.

PubMed

Desveaux, L; Mitchell, J I; Shaw, J; Ivers, N M

2017-11-01

To explore how organizations respond to and interact with the accreditation process and the actual and potential mechanisms through which accreditation may influence quality. Qualitative grounded theory study. Organizations who had participated in Accreditation Canada's Qmentum program during January 2014-June 2016. Individuals who had coordinated the accreditation process or were involved in managing or promoting quality. The accreditation process is largely viewed as a quality assurance process, which often feeds in to quality improvement activities if the feedback aligns with organizational priorities. Three key stages are required for accreditation to impact quality: coherence, organizational buy-in and organizational action. These stages map to constructs outlined in Normalization Process Theory. Coherence is established when an organization and its staff perceive that accreditation aligns with the organization's beliefs, context and model of service delivery. Organizational buy-in is established when there is both a conceptual champion and an operational champion, and is influenced by both internal and external contextual factors. Quality improvement action occurs when organizations take purposeful action in response to observations, feedback or self-reflection resulting from the accreditation process. The accreditation process has the potential to influence quality through a series of three mechanisms: coherence, organizational buy-in and collective quality improvement action. Internal and external contextual factors, including individual characteristics, influence an organization's experience of accreditation. © The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

17 CFR 39.3 - Procedures for registration.

Code of Federal Regulations, 2012 CFR

2012-04-01

... applications to become a registered derivatives clearing organization will be public: first page of the Form... any action taken or to be taken by the Commission based upon actions, activities, or events occurring... registration shall not affect any action taken or to be taken by the Commission based upon actions, activities...

14 CFR 152.411 - Affirmative action steps.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Affirmative action steps. 152.411 Section...) AIRPORTS AIRPORT AID PROGRAM Nondiscrimination in Airport Aid Program § 152.411 Affirmative action steps... its aviation workforce as vacancies occur, by taking the affirmative action steps in § 152.409(b)(3...

21 CFR 123.7 - Corrective actions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Corrective actions. 123.7 Section 123.7 Food and... CONSUMPTION FISH AND FISHERY PRODUCTS General Provisions § 123.7 Corrective actions. (a) Whenever a deviation from a critical limit occurs, a processor shall take corrective action either by: (1) Following a...

Effects of K(+) channel openers on spontaneous action potentials in detrusor smooth muscle of the guinea-pig urinary bladder.

PubMed

Takagi, Hiroaki; Hashitani, Hikaru

2016-10-15

The modulation of spontaneous excitability in detrusor smooth muscle (DSM) upon the pharmacological activation of different populations of K(+) channels was investigated. Effects of distinct K(+) channel openers on spontaneous action potentials in DSM of the guinea-pig bladder were examined using intracellular microelectrode techniques. NS1619 (10μM), a large conductance Ca(2+)-activated K(+) (BK) channel opener, transiently increased action potential frequency and then prevented their generation without hyperpolarizing the membrane in a manner sensitive to iberiotoxin (IbTX, 100nM). A higher concentration of NS1619 (30μM) hyperpolarized the membrane and abolished action potential firing. NS309 (10μM) and SKA31 (100μM), small conductance Ca(2+)-activated K(+) (SK) channel openers, dramatically increased the duration of the after-hyperpolarization and then abolished action potential firing in an apamin (100nM)-sensitive manner. Flupirtine (10μM), a Kv7 channel opener, inhibited action potential firing without hyperpolarizing the membrane in a manner sensitive to XE991 (10μM), a Kv7 channel blocker. BRL37344 (10μM), a β3-adrenceptor agonist, or rolipram (10nM), a phosphodiesterase 4 inhibitor, also inhibited action potential firing. A higher concentration of rolipram (100nM) hyperpolarized the DSM and abolished the action potentials. IbTX (100nM) prevented the rolipram-induced blockade of action potentials but not the hyperpolarization. BK and Kv7 channels appear to predominantly contribute to the stabilization of DSM excitability. Spare SK channels could be pharmacologically activated to suppress DSM excitability. BK channels appear to be involved in the cyclic AMP-induced inhibition of action potentials but not the membrane hyperpolarization. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2018-03-28

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

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

PubMed

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

2017-11-01

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

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

PubMed

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

2014-10-15

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. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

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

PubMed Central

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

2014-01-01

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

The transdermal delivery system of monoamine oxidase inhibitors.

PubMed

VanDenBerg, Chad M

2012-01-01

Monoamine oxidase inhibitors (MAOIs) were once widely used as effective treatments for major depressive disorder, particularly for patients with atypical or treatment-resistant depression. Today, MAOIs have largely been replaced by newer antidepressants because of concerns over potential serious side effects due to their mechanism of action. Monoamine oxidase (MAO) is an enzyme that metabolizes serotonin, norepinephrine, and dopamine, the neurotransmitters that are most associated with depression; inhibiting MAO, therefore, makes more of these neurotransmitters available for synaptic action. However, MAO also metabolizes tyramine, a trace amine found in some foods that acts as a sympathomimetic. Allowing excess tyramine to accumulate via MAO inhibition can result in hypertensive crisis due to the release of norepinephrine; therefore, patients taking an MAOI have had to follow dietary restrictions to avoid tyramine-rich foods. Hypertensive crisis may also be precipitated by using MAOIs in conjunction with other drugs that have vasoconstrictive properties, that act as sympathomimetics, or that inhibit the reuptake of norepinephrine. Serotonin syndrome is another serious adverse effect that can potentially occur when using an MAOI with another drug that inhibits the reuptake of serotonin. In this article, the mechanism of action of MAOIs is reviewed, along with that of a newer MAOI formulation that lessens the need for dietary restrictions and has a greater safety and tolerability profile than the older oral formulations. © Copyright 2012 Physicians Postgraduate Press, Inc.

A modeling comparison of projection neuron- and neuromodulator-elicited oscillations in a central pattern generating network.

PubMed

Kintos, Nickolas; Nusbaum, Michael P; Nadim, Farzan

2008-06-01

Many central pattern generating networks are influenced by synaptic input from modulatory projection neurons. The network response to a projection neuron is sometimes mimicked by bath applying the neuronally-released modulator, despite the absence of network interactions with the projection neuron. One interesting example occurs in the crab stomatogastric ganglion (STG), where bath applying the neuropeptide pyrokinin (PK) elicits a gastric mill rhythm which is similar to that elicited by the projection neuron modulatory commissural neuron 1 (MCN1), despite the absence of PK in MCN1 and the fact that MCN1 is not active during the PK-elicited rhythm. MCN1 terminals have fast and slow synaptic actions on the gastric mill network and are presynaptically inhibited by this network in the STG. These local connections are inactive in the PK-elicited rhythm, and the mechanism underlying this rhythm is unknown. We use mathematical and biophysically-realistic modeling to propose potential mechanisms by which PK can elicit a gastric mill rhythm that is similar to the MCN1-elicited rhythm. We analyze slow-wave network oscillations using simplified mathematical models and, in parallel, develop biophysically-realistic models that account for fast, action potential-driven oscillations and some spatial structure of the network neurons. Our results illustrate how the actions of bath-applied neuromodulators can mimic those of descending projection neurons through mathematically similar but physiologically distinct mechanisms.

Global optogenetic activation of inhibitory interneurons during epileptiform activity.

PubMed

Ledri, Marco; Madsen, Marita Grønning; Nikitidou, Litsa; Kirik, Deniz; Kokaia, Merab

2014-02-26

Optogenetic techniques provide powerful tools for bidirectional control of neuronal activity and investigating alterations occurring in excitability disorders, such as epilepsy. In particular, the possibility to specifically activate by light-determined interneuron populations expressing channelrhodopsin-2 provides an unprecedented opportunity of exploring their contribution to physiological and pathological network activity. There are several subclasses of interneurons in cortical areas with different functional connectivity to the principal neurons (e.g., targeting their perisomatic or dendritic compartments). Therefore, one could optogenetically activate specific or a mixed population of interneurons and dissect their selective or concerted inhibitory action on principal cells. We chose to explore a conceptually novel strategy involving simultaneous activation of mixed populations of interneurons by optogenetics and study their impact on ongoing epileptiform activity in mouse acute hippocampal slices. Here we demonstrate that such approach results in a brief initial action potential discharge in CA3 pyramidal neurons, followed by prolonged suppression of ongoing epileptiform activity during light exposure. Such sequence of events was caused by massive light-induced release of GABA from ChR2-expressing interneurons. The inhibition of epileptiform activity was less pronounced if only parvalbumin- or somatostatin-expressing interneurons were activated by light. Our data suggest that global optogenetic activation of mixed interneuron populations is a more effective approach for development of novel therapeutic strategies for epilepsy, but the initial action potential generation in principal neurons needs to be taken in consideration.

Synaptic depolarization is more effective than back-propagating action potentials during induction of associative long-term potentiation in hippocampal pyramidal neurons.

PubMed

Hardie, Jason; Spruston, Nelson

2009-03-11

Long-term potentiation (LTP) requires postsynaptic depolarization that can result from EPSPs paired with action potentials or larger EPSPs that trigger dendritic spikes. We explored the relative contribution of these sources of depolarization to LTP induction during synaptically driven action potential firing in hippocampal CA1 pyramidal neurons. Pairing of a weak test input with a strong input resulted in large LTP (approximately 75% increase) when the weak and strong inputs were both located in the apical dendrites. This form of LTP did not require somatic action potentials. When the strong input was located in the basal dendrites, the resulting LTP was smaller (< or =25% increase). Pairing the test input with somatically evoked action potentials mimicked this form of LTP. Thus, back-propagating action potentials may contribute to modest LTP, but local synaptic depolarization and/or dendritic spikes mediate a stronger form of LTP that requires spatial proximity of the associated synaptic inputs.

Cardiac action potential imaging

NASA Astrophysics Data System (ADS)

Tian, Qinghai; Lipp, Peter; Kaestner, Lars

2013-06-01

Action potentials in cardiac myocytes have durations in the order of magnitude of 100 milliseconds. In biomedical investigations the documentation of the occurrence of action potentials is often not sufficient, but a recording of the shape of an action potential allows a functional estimation of several molecular players. Therefore a temporal resolution of around 500 images per second is compulsory. In the past such measurements have been performed with photometric approaches limiting the measurement to one cell at a time. In contrast, imaging allows reading out several cells at a time with additional spatial information. Recent developments in camera technologies allow the acquisition with the required speed and sensitivity. We performed action potential imaging on isolated adult cardiomyocytes of guinea pigs utilizing the fluorescent membrane potential sensor di-8-ANEPPS and latest electron-multiplication CCD as well as scientific CMOS cameras of several manufacturers. Furthermore, we characterized the signal to noise ratio of action potential signals of varying sets of cameras, dye concentrations and objective lenses. We ensured that di-8-ANEPPS itself did not alter action potentials by avoiding concentrations above 5 μM. Based on these results we can conclude that imaging is a reliable method to read out action potentials. Compared to conventional current-clamp experiments, this optical approach allows a much higher throughput and due to its contact free concept leaving the cell to a much higher degree undisturbed. Action potential imaging based on isolated adult cardiomyocytes can be utilized in pharmacological cardiac safety screens bearing numerous advantages over approaches based on heterologous expression of hERG channels in cell lines.

Clusianone, a naturally occurring nemorosone regioisomer, uncouples rat liver mitochondria and induces HepG2 cell death.

PubMed

Reis, Felippe H Z; Pardo-Andreu, Gilberto L; Nuñez-Figueredo, Yanier; Cuesta-Rubio, Osmany; Marín-Prida, Javier; Uyemura, Sérgio A; Curti, Carlos; Alberici, Luciane C

2014-04-05

Clusianone is a member of the polycyclic polyprenylated acylphloroglucinol family of natural products; its cytotoxic mechanism is unknown. Clusianone is a structural isomer of nemorosone, which is a mitochondrial uncoupler and a well-known cytotoxic anti-cancer agent; thus, we addressed clusianone action at the mitochondria and its potential cytotoxic effects on cancer cells. In the HepG2 hepatocarcinoma cell line, clusianone induced mitochondrial membrane potential dissipation, ATP depletion and phosphatidyl serine externalization; this later event is indicative of apoptosis induction. In isolated mitochondria from rat liver, clusianone promoted protonophoric mitochondrial uncoupling. This was evidenced by the dissipation of mitochondrial membrane potential, an increase in resting respiration, an inhibition of Ca(2+) influx, stimulation of Ca(2+) efflux in Ca(2+)-loaded mitochondria, a decrease in ATP and NAD(P)H levels, generation of ROS, and swelling of valinomycin-treated organelles in hyposmotic potassium acetate media. The cytotoxic and uncoupling actions of clusianone were appreciably less than those of nemorosone, likely due to the presence of an intra-molecular hydrogen bond with the juxtaposed carbonyl group at the C15 position. Therefore, clusianone is capable of pharmacologically increasing the leakage of protons from the mitochondria and with favorable cytotoxicity in relation to nemorosone. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates.

PubMed

Mahajan, Aman; Shiferaw, Yohannes; Sato, Daisuke; Baher, Ali; Olcese, Riccardo; Xie, Lai-Hua; Yang, Ming-Jim; Chen, Peng-Sheng; Restrepo, Juan G; Karma, Alain; Garfinkel, Alan; Qu, Zhilin; Weiss, James N

2008-01-15

Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Ca(i)) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (I(Ca,L)) and Ca(i) cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35-37 degrees C. Incorporating a minimal seven-state Markovian model of I(Ca,L) that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Ca(i) cycling model, the new model replicates experimentally observed action potential duration and Ca(i) transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing.

Typical gray matter axons in mammalian brain fail to conduct action potentials faithfully at fever-like temperatures.

PubMed

Pekala, Dobromila; Szkudlarek, Hanna; Raastad, Morten

2016-10-01

We studied the ability of typical unmyelinated cortical axons to conduct action potentials at fever-like temperatures because fever often gives CNS symptoms. We investigated such axons in cerebellar and hippocampal slices from 10 to 25 days old rats at temperatures between 30 and 43°C. By recording with two electrodes along axonal pathways, we confirmed that the axons were able to initiate action potentials, but at temperatures >39°C, the propagation of the action potentials to a more distal recording site was reduced. This temperature-sensitive conduction may be specific for the very thin unmyelinated axons because similar recordings from myelinated CNS axons did not show conduction failures. We found that the conduction fidelity improved with 1 mmol/L TEA in the bath, probably due to block of voltage-sensitive potassium channels responsible for the fast repolarization of action potentials. Furthermore, by recording electrically activated antidromic action potentials from the soma of cerebellar granule cells, we showed that the axons failed less if they were triggered 10-30 msec after another action potential. This was because individual action potentials were followed by a depolarizing after-potential, of constant amplitude and shape, which facilitated conduction of the following action potentials. The temperature-sensitive conduction failures above, but not below, normal body temperature, and the failure-reducing effect of the spike's depolarizing after-potential, are two intrinsic mechanisms in normal gray matter axons that may help us understand how the hyperthermic brain functions. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

What Faces Reveal: A Novel Method to Identify Patients at Risk of Deterioration Using Facial Expressions.

PubMed

Madrigal-Garcia, Maria Isabel; Rodrigues, Marcos; Shenfield, Alex; Singer, Mervyn; Moreno-Cuesta, Jeronimo

2018-07-01

To identify facial expressions occurring in patients at risk of deterioration in hospital wards. Prospective observational feasibility study. General ward patients in a London Community Hospital, United Kingdom. Thirty-four patients at risk of clinical deterioration. A 5-minute video (25 frames/s; 7,500 images) was recorded, encrypted, and subsequently analyzed for action units by a trained facial action coding system psychologist blinded to outcome. Action units of the upper face, head position, eyes position, lips and jaw position, and lower face were analyzed in conjunction with clinical measures collected within the National Early Warning Score. The most frequently detected action units were action unit 43 (73%) for upper face, action unit 51 (11.7%) for head position, action unit 62 (5.8%) for eyes position, action unit 25 (44.1%) for lips and jaw, and action unit 15 (67.6%) for lower face. The presence of certain combined face displays was increased in patients requiring admission to intensive care, namely, action units 43 + 15 + 25 (face display 1, p < 0.013), action units 43 + 15 + 51/52 (face display 2, p < 0.003), and action units 43 + 15 + 51 + 25 (face display 3, p < 0.002). Having face display 1, face display 2, and face display 3 increased the risk of being admitted to intensive care eight-fold, 18-fold, and as a sure event, respectively. A logistic regression model with face display 1, face display 2, face display 3, and National Early Warning Score as independent covariates described admission to intensive care with an average concordance statistic (C-index) of 0.71 (p = 0.009). Patterned facial expressions can be identified in deteriorating general ward patients. This tool may potentially augment risk prediction of current scoring systems.

Nothing can be coincidence: synaptic inhibition and plasticity in the cerebellar nuclei

PubMed Central

Pugh, Jason R.; Raman, Indira M.

2009-01-01

Many cerebellar neurons fire spontaneously, generating 10–100 action potentials per second even without synaptic input. This high basal activity correlates with information-coding mechanisms that differ from those of cells that are quiescent until excited synaptically. For example, in the deep cerebellar nuclei, Hebbian patterns of coincident synaptic excitation and postsynaptic firing fail to induce long-term increases in the strength of excitatory inputs. Instead, excitatory synaptic currents are potentiated by combinations of inhibition and excitation that resemble the activity of Purkinje and mossy fiber afferents that is predicted to occur during cerebellar associative learning tasks. Such results indicate that circuits with intrinsically active neurons have rules for information transfer and storage that distinguish them from other brain regions. PMID:19178955

Can observations look back to the beginning of inflation?

NASA Astrophysics Data System (ADS)

Wetterich, C.

2016-03-01

The cosmic microwave background can measure the inflaton potential only if inflation lasts sufficiently long before the time of horizon crossing of observable fluctuations, such that non-linear effects in the time evolution of Green's functions lead to a loss of memory of initial conditions for the ultraviolet tail of the spectrum. Within a derivative expansion of the quantum effective action for an interacting scalar field we discuss the most general solution for the correlation function, including arbitrary pure and mixed quantum states. In this approximation no loss of memory occurs - cosmic microwave observations see the initial spectrum at the beginning of inflation, processed only mildly by the scale-violating effects at horizon crossing induced by the inflaton potential.

A multi-target caffeine derived rhodium(i) N-heterocyclic carbene complex: evaluation of the mechanism of action.

PubMed

Zhang, Jing-Jing; Muenzner, Julienne K; Abu El Maaty, Mohamed A; Karge, Bianka; Schobert, Rainer; Wölfl, Stefan; Ott, Ingo

2016-08-16

A rhodium(i) and a ruthenium(ii) complex with a caffeine derived N-heterocyclic carbene (NHC) ligand were biologically investigated as organometallic conjugates consisting of a metal center and a naturally occurring moiety. While the ruthenium(ii) complex was largely inactive, the rhodium(i) NHC complex displayed selective cytotoxicity and significant anti-metastatic and in vivo anti-vascular activities and acted as both a mammalian and an E. coli thioredoxin reductase inhibitor. In HCT-116 cells it increased the reactive oxygen species level, leading to DNA damage, and it induced cell cycle arrest, decreased the mitochondrial membrane potential, and triggered apoptosis. This rhodium(i) NHC derivative thus represents a multi-target compound with promising anti-cancer potential.

Social Learning in the Real-World: 'Over-Imitation' Occurs in Both Children and Adults Unaware of Participation in an Experiment and Independently of Social Interaction.

PubMed

Whiten, Andrew; Allan, Gillian; Devlin, Siobahn; Kseib, Natalie; Raw, Nicola; McGuigan, Nicola

2016-01-01

The current study avoided the typical laboratory context to determine instead whether over-imitation-the disposition to copy even visibly, causally unnecessary actions-occurs in a real-world context in which participants are unaware of being in an experiment. We disguised a puzzle-box task as an interactive item available to the public within a science engagement zone of Edinburgh Zoo. As a member of the public approached, a confederate acting as a zoo visitor retrieved a reward from the box using a sequence of actions containing both causally relevant and irrelevant elements. Despite the absence of intentional demonstration, or social pressure to copy, a majority of both child and even adult observers included all causally irrelevant actions in their reproduction. This occurred even though causal irrelevance appeared manifest because of the transparency of the puzzle-box. That over-imitation occurred so readily in a naturalistic context, devoid of social interaction and pressure, suggests that humans are opportunistic social learners throughout the lifespan, copying the actions of other individuals even when these actions are not intentionally demonstrated, and their causal significance is not readily apparent. The disposition to copy comprehensively, even when a mere onlooker, likely provides humans, irrespective of their age, with a powerful mechanism to extract maximal information from the social environment.

21 CFR 25.31 - Human drugs and biologics.

Code of Federal Regulations, 2011 CFR

2011-04-01

... approval of a biologic product, or a supplement to such applications, or action on an OTC monograph, if the... a supplement to such applications, or action on an OTC monograph, if the action increases the use of... an OTC monograph, for substances that occur naturally in the environment when the action does not...

Legal liability in bisphosphonate-related osteonecrosis of the jaw.

PubMed

Lo Russo, L; Ciavarella, D; Buccelli, C; Di Fede, O; Campisi, G; Lo Muzio, L; Pellegrino, G; Di Lorenzo, P

2014-09-01

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is an adverse reaction that may occur in patients administered with bisphosphonates (BP). This condition can cause high morbidity and hinder quality of life. Its treatment is complex and often unsatisfactory, and prevention strategies may have limited effectiveness, if any. Thus, managing patients treated with BP may result in exposure of the practitioner to legal liability or malpractice claims: legal actions pursuant to BRONJ are reported to be underway on three continents. Nonetheless, the attribution of liability, if any, is a complex process requiring, on the basis of current knowledge, a robust and pragmatic approach to the facts, which must be identified from the point of view of the time, place and individuals involved. This means a comprehensive consideration of the sequence of actions from bisphosphonates prescription to BRONJ occurrence (as well as immediately after, and any action potentially related to its causation or worsening) is required in order to determine if a breach in informing, diagnosing, managing or referring the patient took place, as well as determining if the patient was compliant in attending to prescriptions and follow-up programmes.

Thrombospondin-1 as a Paradigm for the Development of Antiangiogenic Agents Endowed with Multiple Mechanisms of Action

PubMed Central

Rusnati, Marco; Urbinati, Chiara; Bonifacio, Silvia; Presta, Marco; Taraboletti, Giulia

2010-01-01

Uncontrolled neovascularization occurs in several angiogenesis-dependent diseases, including cancer. Neovascularization is tightly controlled by the balance between angiogenic growth factors and antiangiogenic agents. The various natural angiogenesis inhibitors identified so far affect neovascularization by different mechanisms of action. Thrombospondin-1 (TSP-1) is a matricellular modular glycoprotein that acts as a powerful endogenous inhibitor of angiogenesis. It acts both indirectly, by sequestering angiogenic growth factors and effectors in the extracellular environment, and directly, by inducing an antiangiogenic program in endothelial cells following engagement of specific receptors including CD36, CD47, integrins and proteoglycans (all involved in angiogenesis ). In view of its central, multifaceted role in angiogenesis, TSP-1 has served as a source of antiangiogenic tools, including TSP-1 fragments, synthetic peptides and peptidomimetics, gene therapy strategies, and agents that up-regulate TSP-1 expression. This review discusses TSP-1-based inhibitors of angiogenesis, their mechanisms of action and therapeutic potential, drawing our experience with angiogenic growth factor-interacting TSP-1 peptides, and the possibility of exploiting them to design novel antiangiogenic agents. PMID:27713299

The mechanism of action of Russian propolis ethanol extracts against two antibiotic-resistant biofilm-forming bacteria.

PubMed

Bryan, J; Redden, P; Traba, C

2016-02-01

The interaction between antibiotic-resistant Staphylococcus aureus and antibiotic-sensitive Escherichia coli biofilm-forming bacteria and Russian propolis ethanol extracts was evaluated. In this study, bacterial cell death occurred when the cell membranes of bacteria interacted specifically with the antibacterial compounds found in propolis. In order to understand the Russian propolis ethanol extract mechanism of action, microscopy and bacterial lysis studies were conducted. Results uncovered from these experiments imply that the mechanism of action of Russian propolis ethanol extracts is structural rather than functional. The results obtained throughout this study demonstrate cell membrane damage, resulting in cell lysis and eventually bacterial death. Most strains of bacteria and subsequently biofilms, have evolved and have altered their chemical composition in an attempt to protect themselves from antibiotics. The resistant nature of bacteria stems from the chemical rather than the physical means of inactivation of antibiotics. The results uncovered in this work demonstrate the potential application of Russian propolis ethanol extracts as a very efficient and effective method for bacterial and biofilm inactivation. © 2015 The Society for Applied Microbiology.

Predicting abuse potential of stimulants and other dopaminergic drugs: overview and recommendations.

PubMed

Huskinson, Sally L; Naylor, Jennifer E; Rowlett, James K; Freeman, Kevin B

2014-12-01

Examination of a drug's abuse potential at multiple levels of analysis (molecular/cellular action, whole-organism behavior, epidemiological data) is an essential component to regulating controlled substances under the Controlled Substances Act (CSA). We reviewed studies that examined several central nervous system (CNS) stimulants, focusing on those with primarily dopaminergic actions, in drug self-administration, drug discrimination, and physical dependence. For drug self-administration and drug discrimination, we distinguished between experiments conducted with rats and nonhuman primates (NHP) to highlight the common and unique attributes of each model in the assessment of abuse potential. Our review of drug self-administration studies suggests that this procedure is important in predicting abuse potential of dopaminergic compounds, but there were many false positives. We recommended that tests to determine how reinforcing a drug is relative to a known drug of abuse may be more predictive of abuse potential than tests that yield a binary, yes-or-no classification. Several false positives also occurred with drug discrimination. With this procedure, we recommended that future research follow a standard decision-tree approach that may require examining the drug being tested for abuse potential as the training stimulus. This approach would also allow several known drugs of abuse to be tested for substitution, and this may reduce false positives. Finally, we reviewed evidence of physical dependence with stimulants and discussed the feasibility of modeling these phenomena in nonhuman animals in a rational and practical fashion. This article is part of the Special Issue entitled 'CNS Stimulants'. Copyright © 2014 Elsevier Ltd. All rights reserved.

50 CFR 80.91 - What is a Federal obligation of funds and how does it occur?

Code of Federal Regulations, 2014 CFR

2014-10-01

... result of a series of actions. All of these actions must occur to obligate funds for the formula-based... formulas in the Acts. (b) The agency sends the Regional Director an application for Federal assistance to... grant. (d) The agency accepts the terms and conditions of the grant in one of the following ways: (1...

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

PubMed Central

Crago, Patrick E; Makowski, Nathan S

2014-01-01

Objective 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. Approach 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. Main Results 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. Significance 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. PMID:25161163

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

NASA Astrophysics Data System (ADS)

Crago, Patrick E.; Makowski, Nathaniel S.

2014-10-01

Objective. 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. Approach. 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. Main results. 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. Significance. 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.

Plasticity and response to action observation: a longitudinal FMRI study of potential mirror neurons in patients with subacute stroke.

PubMed

Brunner, Iris C; Skouen, Jan Sture; Ersland, Lars; Grüner, Renate

2014-01-01

Action observation has been suggested as a possible gateway to retraining arm motor function post stroke. However, it is unclear if the neuronal response to action observation is affected by stroke and if it changes during the course of recovery. To examine longitudinal changes in neuronal activity in a group of patients with subacute stroke when observing and executing a bimanual movement task. Eighteen patients were examined twice using 3-T functional magnetic resonance imaging; 1 to 2 weeks and 3 months post stroke symptom onset. Eighteen control participants were examined once. Image time series were analyzed (SPM8) and correlated with clinical motor function scores. During action observation and execution, an overlap of neuronal activation was observed in the superior and inferior parietal lobe, precentral gyrus, insula, and inferior temporal gyrus in both control participants and patients (P < .05; false discovery rate corrected). The neuronal response in the observation task increased from 1 to 2 weeks to 3 months after stroke. Most activated clusters were observed in the inferior temporal gyrus, the thalamus and movement-related areas, such as the premotor, supplementary and motor cortex (BA4, BA6). Increased activation of cerebellum and premotor area correlated with improved arm motor function. Most patients had regained full movement ability. Plastic changes in neurons responding to action observation and action execution occurred in accordance with clinical recovery. The involvement of motor areas when observing actions early and later after stroke may constitute a possible access to the motor system. © The Author(s) 2014.

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

PubMed

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

2017-06-01

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

The sense of agency is action–effect causality perception based on cross-modal grouping

PubMed Central

Kawabe, Takahiro; Roseboom, Warrick; Nishida, Shin'ya

2013-01-01

Sense of agency, the experience of controlling external events through one's actions, stems from contiguity between action- and effect-related signals. Here we show that human observers link their action- and effect-related signals using a computational principle common to cross-modal sensory grouping. We first report that the detection of a delay between tactile and visual stimuli is enhanced when both stimuli are synchronized with separate auditory stimuli (experiment 1). This occurs because the synchronized auditory stimuli hinder the potential grouping between tactile and visual stimuli. We subsequently demonstrate an analogous effect on observers' key press as an action and a sensory event. This change is associated with a modulation in sense of agency; namely, sense of agency, as evaluated by apparent compressions of action–effect intervals (intentional binding) or subjective causality ratings, is impaired when both participant's action and its putative visual effect events are synchronized with auditory tones (experiments 2 and 3). Moreover, a similar role of action–effect grouping in determining sense of agency is demonstrated when the additional signal is presented in the modality identical to an effect event (experiment 4). These results are consistent with the view that sense of agency is the result of general processes of causal perception and that cross-modal grouping plays a central role in these processes. PMID:23740784

Understanding the electrical behavior of the action potential in terms of elementary electrical sources.

PubMed

Rodriguez-Falces, Javier

2015-03-01

A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However, this model is unsuitably complex for teaching purposes. In addition, the Hodgkin and Huxley approach describes the shape of the action potential only in terms of ionic currents, i.e., it is unable to explain the electrical significance of the action potential or describe the electrical field arising from this source using basic concepts of electromagnetic theory. The goal of the present report was to propose a new model to describe the electrical behaviour of the action potential in terms of elementary electrical sources (in particular, dipoles). The efficacy of this model was tested through a closed-book written exam. The proposed model increased the ability of students to appreciate the distributed character of the action potential and also to recognize that this source spreads out along the fiber as function of space. In addition, the new approach allowed students to realize that the amplitude and sign of the extracellular electrical potential arising from the action potential are determined by the spatial derivative of this intracellular source. The proposed model, which incorporates intuitive graphical representations, has improved students' understanding of the electrical potentials generated by bioelectrical sources and has heightened their interest in bioelectricity. Copyright © 2015 The American Physiological Society.

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

PubMed

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

2015-05-01

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

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

PubMed

Yang, Li-Zhen; Zhu, Yi-Chun

2015-07-05

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

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

PubMed

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

2014-01-01

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

Population of Computational Rabbit-Specific Ventricular Action Potential Models for Investigating Sources of Variability in Cellular Repolarisation

PubMed Central

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

2014-01-01

Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K+, inward rectifying K+, L-type Ca2+, 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 observed intercellular variability of rabbit ventricular action potential repolarisation. PMID:24587229

Action potential propagation: ion current or intramembrane electric field?

PubMed

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

2018-01-01

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

Do New Mothers Understand the Risk Factors for Maternal Mortality?

PubMed

Logsdon, M Cynthia; Davis, Deborah Winders; Myers, John A; Masterson, Katlin M; Rushton, Jeffrey A; Lauf, Adrian P

2018-03-16

The purpose of this study was to describe new mothers' knowledge related to maternal mortality. Using a cross-sectional design, new mothers were recruited from a postpartum unit of an academic health sciences center where the population was predominately low-income women. Before hospital discharge, they answered questions on their knowledge of potential postpartum complications that could lead to maternal mortality. Questions were based on recommendations from an expert nursing panel. Descriptive statistics were used for data analysis. One hundred twenty new mothers participated. Results indicated that most new mothers knew that they should watch for heavy bleeding, a severe headache, and swelling after hospital discharge. However, fewer participants knew that a new mother could experience feelings that she could harm herself or her baby, have blood clots larger than a baby's hand, a temperature of 100.4 °F or more, and odor with vaginal discharge. Courses of action new mothers would take if experiencing any of the warning signs included 18% of mothers would take no action, 76.7% would tell their boyfriend/husband/partner, 72.5% would inform their mother. Only 60% who would call the labor and delivery unit. Only 38% of the sample knew that pregnancy-related complications can occur for up to 1 year after birth, and 13% of mothers reported not knowing that complications can occur for up to 6 weeks postpartum. Our findings provide a foundation to enhance postpartum education for new mothers and their families and to potentially decrease rates of maternal mortality in the United States.

Axonal properties determine somatic firing in a model of in vitro CA1 hippocampal sharp wave/ripples and persistent gamma oscillations

PubMed Central

Traub, Roger D.; Schmitz, Dietmar; Maier, Nikolaus; Whittington, Miles A.; Draguhn, Andreas

2012-01-01

Evidence has been presented that CA1 pyramidal cells, during spontaneous in vitro sharp wave/ripple (SPW-R) complexes, generate somatic action potentials that originate in axons. ‘Participating’ (somatically firing) pyramidal cells fire (almost always) at most once during a particular SPW-R whereas non-participating cells virtually never fire during an SPW-R. Somatic spikelets were small or absent, while ripple-frequency EPSCs and IPSCs occurred during the SPW-R in pyramidal neurons. These experimental findings could be replicated with a network model in which electrical coupling was present between small pyramidal cell axonal branches. Here, we explore this model in more depth. Factors that influence somatic participation include: (i) the diameter of axonal branches that contain coupling sites to other axons, because firing in larger branches injects more current into the main axon, increasing antidromic firing probability; (ii) axonal K+ currents; and (iii) somatic hyperpolarization and shunting. We predict that portions of axons fire at high frequency during SPW-R, while somata fire much less. In the model, somatic firing can occur by occasional generation of full action potentials in proximal axonal branches, which are excited by high-frequency spikelets. When the network contains phasic synaptic inhibition, at the axonal gap junction site, gamma oscillations result, again with more frequent axonal firing than somatic firing. Combining the models, so as to generate gamma followed by sharp waves, leads to strong overlap between the population of cells firing during gamma the population of cells firing during a subsequent sharp wave, as observed in vivo. PMID:22697272

A Strategy of Dialogue for Communicating Hazard and Risk Information Between the Science and Emergency Management Sectors

NASA Astrophysics Data System (ADS)

Eisner, R. K.

2015-12-01

This presentation will describe a collaborative dialogue process between earth scientists and emergency management officials that focused on translation of science into policy, building long term trust based relationships between sectors and unified presentation of hazards, risks and consequence management to public officials and the general public. The author will describe the structure and process of the California Earthquake Prediction Evaluation Council (CEPEC) in assessing the credibility of long and short term earthquake predictions, assessment of risk, and the formulation of public communication strategies and preparatory actions by government agencies. For nearly 4 decades, earth scientists, politically appointed state officials and emergency managers have engaged in ongoing discussions of the policy implications of research on potential seismic risk. Some discussions were scheduled and occurred over months, and others were ad hoc and occurred in the minutes between potential precursory incidents and possible large events. The effectiveness of this process was dependent on building respect for ones counterparts expertise, bias and responsibilities, clear communication of data, uncertainty and knowledge of the physical models assumed, history and probabilities; and the physical and political consequences of possible events; and the costs and economic and social disruption of alternative preparedness actions. But, the dialogue included political and social scientists, representatives of the print and broadcast media, political and management officials from federal, state and local governments. The presentation will provide an assessment of the effectiveness of the collaborative dialogue process and lessons on sustaining a long term partnership among the participating federal, state and local officials.

A functional-oriented assessment of environmental criticality due to anthropic actions along the hillslopes of the Somma-Vesuvio volcano (Naples, Italy).

NASA Astrophysics Data System (ADS)

Romano, Nunzio; De Falco, Melania; Speranza, Giuseppe; Tarolli, Paolo

2015-04-01

Mediterranean environments are characterized by a climatic regime with a strong seasonal variability. More uniform precipitations usually occur during the winter season, whereas short and very intense rainfalls occur during the fall and early spring that, in turn, trigger surface runoff and severe soil erosion phenomena. When this typical seasonality interacts with a territory substantially altered by anthropic actions, conditions can easily arise for environmental imbalances with serious risks for flash floods and landslides. Many of the degradation dynamics recorded during the last decades in western countries are also the result of the socio-economic changes after the II world war which yielded land-use changes with the urban sprawl process and the increase in human settlements of the natural environments. We are also witnessing a change in the perception of the natural environment and the relevant values. This study benefits from the availability of historical maps and rainfall time series to analyze the profound landscape changes occurred during the last century along the hillsides of the Somma-Vesuvio volcano, in the renowned piedmont area located at east of Napoli city. We are specifically interested in the changes and disturbances made to the hydrographic network to evaluate the increasing potential risks for flood and landslides along these hillslopes characterized by the presence of highly vulnerable volcanic soils, the construction of roads, and other negative alterations of the natural overland flow patterns.

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

PubMed

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

2012-10-25

Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in the inhibitory effects of minocycline upon AMPH-elicited action potential bursts. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Adaptation, perceptual learning, and plasticity of brain functions.

PubMed

Horton, Jonathan C; Fahle, Manfred; Mulder, Theo; Trauzettel-Klosinski, Susanne

2017-03-01

The capacity for functional restitution after brain damage is quite different in the sensory and motor systems. This series of presentations highlights the potential for adaptation, plasticity, and perceptual learning from an interdisciplinary perspective. The chances for restitution in the primary visual cortex are limited. Some patterns of visual field loss and recovery after stroke are common, whereas others are impossible, which can be explained by the arrangement and plasticity of the cortical map. On the other hand, compensatory mechanisms are effective, can occur spontaneously, and can be enhanced by training. In contrast to the human visual system, the motor system is highly flexible. This is based on special relationships between perception and action and between cognition and action. In addition, the healthy adult brain can learn new functions, e.g. increasing resolution above the retinal one. The significance of these studies for rehabilitation after brain damage will be discussed.

Oleoresin capsicum (Cap-Stun) toxicity from aerosol exposure.

PubMed

Watson, W A; Stremel, K R; Westdorp, E J

1996-01-01

To describe the clinical toxicity caused by oleoresin capsicum (OC) spray during law-enforcement action. A medical record review. Emergency department (ED), Truman Medical Center, Kansas City, MO. Consecutive patients who presented to the ED after OC-spray exposure from law-enforcement action between June 1991 and June 1994. Patient presentation and symptoms at presentation, evaluation, and treatment during ED stay. Eighty-one ED patients, approximately 10% of all individuals sprayed by police officers, presented after exposure to OC. Ocular burning and redness were the most common presenting symptoms. None of the patients required hospitalization due to OC toxicity. Corneal abrasions and respiratory symptoms occurred in 7 and 6 patients, respectively. The need for ED evaluation and treatment was infrequent after exposure to OC. A transient burning sensation, erythema, and localized irritation were the most common findings. While no patients had adverse outcomes attributed to OC exposure, practitioners assessing exposure should consider the potential for pulmonary and ocular toxicity.

Australian recommendations for the integration of emergency care for older people: Consensus Statement.

PubMed

Lowthian, Judy A; Arendts, Glenn; Strivens, Edward

2018-05-07

Management of older patients during acute illness or injury does not occur in isolation in emergency departments. We aimed to develop a collaborative Consensus Statement to enunciate principles of integrated emergency care. Briefing notes, informed by research and evidence reviews, were developed and evaluated by a Consensus Working Party comprising cross-specialty representation from clinical experts, service providers, consumers and policymakers. The Consensus Working Party then convened to discuss and develop the statement's content. A subcommittee produced a draft, which was reviewed and edited by the Consensus Working Party. Consensus was reached after three rounds of discussion, with 12 principles and six recommendations for how to follow these principles, including an integrated care framework for action. Dissemination will encourage stakeholders and associated policy bodies to embrace the principles and priorities for action, potentially leading to collaborative work practices and improvement of care during and after acute illness or injury. © 2018 AJA Inc.

Selective effects of an octopus toxin on action potentials

PubMed Central

Dulhunty, Angela; Gage, Peter W.

1971-01-01

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

Relationship between size and latency of action potentials in human muscle sympathetic nerve activity.

PubMed

Salmanpour, Aryan; Brown, Lyndon J; Steinback, Craig D; Usselman, Charlotte W; Goswami, Ruma; Shoemaker, J Kevin

2011-06-01

We employed a novel action potential detection and classification technique to study the relationship between the recruitment of sympathetic action potentials (i.e., neurons) and the size of integrated sympathetic bursts in human muscle sympathetic nerve activity (MSNA). Multifiber postganglionic sympathetic nerve activity from the common fibular nerve was collected using microneurography in 10 healthy subjects at rest and during activation of sympathetic outflow using lower body negative pressure (LBNP). Burst occurrence increased with LBNP. Integrated burst strength (size) varied from 0.22 ± 0.07 V at rest to 0.28 ± 0.09 V during LBNP. Sympathetic burst size (i.e., peak height) was directly related to the number of action potentials within a sympathetic burst both at baseline (r = 0.75 ± 0.13; P < 0.001) and LBNP (r = 0.75 ± 0.12; P < 0.001). Also, the amplitude of detected action potentials within sympathetic bursts was directly related to the increased burst size at both baseline (r = 0.59 ± 0.16; P < 0.001) and LBNP (r = 0.61 ± 0.12; P < 0.001). In addition, the number of detected action potentials and the number of distinct action potential clusters within a given sympathetic burst were correlated at baseline (r = 0.7 ± 0.1; P < 0.001) and during LBNP (r = 0.74 ± 0.03; P < 0.001). Furthermore, action potential latency (i.e., an inverse index of neural conduction velocity) was decreased as a function of action potential size at baseline and LBNP. LBNP did not change the number of action potentials and unique clusters per sympathetic burst. It was concluded that there exists a hierarchical pattern of recruitment of additional faster conducting neurons of larger amplitude as the sympathetic bursts become stronger (i.e., larger amplitude bursts). This fundamental pattern was evident at rest and was not altered by the level of baroreceptor unloading applied in this study.

All optical experimental design for neuron excitation, inhibition, and action potential detection

NASA Astrophysics Data System (ADS)

Walsh, Alex J.; Tolstykh, Gleb; Martens, Stacey; Sedelnikova, Anna; Ibey, Bennett L.; Beier, Hope T.

2016-03-01

Recently, infrared light has been shown to both stimulate and inhibit excitatory cells. However, studies of infrared light for excitatory cell inhibition have been constrained by the use of invasive and cumbersome electrodes for cell excitation and action potential recording. Here, we present an all optical experimental design for neuronal excitation, inhibition, and action potential detection. Primary rat neurons were transfected with plasmids containing the light sensitive ion channel CheRiff. CheRiff has a peak excitation around 450 nm, allowing excitation of transfected neurons with pulsed blue light. Additionally, primary neurons were transfected with QuasAr2, a fast and sensitive fluorescent voltage indicator. QuasAr2 is excited with yellow or red light and therefore does not spectrally overlap CheRiff, enabling imaging and action potential activation, simultaneously. Using an optic fiber, neurons were exposed to blue light sequentially to generate controlled action potentials. A second optic fiber delivered a single pulse of 1869nm light to the neuron causing inhibition of the evoked action potentials (by the blue light). When used in concert, these optical techniques enable electrode free neuron excitation, inhibition, and action potential recording, allowing research into neuronal behaviors with high spatial fidelity.

AAFES Shopping Center Environmental Assessment

DTIC Science & Technology

2009-08-01

Plan H2S Hydrogen Sulfide SO2 Sulfur Dioxide HWMP Hazardous Waste Management Plan SMW Strategic Missile Wing ICBM Intercontinental Ballistic Missile...the no-action alternative. Land Management and Use. A waiver would be needed prior to construction to change the land use designation from Open...occur under the no-action alternative. Hazardous Materials and Waste Management . No changes to hazardous materials or waste streams would occur

Cortical Action Potential Backpropagation Explains Spike Threshold Variability and Rapid-Onset Kinetics

PubMed Central

Yu, Yuguo; Shu, Yousheng; McCormick, David A.

2008-01-01

Neocortical action potential responses in vivo are characterized by considerable threshold variability, and thus timing and rate variability, even under seemingly identical conditions. This finding suggests that cortical ensembles are required for accurate sensorimotor integration and processing. Intracellularly, trial-to-trial variability results not only from variation in synaptic activities, but also in the transformation of these into patterns of action potentials. Through simultaneous axonal and somatic recordings and computational simulations, we demonstrate that the initiation of action potentials in the axon initial segment followed by backpropagation of these spikes throughout the neuron results in a distortion of the relationship between the timing of synaptic and action potential events. In addition, this backpropagation also results in an unusually high rate of rise of membrane potential at the foot of the action potential. The distortion of the relationship between the amplitude time course of synaptic inputs and action potential output caused by spike back-propagation results in the appearance of high spike threshold variability at the level of the soma. At the point of spike initiation, the axon initial segment, threshold variability is considerably less. Our results indicate that spike generation in cortical neurons is largely as expected by Hodgkin—Huxley theory and is more precise than previously thought. PMID:18632930

Calcium currents and graded synaptic transmission between heart interneurons of the leech.

PubMed

Angstadt, J D; Calabrese, R L

1991-03-01

Synaptic transmission between reciprocally inhibitory heart interneurons (HN cells) of the medicinal leech was examined in the absence of Na-mediated action potentials. Under voltage clamp, depolarizing steps from a holding potential of -60 mV elicited 2 kinetically distinct components of inward current in the presynaptic HN cell: an early transient current that inactivates within 200 msec and a persistent current that only partially decays over several seconds. Both currents begin to activate near -60 mV. Steady-state inactivation occurs over the voltage range between -70 and -45 mV and is completely removed by 1-2-sec hyperpolarizing voltage steps to -80 mV. The inward currents are carried by Ca2+, Ba2+, or Sr2+ ions, but not by Co2+, Mn2+, or Ni2+. These same inward currents underlie the burst-generating plateau potentials previously described in HN cells (Arbas and Calabrese, 1987a,b). With a presynaptic holding potential of -60 mV, the threshold for transmitter release is near -45 mV. Postsynaptic currents in the contralateral HN cell have a reversal potential near -60 mV. The largest postsynaptic currents (300-400 pA) exhibit an initial peak response that is followed by a more slowly decaying component. The persistent component of Ca2+ current in the presynaptic neuron is strongly correlated with the prolonged component of the postsynaptic current, while the transient presynaptic Ca2+ current appears to correspond to the early peak of postsynaptic current. These data are consistent with the hypothesis that voltage-dependent calcium currents contribute to the oscillatory capability of reciprocally inhibitory HN cells by (1) generating the plateau potential that drives the burst of action potentials and (2) underlying the release of inhibitory transmitter onto the contralateral cell.

Median and ulnar muscle and sensory evoked potentials.

PubMed

Felsenthal, G

1978-08-01

The medical literature was reviewed to find suggested clinical applications of the study of the amplitude of evoked muscle action potentials (MAP) and sensory action potentials (SAP). In addition, the literature was reviewed to ascertain the normal amplitude and duration of the evoked MAP and SAP as well as the factors affecting the amplitude: age, sex, temperature, ischemia. The present study determined the normal amplitude and duration of the median and ulnar MAP and SAP in fifty normal subjects. The amplitude of evoked muscle or sensory action potentials depends on multiple factors. Increased skin resistance, capacitance, and impedance at the surface of the recording electrode diminishes the amplitude. Similarly, increased distance from the source of the action potential diminishes its amplitude. Increased interelectrode distance increases the amplitude of the bipolarly recorded sensory action potential until a certain interelectrode distance is exceeded and the diphasic response becomes tri- or tetraphasic. Artifact or poor technique may reduce the potential difference between the recording electrodes or obscure the late positive phase of the action potential and thus diminish the peak to peak amplitude measurement. Intraindividual comparison indicated a marked difference of amplitude in opposite hands. The range of the MAP of the abductor pollicis brevis in one hand was 40.0--100% of the response in the opposite hand. For the abductor digiti minimi, the MAP was 58.5--100% of the response of the opposite hand. The median and ulnar SAP was between 50--100% of the opposite SAP. Consequent to these findings the effect of hand dominance on the amplitude of median and ulnar evoked muscle and sensory action potentials was studied in 41 right handed volunteers. The amplitudes of the median muscle action potential (p less than 0.02) and the median and ulnar sensory action potentials (p less than 0.001) were significantly less in the dominant hand. There was no significant difference between the ulnar muscle action potentials or for the median and ulnar distal motor and sensory latencies in the right and left hands of this group of volunteers.

Meningeal norepinephrine produces headache behaviors in rats via actions both on dural afferents and fibroblasts.

PubMed

Wei, Xiaomei; Yan, Jin; Tillu, Dipti; Asiedu, Marina; Weinstein, Nicole; Melemedjian, Ohannes; Price, Theodore; Dussor, Gregory

2015-10-01

Stress is commonly reported to contribute to migraine although mechanisms by which this may occur are not fully known. The purpose of these studies was to examine whether norepinephrine (NE), the primary sympathetic efferent transmitter, acts on processes in the meninges that may contribute to the pain of migraine. NE was applied to rat dura using a behavioral model of headache. Primary cultures of rat trigeminal ganglia retrogradely labeled from the dura mater and of rat dural fibroblasts were prepared. Patch-clamp electrophysiology, Western blot, and ELISA were performed to examine the effects of NE. Conditioned media from NE-treated fibroblast cultures was applied to the dura using the behavioral headache model. Dural injection both of NE and media from NE-stimulated fibroblasts caused cutaneous facial and hindpaw allodynia in awake rats. NE application to cultured dural afferents increased action potential firing in response to current injections. Application of NE to dural fibroblasts increased phosphorylation of ERK and caused the release of interleukin-6 (IL-6). These data demonstrate that NE can contribute to pro-nociceptive signaling from the meninges via actions on dural afferents and dural fibroblasts. Together, these actions of NE may contribute to the headache phase of migraine. © International Headache Society 2015.

Ionotropic glutamate receptor GluA4 and T-type calcium channel Cav 3.1 subunits control key aspects of synaptic transmission at the mouse L5B-POm giant synapse.

PubMed

Seol, Min; Kuner, Thomas

2015-12-01

The properties and molecular determinants of synaptic transmission at giant synapses connecting layer 5B (L5B) neurons of the somatosensory cortex (S1) with relay neurons of the posteriomedial nucleus (POm) of the thalamus have not been investigated in mice. We addressed this by using direct electrical stimulation of fluorescently labelled single corticothalamic terminals combined with molecular perturbations and whole-cell recordings from POm relay neurons. Consistent with their function as drivers, we found large-amplitude excitatory postsynaptic currents (EPSCs) and multiple postsynaptic action potentials triggered by a single presynaptic action potential. To study the molecular basis of these two features, ionotropic glutamate receptors and low voltage-gated T-type calcium channels were probed by virus-mediated genetic perturbation. Loss of GluA4 almost abolished the EPSC amplitude, strongly delaying the onset of action potential generation, but maintaining the number of action potentials generated per presynaptic action potential. In contrast, knockdown of the Cav 3.1 subunit abrogated the driver function of the synapse at a typical resting membrane potential of -70 mV. However, when depolarizing the membrane potential to -60 mV, the synapse relayed single action potentials. Hence, GluA4 subunits are required to produce an EPSC sufficiently large to trigger postsynaptic action potentials within a defined time window after the presynaptic action potential, while Cav 3.1 expression is essential to establish the driver function of L5B-POm synapses at hyperpolarized membrane potentials. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Low concentrations of procaine and diethylaminoethanol reduce the excitability but not the action potential amplitude of hippocampal pyramidal cells.

PubMed

Butterworth, J F; Cole, L R

1990-10-01

To determine whether concentrations of diethylaminoethanol (DEAE) and procaine below those that reduce the amplitude of action potentials might alter the excitability of brain cells, a single microelectrode intracellular recording technique was used to measure firing threshold and action potential amplitude of pyramidal cells in rat hippocampal slices. At low concentrations of both DEAE (less than or equal to 5 mM) and procaine (less than or equal to 0.5 mM), firing threshold was significantly increased (P less than 0.01), whereas action potential spike amplitude was minimally altered. At higher concentrations, both drugs significantly decreased action potential spike amplitude (P less than 0.025) as well as increased firing threshold (P less than 0.001). Diethylaminoethanol tended to increase threshold relatively more than procaine, when drug concentrations that similarly reduced action potential amplitude were compared. All actions of DEAE and procaine were reversible. Inhibition of action potentials by DEAE and procaine was clearly concentration-dependent (P less than or equal to 0.015). Diethylaminoethanol effects on threshold were marginally concentration-dependent (P = 0.08); procaine did not demonstrate clear concentration-dependent effects (P = 0.33) over the concentrations tested in this study. These similar actions of procaine and DEAE on brain cells suggest a mechanism by which intravenous local anesthetics may contribute to the general anesthetic state. Moreover, it appears possible that procaine metabolism and DEAE accumulation may underlie the prolonged effects sometimes seen after intravenous procaine administration.

Extracellular K+ in the supraoptic nucleus of the rat during reflex bursting activity by oxytocin neurones.

PubMed Central

Coles, J A; Poulain, D A

1991-01-01

1. We have investigated changes in extracellular potassium concentration [K+]o in the supraoptic nucleus of lactating rats and in particular those that occur during the intense burst of firing by the oxytocin neurones involved in the milk ejection reflex. 2. Double-barrelled K(+)-selective microelectrodes containing a highly selective sensor based on valinomycin were lowered through the exposed cortex towards the supraoptic nucleus (SON) of female rats anaesthetized with urethane. The mean resting [K+]o in the hypothalami of five rats was 2.4 mM, S.D. = 0.3 mM. 3. Where the reference barrel recorded extracellular action potentials from an oxytocin cell, the reflex burst of firing (4 s, typical maximum 50 Hz) was accompanied by a mean increase in [K+]o (delta[K+]o) of 0.22 mM (S.E.M. = 0.02 mM, fifty-seven bursts in eight cells in seven rats). The rise in [K+]o did not begin more than 0.1 s before the onset of the burst, and began to fall from its maximum during the burst. Slow field potentials, indicative of spatial buffering of K+, were undetectable (less than 50 microV). When the electrode was advanced in steps, the amplitudes of both delta[K+]o and the action potential declined steeply to about 10% over a distance of 20 microns: K+ from oxytocin cells appears to be prevented from dispersing freely through the extracellular space of the SON. 4. When the electrode recorded action potentials from a vasopressin cell, delta[K+]o during an oxytocin cell burst was very small: 0.021 mM (S.E.M. = 0.005 mM). At other sites in the SON, where antidromic stimulation evoked a field potential but no action potential, delta[K+]o was 0.047 +/- 0.005 mM. We conclude that the reason oxytocin bursts do not affect vasopressin cells is that [K+]o rises very little around vasopressin cells. A fortiori, since the increases in [K+]o were very small except where action potentials from oxytocin cells were recorded, they can make no significant contribution to synchronizing the onsets of bursts in oxytocin cells that are not contiguous. 5. A standard antidromic stimulation from the pituitary stalk, at 40 Hz for 4 s, which stimulated both oxytocin neurones and vasopressin neurones, caused a delta[K+]o of 0.17-1.8 mM, the variation being mainly from rat to rat. The larger delta[K+]o values were accompanied by slow negative potentials of up to 1.5 mV, there was a gradient in delta[K+]o decreasing towards the pia at the inferior limit of the SON, and there was a slow increase in [K+] in the subarachnoid space.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1895242

Recognition and Prevention of Nosocomial Malnutrition: A Review and A Call to Action!

PubMed

Kirkland, Lisa L; Shaughnessy, Erin

2017-12-01

Nosocomial malnutrition in hospitalized adults is a morbid, costly, and potentially preventable and treatable problem. Although recognized as contributing to many serious complications of hospitalization, malnutrition is often missed when present on admission and rarely diagnosed if it occurs during hospital stay. Many routine clinical practices such as holding nutrition for testing or failing to address poor intake, when added to acute inflammatory disease states, cause rapid deterioration in nutritional status in up to 70% of inpatients. Malnutrition during hospitalization is associated with increased mortality for years after discharge. In addition, unrecognized (and under-coded) malnutrition is associated with potential lost revenues for hospital systems. Low-cost interventions of recognizing at-risk patients and providing adequate nutrition have the potential to improve patient outcomes and reduce health care costs. Physicians must champion implementation of these interventions, using guidance from national organizations. Copyright © 2017 Elsevier Inc. All rights reserved.

Potential Anti-Atherosclerotic Properties of Astaxanthin.

PubMed

Kishimoto, Yoshimi; Yoshida, Hiroshi; Kondo, Kazuo

2016-02-05

Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed.

Potential Anti-Atherosclerotic Properties of Astaxanthin

PubMed Central

Kishimoto, Yoshimi; Yoshida, Hiroshi; Kondo, Kazuo

2016-01-01

Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed. PMID:26861359

78 FR 34031 - Burned Area Emergency Response, Forest Service

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

...) Evaluate potential threats to critical values; (2) determine the risk level for each threat; (3) identify... actions that meet the objectives; (6) evaluate potential response actions on likelihood for timely... stabilization actions. Improved the descriptive guidelines for employing response actions involving...

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

PubMed

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

1986-01-01

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

Event-Related Potentials Discriminate Familiar and Unusual Goal Outcomes in 5-Month-Olds and Adults

ERIC Educational Resources Information Center

Michel, Christine; Kaduk, Katharina; Ní Choisdealbha, Áine; Reid, Vincent M.

2017-01-01

Previous event-related potential (ERP) work has indicated that the neural processing of action sequences develops with age. Although adults and 9-month-olds use a semantic processing system, perceiving actions activates attentional processes in 7-month-olds. However, presenting a sequence of action context, action execution and action conclusion…

Actions of (-)-baclofen on rat dorsal horn neurons.

PubMed

Kangrga, I; Jiang, M C; Randić, M

1991-10-25

The actions of a gamma-aminobutyric acid B (GABAB) agonist, (-)-baclofen, on the electrophysiological properties of neurons and synaptic transmission in the spinal dorsal horn (laminae I-IV) were examined by using intracellular recordings in spinal cord slice from young rats. In addition, the effects of baclofen on the dorsal root stimulation-evoked outflow of glutamate and aspartate from the spinal dorsal horn were examined by using high performance liquid chromatography (HPLC) with flourimetric detection. Superfusion of baclofen (5 nM to 10 microM) hyperpolarized, in a stereoselective and bicuculline-insensitive manner, the majority (86%) of tested neurons. The hyperpolarization was associated with a decrease in membrane resistance and persisted in a nominally zero-Ca2+, 10 mM Mg(2+)- or a TTX-containing solution. Our findings indicate that the hyperpolarizing effect of baclofen is probably due to an increase in conductance to potassium ions. Baclofen decreased the direct excitability of dorsal horn neurons, enhanced accommodation of spike discharge, and reduced the duration of Ca(2+)-dependent action potentials. Baclofen depressed, or blocked, excitatory postsynaptic potentials evoked by electrical stimulation of the dorsal roots. Spontaneously occurring synaptic potentials were also reversibly depressed by baclofen. Whereas baclofen did not produce any consistent change in the rate of the basal outflow of glutamate and aspartate, the stimulation-evoked release of the amino acids was blocked. The present results suggest that baclofen, by activating GABAB receptors, may modulate spinal afferent processing in the superficial dorsal horn by at least two mechanisms: (1) baclofen depresses excitatory synaptic transmission primarily by a presynaptic mechanism involving a decrease in the release of excitatory amino acids, and (2) at higher concentrations, the hyperpolarization and increased membrane conductance may contribute to the depressant effect of baclofen on excitatory synaptic transmission in the rat spinal dorsal horn.

Three-Dimensional Computer Model of the Right Atrium Including the Sinoatrial and Atrioventricular Nodes Predicts Classical Nodal Behaviours

PubMed Central

Li, Jue; Inada, Shin; Schneider, Jurgen E.; Zhang, Henggui; Dobrzynski, Halina; Boyett, Mark R.

2014-01-01

The aim of the study was to develop a three-dimensional (3D) anatomically-detailed model of the rabbit right atrium containing the sinoatrial and atrioventricular nodes to study the electrophysiology of the nodes. A model was generated based on 3D images of a rabbit heart (atria and part of ventricles), obtained using high-resolution magnetic resonance imaging. Segmentation was carried out semi-manually. A 3D right atrium array model (∼3.16 million elements), including eighteen objects, was constructed. For description of cellular electrophysiology, the Rogers-modified FitzHugh-Nagumo model was further modified to allow control of the major characteristics of the action potential with relatively low computational resource requirements. Model parameters were chosen to simulate the action potentials in the sinoatrial node, atrial muscle, inferior nodal extension and penetrating bundle. The block zone was simulated as passive tissue. The sinoatrial node, crista terminalis, main branch and roof bundle were considered as anisotropic. We have simulated normal and abnormal electrophysiology of the two nodes. In accordance with experimental findings: (i) during sinus rhythm, conduction occurs down the interatrial septum and into the atrioventricular node via the fast pathway (conduction down the crista terminalis and into the atrioventricular node via the slow pathway is slower); (ii) during atrial fibrillation, the sinoatrial node is protected from overdrive by its long refractory period; and (iii) during atrial fibrillation, the atrioventricular node reduces the frequency of action potentials reaching the ventricles. The model is able to simulate ventricular echo beats. In summary, a 3D anatomical model of the right atrium containing the cardiac conduction system is able to simulate a wide range of classical nodal behaviours. PMID:25380074

Prepubertal Development of Gonadotropin-Releasing Hormone Neuron Activity Is Altered by Sex, Age, and Prenatal Androgen Exposure.

PubMed

Dulka, Eden A; Moenter, Suzanne M

2017-11-01

Gonadotropin-releasing hormone (GnRH) neurons regulate reproduction though pulsatile hormone release. Disruption of GnRH release as measured via luteinizing hormone (LH) pulses occurs in polycystic ovary syndrome (PCOS), and in young hyperandrogenemic girls. In adult prenatally androgenized (PNA) mice, which exhibit many aspects of PCOS, increased LH is associated with increased GnRH neuron action potential firing. How GnRH neuron activity develops over the prepubertal period and whether this is altered by sex or prenatal androgen treatment are unknown. We hypothesized GnRH neurons are active before puberty and that this activity is sexually differentiated and altered by PNA. Dams were injected with dihydrotestosterone (DHT) on days 16 to 18 post copulation to generate PNA mice. Action potential firing of GFP-identified GnRH neurons in brain slices from 1-, 2-, 3-, and 4-week-old and adult mice was monitored. GnRH neurons were active at all ages tested. In control females, activity increased with age through 3 weeks, then decreased to adult levels. In contrast, activity did not change in PNA females and was reduced at 3 weeks. Activity was higher in control females than males from 2 to 3 weeks. PNA did not affect GnRH neuron firing rate in males at any age. Short-term action potential patterns were also affected by age and PNA treatment. GnRH neurons are thus typically more active during the prepubertal period than adulthood, and PNA reduces prepubertal activity in females. Prepubertal activity may play a role in establishing sexually differentiated neuronal networks upstream of GnRH neurons; androgen-induced changes during this time may contribute to the adult PNA, and possibly PCOS, phenotype. Copyright © 2017 Endocrine Society.

Post-evaluation of the neurophaties treatment post-trauma with therapeutic laser. Model in sciatic nerve of frog

DOE Office of Scientific and Technical Information (OSTI.GOV)

Escobar, Antonio S.; Ocampo, Arcelia F. M.; Hernandez, Maria G. H.

2010-05-31

The purpose of this study was to evaluate the compound nerve action potential amplitude and latency measured to determine the degree of myelination and the number of fibers stimulated in a model of stimulated frog sciatic nerve laser at 810 nm as perioperative treatment after injury. It used 30 bullfrogs (Rana catesbeiana) to obtain 60 sciatic nerves forming four groups, groups 1 and 2 worked with nerves in vitro, were dissected in humid chambers for placing isolated organ, was recorded on compound nerve action potential, the second group laser was applied at 24, 48, 72, 96 and 120 hours andmore » at the same time were placed in 10% formalin. Groups 3 and 4 are worked in vivo localizing the nerve and causing damage through compression, occurred over the compound nerve action potential to assess the degree of myelination and the number of fibers stimulated, the group 4 was applied to 810 nm laser (500 Hz, 10 J, 200 mW) after injury, after 48 hours, three frogs were sacrificed by introducing the nerves in 10% formalin. The latency recorded by stimulating the sciatic nerve of frog to 0.5 mA and 100 ms in groups 1 and 2 show significant differences (p<0.001 and p<000) as in the amplitude (p<000 and p<000). Groups 3 and 4, which was stimulated at 100 mA and 100 ms latency showed no statistically significant difference (p>000), as to the extent, if any statistically significant difference. (p<0.001 and p<0.000). The laser produces a favorable response in the treatment of paresthesia (post-traumatic neuropathy).« less

Long-Term Recordings of Arcuate Nucleus Kisspeptin Neurons Reveal Patterned Activity That Is Modulated by Gonadal Steroids in Male Mice.

PubMed

Vanacker, Charlotte; Moya, Manuel Ricu; DeFazio, R Anthony; Johnson, Michael L; Moenter, Suzanne M

2017-10-01

Pulsatile release of gonadotropin-releasing hormone (GnRH) is key to fertility. Pulse frequency is modulated by gonadal steroids and likely arises subsequent to coordination of GnRH neuron firing activity. The source of rhythm generation and the site of steroid feedback remain critical unanswered questions. Arcuate neurons that synthesize kisspeptin, neurokinin B, and dynorphin (KNDy) may be involved in both of these processes. We tested the hypotheses that action potential firing in KNDy neurons is episodic and that gonadal steroids regulate this pattern. Targeted extracellular recordings were made of green fluorescent protein-identified KNDy neurons in brain slices from adult male mice that were intact, castrated, or castrated and treated with estradiol or dihydrotestosterone (DHT). KNDy neurons exhibited marked peaks and nadirs in action potential firing activity during recordings lasting 1 to 3.5 hours. Peaks, identified by Cluster analysis, occurred more frequently in castrated than intact mice, and either estradiol or DHT in vivo or blocking neurokinin type 3 receptor in vitro restored peak frequency to intact levels. The frequency of peaks in firing rate and estradiol regulation of this frequency is similar to that observed for GnRH neurons, whereas DHT suppressed firing in KNDy but not GnRH neurons. We further examined the patterning of action potentials to identify bursts that may be associated with increased neuromodulator release. Burst frequency and duration are increased in castrated compared with intact and steroid-treated mice. The observation that KNDy neurons fire in an episodic manner that is regulated by steroid feedback is consistent with a role for these neurons in GnRH pulse generation and regulation. Copyright © 2017 Endocrine Society.

Mechanisms contributing to cluster formation in the inferior olivary nucleus in brainstem slices from postnatal mice

PubMed Central

Kølvraa, Mathias; Müller, Felix C; Jahnsen, Henrik; Rekling, Jens C

2014-01-01

Abstract The inferior olivary nucleus (IO) in in vitro slices from postnatal mice (P5.5–P15.5) spontaneously generates clusters of neurons with synchronous calcium transients, and intracellular recordings from IO neurons suggest that electrical coupling between neighbouring IO neurons may serve as a synchronizing mechanism. Here, we studied the cluster-forming mechanism and find that clusters overlap extensively with an overlap distribution that resembles the distribution for a random overlap model. The average somatodendritic field size of single curly IO neurons was ∼6400 μm2, which is slightly smaller than the average IO cluster size. Eighty-seven neurons with overlapping dendrites were estimated to be contained in the principal olive mean cluster size, and about six non-overlapping curly IO neurons could be contained within the largest clusters. Clusters could also be induced by iontophoresis with glutamate. Induced clusters were inhibited by tetrodotoxin, carbenoxelone and 18β-glycyrrhetinic acid, suggesting that sodium action potentials and electrical coupling are involved in glutamate-induced cluster formation, which could also be induced by activation of N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Spikelets and a small transient depolarizing response were observed during glutamate-induced cluster formation. Calcium transients spread with decreasing velocity during cluster formation, and somatic action potentials and cluster formation are accompanied by large dendritic calcium transients. In conclusion, cluster formation depends on gap junctions, sodium action potentials and spontaneous clusters occur randomly throughout the IO. The relative slow signal spread during cluster formation, combined with a strong dendritic influx of calcium, may signify that active dendritic properties contribute to cluster formation. PMID:24042500

Post-evaluation of the neurophaties treatment post-trauma with therapeutic laser. Model in sciatic nerve of frog

NASA Astrophysics Data System (ADS)

Escobar, Antonio S.; Ocampo, Arcelia F. M.; Hernández, María G. H.; Jasso, José L. C.; Lira, Maricela O. F.; Flores, Mariana A.; Balderrama, Vicente L.

2010-05-01

The purpose of this study was to evaluate the compound nerve action potential amplitude and latency measured to determine the degree of myelination and the number of fibers stimulated in a model of stimulated frog sciatic nerve laser at 810 nm as perioperative treatment after injury. It used 30 bullfrogs (Rana catesbeiana) to obtain 60 sciatic nerves forming four groups, groups 1 and 2 worked with nerves in vitro, were dissected in humid chambers for placing isolated organ, was recorded on compound nerve action potential, the second group laser was applied at 24, 48, 72, 96 and 120 hours and at the same time were placed in 10% formalin. Groups 3 and 4 are worked in vivo localizing the nerve and causing damage through compression, occurred over the compound nerve action potential to assess the degree of myelination and the number of fibers stimulated, the group 4 was applied to 810 nm laser (500 Hz, 10 J, 200 mW) after injury, after 48 hours, three frogs were sacrificed by introducing the nerves in 10% formalin. The latency recorded by stimulating the sciatic nerve of frog to 0.5 mA and 100 ms in groups 1 and 2 show significant differences (p<0.001 and p<000) as in the amplitude (p<000 and p<000). Groups 3 and 4, which was stimulated at 100 mA and 100 ms latency showed no statistically significant difference (p>000), as to the extent, if any statistically significant difference. (p<0.001 and p<0.000). The laser produces a favorable response in the treatment of paresthesia (post-traumatic neuropathy).

Nitric oxide donors attenuate clongenic potential in rat C6 glioma cells treated with alkylating chemotherapeutic agents.

PubMed

Yang, Jir-Jei; Yin, Jiu-Haw; Yang, Ding-I

2007-05-11

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) kills tumor cells via multiple actions including alkylation and carbamoylation. Previously, we have reported that formation of S-nitrosoglutathione (GSNO) in glioma cells overexpressing inducible nitric oxide synthase (iNOS) contributed to nitric oxide (NO)-dependent carbamoylating chemoresistance against BCNU. To further characterize the effects of NO on alkylating cytotoxicity, colony formation assay was applied to evaluate the effects of various NO donors on rat C6 glioma cells challenged with alkylating agents. We demonstrate that NO donors including GSNO, diethylamine NONOate (DEA/NO), and sodium nitroprusside (SNP) substantially reduced the extent of colony formation in glioma cells treated with alkylating agents, namely methyl methanesulfonate (MMS), N-methyl-N-nitrosourea (MNU), and N-ethyl-N-nitrosourea (ENU). Without alkylating agents these NO-releasing agents alone had no effects on clongenic potential of rat C6 glioma cells. Among these three NO donors used, the effectiveness in potentiating alkylating cytotoxicity is in the order of "GSNO>DEA/NO>SNP" when applied at the same dosages. GSNO also exerted similar synergistic actions reducing the extents of colony formation when co-administrated with 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-hydrazine (compound #1), another alkylating agent that mimics the chloroethylating action of BCNU. Together with our previous findings, we propose that NO donors may be used as adjunct chemotherapy with alkylating agents for such malignant brain tumors as glioblastoma multiforme (GBM). In contrast, production of NO as a result of iNOS induction, such as that occurring after surgical resection of brain tumors, may compromise the efficacy of carbamoylating chemotherapy.

Weaker control of the electrical properties of cerebellar granule cells by tonically active GABAA receptors in the Ts65Dn mouse model of Down’s syndrome

PubMed Central

2013-01-01

Background Down’s syndrome (DS) is caused by triplication of all or part of human chromosome 21 and is characterized by a decrease in the overall size of the brain. One of the brain regions most affected is the cerebellum, in which the number of granule cells (GCs) is markedly decreased. GCs process sensory information entering the cerebellum via mossy fibres and pass it on to Purkinje cells and inhibitory interneurons. How GCs transform incoming signals depends on their input–output relationship, which is adjusted by tonically active GABAA receptor channels. Results We report that in the Ts65Dn mouse model of DS, in which cerebellar volume and GC number are decreased as in DS, the tonic GABAA receptor current in GCs is smaller than in wild-type mice and is less effective in moderating input resistance and raising the minimum current required for action potential firing. We also find that tonically active GABAA receptors curb the height and broaden the width of action potentials in wild-type GCs but not in Ts65Dn GCs. Single-cell real-time quantitative PCR reveals that these electrical differences are accompanied by decreased expression of the gene encoding the GABAA receptor β3 subunit but not genes coding for some of the other GABAA receptor subunits expressed in GCs (α1, α6, β2 and δ). Conclusions Weaker moderation of excitability and action potential waveform in GCs of the Ts65Dn mouse by tonically active GABAA receptors is likely to contribute to atypical transfer of information through the cerebellum. Similar changes may occur in DS. PMID:23870245

Mechanisms and distribution of ion channels in retinal ganglion cells: using temperature as an independent variable.

PubMed

Fohlmeister, Jürgen F; Cohen, Ethan D; Newman, Eric A

2010-03-01

Trains of action potentials of rat and cat retinal ganglion cells (RGCs) were recorded intracellularly across a temperature range of 7-37 degrees C. Phase plots of the experimental impulse trains were precision fit using multicompartment simulations of anatomically reconstructed rat and cat RGCs. Action potential excitation was simulated with a "Five-channel model" [Na, K(delayed rectifier), Ca, K(A), and K(Ca-activated) channels] and the nonspace-clamped condition of the whole cell recording was exploited to determine the channels' distribution on the dendrites, soma, and proximal axon. At each temperature, optimal phase-plot fits for RGCs occurred with the same unique channel distribution. The "waveform" of the electrotonic current was found to be temperature dependent, which reflected the shape changes in the experimental action potentials and confirmed the channel distributions. The distributions are cell-type specific and adequate for soma and dendritic excitation with a safety margin. The highest Na-channel density was found on an axonal segment some 50-130 microm distal to the soma, as determined from the temperature-dependent "initial segment-somadendritic (IS-SD) break." The voltage dependence of the gating rate constants remains invariant between 7 and 23 degrees C and between 30 and 37 degrees C, but undergoes a transition between 23 and 30 degrees C. Both gating-kinetic and ion-permeability Q10s remain virtually constant between 23 and 37 degrees C (kinetic Q10s = 1.9-1.95; permeability Q10s = 1.49-1.64). The Q10s systematically increase for T <23 degrees C (kinetic Q10 = 8 at T = 8 degrees C). The Na channels were consistently "sleepy" (non-Arrhenius) for T <8 degrees C, with a loss of spiking for T <7 degrees C.

Bimodal Action of Protons on ATP Currents of Rat PC12 Cells

PubMed Central

Skorinkin, Andrei; Nistri, Andrea; Giniatullin, Rashid

2003-01-01

The mode of action of extracellular protons on ATP-gated P2X2 receptors remains controversial as either enhancement or depression of ATP-mediated currents has been reported. By investigating, at different pH, the electrophysiological effect of ATP on P2X2 receptors and complementing it with receptor modelling, the present study suggests a unified mechanism for both potentiation and inactivation of ATP receptors by protons. Our experiments on patch-clamped PC12 cells showed that, on the same cell, mild acidification potentiated currents induced by low ATP concentrations (<0.1 mM) and attenuated responses to high ATP concentrations (>1 mM) with emergence of current fading and rebound. To clarify the nature of the ATP/H+ interaction, we used the Ding and Sachs's “loop” receptor model which best describes the behavior of such receptors with two open states linked via one inactivated state. No effects by protons could be ascribed to H+-mediated open channel block. However, by assuming that protons facilitated binding of ATP to resting as well as open receptors, the model could closely replicate H+-induced potentiation of currents evoked by low ATP doses plus fading and rebound induced by high ATP doses. The latter phenomenon was due to receptor transition to the inactive state. The present data suggest that the high concentration of protons released with ATP (and catecholamines) from secretory vesicles may allow a dual action of H+ on P2X2 receptors. This condition might also occur on P2X2 receptors of central neurons exposed to low pH during ischemia. PMID:12810852

Invariance and variability in interaction error-related potentials and their consequences for classification

NASA Astrophysics Data System (ADS)

Abu-Alqumsan, Mohammad; Kapeller, Christoph; Hintermüller, Christoph; Guger, Christoph; Peer, Angelika

2017-12-01

Objective. This paper discusses the invariance and variability in interaction error-related potentials (ErrPs), where a special focus is laid upon the factors of (1) the human mental processing required to assess interface actions (2) time (3) subjects. Approach. Three different experiments were designed as to vary primarily with respect to the mental processes that are necessary to assess whether an interface error has occurred or not. The three experiments were carried out with 11 subjects in a repeated-measures experimental design. To study the effect of time, a subset of the recruited subjects additionally performed the same experiments on different days. Main results. The ErrP variability across the different experiments for the same subjects was found largely attributable to the different mental processing required to assess interface actions. Nonetheless, we found that interaction ErrPs are empirically invariant over time (for the same subject and same interface) and to a lesser extent across subjects (for the same interface). Significance. The obtained results may be used to explain across-study variability of ErrPs, as well as to define guidelines for approaches to the ErrP classifier transferability problem.

The use of failure mode and effect analysis in a radiation oncology setting: the Cancer Treatment Centers of America experience.

PubMed

Denny, Diane S; Allen, Debra K; Worthington, Nicole; Gupta, Digant

2014-01-01

Delivering radiation therapy in an oncology setting is a high-risk process where system failures are more likely to occur because of increasing utilization, complexity, and sophistication of the equipment and related processes. Healthcare failure mode and effect analysis (FMEA) is a method used to proactively detect risks to the patient in a particular healthcare process and correct potential errors before adverse events occur. FMEA is a systematic, multidisciplinary team-based approach to error prevention and enhancing patient safety. We describe our experience of using FMEA as a prospective risk-management technique in radiation oncology at a national network of oncology hospitals in the United States, capitalizing not only on the use of a team-based tool but also creating momentum across a network of collaborative facilities seeking to learn from and share best practices with each other. The major steps of our analysis across 4 sites and collectively were: choosing the process and subprocesses to be studied, assembling a multidisciplinary team at each site responsible for conducting the hazard analysis, and developing and implementing actions related to our findings. We identified 5 areas of performance improvement for which risk-reducing actions were successfully implemented across our enterprise. © 2012 National Association for Healthcare Quality.

A study of antioxidant potential of Perilladehyde

NASA Astrophysics Data System (ADS)

Malu, T. J.; Banerjee, Nitesh; Singh, Avinash Kumar; Kannadasan, S.; Ethiraj, K. R.

2017-11-01

The use of plants as food, medicine is credited to a biological property of their secondary metabolites. These naturally occurring secondary metabolites are found to have great importance in controlling the formation of free radicles. These antioxidants are capable to catch the free radicles present in the body and maintain its balance. Antioxidant activity and potency of Perillaldehyde using various in vitro biochemical assays were studied. The assay involves various levels of antioxidant action such as free radical scavenging activity through DPPH, reducing power determination, nitric oxide scavenging ability, metal chelation power, scavenging of hydrogen peroxide, membrane stabilizing activity, and lipid peroxidation study.

Review of sports-related concussion: Potential for application in military settings.

PubMed

Lew, Henry L; Thomander, Darryl; Chew, Kelvin T L; Bleiberg, Joseph

2007-01-01

This article reviews current issues and practices in the assessment and clinical management of sports-related concussion. An estimated 300,000 sports-related concussions occur annually in the United States. Much of what has been learned about concussion in the sports arena can be applied to the diagnosis and management of concussion in military settings. Current military guidelines for assessing and managing concussion in war zones incorporate information and methods developed through sports-concussion research. We discuss the incidence, definition, and diagnosis of concussion; concussion grading scales; sideline evaluation tools; neuropsychological assessment; return-to-action criteria; and complications of concussion.

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

ERIC Educational Resources Information Center

Rodriguez-Falces, Javier

2015-01-01

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

Detachable glass microelectrodes for recording action potentials in active moving organs.

PubMed

Barbic, Mladen; Moreno, Angel; Harris, Tim D; Kay, Matthew W

2017-06-01

Here, we describe new detachable floating glass micropipette electrode devices that provide targeted action potential recordings in active moving organs without requiring constant mechanical constraint or pharmacological inhibition of tissue motion. The technology is based on the concept of a glass micropipette electrode that is held firmly during cell targeting and intracellular insertion, after which a 100-µg glass microelectrode, a "microdevice," is gently released to remain within the moving organ. The microdevices provide long-term recordings of action potentials, even during millimeter-scale movement of tissue in which the device is embedded. We demonstrate two different glass micropipette electrode holding and detachment designs appropriate for the heart (sharp glass microdevices for cardiac myocytes in rats, guinea pigs, and humans) and the brain (patch glass microdevices for neurons in rats). We explain how microdevices enable measurements of multiple cells within a moving organ that are typically difficult with other technologies. Using sharp microdevices, action potential duration was monitored continuously for 15 min in unconstrained perfused hearts during global ischemia-reperfusion, providing beat-to-beat measurements of changes in action potential duration. Action potentials from neurons in the hippocampus of anesthetized rats were measured with patch microdevices, which provided stable base potentials during long-term recordings. Our results demonstrate that detachable microdevices are an elegant and robust tool to record electrical activity with high temporal resolution and cellular level localization without disturbing the physiological working conditions of the organ. NEW & NOTEWORTHY Cellular action potential measurements within tissue using glass micropipette electrodes usually require tissue immobilization, potentially influencing the physiological relevance of the measurement. Here, we addressed this limitation with novel 100-µg detachable glass microelectrodes that can be precisely positioned to provide long-term measurements of action potential duration during unconstrained tissue movement. Copyright © 2017 the American Physiological Society.

Implications of Incessant Strike Actions on the Implementation of Technical Education Programme in Nigeria

ERIC Educational Resources Information Center

Adavbiele, J. A.

2015-01-01

This paper was designed to x-ray the implications of incessant strike actions on the implementation of Technical education programme in Nigeria. The paper took an exploratory view on the concept of strike actions in Nigeria with particular references on notable strike actions that have occurred in Nigeria. The types of strike were explained and…

Corrective Action Investigation Plan for Corrective Action Unit 410: Waste Disposal Trenches, Tonopah Test Range, Nevada, Revision 0 (includes ROTCs 1, 2, and 3)

DOE Office of Scientific and Technical Information (OSTI.GOV)

NNSA /NV

This Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 410 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 410 is located on the Tonopah Test Range (TTR), which is included in the Nevada Test and Training Range (formerly the Nellis Air Force Range) approximately 140 miles northwest of Las Vegas, Nevada. This CAU is comprised of five Corrective Action Sites (CASs): TA-19-002-TAB2, Debris Mound; TA-21-003-TANL, Disposal Trench; TA-21-002-TAAL,more » Disposal Trench; 09-21-001-TA09, Disposal Trenches; 03-19-001, Waste Disposal Site. This CAU is being investigated because contaminants may be present in concentrations that could potentially pose a threat to human health and/or the environment, and waste may have been disposed of with out appropriate controls. Four out of five of these CASs are the result of weapons testing and disposal activities at the TTR, and they are grouped together for site closure based on the similarity of the sites (waste disposal sites and trenches). The fifth CAS, CAS 03-19-001, is a hydrocarbon spill related to activities in the area. This site is grouped with this CAU because of the location (TTR). Based on historical documentation and process know-ledge, vertical and lateral migration routes are possible for all CASs. Migration of contaminants may have occurred through transport by infiltration of precipitation through surface soil which serves as a driving force for downward migration of contaminants. Land-use scenarios limit future use of these CASs to industrial activities. The suspected contaminants of potential concern which have been identified are volatile organic compounds; semivolatile organic compounds; high explosives; radiological constituents including depleted uranium, beryllium, total petroleum hydrocarbons; and total Resource Conservation and Recovery Act metals. Field activities will consist of geophysical and radiological surveys, and collecting soil samples at biased locations by appropriate methods. A two-step data quality objective strategy will be followed: (1) define the nature of contamination at each CAS location by identifying any contamination above preliminary action levels (PALs); and, (2) determine the extent of contamination identified above PALs. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document.« less

Linking express saccade occurance to stimulus properties and sensorimotor integration in the superior colliculus.

PubMed

Marino, Robert A; Levy, Ron; Munoz, Douglas P

2015-08-01

Express saccades represent the fastest possible eye movements to visual targets with reaction times that approach minimum sensory-motor conduction delays. Previous work in monkeys has identified two specific neural signals in the superior colliculus (SC: a midbrain sensorimotor integration structure involved in gaze control) that are required to execute express saccades: 1) previsual activity consisting of a low-frequency increase in action potentials in sensory-motor neurons immediately before the arrival of a visual response; and 2) a transient visual-sensory response consisting of a high-frequency burst of action potentials in visually responsive neurons resulting from the appearance of a visual target stimulus. To better understand how these two neural signals interact to produce express saccades, we manipulated the arrival time and magnitude of visual responses in the SC by altering target luminance and we examined the corresponding influences on SC activity and express saccade generation. We recorded from saccade neurons with visual-, motor-, and previsual-related activity in the SC of monkeys performing the gap saccade task while target luminance was systematically varied between 0.001 and 42.5 cd/m(2) against a black background (∼0.0001 cd/m(2)). Our results demonstrated that 1) express saccade latencies were linked directly to the arrival time in the SC of visual responses produced by abruptly appearing visual stimuli; 2) express saccades were generated toward both dim and bright targets whenever sufficient previsual activity was present; and 3) target luminance altered the likelihood of producing an express saccade. When an express saccade was generated, visuomotor neurons increased their activity immediately before the arrival of the visual response in the SC and saccade initiation. Furthermore, the visual and motor responses of visuomotor neurons merged into a single burst of action potentials, while the visual response of visual-only neurons was unaffected. A linear combination model was used to test which SC signals best predicted the likelihood of producing an express saccade. In addition to visual response magnitude and previsual activity of saccade neurons, the model identified presaccadic activity (activity occurring during the 30-ms epoch immediately before saccade initiation) as a third important signal for predicting express saccades. We conclude that express saccades can be predicted by visual, previsual, and presaccadic signals recorded from visuomotor neurons in the intermediate layers of the SC. Copyright © 2015 the American Physiological Society.

Linking express saccade occurance to stimulus properties and sensorimotor integration in the superior colliculus

PubMed Central

Levy, Ron; Munoz, Douglas P.

2015-01-01

Express saccades represent the fastest possible eye movements to visual targets with reaction times that approach minimum sensory-motor conduction delays. Previous work in monkeys has identified two specific neural signals in the superior colliculus (SC: a midbrain sensorimotor integration structure involved in gaze control) that are required to execute express saccades: 1) previsual activity consisting of a low-frequency increase in action potentials in sensory-motor neurons immediately before the arrival of a visual response; and 2) a transient visual-sensory response consisting of a high-frequency burst of action potentials in visually responsive neurons resulting from the appearance of a visual target stimulus. To better understand how these two neural signals interact to produce express saccades, we manipulated the arrival time and magnitude of visual responses in the SC by altering target luminance and we examined the corresponding influences on SC activity and express saccade generation. We recorded from saccade neurons with visual-, motor-, and previsual-related activity in the SC of monkeys performing the gap saccade task while target luminance was systematically varied between 0.001 and 42.5 cd/m2 against a black background (∼0.0001 cd/m2). Our results demonstrated that 1) express saccade latencies were linked directly to the arrival time in the SC of visual responses produced by abruptly appearing visual stimuli; 2) express saccades were generated toward both dim and bright targets whenever sufficient previsual activity was present; and 3) target luminance altered the likelihood of producing an express saccade. When an express saccade was generated, visuomotor neurons increased their activity immediately before the arrival of the visual response in the SC and saccade initiation. Furthermore, the visual and motor responses of visuomotor neurons merged into a single burst of action potentials, while the visual response of visual-only neurons was unaffected. A linear combination model was used to test which SC signals best predicted the likelihood of producing an express saccade. In addition to visual response magnitude and previsual activity of saccade neurons, the model identified presaccadic activity (activity occurring during the 30-ms epoch immediately before saccade initiation) as a third important signal for predicting express saccades. We conclude that express saccades can be predicted by visual, previsual, and presaccadic signals recorded from visuomotor neurons in the intermediate layers of the SC. PMID:26063770

Biological assessment of the effects of construction and operation of adepleted uranium hexafluoride conversion facility at the Portsmouth, Ohio,site.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Lonkhuyzen, R.

The U.S. Department of Energy (DOE) Depleted Uranium Hexafluoride (DUF{sub 6}) Management Program evaluated alternatives for managing its inventory of DUF{sub 6} and issued the ''Programmatic Environmental Impact Statement for Alternative Strategies for the Long-Term Management and Use of Depleted Uranium Hexafluoride'' (DUF{sub 6} PEIS) in April 1999 (DOE 1999). The DUF{sub 6} inventory is stored in cylinders at three DOE sites: Paducah, Kentucky; Portsmouth, Ohio; and East Tennessee Technology Park (ETTP), near Oak Ridge, Tennessee. In the Record of Decision for the DUF{sub 6} PEIS, DOE stated its decision to promptly convert the DUF{sub 6} inventory to a moremore » stable chemical form. Subsequently, the U.S. Congress passed, and the President signed, the ''2002 Supplemental Appropriations Act for Further Recovery from and Response to Terrorist Attacks on the United States'' (Public Law No. 107-206). This law stipulated in part that, within 30 days of enactment, DOE must award a contract for the design, construction, and operation of a DUF{sub 6} conversion plant at the Department's Paducah, Kentucky, and Portsmouth, Ohio, sites, and for the shipment of DUF{sub 6} cylinders stored at ETTP to the Portsmouth site for conversion. This biological assessment (BA) has been prepared by DOE, pursuant to the National Environmental Policy Act of 1969 and the Endangered Species Act of 1974, to evaluate potential impacts to federally listed species from the construction and operation of a conversion facility at the DOE Portsmouth site. The Indiana bat is known to occur in the area of the Portsmouth site and may potentially occur on the site during spring or summer. Evaluations of the Portsmouth site indicated that most of the site was found to have poor summer habitat for the Indiana bat because of the small size, isolation, and insufficient maturity of the few woodlands on the site. Potential summer habitat for the Indiana bat was identified outside the developed area bounded by Perimeter Road, within the corridors along Little Beaver Creek, the Northwest Tributary stream, and a wooded area east of the X-100 facility. However, no Indiana bats were collected during surveys of these areas in 1994 and 1996. Locations A, B, and C do not support suitable habitat for the Indiana bat and would be unlikely to be used by Indiana bats. Indiana bat habitat also does not occur at Proposed Areas 1 and 2. Although Locations A and C contain small wooded areas, the small size and lack of suitable maturity of these areas indicate that they would provide poor habitat for Indiana bats. Trees that may be removed during construction would not be expected to be used for summer roosting by Indiana bats. Disturbance of Indiana bats potentially roosting or foraging in the vicinity of the facility during operations would be very unlikely, and any disturbance would be expected to be negligible. On the basis of these considerations, DOE concludes that the proposed action is not likely to adversely affect the Indiana bat. No critical habitat exists for this species in the action area. Although the timber rattlesnake occurs in the vicinity of the Portsmouth site, it has not been observed on the site. In addition, habitat for the timber rattlesnake is not present on the Portsmouth site. Therefore, DOE concludes that the proposed action would not affect the timber rattlesnake.« less

Quadratic adaptive algorithm for solving cardiac action potential models.

PubMed

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

2016-10-01

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

Biological indicators in response to radiofrequency/microwave exposure.

PubMed

Marjanović, Ana Marija; Pavičić, Ivan; Trošić, Ivančica

2012-09-01

Over the years, due to rapid technological progress, radiation from man-made sources exceeded that of natural origin. There is a general concern regarding a growing number of appliances that use radiofrequency/ microwave (RF/MW) radiation with particular emphasis on mobile communication systems. Since nonthermal biological effects and mechanisms of RF/MW radiation are still uncertain, laboratory studies on animal models, tissues, cells, and cell free system are of extraordinary importance in bioelectromagnetic research. We believe that such investigations play a supporting role in public risk assessment. Cellular systems with the potential for a clear response to RF/MW exposures should be used in those studies. It is known that organism is a complex electrochemical system where processes of oxidation and reduction regularly occur. One of the plausible mechanisms is connected with generation of reactive oxygen species (ROS). Depending on concentration, ROS can have both beneficial and deleterious effects. Positive effects are connected with cell signalling, defence against infectious agents, and proliferative cell ability. On the other hand, excessive production, which overloads antioxidant defence mechanism, leads to cellular damage with serious potential for disease development. ROS concentration increase within the cell caused by RF/MW radiation seems to be a biologically relevant hypothesis to give clear insight into the RF/MW action at non-thermal level of radiation. In order to better understand the exact mechanism of action and its consequences, further research is needed in the field. We would like to present current knowledge on possible biological mechanisms of RF/MW actions.

Group II Metabotropic Glutamate Receptor Agonist Ameliorates MK801-Induced Dysfunction of NMDA Receptors via the Akt/GSK-3β Pathway in Adult Rat Prefrontal Cortex

PubMed Central

Xi, Dong; Li, Yan-Chun; Snyder, Melissa A; Gao, Ruby Y; Adelman, Alicia E; Zhang, Wentong; Shumsky, Jed S; Gao, Wen-Jun

2011-01-01

Pharmacological intervention targeting mGluRs has emerged as a potential treatment for schizophrenia, whereas the mechanisms involved remain elusive. We explored the antipsychotic effects of an mGluR2/3 agonist in the MK-801 model of schizophrenia in the rat prefrontal cortex. We found that the mGluR2/3 agonist LY379268 effectively recovered the disrupted expression of NMDA receptors induced by MK-801 administration. This effect was attributable to the direct regulatory action of LY379268 on NMDA receptors via activation of the Akt/GSK-3β signaling pathway. As occurs with the antipsychotic drug clozapine, acute treatment with LY379268 significantly increased the expression and phosphorylation of NMDA receptors, as well as Akt and GSK-3β. Physiologically, LY379268 significantly enhanced NMDA-induced current in prefrontal neurons and a GSK-3β inhibitor occluded this effect. In contrast to the widely proposed mechanism of modulating presynaptic glutamate release, our results strongly argue that mGluR2/3 agonists modulate the function of NMDA receptors through postsynaptic actions and reverse the MK-801-induced NMDA dysfunction via the Akt/GSK-3β pathway. This study provides novel evidence for postsynaptic mechanisms of mGluR2/3 in regulation of NMDA receptors and presents useful insights into the mechanistic actions of mGluR2/3 agonists as potential antipsychotic agents for treating schizophrenia. PMID:21326193

Endocrine-Disrupting Chemicals and Public Health Protection: A Statement of Principles from The Endocrine Society

PubMed Central

Brown, T. R.; Doan, L. L.; Gore, A. C.; Skakkebaek, N. E.; Soto, A. M.; Woodruff, T. J.; Vom Saal, F. S.

2012-01-01

An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action. The potential for deleterious effects of EDC must be considered relative to the regulation of hormone synthesis, secretion, and actions and the variability in regulation of these events across the life cycle. The developmental age at which EDC exposures occur is a critical consideration in understanding their effects. Because endocrine systems exhibit tissue-, cell-, and receptor-specific actions during the life cycle, EDC can produce complex, mosaic effects. This complexity causes difficulty when a static approach to toxicity through endocrine mechanisms driven by rigid guidelines is used to identify EDC and manage risk to human and wildlife populations. We propose that principles taken from fundamental endocrinology be employed to identify EDC and manage their risk to exposed populations. We emphasize the importance of developmental stage and, in particular, the realization that exposure to a presumptive “safe” dose of chemical may impact a life stage when there is normally no endogenous hormone exposure, thereby underscoring the potential for very low-dose EDC exposures to have potent and irreversible effects. Finally, with regard to the current program designed to detect putative EDC, namely, the Endocrine Disruptor Screening Program, we offer recommendations for strengthening this program through the incorporation of basic endocrine principles to promote further understanding of complex EDC effects, especially due to developmental exposures. PMID:22733974

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

PubMed

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

2013-03-01

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

Critical Action as a Pathway to Social Mobility among Marginalized Youth

ERIC Educational Resources Information Center

Rapa, Luke J.; Diemer, Matthew A.; Bañales, Josefina

2018-01-01

Marginalized youth's development occurs in contexts rife with racialized, gendered, and socioeconomic social identity threats and barriers to social mobility. An emergent line of inquiry suggests critical action--a component of critical consciousness, defined as engaging in individual or collective social action to produce social change--may…

Action Research Empowers School Librarians

ERIC Educational Resources Information Center

Robins, Jennifer

2015-01-01

Successful school library programs occur through careful planning and reflection. This reflective process is improved when it is applied in a systematic way through action research. The action research described in this paper enabled school librarians to reflect based on evidence, using data they had collected. This study presents examples of the…

Alaska State Legislature

Science.gov Websites

Teleconferencing Handouts Directory of State Officials ($3 plus s&h) Bill Action & Status Inquiry System - (BASIS) Each of the LIOs has computer access to information on floor and committee action as it occurs via BASIS (Bill Action Status Inquiry System). For each bill introduced, a file is created in BASIS

32 CFR 735.3 - Action.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 5 2011-07-01 2011-07-01 false Action. 735.3 Section 735.3 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL REPORTING BIRTHS AND DEATHS IN COOPERATION WITH OTHER AGENCIES § 735.3 Action. When a medical officer has knowledge of a birth or death occurring...

32 CFR 735.3 - Action.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Action. 735.3 Section 735.3 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL REPORTING BIRTHS AND DEATHS IN COOPERATION WITH OTHER AGENCIES § 735.3 Action. When a medical officer has knowledge of a birth or death occurring...

Decoding of intentional actions from scalp electroencephalography (EEG) in freely-behaving infants.

PubMed

Hernandez, Zachery R; Cruz-Garza, Jesus; Tse, Teresa; Contreras-Vidal, Jose L

2014-01-01

The mirror neuron system (MNS) in humans is thought to enable an individual's understanding of the meaning of actions performed by others and the potential imitation and learning of those actions. In humans, electroencephalographic (EEG) changes in sensorimotor a-band at central electrodes, which desynchronizes both during execution and observation of goal-directed actions (i.e., μ suppression), have been considered an analog to MNS function. However, methodological and developmental issues, as well as the nature of generalized μ suppression to imagined, observed, and performed actions, have yet to provide a mechanistic relationship between EEG μ-rhythm and MNS function, and the extent to which EEG can be used to infer intent during MNS tasks remains unknown. In this study we present a novel methodology using active EEG and inertial sensors to record brain activity and behavioral actions from freely-behaving infants during exploration, imitation, attentive rest, pointing, reaching and grasping, and interaction with an actor. We used 5-band (1-4Hz) EEG as input to a dimensionality reduction algorithm (locality-preserving Fisher's discriminant analysis, LFDA) followed by a neural classifier (Gaussian mixture models, GMMs) to decode the each MNS task performed by freely-behaving 6-24 month old infants during interaction with an adult actor. Here, we present results from a 20-month male infant to illustrate our approach and show the feasibility of EEG-based classification of freely occurring MNS behaviors displayed by an infant. These results, which provide an alternative to the μ-rhythm theory of MNS function, indicate the informative nature of EEG in relation to intentionality (goal) for MNS tasks which may support action-understanding and thus bear implications for advancing the understanding of MNS function.

Convergent mechanisms underlying rapid antidepressant action

PubMed Central

Zanos, Panos; Thompson, Scott M.; Duman, Ronald S.; Zarate, Carlos A.; Gould, Todd D.

2018-01-01

Traditional pharmacological treatments for depression have a delayed therapeutic onset, ranging from several weeks to months, and there is a high percentage of individuals who never respond to treatment. In contrast, ketamine produces rapid-onset antidepressant, anti-suicidal and anti-anhedonic actions following a single administration to depressed patients. Proposed mechanisms of ketamine’s antidepressant action include N-methyl-D-aspartate receptor (NMDAR) modulation, GABAergic interneuron disinhibition, and direct actions of its hydroxynorketamine (HNK) metabolites. Downstream actions include activation of mechanistic target of rapamycin (mTOR), deactivation of glycogen synthase kinase-3 and eukaryotic elongation factor 2 (eEF2), enhanced brain-derived neurotrophic factor (BDNF) signaling, and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs). These putative mechanisms of ketamine action are not mutually exclusive and may complement each other to induce potentiation of excitatory synapses in affective-regulating brain circuits, which results in amelioration of depression symptoms. We review these proposed mechanisms of ketamine action in the context of how such mechanisms are informing the development of novel putative rapid-acting antidepressant drugs. Such drugs that have undergoing pre-clinical, and in some cases clinical, testing include the muscarinic acetylcholine receptor antagonist scopolamine, GluN2B-NMDAR antagonists (i.e., CP-101,606, MK-0657), (2R,6R)-HNK, NMDAR glycine site modulators (i.e., 4-chlorokynurenine - pro-drug of the glycineB NMDAR antagonist 7-chlorokynurenic acid), NMDAR agonists (i.e. GLYX-13 (rapastinel)), metabotropic glutamate receptor 2/3 (mGluR2/3) antagonists, GABAA receptor modulators, and drugs acting on various serotonin receptor subtypes. These ongoing studies suggest that the future acute treatment of depression will typically occur within hours, rather than months, of treatment initiation. PMID:29516301

TRPM4 non-selective cation channels influence action potentials in rabbit Purkinje fibres.

PubMed

Hof, Thomas; Sallé, Laurent; Coulbault, Laurent; Richer, Romain; Alexandre, Joachim; Rouet, René; Manrique, Alain; Guinamard, Romain

2016-01-15

The transient receptor potential melastatin 4 (TRPM4) inhibitor 9-phenanthrol reduces action potential duration in rabbit Purkinje fibres but not in ventricle. TRPM4-like single channel activity is observed in isolated rabbit Purkinje cells but not in ventricular cells. The TRPM4-like current develops during the notch and early repolarization phases of the action potential in Purkinje cells. Transient receptor potential melastatin 4 (TRPM4) Ca(2+)-activated non-selective cation channel activity has been recorded in cardiomyocytes and sinus node cells from mammals. In addition, TRPM4 gene mutations are associated with human diseases of cardiac conduction, suggesting that TRPM4 plays a role in this aspect of cardiac function. Here we evaluate the TRPM4 contribution to cardiac electrophysiology of Purkinje fibres. Ventricular strips with Purkinje fibres were isolated from rabbit hearts. Intracellular microelectrodes recorded Purkinje fibre activity and the TRPM4 inhibitor 9-phenanthrol was applied to unmask potential TRPM4 contributions to the action potential. 9-Phenanthrol reduced action potential duration measured at the point of 50 and 90% repolarization with an EC50 of 32.8 and 36.1×10(-6) mol l(-1), respectively, but did not modulate ventricular action potentials. Inside-out patch-clamp recordings were used to monitor TRPM4 activity in isolated Purkinje cells. TRPM4-like single channel activity (conductance = 23.8 pS; equal permeability for Na(+) and K(+); sensitivity to voltage, Ca(2+) and 9-phenanthrol) was observed in 43% of patches from Purkinje cells but not from ventricular cells (0/16). Action potential clamp experiments performed in the whole-cell configuration revealed a transient inward 9-phenanthrol-sensitive current (peak density = -0.65 ± 0.15 pA pF(-1); n = 5) during the plateau phases of the Purkinje fibre action potential. These results show that TRPM4 influences action potential characteristics in rabbit Purkinje fibres and thus could modulate cardiac conduction and be involved in triggering arrhythmias. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

14 CFR 1216.306 - Actions normally requiring an EIS.

Code of Federal Regulations, 2013 CFR

2013-01-01

... normally requiring an EIS. (a) NASA will prepare an EIS for actions with the potential to significantly... action or mitigation of its potentially significant impacts. (b) Typical NASA actions normally requiring... material greater than the quantity for which the NASA Nuclear Flight Safety Assurance Manager may grant...

EEG error potentials detection and classification using time-frequency features for robot reinforcement learning.

PubMed

Boubchir, Larbi; Touati, Youcef; Daachi, Boubaker; Chérif, Arab Ali

2015-08-01

In thought-based steering of robots, error potentials (ErrP) can appear when the action resulting from the brain-machine interface (BMI) classifier/controller does not correspond to the user's thought. Using the Steady State Visual Evoked Potentials (SSVEP) techniques, ErrP, which appear when a classification error occurs, are not easily recognizable by only examining the temporal or frequency characteristics of EEG signals. A supplementary classification process is therefore needed to identify them in order to stop the course of the action and back up to a recovery state. This paper presents a set of time-frequency (t-f) features for the detection and classification of EEG ErrP in extra-brain activities due to misclassification observed by a user exploiting non-invasive BMI and robot control in the task space. The proposed features are able to characterize and detect ErrP activities in the t-f domain. These features are derived from the information embedded in the t-f representation of EEG signals, and include the Instantaneous Frequency (IF), t-f information complexity, SVD information, energy concentration and sub-bands' energies. The experiment results on real EEG data show that the use of the proposed t-f features for detecting and classifying EEG ErrP achieved an overall classification accuracy up to 97% for 50 EEG segments using 2-class SVM classifier.

Bicycle Safety Action Plan

DOT National Transportation Integrated Search

2012-09-01

The Arizona Department of Transportation (ADOT) Bicycle Safety Action Plan (BSAP) : identifies improvements, programs, and strategies that, upon their implementation, will : reduce the frequency of bicyclist fatalities and injury crashes that occur o...

ATM C and D panel/EREP cooling system contamination problem. [on Skylab

NASA Technical Reports Server (NTRS)

Williamson, J. G.

1973-01-01

This report presents the history of a preflight contamination problem that occurred in the ATM C and D panel/EREP cooling system on the Skylab, the studies that were made to determine the cause of the problem, and corrective actions that were made prior to lift-off. The results of all the observations, analyses and laboratory testing indicated that the contamination came from one or more of the EREP tape recorder coldplates and was caused by some abnormal electrolytic action, either during bench testing or in the spacecraft. Studies indicate that no such electrolytic action is likely to occur under normal operating conditions.

Time flies when we intend to act: temporal distortion in a go/no-go task.

PubMed

Yabe, Yoshiko; Goodale, Melvyn A

2015-03-25

Although many of our actions are triggered by sensory events, almost nothing is known about our perception of the timing of those sensory events. Here we show that, when people react to a sudden visual stimulus that triggers an action, that stimulus is perceived to occur later than an identical stimulus that does not trigger an action. In our experiments, participants fixated the center of a clock face with a rotating second hand. When the clock changed color, they were required to make a motor response and then to report the position of the second hand at the moment the clock changed color. In Experiment 1, in which participants made a target-directed saccade, the color change was perceived to occur 59 ms later than when they maintained fixation. In Experiment 2, in which we used a go/no-go paradigm, this temporal distortion was observed even when participants were required to cancel a prepared saccade. Finally, in Experiment 3, the same distortion in perceived time was observed for both go and no-go trials in a manual task in which no eye movements were required. These results suggest that, when a visual stimulus triggers an action, it is perceived to occur significantly later than an identical stimulus unrelated to action. Moreover, this temporal distortion appears to be related not to the execution of the action (or its effect) but rather to the programming of the action. In short, there seems to be a temporal binding between a triggering event and the triggered action. Copyright © 2015 the authors 0270-6474/15/355023-07$15.00/0.

Action-effect binding is decreased in motor conversion disorder: implications for sense of agency.

PubMed

Kranick, Sarah M; Moore, James W; Yusuf, Nadia; Martinez, Valeria T; LaFaver, Kathrin; Edwards, Mark J; Mehta, Arpan R; Collins, Phoebe; Harrison, Neil A; Haggard, Patrick; Hallett, Mark; Voon, Valerie

2013-07-01

The abnormal movements seen in motor conversion disorder are affected by distraction and entrainment, similar to voluntary movement. Unlike voluntary movement, however, patients lack a sense of control for the abnormal movements, a failure of "self-agency." The action-effect binding paradigm has been used to quantify the sense of self-agency, because subjective contraction of time between an action and its effect only occurs if the patient feels that they are the agent responsible for the action. We used this paradigm, coupled with emotional stimuli, to investigate the sense of agency with voluntary movements in patients with motor conversion disorder. Twenty patients with motor conversion disorder and 20 age-matched and sex-matched healthy volunteers used a rotating clock to judge the time of their own voluntary key presses (action) and a subsequent auditory tone (effect) after they completed conditioning blocks in which high, medium, and low tones were coupled to images of happy, fearful, and neutral faces. The results replicated those produced previously: it was reported that an effect after a voluntary action occurred earlier, and the preceding action occurred later, compared with trials that used only key presses or tones. Patients had reduced overall binding scores relative to healthy volunteers, suggesting a reduced sense of agency. There was no effect of the emotional stimuli (faces) or other interaction effects. Healthy volunteers with subclinical depressive symptoms had higher overall binding scores. We demonstrate that patients with motor conversion disorder have decreased action-effect binding for normal voluntary movements compared with healthy volunteers, consistent with the greater experience of lack of control. Copyright © 2013 Movement Disorder Society.

Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds.

PubMed

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

2014-01-01

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.

The optimal distance between two electrode tips during recording of compound nerve action potentials in the rat median nerve

PubMed Central

Li, Yongping; Lao, Jie; Zhao, Xin; Tian, Dong; Zhu, Yi; Wei, Xiaochun

2014-01-01

The distance between the two electrode tips can greatly influence the parameters used for recording compound nerve action potentials. To investigate the optimal parameters for these recordings in the rat median nerve, we dissociated the nerve using different methods and compound nerve action potentials were orthodromically or antidromically recorded with different electrode spacings. Compound nerve action potentials could be consistently recorded using a method in which the middle part of the median nerve was intact, with both ends dissociated from the surrounding fascia and a ground wire inserted into the muscle close to the intact part. When the distance between two stimulating electrode tips was increased, the threshold and supramaximal stimulating intensity of compound nerve action potentials were gradually decreased, but the amplitude was not changed significantly. When the distance between two recording electrode tips was increased, the amplitude was gradually increased, but the threshold and supramaximal stimulating intensity exhibited no significant change. Different distances between recording and stimulating sites did not produce significant effects on the aforementioned parameters. A distance of 5 mm between recording and stimulating electrodes and a distance of 10 mm between recording and stimulating sites were found to be optimal for compound nerve action potential recording in the rat median nerve. In addition, the orthodromic compound action potential, with a biphasic waveform that was more stable and displayed less interference (however also required a higher threshold and higher supramaximal stimulus), was found to be superior to the antidromic compound action potential. PMID:25206798

Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel

PubMed Central

Zhang, Hongkang; Zou, Beiyan; Yu, Haibo; Moretti, Alessandra; Wang, Xiaoying; Yan, Wei; Babcock, Joseph J.; Bellin, Milena; McManus, Owen B.; Tomaselli, Gordon; Nan, Fajun; Laugwitz, Karl-Ludwig; Li, Min

2012-01-01

Long QT syndrome (LQTS) is a genetic disease characterized by a prolonged QT interval in an electrocardiogram (ECG), leading to higher risk of sudden cardiac death. Among the 12 identified genes causal to heritable LQTS, ∼90% of affected individuals harbor mutations in either KCNQ1 or human ether-a-go-go related genes (hERG), which encode two repolarizing potassium currents known as IKs and IKr. The ability to quantitatively assess contributions of different current components is therefore important for investigating disease phenotypes and testing effectiveness of pharmacological modulation. Here we report a quantitative analysis by simulating cardiac action potentials of cultured human cardiomyocytes to match the experimental waveforms of both healthy control and LQT syndrome type 1 (LQT1) action potentials. The quantitative evaluation suggests that elevation of IKr by reducing voltage sensitivity of inactivation, not via slowing of deactivation, could more effectively restore normal QT duration if IKs is reduced. Using a unique specific chemical activator for IKr that has a primary effect of causing a right shift of V1/2 for inactivation, we then examined the duration changes of autonomous action potentials from differentiated human cardiomyocytes. Indeed, this activator causes dose-dependent shortening of the action potential durations and is able to normalize action potentials of cells of patients with LQT1. In contrast, an IKr chemical activator of primary effects in slowing channel deactivation was not effective in modulating action potential durations. Our studies provide both the theoretical basis and experimental support for compensatory normalization of action potential duration by a pharmacological agent. PMID:22745159

Short infrared laser pulses block action potentials in neurons

NASA Astrophysics Data System (ADS)

Walsh, Alex J.; Tolstykh, Gleb P.; Martens, Stacey L.; Ibey, Bennett L.; Beier, Hope T.

2017-02-01

Short infrared laser pulses have many physiological effects on cells including the ability to stimulate action potentials in neurons. Here we show that short infrared laser pulses can also reversibly block action potentials. Primary rat hippocampal neurons were transfected with the Optopatch2 plasmid, which contains both a blue-light activated channel rhodopsin (CheRiff) and a red-light fluorescent membrane voltage reporter (QuasAr2). This optogenetic platform allows robust stimulation and recording of action potential activity in neurons in a non-contact, low noise manner. For all experiments, QuasAr2 was imaged continuously on a wide-field fluorescent microscope using a Krypton laser (647 nm) as the excitation source and an EMCCD camera operating at 1000 Hz to collect emitted fluorescence. A co-aligned Argon laser (488 nm, 5 ms at 10Hz) provided activation light for CheRiff. A 200 mm fiber delivered infrared light locally to the target neuron. Reversible action potential block in neurons was observed following a short infrared laser pulse (0.26-0.96 J/cm2; 1.37-5.01 ms; 1869 nm), with the block persisting for more than 1 s with exposures greater than 0.69 J/cm2. Action potential block was sustained for 30 s with the short infrared laser pulsed at 1-7 Hz. Full recovery of neuronal activity was observed 5-30s post-infrared exposure. These results indicate that optogenetics provides a robust platform for the study of action potential block and that short infrared laser pulses can be used for non-contact, reversible action potential block.

Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Yan-Jie; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Juan, Chi-Chang

Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET{sub A}R during insulin resistance,more » ET{sub A}R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET{sub A}R expression, but not ET{sub B}R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET{sub A}R pathway suppressed insulin-induced AKT activation, whereas remained insulin-induced ERK activation. ET-1 and insulin synergistically potentiated migration and proliferation mainly through ET{sub A}R/ERK dependent pathway, which is dominant in VSMCs during modest insulin resistance syndrome. Therefore, ET-1 and ET{sub A}R are potential targets responsible for the observed synergism effect in the hypertensive atherosclerotic process through enhancement of ET-1 binding, ET-1 binding, ET{sub A}R expression, and ET-1-induced mitogenic actions in aortic VSMCs. - Highlights: • ET-1/ET{sub A}R signaling and insulin-induced pERK were high in modest insulin resistance. • ET-1 via ET{sub A}R suppressed insulin-induced pAKT but remained intact pERK in VSMCs. • Insulin potentiated ET-1-induced VSMC mitogenic action was ET{sub A}R/ERK dependent.« less

Transient Outward K+ Current (Ito) Underlies the Right Ventricular Initiation of Polymorphic Ventricular Tachycardia in a Transgenic Rabbit Model of Long-QT Syndrome Type 1.

PubMed

Choi, Bum-Rak; Li, Weiyan; Terentyev, Dmitry; Kabakov, Anatoli Y; Zhong, Mingwang; Rees, Colin M; Terentyeva, Radmila; Kim, Tae Yun; Qu, Zhilin; Peng, Xuwen; Karma, Alain; Koren, Gideon

2018-06-01

Sudden death in long-QT syndrome type 1 (LQT1), an inherited disease caused by loss-of-function mutations in KCNQ1, is triggered by early afterdepolarizations (EADs) that initiate polymorphic ventricular tachycardia (pVT). We investigated ionic mechanisms that underlie pVT in LQT1 using a transgenic rabbit model of LQT1. Optical mapping, cellular patch clamping, and computer modeling were used to elucidate the mechanisms of EADs in transgenic LQT1 rabbits. The results showed that shorter action potential duration in the right ventricle (RV) was associated with focal activity during pVT initiation. RV cardiomyocytes demonstrated higher incidence of EADs under 50 nmol/L isoproterenol. Voltage-clamp studies revealed that the transient outward potassium current (I to ) magnitude was 28% greater in RV associated with KChiP2 but with no differences in terms of calcium-cycling kinetics and other sarcolemmal currents. Perfusing with the I to blocker 4-aminopyridine changed the initial focal sites of pVT from the RV to the left ventricle, corroborating the role of I to in pVT initiation. Computer modeling showed that EADs occur preferentially in the RV because of the larger conductance of the slow-inactivating component of I to , which repolarizes the membrane potential sufficiently rapidly to allow reactivation of I Ca,L before I Kr has had sufficient time to activate. I to heterogeneity creates both triggers and an arrhythmogenic substrate in LQT1. In the absence of I Ks , I to interactions with I Ca,L and I Kr promote EADs in the RV while prolonging action potential duration in the left ventricle. This heterogeneity of action potential enhances dispersion of refractoriness and facilitates conduction blocks that initiate pVTs. © 2018 American Heart Association, Inc.

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

PubMed Central

Saung, Wint Thu; Foskett, J. Kevin

2017-01-01

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

Somatic spikes regulate dendritic signaling in small neurons in the absence of backpropagating action potentials.

PubMed

Myoga, Michael H; Beierlein, Michael; Regehr, Wade G

2009-06-17

Somatic spiking is known to regulate dendritic signaling and associative synaptic plasticity in many types of large neurons, but it is unclear whether somatic action potentials play similar roles in small neurons. Here we ask whether somatic action potentials can also influence dendritic signaling in an electrically compact neuron, the cerebellar stellate cell (SC). Experiments were conducted in rat brain slices using a combination of imaging and electrophysiology. We find that somatic action potentials elevate dendritic calcium levels in SCs. There was little attenuation of calcium signals with distance from the soma in SCs from postnatal day 17 (P17)-P19 rats, which had dendrites that averaged 60 microm in length, and in short SC dendrites from P30-P33 rats. Somatic action potentials evoke dendritic calcium increases that are not affected by blocking dendritic sodium channels. This indicates that dendritic signals in SCs do not rely on dendritic sodium channels, which differs from many types of large neurons, in which dendritic sodium channels and backpropagating action potentials allow somatic spikes to control dendritic calcium signaling. Despite the lack of active backpropagating action potentials, we find that trains of somatic action potentials elevate dendritic calcium sufficiently to release endocannabinoids and retrogradely suppress parallel fiber to SC synapses in P17-P19 rats. Prolonged SC firing at physiologically realistic frequencies produces retrograde suppression when combined with low-level group I metabotropic glutamate receptor activation. Somatic spiking also interacts with synaptic stimulation to promote associative plasticity. These findings indicate that in small neurons the passive spread of potential within dendrites can allow somatic spiking to regulate dendritic calcium signaling and synaptic plasticity.

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

PubMed

Ma, Zhongming; Saung, Wint Thu; Foskett, J Kevin

2017-05-01

Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na + currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na + and K + channels but contributed modestly to the kinetics of action potentials. Copyright © 2017 the American Physiological Society.

Post Occupancy Evaluation of a Remote Australian Community: Shay Gap, Australia.

DTIC Science & Technology

1980-07-01

AD-AOB 675 ENVIRONENTAL RESARCH AND DEVELOPMENT FOUNDATION TU ETC F G 5 11 POST OCCUPANCY EVALUATION OF A REMOTE AUSTRALIAN COMMUNITY: SHA--ETC(U...conditions. Lessons learned have aided design and community planning guidelines used by the military, government , and private business to produce more cost...occurs. The education action pattern is scored when formal teaching and learning occur, as in a school classroom. The government action pattern is

On Motion Planning with Uncertainty. Revised.

DTIC Science & Technology

1984-01-01

drift to the right, sticking at the right corner. See Fig. 1.6. Given the uncertainty in the position sensor, it is impossible to execute corrective ...action once * sticking is detected. This is because the corrective action depends on knowing the side at which sticking occurred. Worse than being...unable to correct errors should they occur, is the inability to detect success. In the given example, it is possible that the peg may move smoothly into

Action Monitoring Cortical Activity Coupled to Submovements

PubMed Central

Sobolewski, Aleksander

2017-01-01

Numerous studies have examined neural correlates of the human brain’s action-monitoring system during experimentally segmented tasks. However, it remains unknown how such a system operates during continuous motor output when no experimental time marker is available (such as button presses or stimulus onset). We set out to investigate the electrophysiological correlates of action monitoring when hand position has to be repeatedly monitored and corrected. For this, we recorded high-density electroencephalography (EEG) during a visuomotor tracking task during which participants had to follow a target with the mouse cursor along a visible trajectory. By decomposing hand kinematics into naturally occurring periodic submovements, we found an event-related potential (ERP) time-locked to these submovements and localized in a sensorimotor cortical network comprising the supplementary motor area (SMA) and the precentral gyrus. Critically, the amplitude of the ERP correlated with the deviation of the cursor, 110 ms before the submovement. Control analyses showed that this correlation was truly due to the cursor deviation and not to differences in submovement kinematics or to the visual content of the task. The ERP closely resembled those found in response to mismatch events in typical cognitive neuroscience experiments. Our results demonstrate the existence of a cortical process in the SMA, evaluating hand position in synchrony with submovements. These findings suggest a functional role of submovements in a sensorimotor loop of periodic monitoring and correction and generalize previous results from the field of action monitoring to cases where action has to be repeatedly monitored. PMID:29071301

An Emotion-Enriched Context Influences the Effect of Action Observation on Cortical Excitability.

PubMed

Lagravinese, Giovanna; Bisio, Ambra; De Ferrari, Alessia Raffo; Pelosin, Elisa; Ruggeri, Piero; Bove, Marco; Avanzino, Laura

2017-01-01

Observing other people in action activates the "mirror neuron system" that serves for action comprehension and prediction. Recent evidence suggests that this function requires a high level codification triggered not only by components of motor behavior, but also by the environment where the action is embedded. An overlooked component of action perceiving is the one related to the emotional information provided by the context where the observed action takes place. Indeed, whether valence and arousal associated to an emotion might exert an influence on motor system activation during action observation has not been assessed so far. Here, cortico-spinal excitability of the left motor cortex was recorded in three groups of subjects. In the first condition, motor-evoked potential (MEPs) were recorded from a muscle involved in the grasping movement (i.e., abductor pollicis brevis, APB) while participants were watching the same reach-to-grasp movement embedded in contexts with negative emotional valence, but different levels of arousal: sadness (low arousal), and disgust (high arousal) ("Context plus Movement-APB" condition). In the second condition, MEPs were recorded from APB muscle while participants were observing static images representing the contexts in which the movement observed by participants in "Context plus Movement-APB" condition took place ("Context Only-APB" condition). Finally, in the third condition, MEPS were recorded from a muscle not involved in the grasping action, i.e., abductor digiti minimi, ADM, while participants were watching the same videos shown during the "Context plus Movement-APB" condition ("Context plus Movement-ADM" condition). Results showed a greater increase of cortical excitability only during the observation of the hand moving in the context eliciting disgust, and these changes were specific for the muscle involved in the observed action. Our findings show that the emotional context in which a movement occurs modulates motor resonance and that the combination of negative valence/high arousal drives the greater response in the observer's mirror neuron system in a strictly muscle specific fashion.

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

PubMed

Levic, Snezana; Lv, Ping; Yamoah, Ebenezer N

2011-01-01

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. © 2011 Levic et al.

78 FR 23740 - Notice of Availability of a Swine Brucellosis and Pseudorabies Proposed Action Plan

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-22

...] Notice of Availability of a Swine Brucellosis and Pseudorabies Proposed Action Plan AGENCY: Animal and... proposed action plan describing a potential new approach to managing swine brucellosis and pseudorabies...-0086) a notice that made a proposed action plan describing a potential new approach to managing swine...

The statistics of calcium-mediated focal excitations on a one-dimensional cable.

PubMed

Chen, Wei; Asfaw, Mesfin; Shiferaw, Yohannes

2012-02-08

It is well known that various cardiac arrhythmias are initiated by an ill-timed excitation that originates from a focal region of the heart. However, up to now, it is not known what governs the timing, location, and morphology of these focal excitations. Recent studies have shown that these excitations can be caused by abnormalities in the calcium (Ca) cycling system. However, the cause-and-effect relationships linking subcellular Ca dynamics and focal activity in cardiac tissue is not completely understood. In this article, we present a minimal model of Ca-mediated focal excitations in cardiac tissue. This model accounts for the stochastic nature of spontaneous Ca release on a one-dimensional cable of cardiac cells. Using this model, we show that the timing of focal excitations is equivalent to a first passage time problem in a spatially extended system. In particular, we find that for a short cable the mean first passage time increases exponentially with the number of cells in tissue, and is critically dependent on the ratio of inward to outward currents near the threshold for an action potential. For long cables excitations occurs due to ectopic foci that occur on a length scale determined by the minimum length of tissue that can induce an action potential. Furthermore, we find that for long cables the mean first passage time decreases as a power law in the number cells. These results provide precise criteria for the occurrence of focal excitations in cardiac tissue, and will serve as a guide to determine the propensity of Ca-mediated triggered arrhythmias in the heart. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

KLIMOPASS: Water-use conflicts during periods of low flow - a stakeholder analysis of the rivers Murg and Kocher in Baden-Wuerttemberg and sustainable recommendations for action

NASA Astrophysics Data System (ADS)

Zeitler, Florian; Dotterweich, Markus; Rothstein, Benno

2017-04-01

The 2003 and 2015 occurring heatwaves in Central Europe demonstrated on how dangerous long-lasting droughts and water stress can be for nature, people and companies relying on water. Climate change will increase the chance of low flow events along rivers in Baden-Wuerttemberg in the future leading to possible water-use conflicts amongst the users. This KLIMOPASS project focuses on the identification of existing and potential occurring conflicts of usage and interest for water resources. The main research concentrates on two exemplary river basins in Baden-Wuerttemberg (the Murg and the Kocher River) including all involved stakeholders and sectors (hydropower, agriculture, industry, sewage plants, ecology, tourism etc.). With the examples of the two rivers, the identification of conflicts, possible strategies for solutions and recommendations for action during current and future events of low flow have been researched. Quantitative and qualitative surveys, interviews, excursions and workshops have been conducted to analyse the stakeholder's potential for conflict. For this process it is necessary to equally consider all economic, societal and ecological interests and include all relevant stakeholders in the participatory process. According to the results, water related conflicts are not present in all sectors, but rather exclusive to certain sectors. Furthermore, these sectors are in conflict with more than one stakeholder group at the same time. In contrast, other users have not experienced any water related conflicts yet. Moreover, it is noticeable that conflicts in water use are only partly caused due to low flow events: regarding both rivers, low flow events are not only related to natural causes but particularly to anthropogenic influences.

Visual recognition and visually guided action after early bilateral lesion of occipital cortex: a behavioral study of a 4.6-year-old girl.

PubMed

Amicuzi, Ileana; Stortini, Massimo; Petrarca, Maurizio; Di Giulio, Paola; Di Rosa, Giuseppe; Fariello, Giuseppe; Longo, Daniela; Cannatà, Vittorio; Genovese, Elisabetta; Castelli, Enrico

2006-10-01

We report the case of a 4.6-year-old girl born pre-term with early bilateral occipital damage. It was revealed that the child had non-severely impaired basic visual abilities and ocular motility, a selective perceptual deficit of figure-ground segregation, impaired visual recognition and abnormal navigating through space. Even if the child's visual functioning was not optimal, this was the expression of adaptive anatomic and functional brain modifications that occurred following the early lesion. Anatomic brain structure was studied with anatomic MRI and Diffusor Tensor Imaging (DTI)-MRI. This behavioral study may provide an important contribution to understanding the impact of an early lesion of the visual system on the development of visual functions and on the immature brain's potential for reorganisation related to when the damage occurred.

Novel natural food antimicrobials.

PubMed

Juneja, Vijay K; Dwivedi, Hari P; Yan, Xianghe

2012-01-01

Naturally occurring antimicrobial compounds could be applied as food preservatives to protect food quality and extend the shelf life of foods and beverages. These compounds are naturally produced and isolated from various sources, including plants, animals and microorganisms, in which they constitute part of host defense systems. Many naturally occurring compounds, such as nisin, plant essential oils, and natamycin, have been widely studied and are reported to be effective in their potential role as antimicrobial agents against spoilage and pathogenic microorganisms. Although some of these natural antimicrobials are commercially available and applied in food processing, their efficacy, consumer acceptance and regulation are not well defined. This manuscript reviews natural antimicrobial compounds with reference to their applications in food when applied individually or in combination with other hurdles. It also reviews the mechanism of action of selected natural antimicrobials, factors affecting their antimicrobial activities, and future prospects for use of natural antimicrobials in the food industry.

[Effect of veralipride on the estral cycle, genital tract, mammary gland and pituitary gland in female rats (author's transl)].

PubMed

Tuchmann-Duplessis, H

1980-10-15

A study of the potential biological effects of veralipride was conducted in female rats. A definite stimulating action on the mammary gland was noted, but doses of 5 to 20 mg/kg/day are required to produce secretion, which is varying from one animal to another. Follicular maturation is preserved, though there is an increase in the number of corpora lutea with more marked development in some of them. Progesterone impregnation of the uterus occurs in a variable way and then only at doses of 5 + 0 20 mg/kg/day. Vaginal mucification, from a reduction in estrogen in relation to progesterone impregnation, is noted after 1 mg/kg/day (though 25 p. cent of the animals still demonstrate vaginal keratinization after 20 mg/kg/day). Finally, degranulation of the carminophile cells of the anterior pituitary gland, occurs after 5 mg/kg/day.

Discontinuities, cross-scale patterns, and the organization of ecosystems

USGS Publications Warehouse

Nash, Kirsty L.; Allen, Craig R.; Angeler, David G.; Barichievy, Chris; Eason, Tarsha; Garmestani, Ahjond S.; Graham, Nicholas A.J.; Granholm, Dean; Knutson, Melinda; Nelson, R. John; Nystrom, Magnus; Stow, Craig A.; Sandstrom, Shana M.

2014-01-01

Ecological structures and processes occur at specific spatiotemporal scales, and interactions that occur across multiple scales mediate scale-specific (e.g., individual, community, local, or regional) responses to disturbance. Despite the importance of scale, explicitly incorporating a multi-scale perspective into research and management actions remains a challenge. The discontinuity hypothesis provides a fertile avenue for addressing this problem by linking measureable proxies to inherent scales of structure within ecosystems. Here we outline the conceptual framework underlying discontinuities and review the evidence supporting the discontinuity hypothesis in ecological systems. Next we explore the utility of this approach for understanding cross-scale patterns and the organization of ecosystems by describing recent advances for examining nonlinear responses to disturbance and phenomena such as extinctions, invasions, and resilience. To stimulate new research, we present methods for performing discontinuity analysis, detail outstanding knowledge gaps, and discuss potential approaches for addressing these gaps.

Pair production in the gravitational field of a cosmic string

NASA Astrophysics Data System (ADS)

Harari, Diego D.; Skarzhinsky, Vladimir D.

1990-04-01

We show that many elementary particle physics processes, such as pair production by a high energy photon, that take place in Minkowski space only if a non-uniform external field provides for momentum non-conservation, do occur in the space-time around a straight cosmic string, even though the space is locally flat and there is no local gravitational potential. We exemplify this mechanism through the evaluation of the cross section per unit length of string for the decay of a massless scalar particle into a pair of massive particles. The cross sections for this kind of processes are typically small. Nevertheless, it is interesting to realize how these reactions occur due to topological properties of space, rather than to the action of a local field. V.S. is grateful to Mario Castagnino for hospitality at the Instituto de Astronomía y Física del Espacio during a visit while this work was done.

[Preliminary analysis on relationship between traditional efficacy of Chinese medicine and modern pharmacological action].

PubMed

Ren, Jun-Guo; Wang, Dong-Zhi; Lei, Lei; Kang, Li; Liu, Jian-Xun

2017-05-01

To find the relationship between traditional efficacy of Chinese medicine and modern pharmacological action by using data mining, and provide information and reference for further research and development for the pharmacology research of traditional Chinese medicine.The information of 547 kinds of traditional Chinese medicines, 335 kinds of Chinese medicine effects and 86 kinds of pharmacological actions were collected and processed in Clinical Guide to the Chinese Pharmacopoeia published in 2010; Access and Excel software were used to analyze the frequence and frequency of single effect, pharmacological action, and both. In addition, the relationship between efficacy and pharmacology was analyzed with the clearing heat and antibacterial effects as the example. The analysis results showed that 547 kinds of Chinese medicines involved 335 kinds of Chinese medicine effects and 86 kinds of pharmacological actions. Among them, the most frequent Chinese medicine effect was"clearing heat", whose frequence was 130 and the frequency was 0.24; the most frequent pharmacological action was "anti-inflammatory action" whose frequence was 191 and the frequency was 0.35. The most common efficacy-pharmacological action group was "clearing heat" and "anti-bacterial action", whose frequence was 75 and the frequency was 0.26. The couple of "purgation" and "cathartic effect" had the largest frequency of 0.30, but they just appeared together for 3 times. There were 52 kinds of pharmacological actions that occurred together with clearing heat, of which, the top 10 were anti-bacterial action, anti-inflammatory action, antineoplastic action, anti-hepatic injury action, immunoregulation action, antipyretic action, antiviralaction, hypoglycemic action, antioxidant action and analgesic action. There were 161 kinds of Chinese medicine effects that occurred together with anti-bacterial action, of which, the top 10 were clearing heat, detoxification, detumescence, analgesia, resolving dampness, pesticide, cooling blood, expelling wind, eliminating dampness and hemostasis. These results suggested that there was a certain relationship between traditional Chinese medicine effects and modern pharmacological actions. Copyright© by the Chinese Pharmaceutical Association.

A comparison of muscle activity in concentric and counter movement maximum bench press.

PubMed

van den Tillaar, Roland; Ettema, Gertjan

2013-01-01

The purpose of this study was to compare the kinematics and muscle activation patterns of regular free-weight bench press (counter movement) with pure concentric lifts in the ascending phase of a successful one repetition maximum (1-RM) attempt in the bench press. Our aim was to evaluate if diminishing potentiation could be the cause of the sticking region. Since diminishing potentiation cannot occur in pure concentric lifts, the occurrence of a sticking region in this type of muscle actions would support the hypothesis that the sticking region is due to a poor mechanical position. Eleven male participants (age 21.9 ± 1.7 yrs, body mass 80.7 ± 10.9 kg, body height 1.79 ± 0.07 m) conducted 1-RM lifts in counter movement and in pure concentric bench presses in which kinematics and EMG activity were measured. In both conditions, a sticking region occurred. However, the start of the sticking region was different between the two bench presses. In addition, in four of six muscles, the muscle activity was higher in the counter movement bench press compared to the concentric one. Considering the findings of the muscle activity of six muscles during the maximal lifts it was concluded that the diminishing effect of force potentiation, which occurs in the counter movement bench press, in combination with a delayed muscle activation unlikely explains the existence of the sticking region in a 1-RM bench press. Most likely, the sticking region is the result of a poor mechanical force position.

Using geographic distribution of well-screen depths and hydrogeologic conditions to identify areas of concern for contaminant migration through inactive supply wells

NASA Astrophysics Data System (ADS)

Gailey, Robert M.

2018-02-01

Contaminant migration through inactive supply wells can negatively affect groundwater quality and the combined effects from groups of such wells may cause greater impacts. Because the number of wells in many basins is often large and the geographic areas involved can be vast, approaches are needed to estimate potential impacts and focus limited resources for investigation and corrective measures on the most important areas. One possibility is to evaluate the geographic distribution of well-screen depths relative to hydrogeologic conditions and assess where contaminant migration through wells may be impacting groundwater quality. This approach is demonstrated for a geographically extensive area in the southern Central Valley of California, USA. The conditions that lead to wells acting as conduits for contaminant migration are evaluated and areas where the problem likely occurs are identified. Although only a small fraction of all wells appear to act as conduits, potential impacts may be significant considering needs to control nonpoint-source pollution and improve drinking water quality for rural residents. Addressing a limited number of areas where contaminant migration rates are expected to be high may cost-effectively accomplish the most beneficial groundwater quality protection and improvement. While this work focuses on a specific region, the results indicate that impacts from groups of wells may occur in other areas with similar conditions. Analyses similar to that demonstrated here may guide efficient investigation and corrective action in such areas with benefits occurring for groundwater quality. Potential benefits may justify expenditures to develop the necessary data for performing the analyses.

A Comparison of Muscle Activity in Concentric and Counter Movement Maximum Bench Press

PubMed Central

van den Tillaar, Roland; Ettema, Gertjan

2013-01-01

The purpose of this study was to compare the kinematics and muscle activation patterns of regular free-weight bench press (counter movement) with pure concentric lifts in the ascending phase of a successful one repetition maximum (1-RM) attempt in the bench press. Our aim was to evaluate if diminishing potentiation could be the cause of the sticking region. Since diminishing potentiation cannot occur in pure concentric lifts, the occurrence of a sticking region in this type of muscle actions would support the hypothesis that the sticking region is due to a poor mechanical position. Eleven male participants (age 21.9 ± 1.7 yrs, body mass 80.7 ± 10.9 kg, body height 1.79 ± 0.07 m) conducted 1-RM lifts in counter movement and in pure concentric bench presses in which kinematics and EMG activity were measured. In both conditions, a sticking region occurred. However, the start of the sticking region was different between the two bench presses. In addition, in four of six muscles, the muscle activity was higher in the counter movement bench press compared to the concentric one. Considering the findings of the muscle activity of six muscles during the maximal lifts it was concluded that the diminishing effect of force potentiation, which occurs in the counter movement bench press, in combination with a delayed muscle activation unlikely explains the existence of the sticking region in a 1-RM bench press. Most likely, the sticking region is the result of a poor mechanical force position. PMID:24235985

The Impact of Action Learning Experience on Reflective Practice

ERIC Educational Resources Information Center

Harris, Nicole S.

2012-01-01

This case study examines the changes that occur with respect to reflective practices as a result of participating in an action learning group through the identification of aspects/activities of action learning that contribute to such changes and the impact these aspects/activities had on the program participants at a department of the federal…

The Meaning and Organization of Physical Education Teachers' Actions during Conflict with Students.

ERIC Educational Resources Information Center

Flavier, Eric; Bertone, Stefano; Hauw, Denis; Durand, Marc

2002-01-01

Used course-of-action theory to identify typical organization of teachers' actions when in conflict with students. Middle school physical educators were interviewed and filmed during lessons. Overall, teacher-student conflicts were infrequent. When conflict occurred, teacher attempts at resolution were under strong time pressure, leading to risk…

The Performance and Observation of Action Shape Future Behaviour

ERIC Educational Resources Information Center

Welsh, Timothy N.; McDougall, Laura M.; Weeks, Daniel J.

2009-01-01

The observation of other people's actions plays an important role in shaping the perceptual, cognitive, and motor processes of the observer. It has been suggested that these social influences occur because the observation of action evokes a representation of that response in the observer and that these codes are subsequently accessed by other…

Collaborative Developmental Action Inquiry: An Opportunity for Transformative Learning to Occur?

ERIC Educational Resources Information Center

Nicolaides, Aliki; Dzubinski, Leanne

2016-01-01

Life in the 21st century is increasingly complex, paradoxical, and ambiguous, bringing into question the ways that graduate adult education programs function. In this article, we describe an action research study involving the method of collaborative developmental action inquiry conducted with key stakeholders of a program in adult education at a…

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2010 CFR

2010-04-01

... identification number and adverse reaction term(s)); and (c) a history of actions taken since the last report...; an adverse event occurring from drug withdrawal; and any failure of expected pharmacological action... circumstance, the nonapplicant shall maintain a record of this action which shall include: (A) A copy of each...

78 FR 64896 - EPA-R04-OAR-2013-0563; FRL-9902-18-Region 4

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-30

...: Environmental Protection Agency (EPA). ACTION: Proposed rule. SUMMARY: EPA is proposing to approve the State of..., such action will occur in a subsequent rulemaking. DATES: Written comments must be received on or... Emission Budgets Update VII. Proposed Action VIII. Statutory and Executive Order Reviews I. What is being...

Sexual Conflict and Seminal Fluid Proteins: A Dynamic Landscape of Sexual Interactions

PubMed Central

Sirot, Laura K.; Wong, Alex; Chapman, Tracey; Wolfner, Mariana F.

2015-01-01

Sexual reproduction requires coordinated contributions from both sexes to proceed efficiently. However, the reproductive strategies that the sexes adopt often have the potential to give rise to sexual conflict because they can result in divergent, sex-specific costs and benefits. These conflicts can occur at many levels, from molecular to behavioral. Here, we consider sexual conflict mediated through the actions of seminal fluid proteins. These proteins provide many excellent examples in which to trace the operation of sexual conflict from molecules through to behavior. Seminal fluid proteins are made by males and provided to females during mating. As agents that can modulate egg production at several steps, as well as reproductive behavior, sperm “management,” and female feeding, activity, and longevity, the actions of seminal proteins are prime targets for sexual conflict. We review these actions in the context of sexual conflict. We discuss genomic signatures in seminal protein (and related) genes that are consistent with current or previous sexual conflict. Finally, we note promising areas for future study and highlight real-world practical situations that will benefit from understanding the nature of sexual conflicts mediated by seminal proteins. PMID:25502515

Sexual conflict and seminal fluid proteins: a dynamic landscape of sexual interactions.

PubMed

Sirot, Laura K; Wong, Alex; Chapman, Tracey; Wolfner, Mariana F

2014-12-11

Sexual reproduction requires coordinated contributions from both sexes to proceed efficiently. However, the reproductive strategies that the sexes adopt often have the potential to give rise to sexual conflict because they can result in divergent, sex-specific costs and benefits. These conflicts can occur at many levels, from molecular to behavioral. Here, we consider sexual conflict mediated through the actions of seminal fluid proteins. These proteins provide many excellent examples in which to trace the operation of sexual conflict from molecules through to behavior. Seminal fluid proteins are made by males and provided to females during mating. As agents that can modulate egg production at several steps, as well as reproductive behavior, sperm "management," and female feeding, activity, and longevity, the actions of seminal proteins are prime targets for sexual conflict. We review these actions in the context of sexual conflict. We discuss genomic signatures in seminal protein (and related) genes that are consistent with current or previous sexual conflict. Finally, we note promising areas for future study and highlight real-world practical situations that will benefit from understanding the nature of sexual conflicts mediated by seminal proteins. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

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

PubMed

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

2014-08-25

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

Emergency Response Alternatives

EPA Pesticide Factsheets

Based on the National Contingency Plan, EPA defines the following types: classic emergencies, requiring on-site activities within minutes/hours; time-critical actions, which must occur within 6 months; and non-time-critical actions, which can take longer.

Bicycle Safety Action Plan : Appendix A

DOT National Transportation Integrated Search

2012-09-01

The Arizona Department of Transportation (ADOT) Bicycle Safety Action Plan (BSAP) identifies improvements, programs, and strategies that, upon their implementation, will reduce the frequency of bicyclist fatalities and injury crashes that occur on th...

Intracellular recording of action potentials by nanopillar electroporation.

PubMed

Xie, Chong; Lin, Ziliang; Hanson, Lindsey; Cui, Yi; Cui, Bianxiao

2012-02-12

Action potentials have a central role in the nervous system and in many cellular processes, notably those involving ion channels. The accurate measurement of action potentials requires efficient coupling between the cell membrane and the measuring electrodes. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios. However, the invasive nature of intracellular methods usually limits the recording time to a few hours, and their complexity makes it difficult to simultaneously record more than a few cells. Extracellular recording methods, such as multielectrode arrays and multitransistor arrays, are non-invasive and allow long-term and multiplexed measurements. However, extracellular recording sacrifices the one-to-one correspondence between the cells and electrodes, and also suffers from significantly reduced signal strength and quality. Extracellular techniques are not, therefore, able to record action potentials with the accuracy needed to explore the properties of ion channels. As a result, the pharmacological screening of ion-channel drugs is usually performed by low-throughput intracellular recording methods. The use of nanowire transistors, nanotube-coupled transistors and micro gold-spine and related electrodes can significantly improve the signal strength of recorded action potentials. Here, we show that vertical nanopillar electrodes can record both the extracellular and intracellular action potentials of cultured cardiomyocytes over a long period of time with excellent signal strength and quality. Moreover, it is possible to repeatedly switch between extracellular and intracellular recording by nanoscale electroporation and resealing processes. Furthermore, vertical nanopillar electrodes can detect subtle changes in action potentials induced by drugs that target ion channels.

Intracellular recording of action potentials by nanopillar electroporation

NASA Astrophysics Data System (ADS)

Xie, Chong; Lin, Ziliang; Hanson, Lindsey; Cui, Yi; Cui, Bianxiao

2012-03-01

Action potentials have a central role in the nervous system and in many cellular processes, notably those involving ion channels. The accurate measurement of action potentials requires efficient coupling between the cell membrane and the measuring electrodes. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios. However, the invasive nature of intracellular methods usually limits the recording time to a few hours, and their complexity makes it difficult to simultaneously record more than a few cells. Extracellular recording methods, such as multielectrode arrays and multitransistor arrays, are non-invasive and allow long-term and multiplexed measurements. However, extracellular recording sacrifices the one-to-one correspondence between the cells and electrodes, and also suffers from significantly reduced signal strength and quality. Extracellular techniques are not, therefore, able to record action potentials with the accuracy needed to explore the properties of ion channels. As a result, the pharmacological screening of ion-channel drugs is usually performed by low-throughput intracellular recording methods. The use of nanowire transistors, nanotube-coupled transistors and micro gold-spine and related electrodes can significantly improve the signal strength of recorded action potentials. Here, we show that vertical nanopillar electrodes can record both the extracellular and intracellular action potentials of cultured cardiomyocytes over a long period of time with excellent signal strength and quality. Moreover, it is possible to repeatedly switch between extracellular and intracellular recording by nanoscale electroporation and resealing processes. Furthermore, vertical nanopillar electrodes can detect subtle changes in action potentials induced by drugs that target ion channels.

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

PubMed Central

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

2010-01-01

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

Consequences of converting graded to action potentials upon neural information coding and energy efficiency.

PubMed

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

2014-01-01

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

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

PubMed Central

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

2014-01-01

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

Both Motor Prediction and Conceptual Congruency between Preview and Action-Effect Contribute to Explicit Judgment of Agency

ERIC Educational Resources Information Center

Sato, Atsushi

2009-01-01

The sense of agency is the sense that one is causing an action. The inferential account of the sense of agency proposes that we experience the sense of agency when we infer that one's own thoughts are the cause of an action. According to this account, the inference occurs when a thought appears in consciousness prior to an action, is consistent…

Millisecond infrared laser pulses depolarize and elicit action potentials on in-vitro dorsal root ganglion neurons

PubMed Central

Paris, Lambert; Marc, Isabelle; Charlot, Benoit; Dumas, Michel; Valmier, Jean; Bardin, Fabrice

2017-01-01

This work focuses on the optical stimulation of dorsal root ganglion (DRG) neurons through infrared laser light stimulation. We show that a few millisecond laser pulse at 1875 nm induces a membrane depolarization, which was observed by the patch-clamp technique. This stimulation led to action potentials firing on a minority of neurons beyond an energy threshold. A depolarization without action potential was observed for the majority of DRG neurons, even beyond the action potential energy threshold. The use of ruthenium red, a thermal channel blocker, stops the action potential generation, but has no effects on membrane depolarization. Local temperature measurements reveal that the depolarization amplitude is sensitive to the amplitude of the temperature rise as well as to the time rate of change of temperature, but in a way which may not fully follow a photothermal capacitive mechanism, suggesting that more complex mechanisms are involved. PMID:29082085

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

PubMed

Li, S N; Zhang, K Y

1992-11-01

Effects of dauricine (Dau) on the action potentials (AP), the slow action potentials (SAP), and the slow inward currents (Isi) of guinea pig ventricular papillary muscles were observed by means of intracellular microelectrode and single sucrose gap voltage clamp technique. In the early stage, Dau shortened action potential duration 100 (APD100) and effective refractory period (ERP) (ERP/APD < 1; P < 0.01), but did not affect APD20 and other parameters. In the late stage, Dau prolonged APD100, ERP, and APD20, significantly decreased action potential amplitude (APA), maximum velocity (Vmax), and overshot (OS) (ERP/APD > 1; P < 0.01), greatly diminished APA and OS of 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.

Simulation of axonal excitability using a Spreadsheet template created in Microsoft Excel.

PubMed

Brown, A M

2000-08-01

The objective of this present study was to implement an established simulation protocol (A.M. Brown, A methodology for simulating biological systems using Microsoft Excel, Comp. Methods Prog. Biomed. 58 (1999) 181-90) to model axonal excitability. The simulation protocol involves the use of in-cell formulas directly typed into a spreadsheet and does not require any programming skills or use of the macro language. Once the initial spreadsheet template has been set up the simulations described in this paper can be executed with a few simple keystrokes. The model axon contained voltage-gated ion channels that were modeled using Hodgkin Huxley style kinetics. The basic properties of axonal excitability modeled were: (1) threshold of action potential firing, demonstrating that not only are the stimulus amplitude and duration critical in the generation of an action potential, but also the resting membrane potential; (2) refractoriness, the phenomenon of reduced excitability immediately following an action potential. The difference between the absolute refractory period, when no amount of stimulus will elicit an action potential, and relative refractory period, when an action potential may be generated by applying increased stimulus, was demonstrated with regard to the underlying state of the Na(+) and K(+) channels; (3) temporal summation, a process by which two sub-threshold stimuli can unite to elicit an action potential was shown to be due to conductance changes outlasting the first stimulus and summing with the second stimulus-induced conductance changes to drive the membrane potential past threshold; (4) anode break excitation, where membrane hyperpolarization was shown to produce an action potential by removing Na(+) channel inactivation that is present at resting membrane potential. The simulations described in this paper provide insights into mechanisms of axonal excitation that can be carried out by following an easily understood protocol.

Toxicity, sublethal effects, and potential modes of action of select fungicides on freshwater fish and invertebrates

USGS Publications Warehouse

Elskus, Adria A.

2012-01-01

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 organic matter in sediment and soils, it is particularly important to determine their effects on freshwater mussels and other freshwater benthic invertebrates in contact with sediments, as available toxicity studies with pelagic species, mainly Daphnia magna, may not be representative of these benthic organisms. Finally, there is a critical need for studies of the chronic effects of fungicides on reproduction, immunocompetence, and ecosystem function; sublethal endpoints with population and community-level relevance.

Optical mapping of optogenetically shaped cardiac action potentials.

PubMed

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

2014-08-19

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.

Optical mapping of optogenetically shaped cardiac action potentials

PubMed Central

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

2014-01-01

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

Interservice Procedures for Instructional Systems Development. Phase 3. Develop

DTIC Science & Technology

1975-08-01

Occur at wide intervals to be learned *Reads about the actions to *Occur at the end, but before be learned tests or on-the-job performance *Watches a...the particular sub-category. Use the learning objective action statement, conditions, standards, and the test item to help select which guidelines to...objective. EXAMPLE If you have a CLASSIFYING objective like "identifying poisonous plants,’ when you get to guideline 16. "To test learning, require the

48 CFR 2803.104-10 - Violations or possible violations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... General IMPROPER BUSINESS PRACTICES AND PERSONAL CONFLICTS OF INTEREST Safeguards 2803.104-10 Violations... action to be taken. The types of actions that would normally be taken when a violation has occurred that...

Automatic imitation effects are influenced by experience of synchronous action in children.

PubMed

O'Sullivan, Eoin P; Bijvoet-van den Berg, Simone; Caldwell, Christine A

2018-07-01

By their fourth year of life, children are expert imitators, but it is unclear how this ability develops. One approach suggests that certain types of experience might forge associations between the sensory and motor representations of an action that may facilitate imitation at a later time. Sensorimotor experience of this sort may occur when an infant's action is imitated by a caregiver or when socially synchronous action occurs. This learning approach, therefore, predicts that the strength of sensory-motor associations should depend on the frequency and quality of previous experience. Here, we tested this prediction by examining automatic imitation, that is, the tendency of an action stimulus to facilitate the performance of that action and interfere with the performance of an incompatible action. We required children (aged between 3 years 8 months and 7 years 11 months) to respond to actions performed by an experimenter (e.g., two hands clapping) with both compatible actions (i.e., two hands clapping) and incompatible actions (i.e., two hands waving) at different stages in the experimental procedure. As predicted by a learning account, actions thought to be performed in synchrony (i.e., clapping/waving) produced stronger automatic imitation effects when compared with actions where previous sensorimotor experience is likely to be more limited (e.g., pointing/hand closing). Furthermore, these automatic imitation effects were not found to vary with age, with both compatible and incompatible responses quickening with age. These findings suggest a role for sensorimotor experience in the development of imitative ability. Copyright © 2018 Elsevier Inc. All rights reserved.

Spontaneous action potentials and neural coding in unmyelinated axons.

PubMed

O'Donnell, Cian; van Rossum, Mark C W

2015-04-01

The voltage-gated Na and K channels in neurons are responsible for action potential generation. Because ion channels open and close in a stochastic fashion, spontaneous (ectopic) action potentials can result even in the absence of stimulation. While spontaneous action potentials have been studied in detail in single-compartment models, studies on spatially extended processes have been limited. The simulations and analysis presented here show that spontaneous rate in unmyelinated axon depends nonmonotonically on the length of the axon, that the spontaneous activity has sub-Poisson statistics, and that neural coding can be hampered by the spontaneous spikes by reducing the probability of transmitting the first spike in a train.

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

PubMed

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

2015-11-01

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

Action potentials contribute to epileptic high-frequency oscillations recorded with electrodes remote from neurons.

PubMed

Kobayashi, Katsuhiro; Akiyama, Tomoyuki; Ohmori, Iori; Yoshinaga, Harumi; Gotman, Jean

2015-05-01

The importance of epileptic high-frequency oscillations (HFOs) in electroencephalogram (EEG) is growing. Action potentials generating some HFOs are observed in the vicinity of neurons in experimental animals. However electrodes that are remote from neurons, as in case of clinical situations, should not record action potentials. We propose to resolve this question by a realistic simulation of epileptic neuronal network. The rat dentate gyrus with sclerosis was simulated in silico. We computed the current dipole moment generated by each granule cell and the field potentials in a measurement area far from neurons. The dentate gyrus was stimulated through synaptic input to evoke discharges resembling interictal epileptiform discharges, which had superimposed HFOs⩽295Hz that were recordable with remote electrodes and represented bursts of action potentials of granule cells. The increase in power of HFOs was associated with the progression of sclerosis, the reduction of GABAergic inhibition, and the increase in cell connectivity. Spectral frequency of HFOs had similar tendencies. HFOs recorded with electrodes remote from neurons could actually be generated by clusters of action potentials. The phenomenon of action potentials recorded with remote electrodes can possibly extend the clinical meaning of EEG. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2015-01-01

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

Neuroprotective effects of resveratrol in Alzheimer disease pathology.

PubMed

Rege, Shraddha D; Geetha, Thangiah; Griffin, Gerald D; Broderick, Tom L; Babu, Jeganathan Ramesh

2014-01-01

Alzheimer's disease is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and behavioral abilities. Extracellular senile plaques and intracellular neurofibrillary tangles are hallmarks of AD. Researchers aim to analyze the molecular mechanisms underlying AD pathogenesis; however, the therapeutic options available to treat this disease are inadequate. In the past few years, several studies have reported interesting insights about the neuroprotective properties of the polyphenolic compound resveratrol (3, 5, 4'-trihydroxy-trans-stilbene) when used with in vitro and in vivo models of AD. The aim of this review is to focus on the neuroprotective and antioxidant effects of resveratrol on AD and its multiple potential mechanisms of action. In addition, because the naturally occurring forms of resveratrol have a very limited half-life in plasma, a description of potential analogs aimed at increasing the bioavailability in plasma is also discussed.

Radiological emergency: Malaysian preparedness and response.

PubMed

Yusof, Mohd Abd Wahab; Ali, Hamrah Mohd

2011-07-01

Planning and preparation in advance for radiological emergencies can help to minimise potential public health and environmental threats if and when an actual emergency occurs. During the planning process, emergency response organisations think through how they would respond to each type of incident and the resources that will be needed. In Malaysia, planning, preparation for and response to radiological emergencies involve many parties. In the event of a radiological emergency and if it is considered a disaster, the National Security Council, the Atomic Energy Licensing Board and the Malaysian Nuclear Agency (Nuclear Malaysia) will work together with other federal agencies, state and local governments, first responders and international organisations to monitor the situation, contain the release, and clean up the contaminated site. Throughout the response, these agencies use their protective action guidelines. This paper discusses Malaysian preparedness for, and response to, any potential radiological emergency.

Nerve Fiber Activation During Peripheral Nerve Field Stimulation: Importance of Electrode Orientation and Estimation of Area of Paresthesia.

PubMed

Frahm, Ken Steffen; Hennings, Kristian; Vera-Portocarrero, Louis; Wacnik, Paul W; Mørch, Carsten Dahl

2016-04-01

Low back pain is one of the indications for using peripheral nerve field stimulation (PNFS). However, the effect of PNFS varies between patients; several stimulation parameters have not been investigated in depth, such as orientation of the nerve fiber in relation to the electrode. While placing the electrode parallel to the nerve fiber may give lower activation thresholds, anodal blocking may occur when the propagating action potential passes an anode. A finite element model was used to simulate the extracellular potential during PNFS. This was combined with an active cable model of Aβ and Aδ nerve fibers. It was investigated how the angle between the nerve fiber and electrode affected the nerve activation and whether anodal blocking could occur. Finally, the area of paresthesia was estimated and compared with any concomitant Aδ fiber activation. The lowest threshold was found when nerve and electrode were in parallel, and that anodal blocking did not appear to occur during PNFS. The activation of Aβ fibers was within therapeutic range (<10V) of PNFS; however, within this range, Aδ fiber activation also may occur. The combined area of activated Aβ fibers (paresthesia) was at least two times larger than Aδ fibers for similar stimulation intensities. No evidence of anodal blocking was observed in this PNFS model. The thresholds were lowest when the nerves and electrodes were parallel; thus, it may be relevant to investigate the overall position of the target nerve fibers prior to electrode placement. © 2015 International Neuromodulation Society.

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

PubMed

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

2013-02-01

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

Guns on Campus: The Architecture and Momentum of State Policy Action

ERIC Educational Resources Information Center

Morse, Andrew; Sisneros, Lauren; Perez, Zeke; Sponsler, Brian A.

2016-01-01

"Guns on Campus: The Architecture and Momentum of State Policy Action" offers a detailed summary of state legislative action and higher education system policy decisions that have occurred in two specific categories: (1) States that have permitted or are seeking to permit guns on campus; and (2) States that have prohibited or are seeking…

The Student Actions Coding Sheet (SACS): An Instrument for Illuminating the Shifts toward Student-Centered Science Classrooms

ERIC Educational Resources Information Center

Erdogan, Ibrahim; Campbell, Todd; Abd-Hamid, Nor Hashidah

2011-01-01

This study describes the development of an instrument to investigate the extent to which student-centered actions are occurring in science classrooms. The instrument was developed through the following five stages: (1) student action identification, (2) use of both national and international content experts to establish content validity, (3)…

EDCs Mixtures: A Stealthy Hazard for Human Health?

PubMed

Ribeiro, Edna; Ladeira, Carina; Viegas, Susana

2017-02-07

Endocrine disrupting chemicals (EDCs) are exogenous chemicals that may occur naturally (e.g., phytoestrogens), while others are industrial substances and plasticizers commonly utilized worldwide to which human exposure, particularly at low-doses, is omnipresent, persistent and occurs in complex mixtures. EDCs can interfere with/or mimic estrogenic hormones and, consequently, can simultaneously trigger diverse signaling pathways which result in diverse and divergent biological responses. Additionally, EDCs can also bioaccumulate in lipid compartments of the organism forming a mixed "body burden" of contaminants. Although the independent action of chemicals has been considered the main principle in EDCs mixture toxicity, recent studies have demonstrated that numerous effects cannot be predicted when analyzing single compounds independently. Co-exposure to these agents, particularly in critical windows of exposure, may induce hazardous health effects potentially associated with a complex "body burden" of different origins. Here, we performed an exhaustive review of the available literature regarding EDCs mixtures exposure, toxicity mechanisms and effects, particularly at the most vulnerable human life stages. Although the assessment of potential risks to human health due to exposure to EDCs mixtures is a major topic for consumer safety, information regarding effective mixtures effects is still scarce.

EDCs Mixtures: A Stealthy Hazard for Human Health?

PubMed Central

Ribeiro, Edna; Ladeira, Carina; Viegas, Susana

2017-01-01

Endocrine disrupting chemicals (EDCs) are exogenous chemicals that may occur naturally (e.g., phytoestrogens), while others are industrial substances and plasticizers commonly utilized worldwide to which human exposure, particularly at low-doses, is omnipresent, persistent and occurs in complex mixtures. EDCs can interfere with/or mimic estrogenic hormones and, consequently, can simultaneously trigger diverse signaling pathways which result in diverse and divergent biological responses. Additionally, EDCs can also bioaccumulate in lipid compartments of the organism forming a mixed “body burden” of contaminants. Although the independent action of chemicals has been considered the main principle in EDCs mixture toxicity, recent studies have demonstrated that numerous effects cannot be predicted when analyzing single compounds independently. Co-exposure to these agents, particularly in critical windows of exposure, may induce hazardous health effects potentially associated with a complex “body burden” of different origins. Here, we performed an exhaustive review of the available literature regarding EDCs mixtures exposure, toxicity mechanisms and effects, particularly at the most vulnerable human life stages. Although the assessment of potential risks to human health due to exposure to EDCs mixtures is a major topic for consumer safety, information regarding effective mixtures effects is still scarce. PMID:29051438

Behavioural effects of compounds co-consumed in dietary forms of caffeinated plants.

PubMed

Haskell, C F; Dodd, F L; Wightman, E L; Kennedy, D O

2013-06-01

Research into the cognitive and mood effects of caffeine in human subjects has highlighted some fairly robust and well-accepted effects. However, the majority of these studies have focused on caffeine in isolation; whilst caffeine is normally consumed in the form of plant-derived products and extracts that invariably contain other potentially bioactive phytochemicals. The aim of the present review is to consider the possible mechanisms of action of co-occurring phytochemicals, and any epidemiological evidence suggesting that they contribute to potential health benefits ascribed to caffeine. Intervention studies to date that have been conducted to explore the effects on brain function of the non-caffeine components in caffeine-bearing plants (coffee, tea, cocoa, guaraná), either alone or in combination with caffeine, will also be summarised. Research is beginning to accumulate showing independent effects for several of the phytochemicals that co-occur with caffeine, and/or a modulation of the effects of caffeine when it is co-consumed with these naturally concomitant phytochemicals. The present review highlights that more research aimed at understanding the effects of these compounds is needed and, more importantly, the synergistic relationship that they may have with caffeine.

Preictal Activity of Subicular, CA1, and Dentate Gyrus Principal Neurons in the Dorsal Hippocampus before Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

PubMed Central

Fujita, Satoshi; Toyoda, Izumi; Thamattoor, Ajoy K.

2014-01-01

Previous studies suggest that spontaneous seizures in patients with temporal lobe epilepsy might be preceded by increased action potential firing of hippocampal neurons. Preictal activity is potentially important because it might provide new opportunities for predicting when a seizure is about to occur and insight into how spontaneous seizures are generated. We evaluated local field potentials and unit activity of single, putative excitatory neurons in the subiculum, CA1, CA3, and dentate gyrus of the dorsal hippocampus in epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Average action potential firing rates of neurons in the subiculum, CA1, and dentate gyrus, but not CA3, increased significantly and progressively beginning 2–4 min before locally recorded spontaneous seizures. In the subiculum, CA1, and dentate gyrus, but not CA3, 41–57% of neurons displayed increased preictal activity with significant consistency across multiple seizures. Much of the increased preictal firing of neurons in the subiculum and CA1 correlated with preictal theta activity, whereas preictal firing of neurons in the dentate gyrus was independent of theta. In addition, some CA1 and dentate gyrus neurons displayed reduced firing rates preictally. These results reveal that different hippocampal subregions exhibit differences in the extent and potential underlying mechanisms of preictal activity. The finding of robust and significantly consistent preictal activity of subicular, CA1, and dentate neurons in the dorsal hippocampus, despite the likelihood that many seizures initiated in other brain regions, suggests the existence of a broader neuronal network whose activity changes minutes before spontaneous seizures initiate. PMID:25505320

Sodium and calcium currents shape action potentials in immature mouse inner hair cells

PubMed Central

Marcotti, Walter; Johnson, Stuart L; Rüsch, Alfons; Kros, Corné J

2003-01-01

Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both α1D (Cav1.3) Ca2+ and Na+ currents that activate near the resting potential, we examined whether these two conductances are involved in shaping the action potentials. Both had extremely rapid activation kinetics, followed by fast and complete voltage-dependent inactivation for the Na+ current, and slower, partially Ca2+-dependent inactivation for the Ca2+ current. Only the Ca2+ current is necessary for spontaneous and induced action potentials, and 29 % of cells lacked a Na+ current. The Na+ current does, however, shorten the time to reach the action-potential threshold, whereas the Ca2+ current is mainly involved, together with the K+ currents, in determining the speed and size of the spikes. Both currents increased in size up to the end of the first postnatal week. After this, the Ca2+ current reduced to about 30 % of its maximum size and persisted in mature IHCs. The Na+ current was downregulated around the onset of hearing, when the spiking is also known to disappear. Although the Na+ current was observed as early as embryonic day 16.5, its role in action-potential generation was only evident from just after birth, when the resting membrane potential became sufficiently negative to remove a sizeable fraction of the inactivation (half inactivation was at −71 mV). The size of both currents was positively correlated with the developmental change in action-potential frequency. PMID:12937295

Advances in neuroprosthetic learning and control.

PubMed

Carmena, Jose M

2013-01-01

Significant progress has occurred in the field of brain-machine interfaces (BMI) since the first demonstrations with rodents, monkeys, and humans controlling different prosthetic devices directly with neural activity. This technology holds great potential to aid large numbers of people with neurological disorders. However, despite this initial enthusiasm and the plethora of available robotic technologies, existing neural interfaces cannot as yet master the control of prosthetic, paralyzed, or otherwise disabled limbs. Here I briefly discuss recent advances from our laboratory into the neural basis of BMIs that should lead to better prosthetic control and clinically viable solutions, as well as new insights into the neurobiology of action.

[Extravasation of Cytostatic Drugs - Prevention and Best Practices].

PubMed

Maňásek, V

2016-01-01

Extravasation is the leakage of a drug (intended primarily for intravenous administration) into tissues surrounding the vascular system. The damage to surrounding varies depending on the nature and volume of extravasation. Cytostatic extravasation is associated with poor outcomes for patients. This paper summarizes the types of risk associated with cytostatic extravasation, and the preventative measures that can be used when such an event occurs. We also provide information on potential treatments. However, justification for their use has only been substantiated in papers with different levels of significance and these papers are not available in all countries. We summarize current international recommendations for actions to be taken in the event of extravasation.

Advances in Neuroprosthetic Learning and Control

PubMed Central

Carmena, Jose M.

2013-01-01

Significant progress has occurred in the field of brain–machine interfaces (BMI) since the first demonstrations with rodents, monkeys, and humans controlling different prosthetic devices directly with neural activity. This technology holds great potential to aid large numbers of people with neurological disorders. However, despite this initial enthusiasm and the plethora of available robotic technologies, existing neural interfaces cannot as yet master the control of prosthetic, paralyzed, or otherwise disabled limbs. Here I briefly discuss recent advances from our laboratory into the neural basis of BMIs that should lead to better prosthetic control and clinically viable solutions, as well as new insights into the neurobiology of action. PMID:23700383

Biochar from Biomass and its Potential Agronomic and Environmental Use in Washington: A Promising Alternative to Drawdown Carbon from the Atmosphere and Develop a New Industry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amonette, James E.; Garcia-Perez, Manuel; Sjoding, David

2016-03-04

Climate change is one of the most serious issues facing the world today. Increasing concentrations of carbon dioxide (CO 2) and other long-lived greenhouse gases (GHGs) in the atmosphere continue to warm the planet and destabilize the climate. It has been estimated that the impact from this warming could cost the state 10 billion per year by 2020, and 16 billion per year by 2040. Long-term solutions to the climate problem likely will require that large quantities of CO 2 be removed from the atmosphere. In fact, massive CO 2 drawdowns from the atmosphere have occurred in earth’s recent pastmore » from events occurring in our hemisphere. Studies of those analogs provide insight into the potential magnitude for specific actions to drawdown significant CO 2 from the atmosphere. One of these potential actions is the large-scale production of biochar from abundant woody biomass waste and its storage in soils, where it remains stable for hundreds to thousands of years. Moreover, for the carbon emission intensity of Washington’s fuel mix, biochar production from biomass is twice as effective in offsetting GHG emissions as complete biomass combustion of the same biomass. Washington State has large quantities of wood waste biomass that could be purposed for production of combined heat/power/biochar (CHPB) through existing biomass boilers. We propose to 1) evaluate the quantities of Washington wood waste biomass, 2) inventory existing boiler capacity and assess the technical merits and challenges to repurpose the boilers to CHPB, and 3) apply literature values and analog biochar examples to better quantify the extent of CO 2 drawdown that could be achieved in Washington State over the next century using engineered biochar. This white paper explores the potential to replicate the historical drawdowns of atmospheric CO 2, a topic the authors think should be part of current climate-change mitigation discussions. This document is a companion to a white paper titled Biochar from Wood Biomass and Agricultural Residues and its Potential Agronomic Use in Washington: A Tool to Improve Irrigation Water Use Efficiency, Energy Efficiency and Sequester Carbon (Amonette, et al., 2016, in preparation).« less

Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings.

PubMed

Zoeller, R T; Rovet, J

2004-10-01

Abstract The original concept of the critical period of thyroid hormone (TH) action on brain development was proposed to identify the postnatal period during which TH supplement must be provided to a child with congenital hypothyroidism to prevent mental retardation. As neuropsychological tools have become more sensitive, it has become apparent that even mild TH insufficiency in humans can produce measurable deficits in very specific neuropsychological functions, and that the specific consequences of TH deficiency depends on the precise developmental timing of the deficiency. Models of maternal hypothyroidism, hypothyroxinaemia and congenital hyperthyroidism have provided these insights. If the TH deficiency occurs early in pregnancy, the offspring display problems in visual attention, visual processing (i.e. acuity and strabismus) and gross motor skills. If it occurs later in pregnancy, children are at additional risk of subnormal visual (i.e. contrast sensitivity) and visuospatial skills, as well as slower response speeds and fine motor deficits. Finally, if TH insufficiency occurs after birth, language and memory skills are most predominantly affected. Although the experimental literature lags behind clinical studies in providing a mechanistic explanation for each of these observations, recent studies confirm that the specific action of TH on brain development depends upon developmental timing, and studies informing us about molecular mechanisms of TH action are generating hypotheses concerning possible mechanisms to account for these pleiotropic actions.

Opioids and the immune system: what is their mechanism of action?

PubMed Central

Eisenstein, Toby K

2011-01-01

There is a significant amount of literature showing that morphine and other opioids modulate immune responses. The findings support many mechanisms by which this may occur. In vitro experiments provide evidence for direct actions of opioids on immune cells using a variety of functional end points. When these drugs are given in vivo, a plethora of immune parameters are also altered. The paper in this issue of the journal by Zhang et al. provides new information on morphine alteration of immune cell subsets in the spleen and thymus of mice and the potential role of glucocorticoids in these observed phenomena. This Commentary reviews the in vitro activities of morphine on leucocytes, as well as other documented mechanisms by which morphine can alter immune function in vivo. LINKED ARTICLE This article is a commentary on Zhang et al., pp. 1829–1844 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2011.01475.x PMID:21627636

Associations between errors and contributing factors in aircraft maintenance

NASA Technical Reports Server (NTRS)

Hobbs, Alan; Williamson, Ann

2003-01-01

In recent years cognitive error models have provided insights into the unsafe acts that lead to many accidents in safety-critical environments. Most models of accident causation are based on the notion that human errors occur in the context of contributing factors. However, there is a lack of published information on possible links between specific errors and contributing factors. A total of 619 safety occurrences involving aircraft maintenance were reported using a self-completed questionnaire. Of these occurrences, 96% were related to the actions of maintenance personnel. The types of errors that were involved, and the contributing factors associated with those actions, were determined. Each type of error was associated with a particular set of contributing factors and with specific occurrence outcomes. Among the associations were links between memory lapses and fatigue and between rule violations and time pressure. Potential applications of this research include assisting with the design of accident prevention strategies, the estimation of human error probabilities, and the monitoring of organizational safety performance.

How the Context Matters. Literal and Figurative Meaning in the Embodied Language Paradigm

PubMed Central

Cuccio, Valentina; Ambrosecchia, Marianna; Ferri, Francesca; Carapezza, Marco; Lo Piparo, Franco; Fogassi, Leonardo; Gallese, Vittorio

2014-01-01

The involvement of the sensorimotor system in language understanding has been widely demonstrated. However, the role of context in these studies has only recently started to be addressed. Though words are bearers of a semantic potential, meaning is the product of a pragmatic process. It needs to be situated in a context to be disambiguated. The aim of this study was to test the hypothesis that embodied simulation occurring during linguistic processing is contextually modulated to the extent that the same sentence, depending on the context of utterance, leads to the activation of different effector-specific brain motor areas. In order to test this hypothesis, we asked subjects to give a motor response with the hand or the foot to the presentation of ambiguous idioms containing action-related words when these are preceded by context sentences. The results directly support our hypothesis only in relation to the comprehension of hand-related action sentences. PMID:25531530

Who Is Experiencing What Kind of Moral Distress? Distinctions for Moving from a Narrow to a Broad Definition of Moral Distress.

PubMed

Fourie, Carina

2017-06-01

Moral distress, according to Andrew Jameton's highly influential definition, occurs when a nurse knows the morally correct action to take but is constrained in some way from taking this action. The definition of moral distress has been broadened, first, to include morally challenging situations that give rise to distress but which are not necessarily linked to nurses feeling constrained, such as those associated with moral uncertainty. Second, moral distress has been broadened so that it is not confined to the experiences of nurses. However, such a broadening of the concept does not mean that the kind of moral distress being experienced, or the role of the person experiencing it, is morally irrelevant. I argue that differentiating between categories of distress-e.g., constraint and uncertainty-and between groups of health professionals who might experience moral distress is potentially morally relevant and should influence the analysis, measurement, and amelioration of moral distress in the clinic. © 2017 American Medical Association. All Rights Reserved.

[Effect of arsenic and its compounds on the circulatory system].

PubMed

Sieradzki, A; Skoczyńska, A; Andrzejak, R

2000-01-01

Arsenic is a metal which occurs widely in both occupational and physical environments. Therefore, its easy accessibility and high toxicity raise the question on whether arsenic, particularly in relatively small doses, can cause damage of relevant molecular, biochemical and clinical significance to the cardiovascular system. The present review is focused on the confirmed and potential mechanisms of arsenic effect on the function and structure of vascular endothelium (nitric oxide, peroxynitrite), its role in stimulating the oxidative species formation (hydroxyperoxide, superoxide and lipid peroxide formation), as well as in decreasing the antioxidative response (enzymes: superoxide dysmutase, catalase, glutation peroxidase), its cytotoxic effects, including immunotoxic properties, arsenic action in the signal transduction pathways network (kinases and DNA transcription factors), impact on cell proliferation, differentiation and apoptosis, not to mention its interference with DNA synthesis and repair processes. Apart from mechanisms of arsenic action, the article provides the up-to-date information on various cardiovascular diseases of the established or presumed arsenic origin.

Resveratrol and diabetes: A critical review of clinical studies.

PubMed

Öztürk, Ebru; Arslan, Ayşe Kübra Karaboğa; Yerer, Mükerrem Betül; Bishayee, Anupam

2017-11-01

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia. The disease results from the defects of insulin secretion and/or action. Resveratrol is a non-flavonoid polyphenol that naturally occurs as phytoalexin. The shell and stem of Vitis vinifera L. (Vitaceae) are the richest source of this compound. In addition to various in vitro and in vivo studies revealing the effectiveness of resveratrol in DM, there are many clinical trials indicating that resveratrol has the potential to benefit in DM patients. The therapeutic action of this compound in relation to diabetes is complex and involves in several beneficial roles. In view of this, clinical studies are necessary to elucidate these roles. In the near future, the use of resveratrol, alone or in combination with current anti-diabetic therapies, might be a conventional approach to effectively manage DM or its complications. This mini-review provides a critical overview of currently available clinical studies examining the effects of resveratrol in DM last decade. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Visible-light vertical-cavity surface-emitting lasers grown by solid-source molecular beam epitaxy

NASA Astrophysics Data System (ADS)

Saarinen, Mika J.; Xiang, Ning; Dumitrescu, Mihail M.; Vilokkinen, Ville; Melanen, Petri; Orsila, Seppo; Uusimaa, Petteri; Savolainen, Pekka; Pessa, Markus

2001-05-01

Visible vertical-cavity surface-emitting lasers (VCSELs) are potential light sources for polymer optical fibre (POF) data transmission systems. Minimum attenuation of light in standard PMMA-POFs occurs at about 650 nm. For POFs of a few tens of meters in length VCSELs at slightly longer wavelengths (670 - 690 nm) are also acceptable. So far, the visible VCSELs have been grown by metal organic chemical vapour deposition (MOCVD). They may also be grown by a novel variant of molecular beam epitaxy (MBE), a so-called all-solid-source MBE or SSMBE. In this paper, we describe growth of the first visible-light VCSELs by SSMBE and present the main results obtained. In particular, we have achieved lasing action at a sub-milliamp cw drive current for a VCSEL having the emission window of 8um in diameter, while a 10um device exhibited an external quantum efficiency of 6.65% in CW operation at room temperature. The lasing action up to temperature of 45°C has been demonstrated.

A method for recording resistance changes non-invasively during neuronal depolarization with a view to imaging brain activity with electrical impedance tomography.

PubMed

Gilad, Ori; Ghosh, Anthony; Oh, Dongin; Holder, David S

2009-05-30

Electrical impedance tomography (EIT) is a recently developed medical imaging method which has the potential to produce images of fast neuronal depolarization in the brain. The principle is that current remains in the extracellular space at rest but passes into the intracellular space during depolarization through open ion channels. As current passes into the intracellular space across the capacitance of cell membranes at higher frequencies, applied current needs to be below 100 Hz. A method is presented for its measurement with subtraction of the contemporaneous evoked potentials which occur in the same frequency band. Neuronal activity is evoked by stimulation and resistance is recorded from the potentials resulting from injection of a constant current square wave at 1 Hz with amplitude less than 25% of the threshold for stimulating neuronal activity. Potentials due to the evoked activity and the injected square wave are removed by subtraction. The method was validated with compound action potentials in crab walking leg nerve. Resistance changes of -0.85+/-0.4% (mean+/-SD) occurred which decreased from -0.97+/-0.43% to -0.46+/-0.16% with spacing of impedance current application electrodes from 2 to 8 mm but did not vary significantly with applied currents of 1-10 microA. These tallied with biophysical modelling, and so were consistent with a genuine physiological origin. This method appears to provide a reproducible and artefact free means for recording resistance changes during neuronal activity which could lead to the long-term goal of imaging of fast neural activity in the brain.

Mood effects of antiepileptic drugs.

PubMed

Reijs, Rianne; Aldenkamp, Albert P; De Krom, Marc

2004-02-01

This article reviews our knowledge about a specific subgroup of chronic CNS-related side effects of antiepileptic drugs (AED) treatment, i.e., the effects of AEDs on mood. In line with a recent hypothesis, using the experience of AED treatment in psychiatry, we examined whether mood effects are related to the known anticonvulsant mechanisms of action of the AEDs. Specifically we examined whether AEDs, acting through potentiation of GABAergic neurotransmitter release, have "sedating" effects on mood, whereas AEDs that act through the reduction of excitatory glutamate neurotransmitter release have "activating" effects on mood. The results of this review yield evidence that there are relationships between the known anticonvulsant mechanisms of action of the AEDs and mood effects. Mood effects occur especially when the drugs have a sustained effect on neuronal mechanisms, in particular when the inhibitory or excitatory neurotransmitter release is altered. Drugs with "use-dependent" impact on sodium or calcium channels probably have a more transient impact and do not lead to interictal stable mood effects. Drugs with multiple mechanisms of action seem to combine a favorable efficacy profile with an increased risk of severe mood problems. The quality of the evidence, however, is not conclusive and there are many paradoxical results. One reason for this lack of "fit" may be the use in this review of a simplified classification, based only on the predominant mechanism of action to classify a drug. Only a limited number of AEDs (ethosuximide, tiagabine) are characterized by a single anticonvulsant mechanism of action. Probably more detailed coupling of mechanisms of action (e.g., inspecting the type and route of impact on GABA release) and mood effects may give less confusing results. The use of magnetic resonance imaging techniques such as spectroscopy may provide interesting results.

Formation of correlated states and tunneling for a low energy and controlled pulsed action on particles

NASA Astrophysics Data System (ADS)

Vysotskii, V. I.; Vysotskyy, M. V.

2017-08-01

We consider a method for optimizing the tunnel effect for low-energy particles by using coherent correlated states formed under controllable pulsed action on these particles. Typical examples of such actions are the effect of a pulsed magnetic field on charged particles in a gas or plasma. Coherent correlated states are characterized most comprehensively by the correlation coefficient r( t); an increase of this factor elevates the probability of particle tunneling through a high potential barrier by several orders of magnitude without an appreciable increase in their energy. It is shown for the first time that the formation of coherent correlated states, as well as maximal | r( t)|max and time-averaged 〈| r( t)|〉 amplitudes of the correlation coefficient and the corresponding tunneling probability are characterized by a nonmonotonic (oscillating) dependence on the forming pulse duration and amplitude. This result makes it possible to optimize experiments on the realization of low-energy nuclear fusion and demonstrates the incorrectness of the intuitive idea that the tunneling probability always increases with the amplitude of an external action on a particle. Our conclusions can be used, in particular, for explaining random (unpredictable and low-repeatability) experimental results on optimization of energy release from nuclear reactions occurring under a pulsed action with fluctuations of the amplitude and duration. We also consider physical premises for the observed dependences and obtain optimal relations between the aforementioned parameters, which ensure the formation of an optimal coherent correlated state and optimal low-energy tunneling in various physical systems with allowance for the dephasing action of a random force. The results of theoretical analysis are compared with the data of successful experiments on the generation of neutrons and alpha particles in an electric discharge in air and gaseous deuterium.

Fitness Assessment Comparison Between the “Jackie Chan Action Run” Videogame, 1-Mile Run/Walk, and the PACER

PubMed Central

Siegel, Shannon; Costa, Pablo; Jarvis, Sarah; Klug, Nicholas; Medina, Ernie; Wilkin, Linda

2012-01-01

Abstract Objective The purpose of this study was to examine whether a correlation existed among the scores of the “Jackie Chan Studio Fitness™ Action Run” active videogame (XaviX®, SSD Company, Ltd., Kusatsu, Japan), the 1-mile run/walk, and Progressive Aerobic Cardiovascular Endurance Run (PACER) aerobic fitness tests of the FITNESSGRAM® (The Cooper Institute, Dallas, TX) in order to provide a potential alternative testing method for days that are not environmentally desirable for outdoor testing. Subjects and Methods Participants were a convenience sample from physical education classes of students between the ages of 10 and 15 years. Participants (n=108) were randomly assigned to one of three groups with the only difference being the order of testing. The tests included the “Jackie Chan Action Run” active videogame, the 1-mile run/walk, and the PACER. Testing occurred on three different days during the physical education class. Rating of perceived exertion (RPE) was reported. Results Significant correlations (r=−0.598 to 0.312) were found among the three aerobic fitness tests administered (P<0.05). The RPE for the “Jackie Chan Action Run” was lower than the RPE for the 1-mile run/walk and the PACER (3.81±1.89, 5.93±1.77, and 5.71±2.14, respectively). Conclusions The results suggest that the “Jackie Chan Action Run” test could be an alternative to the 1-mile run/walk and PACER, allowing physical education teachers to perform aerobic fitness testing in an indoor setting that requires less space. Also, children may be more willing to participate in the “Jackie Chan Action Run” based on the lower RPE. PMID:26193440

Fitness Assessment Comparison Between the "Jackie Chan Action Run" Videogame, 1-Mile Run/Walk, and the PACER.

PubMed

Haddock, Bryan; Siegel, Shannon; Costa, Pablo; Jarvis, Sarah; Klug, Nicholas; Medina, Ernie; Wilkin, Linda

2012-06-01

The purpose of this study was to examine whether a correlation existed among the scores of the "Jackie Chan Studio Fitness(™) Action Run" active videogame (XaviX(®), SSD Company, Ltd., Kusatsu, Japan), the 1-mile run/walk, and Progressive Aerobic Cardiovascular Endurance Run (PACER) aerobic fitness tests of the FITNESSGRAM(®) (The Cooper Institute, Dallas, TX) in order to provide a potential alternative testing method for days that are not environmentally desirable for outdoor testing. Participants were a convenience sample from physical education classes of students between the ages of 10 and 15 years. Participants (n=108) were randomly assigned to one of three groups with the only difference being the order of testing. The tests included the "Jackie Chan Action Run" active videogame, the 1-mile run/walk, and the PACER. Testing occurred on three different days during the physical education class. Rating of perceived exertion (RPE) was reported. Significant correlations (r=-0.598 to 0.312) were found among the three aerobic fitness tests administered (P<0.05). The RPE for the "Jackie Chan Action Run" was lower than the RPE for the 1-mile run/walk and the PACER (3.81±1.89, 5.93±1.77, and 5.71±2.14, respectively). The results suggest that the "Jackie Chan Action Run" test could be an alternative to the 1-mile run/walk and PACER, allowing physical education teachers to perform aerobic fitness testing in an indoor setting that requires less space. Also, children may be more willing to participate in the "Jackie Chan Action Run" based on the lower RPE.

Rapid Ca2+ flux through the transverse tubular membrane, activated by individual action potentials in mammalian skeletal muscle

PubMed Central

Launikonis, Bradley S; Stephenson, D George; Friedrich, Oliver

2009-01-01

Periods of low frequency stimulation are known to increase the net Ca2+ uptake in skeletal muscle but the mechanism responsible for this Ca2+ entry is not known. In this study a novel high-resolution fluorescence microscopy approach allowed the detection of an action potential-induced Ca2+ flux across the tubular (t-) system of rat extensor digitorum longus muscle fibres that appears to be responsible for the net uptake of Ca2+ in working muscle. Action potentials were triggered in the t-system of mechanically skinned fibres from rat by brief field stimulation and t-system [Ca2+] ([Ca2+]t-sys) and cytoplasmic [Ca2+] ([Ca2+]cyto) were simultaneously resolved on a confocal microscope. When initial [Ca2+]t-sys was ≥ 0.2 mm a Ca2+ flux from t-system to the cytoplasm was observed following a single action potential. The action potential-induced Ca2+ flux and associated t-system Ca2+ permeability decayed exponentially and displayed inactivation characteristics such that further Ca2+ entry across the t-system could not be observed after 2–3 action potentials at 10 Hz stimulation rate. When [Ca2+]t-sys was closer to 0.1 mm, a transient rise in [Ca2+]t-sys was observed almost concurrently with the increase in [Ca2+]cyto following the action potential. The change in direction of Ca2+ flux was consistent with changes in the direction of the driving force for Ca2+. This is the first demonstration of a rapid t-system Ca2+ flux associated with a single action potential in mammalian skeletal muscle. The properties of this channel are inconsistent with a flux through the L-type Ca2+ channel suggesting that an as yet unidentified t-system protein is conducting this current. This action potential-activated Ca2+ flux provides an explanation for the previously described Ca2+ entry and accumulation observed with prolonged, intermittent muscle activity. PMID:19332499

Botulinum Toxin Type a as a Therapeutic Agent against Headache and Related Disorders.

PubMed

Luvisetto, Siro; Gazerani, Parisa; Cianchetti, Carlo; Pavone, Flaminia

2015-09-23

Botulinum neurotoxin A (BoNT/A) is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a "glamour" drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A.

Amphetamine Paradoxically Augments Exocytotic Dopamine Release and Phasic Dopamine Signals

PubMed Central

Daberkow, DP; Brown, HD; Bunner, KD; Kraniotis, SA; Doellman, MA; Ragozzino, ME; Garris, PA; Roitman, MF

2013-01-01

Drugs of abuse hijack brain reward circuitry during the addiction process by augmenting action potential-dependent phasic dopamine release events associated with learning and goal-directed behavior. One prominent exception to this notion would appear to be amphetamine (AMPH) and related analogs, which are proposed instead to disrupt normal patterns of dopamine neurotransmission by depleting vesicular stores and promoting non-exocytotic dopamine efflux via reverse transport. This mechanism of AMPH action, though, is inconsistent with its therapeutic effects and addictive properties - which are thought to be reliant on phasic dopamine signaling. Here we used fast-scan cyclic voltammetry in freely moving rats to interrogate principal neurochemical responses to AMPH in the striatum and relate these changes to behavior. First, we showed that AMPH dose-dependently enhanced evoked dopamine responses to phasic-like current pulse trains for up to two hours. Modeling the data revealed that AMPH inhibited dopamine uptake but also unexpectedly potentiated vesicular dopamine release. Second, we found that AMPH increased the amplitude, duration and frequency of spontaneous dopamine transients, the naturally occurring, non-electrically evoked, phasic increases in extracellular dopamine. Finally, using an operant sucrose reward paradigm, we showed that low-dose AMPH augmented dopamine transients elicited by sucrose-predictive cues. However, operant behavior failed at high-dose AMPH, which was due to phasic dopamine hyperactivity and the decoupling of dopamine transients from the reward predictive cue. These findings identify up-regulation of exocytotic dopamine release as a key AMPH action in behaving animals and support a unified mechanism of abused drugs to activate phasic dopamine signaling. PMID:23303926

Using a food web model to inform the design of river restoration—An example at the Barkley Bear Segment, Methow River, north-central Washington

USGS Publications Warehouse

Benjamin, Joseph R.; Bellmore, J. Ryan; Dombroski, Daniel

2018-01-29

With the decline of Chinook salmon (Oncorhynchus tshawytscha) and steelhead (O. mykiss), habitat restoration actions in freshwater tributaries have been implemented to improve conditions for juveniles. Typically, physical (for example, hydrologic and engineering) based models are used to design restoration alternatives with the assumption that biological responses will be improved with changes to the physical habitat. Biological models rarely are used. Here, we describe simulations of a food web model, the Aquatic Trophic Productivity (ATP) model, to aid in the design of a restoration project in the Methow River, north-central Washington. The ATP model mechanistically links environmental conditions of the stream to the dynamics of river food webs, and can be used to simulate how alternative river restoration designs influence the potential for river reaches to sustain fish production. Four restoration design alternatives were identified that encompassed varying levels of side channel and floodplain reconnection and large wood addition. Our model simulations suggest that design alternatives focused on reconnecting side channels and the adjacent floodplain may provide the greatest increase in fish capacity. These results were robust to a range of discharge and thermal regimes that naturally occur in the Methow River. Our results suggest that biological models, such as the ATP model, can be used during the restoration planning phase to increase the effectiveness of restoration actions. Moreover, the use of multiple modeling efforts, both physical and biological, when evaluating restoration design alternatives provides a better understanding of the potential outcome of restoration actions.

Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders

PubMed Central

Luvisetto, Siro; Gazerani, Parisa; Cianchetti, Carlo; Pavone, Flaminia

2015-01-01

Botulinum neurotoxin A (BoNT/A) is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a “glamour” drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A. PMID:26404377

Factual and Counterfactual Action-Outcome Mappings Control Choice between Goal-Directed Actions in Rats.

PubMed

Laurent, Vincent; Balleine, Bernard W

2015-04-20

The capacity to extract causal knowledge from the environment allows us to predict future events and to use those predictions to decide on a course of action. Although evidence of such causal reasoning has long been described, recent evidence suggests that using predictive knowledge to guide decision-making in this way is predicated on reasoning about causes in two quite distinct ways: choosing an action can be based on the interaction between predictive information and the consequences of that action, or, alternatively, actions can be selected based on the consequences that they do not produce. The latter counterfactual reasoning is highly adaptive because it allows us to use information about both present and absent events to guide decision-making. Nevertheless, although there is now evidence to suggest that animals other than humans, including rats and birds, can engage in causal reasoning of one kind or another, there is currently no evidence that they use counterfactual reasoning to guide choice. To assess this question, we gave rats the opportunity to learn new action-outcome relationships, after which we probed the structure of this learning by presenting excitatory and inhibitory cues predicting that the specific outcomes of their actions would either occur or would not occur. Whereas the excitors biased choice toward the action delivering the predicted outcome, the inhibitory cues selectively elevated actions predicting the absence of the inhibited outcome, suggesting that rats encoded the counterfactual action-outcome mappings and were able to use them to guide choice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Corrective Action Investigation Plan for Corrective Action Unit 127: Areas 25 and 26 Storage Tanks, Nevada Test Site, Nevada (Rev. No.: 0, August 2002)

DOE Office of Scientific and Technical Information (OSTI.GOV)

NNSA /NV

This Corrective Action Investigation Plan (CAIP) contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Offices's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 127 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 127 is located on the Nevada Test Site approximately 65 miles northwest of Las Vegas, Nevada. This CAU is comprised of 12 Corrective Action Sites (CASs) located at Test Cell C; the Engine Maintenance, Assembly, and Disassembly (E-MAD) Facility; the X-Tunnel in Area 25; the Pluto Disassembly Facility; themore » Pluto Check Station; and the Port Gaston Training Facility in Area 26. These CASs include: CAS 25-01-05, Aboveground Storage Tank (AST); CAS 25-02-02, Underground Storage Tank (UST); CAS 25-23-11, Contaminated Materials; CAS 25-12-01, Boiler; CAS 25-01-06, AST; CAS 25-01-07, AST; CAS 25-02-13, UST; CAS 26- 01-01, Filter Tank (Rad) and Piping; CAS 26-01-02, Filter Tank (Rad); CAS 26-99-01, Radioactively Contaminated Filters; CAS 26-02-01, UST; CAS 26-23-01, Contaminated Liquids Spreader. Based on site history, process knowledge, and previous field efforts, contaminants of potential concern for CAU 127 include radionuclides, metals, total petroleum hydrocarbons, volatile organic compounds, asbestos, and polychlorinated biphenyls. Additionally, beryllium may be present at some locations. The sources of potential releases are varied, but releases of contaminated liquids may have occurred and may have migrated into and impacted soil below and surrounding storage vessels at some of the CASs. Also, at several CASs, asbestos-containing materials may be present on the aboveground structures and may be friable. Exposure pathways are limited to ingestion, inhalation, and dermal contact (adsorption) of soils/sediments or liquids, or inhalation of contaminants by site workers due to disturbance of contaminated materials. Future land-use scenarios limit subsequent uses of the CASs to various nonresidential (i.e., industrial) activities. Field activities will consist of radiological walkover and screening surveys, and field-screening and collecting of both tank content and soil samples, and further sample testing as appropriate. A two-step data quality objective strategy will be followed: (1) Phase I will be to collect environmental samples for laboratory analysis to confirm the presence or absence of contaminants at concentrations exceeding preliminary action levels; and (2) Phase II will be to collect additional environmental samples for laboratory analysis to determine the extent of contamination identified in Phase I. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document.« less

Controlled free radical attack in the apoplast: A hypothesis for roles of O, N and S species in regulatory and polysaccharide cleavage events during rapid abscission by Azolla

PubMed Central

Cohen, Michael F.; Gurung, Sushma; Fukuto, Jon M.; Yamasaki, Hideo

2014-01-01

Shedding of organs by abscission is a key terminal step in plant development and stress responses. Cell wall (CW) loosening at the abscission zone can occur through a combination chain breakage of apoplastic polysaccharides and tension release of cellulose microfibrils. Two distinctly regulated abscission cleavage events are amenable to study in small water ferns of the genus Azolla; one is a rapid abscission induced by environmental stimuli such as heat or chemicals, and the other is an ethylene-induced process occurring more slowly through the action of hydrolytic enzymes. Although free radicals are suggested to be involved in the induction of rapid root abscission, its mechanism is not fully understood. The apoplast contains peroxidases, metal-binding proteins and phenolic compounds that potentially generate free radicals from H2O2 to cleave polysaccharides in the CW and middle lamella. Effects of various thiol-reactive agents implicate the action of apoplastic peroxidases having accessible cysteine thiols in rapid abscission. The Ca2+ dependency of rapid abscission may reflect the stabilization Ca2+ confers to peroxidase structure and binding to pectin. To spur further investigation, we present a hypothetical model for small signaling molecules H2O2 and NO and their derivatives in regulating, via modification of putative protein thiols, free radical attack of apoplastic polysaccharides. PMID:24467903

Common psychotic symptoms can be explained by the theory of ecological perception.

PubMed

Golembiewski, Jan Alexander

2012-01-01

The symptoms of psychiatric illness are diverse, as are the causes of the conditions that cause them. Yet, regardless of the heterogeneity of cause and presentation, a great deal of symptoms can be explained by the failure of a single perceptual function--the reprocessing of ecological perception. It is a central tenet of the ecological theory of perception that we perceive opportunities to act. It has also been found that perception automatically causes actions and thoughts to occur unless this primary action pathway is inhibited. Inhibition allows perceptions to be reprocessed into more appropriate alternative actions and thoughts. Reprocessing of this kind takes place over the entire frontal lobe and it renders action optional. Choice about what action to take (if any) is the basis for the feeling of autonomy and ultimately for the sense-of-self. When thoughts and actions occur automatically (without choice) they appear to originate outside of the self, thereby providing prima facie evidence for some of the bizarre delusions that define schizophrenia such as delusional misidentification, delusions of control and Cotard's delusion. Automatic actions and thoughts are triggered by residual stimulation whenever reprocessing is insufficient to balance automatic excitatory cues (for whatever reason). These may not be noticed if they are neutral and therefore unimportant or where actions and thoughts have a positive bias and are desirable. Responses to negative stimulus, on the other hand, are always unwelcome, because the actions that are triggered will carry the negative bias. Automatic thoughts may include spontaneous positive feelings of love and joy, but automatic negative thoughts and visualisations are experienced as hallucinations. Not only do these feel like they emerge from elsewhere but they carry a negative bias (they are most commonly critical, rude and are irrationally paranoid). Automatic positive actions may include laughter and smiling and these are welcome. Automatic behaviours that carry a negative bias, however, are unwelcome and like hallucinations, occur without a sense of choice. These include crying, stereotypies, perseveration, ataxia, utilization and imitation behaviours and catatonia. Copyright © 2011 Elsevier Ltd. All rights reserved.

Spiral-wave dynamics in a mathematical model of human ventricular tissue with myocytes and Purkinje fibers.

PubMed

Nayak, Alok Ranjan; Panfilov, A V; Pandit, Rahul

2017-02-01

We present systematic numerical studies of the possible effects of the coupling of human endocardial and Purkinje cells at cellular and two-dimensional tissue levels. We find that the autorhythmic-activity frequency of the Purkinje cell in a composite decreases with an increase in the coupling strength; this can even eliminate the autorhythmicity. We observe a delay between the beginning of the action potentials of endocardial and Purkinje cells in a composite; such a delay increases as we decrease the diffusive coupling, and eventually a failure of transmission occurs. An increase in the diffusive coupling decreases the slope of the action-potential-duration-restitution curve of an endocardial cell in a composite. By using a minimal model for the Purkinje network, in which we have a two-dimensional, bilayer tissue, with a layer of Purkinje cells on top of a layer of endocardial cells, we can stabilize spiral-wave turbulence; however, for a sparse distribution of Purkinje-ventricular junctions, at which these two layers are coupled, we can also obtain additional focal activity and many complex transient regimes. We also present additional effects resulting from the coupling of Purkinje and endocardial layers and discuss the relation of our results to the studies performed in anatomically accurate models of the Purkinje network.

Review article: potential mechanisms of action of rifaximin in the management of hepatic encephalopathy and other complications of cirrhosis.

PubMed

Bajaj, J S

2016-01-01

Progressive gut milieu (microbiota) changes occur in patients with cirrhosis and are associated with complications [e.g. hepatic encephalopathy (HE)]. To examine the role of rifaximin in the management of HE and other complications of cirrhosis, including potential mechanisms of action and the need for future studies. A literature search was conducted using the keywords 'rifaximin', 'hepatic encephalopathy', 'ascites', 'variceal bleeding', 'peritonitis', 'portal hypertension', 'portopulmonary hypertension' and 'hepatorenal syndrome'. The nonsystemic agent rifaximin reduces the risk of HE recurrence and HE-related hospitalisations in cirrhosis. In patients with cirrhosis, rifaximin modulates the bacterial composition of the gut microbiota without a consistent effect on overall faecal microbiota composition. However, rifaximin can impact the function or activities of the gut microbiota. For example, rifaximin significantly increased serum levels of long-chain fatty acids and carbohydrate metabolism intermediates in patients with minimal HE. Rifaximin also favourably affects serum proinflammatory cytokine and faecal secondary bile acid levels. The gut microenvironment and associated microbiota play an important role in the pathogenesis of HE and other cirrhosis-related complications. Rifaximin's clinical activity may be attributed to effects on metabolic function of the gut microbiota, rather than a change in the relative bacterial abundance. © 2015 John Wiley & Sons Ltd.

A cardiac electrical activity model based on a cellular automata system in comparison with neural network model.

PubMed

Khan, Muhammad Sadiq Ali; Yousuf, Sidrah

2016-03-01

Cardiac Electrical Activity is commonly distributed into three dimensions of Cardiac Tissue (Myocardium) and evolves with duration of time. The indicator of heart diseases can occur randomly at any time of a day. Heart rate, conduction and each electrical activity during cardiac cycle should be monitor non-invasively for the assessment of "Action Potential" (regular) and "Arrhythmia" (irregular) rhythms. Many heart diseases can easily be examined through Automata model like Cellular Automata concepts. This paper deals with the different states of cardiac rhythms using cellular automata with the comparison of neural network also provides fast and highly effective stimulation for the contraction of cardiac muscles on the Atria in the result of genesis of electrical spark or wave. The specific formulated model named as "States of automaton Proposed Model for CEA (Cardiac Electrical Activity)" by using Cellular Automata Methodology is commonly shows the three states of cardiac tissues conduction phenomena (i) Resting (Relax and Excitable state), (ii) ARP (Excited but Absolutely refractory Phase i.e. Excited but not able to excite neighboring cells) (iii) RRP (Excited but Relatively Refractory Phase i.e. Excited and able to excite neighboring cells). The result indicates most efficient modeling with few burden of computation and it is Action Potential during the pumping of blood in cardiac cycle.

Spontaneous and evoked release are independently regulated at individual active zones.

PubMed

Melom, Jan E; Akbergenova, Yulia; Gavornik, Jeffrey P; Littleton, J Troy

2013-10-30

Neurotransmitter release from synaptic vesicle fusion is the fundamental mechanism for neuronal communication at synapses. Evoked release following an action potential has been well characterized for its function in activating the postsynaptic cell, but the significance of spontaneous release is less clear. Using transgenic tools to image single synaptic vesicle fusion events at individual release sites (active zones) in Drosophila, we characterized the spatial and temporal dynamics of exocytotic events that occur spontaneously or in response to an action potential. We also analyzed the relationship between these two modes of fusion at single release sites. A majority of active zones participate in both modes of fusion, although release probability is not correlated between the two modes of release and is highly variable across the population. A subset of active zones is specifically dedicated to spontaneous release, indicating a population of postsynaptic receptors is uniquely activated by this mode of vesicle fusion. Imaging synaptic transmission at individual release sites also revealed general rules for spontaneous and evoked release, and indicate that active zones with similar release probability can cluster spatially within individual synaptic boutons. These findings suggest neuronal connections contain two information channels that can be spatially segregated and independently regulated to transmit evoked or spontaneous fusion signals.

Spiral-wave dynamics in a mathematical model of human ventricular tissue with myocytes and Purkinje fibers

NASA Astrophysics Data System (ADS)

Nayak, Alok Ranjan; Panfilov, A. V.; Pandit, Rahul

2017-02-01

We present systematic numerical studies of the possible effects of the coupling of human endocardial and Purkinje cells at cellular and two-dimensional tissue levels. We find that the autorhythmic-activity frequency of the Purkinje cell in a composite decreases with an increase in the coupling strength; this can even eliminate the autorhythmicity. We observe a delay between the beginning of the action potentials of endocardial and Purkinje cells in a composite; such a delay increases as we decrease the diffusive coupling, and eventually a failure of transmission occurs. An increase in the diffusive coupling decreases the slope of the action-potential-duration-restitution curve of an endocardial cell in a composite. By using a minimal model for the Purkinje network, in which we have a two-dimensional, bilayer tissue, with a layer of Purkinje cells on top of a layer of endocardial cells, we can stabilize spiral-wave turbulence; however, for a sparse distribution of Purkinje-ventricular junctions, at which these two layers are coupled, we can also obtain additional focal activity and many complex transient regimes. We also present additional effects resulting from the coupling of Purkinje and endocardial layers and discuss the relation of our results to the studies performed in anatomically accurate models of the Purkinje network.

29 CFR 1990.147 - Final action.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) IDENTIFICATION, CLASSIFICATION, AND REGULATION OF POTENTIAL OCCUPATIONAL CARCINOGENS Regulation of Potential Occupational Carcinogens § 1990.147 Final action. (a) Within one hundred twenty (120) days from the last day of... is classified as a Category I Potential Carcinogen or as a Category II Potential Carcinogen. If the...

29 CFR 1990.147 - Final action.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) IDENTIFICATION, CLASSIFICATION, AND REGULATION OF POTENTIAL OCCUPATIONAL CARCINOGENS Regulation of Potential Occupational Carcinogens § 1990.147 Final action. (a) Within one hundred twenty (120) days from the last day of... is classified as a Category I Potential Carcinogen or as a Category II Potential Carcinogen. If the...

29 CFR 1990.147 - Final action.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) IDENTIFICATION, CLASSIFICATION, AND REGULATION OF POTENTIAL OCCUPATIONAL CARCINOGENS Regulation of Potential Occupational Carcinogens § 1990.147 Final action. (a) Within one hundred twenty (120) days from the last day of... is classified as a Category I Potential Carcinogen or as a Category II Potential Carcinogen. If the...

29 CFR 1990.147 - Final action.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) IDENTIFICATION, CLASSIFICATION, AND REGULATION OF POTENTIAL OCCUPATIONAL CARCINOGENS Regulation of Potential Occupational Carcinogens § 1990.147 Final action. (a) Within one hundred twenty (120) days from the last day of... is classified as a Category I Potential Carcinogen or as a Category II Potential Carcinogen. If the...

Effect of Exogenous Extracellular Nicotinamide Adenine Dinucleotide (NAD⁺) on Bioelectric Activity of the Pacemaker and Conduction System of the Heart.

PubMed

Pustovit, K B; Kuz'min, V S; Sukhova, G S

2015-06-01

In rat sinoatrial node, NAD(+) (10 μM) reduced the rate of spontaneous action potentials, duration of action potentials, and the velocity of slow diastolic depolarization, but the rate of action potential front propagation increases. In passed rabbit Purkinje fibers, NAD(+) (10 μM) reduced the duration of action potentials. Under conditions of spontaneous activity of Purkinje fibers, NAD(+) reduced the fi ring rate and the rate of slow diastolic depolarization. The effects of extracellular NAD(+) on bioelectric activity of the pacemaker (sinoatrial node) and conduction system of the heart (Purkinje fibers) are probably related to activation of P1 and P2 purinoceptors.

ShakeCast: Automating and improving the use of shakemap for post-earthquake deeision-making and response

USGS Publications Warehouse

Wald, D.; Lin, K.-W.; Porter, K.; Turner, Loren

2008-01-01

When a potentially damaging earthquake occurs, utility and other lifeline managers, emergency responders, and other critical users have an urgent need for information about the impact on their particular facilities so they can make appropriate decisions and take quick actions to ensure safety and restore system functionality. ShakeMap, a tool used to portray the extent of potentially damaging shaking following an earthquake, on its own can be useful for emergency response, loss estimation, and public information. However, to take full advantage of the potential of ShakeMap, we introduce ShakeCast. ShakeCast facilitates the complicated assessment of potential damage to a user's widely distributed facilities by comparing the complex shaking distribution with the potentially highly variable damageability of their inventory to provide a simple, hierarchical list and maps of structures or facilities most likely impacted. ShakeCast is a freely available, post-earthquake situational awareness application that automatically retrieves earthquake shaking data from ShakeMap, compares intensity measures against users' facilities, sends notifications of potential damage to responsible parties, and generates facility damage maps and other Web-based products for both public and private emergency managers and responders. ?? 2008, Earthquake Engineering Research Institute.

Free-Riding and Free-Labor in Combinatorial Agency

NASA Astrophysics Data System (ADS)

Babaioff, Moshe; Feldman, Michal; Nisan, Noam

This paper studies a setting where a principal needs to motivate teams of agents whose efforts lead to an outcome that stochastically depends on the combination of agents’ actions, which are not directly observable by the principal. In [1] we suggest and study a basic “combinatorial agency” model for this setting. In this paper we expose a somewhat surprising phenomenon found in this setting: cases where the principal can gain by asking agents to reduce their effort level, even when this increased effort comes for free. This phenomenon cannot occur in a setting where the principal can observe the agents’ actions, but we show that it can occur in the hidden-actions setting. We prove that for the family of technologies that exhibit “increasing returns to scale” this phenomenon cannot happen, and that in some sense this is a maximal family of technologies for which the phenomenon cannot occur. Finally, we relate our results to a basic question in production design in firms.

Pyrrolizidine alkaloids (PAs) in honey and pollen-legal regulation of PA levels in food and animal feed required.

PubMed

Kempf, Michael; Reinhard, Annika; Beuerle, Till

2010-01-01

Pyrrolizidine alkaloids (PAs) are secondary plant constituents that comprise about 400 different structures and occur in two major forms, a tertiary form and the corresponding N-oxide. PAs containing a 1,2-double bond are pre-toxins and metabolically activated by the action of hepatic P-450 enzymes to toxic pyrroles. Besides the acute toxic effects, the genotoxic and tumorigenicity potential of PAs was demonstrated in some eukaryotic model systems. Recently, the potential PA contamination of food and feeding stuff attracted recurrent great deals of attention. Humans are exposed to these toxins by consumption of herbal medicine, herbal teas, dietary supplements or food containing PA plant material. In numerous studies the potential threat to human health by PAs is stated. In pharmaceuticals, the use of these plants is regulated. Considering the PA concentrations observed especially in authentic honey from PA producing plants and pollen products, the results provoke an international regulation of PAs in food.

Rapid time course of action potentials in spines and remote dendrites of mouse visual cortex neurons.

PubMed

Holthoff, Knut; Zecevic, Dejan; Konnerth, Arthur

2010-04-01

Axonally initiated action potentials back-propagate into spiny dendrites of central mammalian neurons and thereby regulate plasticity at excitatory synapses on individual spines as well as linear and supralinear integration of synaptic inputs along dendritic branches. Thus, the electrical behaviour of individual dendritic spines and terminal dendritic branches is critical for the integrative function of nerve cells. The actual dynamics of action potentials in spines and terminal branches, however, are not entirely clear, mostly because electrode recording from such small structures is not feasible. Additionally, the available membrane potential imaging techniques are limited in their sensitivity and require substantial signal averaging for the detection of electrical events at the spatial scale of individual spines. We made a critical improvement in the voltage-sensitive dye imaging technique to achieve multisite recordings of backpropagating action potentials from individual dendritic spines at a high frame rate. With this approach, we obtained direct evidence that in layer 5 pyramidal neurons from the visual cortex of juvenile mice, the rapid time course of somatic action potentials is preserved throughout all cellular compartments, including dendritic spines and terminal branches of basal and apical dendrites. The rapid time course of the action potential in spines may be a critical determinant for the precise regulation of spike timing-dependent synaptic plasticity within a narrow time window.

Spatio-temporal dynamics of action-effect associations in oculomotor control.

PubMed

Riechelmann, Eva; Pieczykolan, Aleksandra; Horstmann, Gernot; Herwig, Arvid; Huestegge, Lynn

2017-10-01

While there is ample evidence that actions are guided by anticipating their effects (ideomotor control) in the manual domain, much less is known about the underlying characteristics and dynamics of effect-based oculomotor control. Here, we address three open issues. 1) Is action-effect anticipation in oculomotor control reflected in corresponding spatial saccade characteristics in inanimate environments? 2) Does the previously reported dependency of action latency on the temporal effect delay (action-effect interval) also occur in the oculomotor domain? 3) Which temporal effect delay is optimally suited to develop strong action-effect associations over time in the oculomotor domain? Participants executed left or right free-choice saccades to peripheral traffic lights, causing an (immediate or delayed) action-contingent light switch in the upper vs. lower part of the traffic light. Results indicated that saccades were spatially shifted toward the location of the upcoming change, indicating anticipation of the effect (location). Saccade latency was affected by effect delay, suggesting that corresponding time information is integrated into event representations. Finally, delayed (vs. immediate) effects were more effective in strengthening action-effect associations over the course of the experiment, likely due to greater saliency of perceptual changes occurring during target fixation as opposed to changes during saccades (saccadic suppression). Overall, basic principles underlying ideomotor control appear to generalize to the oculomotor domain. Copyright © 2017 Elsevier B.V. All rights reserved.

22 CFR 161.8 - General description of the Department's NEPA process.

Code of Federal Regulations, 2010 CFR

2010-04-01

... § 161.8 General description of the Department's NEPA process. In reviewing proposed actions for potential environmental effects in the United States responsible action officers will follow the procedural... review the action to determine if it may cause potential significant environmental effects on the...

Prolonged action potential duration in cardiac ablation of PDK1 mice.

PubMed

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

2015-01-01

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

Back-Propagation of Physiological Action Potential Output in Dendrites of Slender-Tufted L5A Pyramidal Neurons

PubMed Central

Grewe, Benjamin F.; Bonnan, Audrey; Frick, Andreas

2009-01-01

Pyramidal neurons of layer 5A are a major neocortical output type and clearly distinguished from layer 5B pyramidal neurons with respect to morphology, in vivo firing patterns, and connectivity; yet knowledge of their dendritic properties is scant. We used a combination of whole-cell recordings and Ca2+ imaging techniques in vitro to explore the specific dendritic signaling role of physiological action potential patterns recorded in vivo in layer 5A pyramidal neurons of the whisker-related ‘barrel cortex’. Our data provide evidence that the temporal structure of physiological action potential patterns is crucial for an effective invasion of the main apical dendrites up to the major branch point. Both the critical frequency enabling action potential trains to invade efficiently and the dendritic calcium profile changed during postnatal development. In contrast to the main apical dendrite, the more passive properties of the short basal and apical tuft dendrites prevented an efficient back-propagation. Various Ca2+ channel types contributed to the enhanced calcium signals during high-frequency firing activity, whereas A-type K+ and BKCa channels strongly suppressed it. Our data support models in which the interaction of synaptic input with action potential output is a function of the timing, rate and pattern of action potentials, and dendritic location. PMID:20508744

Evoked potentials in final epoch of self-initiated hand movement: A study in patients with depth electrodes.

PubMed

Kukleta, Miloslav; Damborská, Alena; Turak, Baris; Louvel, Jacques

2017-07-01

Comparison between the intended and performed motor action can be expected to occur in the final epoch of a voluntary movement. In search for electrophysiological correlates of this mental process the purpose of the current study was to identify intracerebral sites activated in final epoch of self-paced voluntary movement. Intracerebral EEG was recorded from 235 brain regions of 42 epileptic patients who performed self-paced voluntary movement task. Evoked potentials starting at 0 to 243ms after the peak of averaged, rectified electromyogram were identified in 21 regions of 13 subjects. The mean amplitude value of these late movement potentials (LMP) was 56.4±27.5μV. LMPs were observed in remote regions of mesiotemporal structures, cingulate, frontal, temporal, parietal, and occipital cortices. Closely before the LMP onset, a significant increase of phase synchronization was observed in all EEG record pairs in 9 of 10 examined subjects; p<0.001, Mann-Whitney U test. In conclusion, mesiotemporal structures, cingulate, frontal, temporal, parietal, and occipital cortices seem to represent integral functionally linked parts of network activated in final epoch of self-paced voluntary movement. Activation of this large-scale neuronal network was suggested to reflect a comparison process between the intended and actually performed motor action. Our results contribute to better understanding of neural mechanisms underlying goal-directed behavior crucial for creation of agentive experience. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-08-01

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

Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus.

PubMed

Atherton, Jeremy F; Wokosin, David L; Ramanathan, Sankari; Bevan, Mark D

2008-12-01

The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na(+) (Na(v)) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrin G labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of approximately 5 m s(-1) and approximately 0.7 m s(-1), respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na(+)] ACSF or the selective Na(v) channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Na(v) channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABA(A) receptors regulates the axonal initiation of action potentials.

Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus

PubMed Central

Atherton, Jeremy F; Wokosin, David L; Ramanathan, Sankari; Bevan, Mark D

2008-01-01

The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na+ (Nav) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrin G labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of ∼5 m s−1 and ∼0.7 m s−1, respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na+] ACSF or the selective Nav channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Nav channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABAA receptors regulates the axonal initiation of action potentials. PMID:18832425

Ling's Adsorption Theory as a Mechanism of Membrane Potential Generation Observed in Both Living and Nonliving Systems.

PubMed

Tamagawa, Hirohisa; Funatani, Makoto; Ikeda, Kota

2016-01-26

The potential between two electrolytic solutions separated by a membrane impermeable to ions was measured and the generation mechanism of potential measured was investigated. From the physiological point of view, a nonzero membrane potential or action potential cannot be observed across the impermeable membrane. However, a nonzero membrane potential including action potential-like potential was clearly observed. Those observations gave rise to a doubt concerning the validity of currently accepted generation mechanism of membrane potential and action potential of cell. As an alternative theory, we found that the long-forgotten Ling's adsorption theory was the most plausible theory. Ling's adsorption theory suggests that the membrane potential and action potential of a living cell is due to the adsorption of mobile ions onto the adsorption site of cell, and this theory is applicable even to nonliving (or non-biological) system as well as living system. Through this paper, the authors emphasize that it is necessary to reconsider the validity of current membrane theory and also would like to urge the readers to pay keen attention to the Ling's adsorption theory which has for long years been forgotten in the history of physiology.

15 CFR 736.2 - General prohibitions and determination of applicability.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., Administrative Enforcement Proceedings. These orders prohibit many actions in addition to direct exports by the... knowledge that a violation has occurred or is about to occur (Knowledge Violation to Occur). You may not... to be exported with knowledge that a violation of the Export Administration Regulations, the Export...

Effects of acetylcholine and noradrenalin on action potentials of isolated rabbit sinoatrial and atrial myocytes.

PubMed

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

2012-01-01

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

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

PubMed Central

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

2012-01-01

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

The effects of gentamicin and penicillin/streptomycin on the electrophysiology of human induced pluripotent stem cell-derived cardiomyocytes in manual patch clamp and multi-electrode array system.

PubMed

Hyun, Soo-Wang; Kim, Bo-Ram; Lin, Dan; Hyun, Sung-Ae; Yoon, Seong Shoon; Seo, Joung-Wook

Cell culture media usually contains antibiotics including gentamicin or penicillin/streptomycin (PS) to protect cells from bacterial contamination. However, little is known about the effects of antibiotics on action potential and field potential parameters in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The present study examined the effects of gentamicin (10, 25, and 50μg/ml) and PS (50, 100, and 200U/μg/ml) on electrophysiological activity in spontaneously beating hiPSC-CMs using manual patch clamp and multi-electrode array. We also measured mRNA expression of cardiac ion channels in hiPSC-CMs grown in media with or without gentamicin (25μg/ml) using reverse transcription-polymerase chain reaction. We recorded action potential and field potential of hiPSC-CMs grown in the presence or absence of gentamicin or PS. We also observed action potential parameters in hiPSC-CMs after short-term treatment with these antibiotics. Changes in action potential and field potential parameters were observed in hiPSC-CMs grown in media containing gentamicin or PS. Treatment with PS also affected action potential parameters in hiPSC-CMs. In addition, the mRNA expression of cardiac sodium and potassium ion channels was significantly attenuated in hiPSC-CMs grown in the presence of gentamicin (25μg/ml). The present findings suggested that gentamicin should not be used in the culture media of hiPSC-CMs used for the measurement of electrophysiological parameters. Our findings also suggest that 100U/100μg/ml of PS are the maximum appropriate concentrations of these antibiotics for recording action potential waveform, because they did not influence action potential parameters in these cells. Copyright © 2017. Published by Elsevier Inc.

Beta Function Quintessence Cosmological Parameters and Fundamental Constants I: Power and Inverse Power Law Dark Energy Potentials

NASA Astrophysics Data System (ADS)

Thompson, Rodger I.

2018-04-01

This investigation explores using the beta function formalism to calculate analytic solutions for the observable parameters in rolling scalar field cosmologies. The beta function in this case is the derivative of the scalar ϕ with respect to the natural log of the scale factor a, β (φ )=d φ /d ln (a). Once the beta function is specified, modulo a boundary condition, the evolution of the scalar ϕ as a function of the scale factor is completely determined. A rolling scalar field cosmology is defined by its action which can contain a range of physically motivated dark energy potentials. The beta function is chosen so that the associated "beta potential" is an accurate, but not exact, representation of the appropriate dark energy model potential. The basic concept is that the action with the beta potential is so similar to the action with the model potential that solutions using the beta action are accurate representations of solutions using the model action. The beta function provides an extra equation to calculate analytic functions of the cosmologies parameters as a function of the scale factor that are that are not calculable using only the model action. As an example this investigation uses a quintessence cosmology to demonstrate the method for power and inverse power law dark energy potentials. An interesting result of the investigation is that the Hubble parameter H is almost completely insensitive to the power of the potentials and that ΛCDM is part of the family of quintessence cosmology power law potentials with a power of zero.

Beta function quintessence cosmological parameters and fundamental constants - I. Power and inverse power law dark energy potentials

NASA Astrophysics Data System (ADS)

Thompson, Rodger I.

2018-07-01

This investigation explores using the beta function formalism to calculate analytic solutions for the observable parameters in rolling scalar field cosmologies. The beta function in this case is the derivative of the scalar φ with respect to the natural log of the scale factor a, β (φ)=d φ/d ln (a). Once the beta function is specified, modulo a boundary condition, the evolution of the scalar φ as a function of the scale factor is completely determined. A rolling scalar field cosmology is defined by its action which can contain a range of physically motivated dark energy potentials. The beta function is chosen so that the associated `beta potential' is an accurate, but not exact, representation of the appropriate dark energy model potential. The basic concept is that the action with the beta potential is so similar to the action with the model potential that solutions using the beta action are accurate representations of solutions using the model action. The beta function provides an extra equation to calculate analytic functions of the cosmologies parameters as a function of the scale factor that are not calculable using only the model action. As an example, this investigation uses a quintessence cosmology to demonstrate the method for power and inverse power law dark energy potentials. An interesting result of the investigation is that the Hubble parameter H is almost completely insensitive to the power of the potentials and that Λ cold dark matter is part of the family of quintessence cosmology power-law potentials with a power of zero.

Pulsed magnetic stimulation modifies amplitude of action potentials in vitro via ionic channels-dependent mechanism.

PubMed

Ahmed, Zaghloul; Wieraszko, Andrzej

2015-07-01

This paper investigates the influence of pulsed magnetic fields (PMFs) on amplitude of evoked, compound action potential (CAP) recorded from the segments of sciatic nerve in vitro. PMFs were applied for 30 min at frequency of 0.16 Hz and intensity of 15 mT. In confirmation of our previous reports, PMF exposure enhanced amplitude of CAPs. The effect persisted beyond PMF activation period. As expected, CAP amplitude was attenuated by antagonists of sodium channel, lidocaine, and tetrodotoxin. Depression of the potential by sodium channels antagonists was reversed by subsequent exposure to PMFs. The effect of elevated potassium concentration and veratridine on the action potential was modified by exposure to PMFs as well. Neither inhibitors of protein kinase C and protein kinase A, nor known free radicals scavengers had any effects on PMF action. Possible mechanisms of PMF action are discussed. © 2015 Wiley Periodicals, Inc.

Trends in Compulsory Licensing of Pharmaceuticals Since the Doha Declaration: A Database Analysis

PubMed Central

Beall, Reed; Kuhn, Randall

2012-01-01

Background It is now a decade since the World Trade Organization (WTO) adopted the “Declaration on the TRIPS Agreement and Public Health” at its 4th Ministerial Conference in Doha. Many anticipated that these actions would lead nations to claim compulsory licenses (CLs) for pharmaceutical products with greater regularity. A CL is the use of a patented innovation that has been licensed by a state without the permission of the patent title holder. Skeptics doubted that many CLs would occur, given political pressure against CL activity and continued health system weakness in poor countries. The subsequent decade has seen little systematic assessment of the Doha Declaration's impact. Methods and Findings We assembled a database of all episodes in which a CL was publically entertained or announced by a WTO member state since 1995. Broad searches of CL activity were conducted using media, academic, and legal databases, yielding 34 potential CL episodes in 26 countries. Country- and product-specific searches were used to verify government participation, resulting in a final database of 24 verified CLs in 17 nations. We coded CL episodes in terms of outcome, national income, and disease group over three distinct periods of CL activity. Most CL episodes occurred between 2003 and 2005, involved drugs for HIV/AIDS, and occurred in upper-middle-income countries (UMICs). Aside from HIV/AIDS, few CL episodes involved communicable disease, and none occurred in least-developed or low-income countries. Conclusions Given skepticism about the Doha Declaration's likely impact, we note the relatively high occurrence of CLs, yet CL activity has diminished markedly since 2006. While UMICs have high CL activity and strong incentives to use CLs compared to other countries, we note considerable countervailing pressures against CL use even in UMICs. We conclude that there is a low probability of continued CL activity. We highlight the need for further systematic evaluation of global health governance actions. Please see later in the article for the Editors' Summary PMID:22253577

Trends in compulsory licensing of pharmaceuticals since the Doha Declaration: a database analysis.

PubMed

Beall, Reed; Kuhn, Randall

2012-01-01

It is now a decade since the World Trade Organization (WTO) adopted the "Declaration on the TRIPS Agreement and Public Health" at its 4th Ministerial Conference in Doha. Many anticipated that these actions would lead nations to claim compulsory licenses (CLs) for pharmaceutical products with greater regularity. A CL is the use of a patented innovation that has been licensed by a state without the permission of the patent title holder. Skeptics doubted that many CLs would occur, given political pressure against CL activity and continued health system weakness in poor countries. The subsequent decade has seen little systematic assessment of the Doha Declaration's impact. We assembled a database of all episodes in which a CL was publically entertained or announced by a WTO member state since 1995. Broad searches of CL activity were conducted using media, academic, and legal databases, yielding 34 potential CL episodes in 26 countries. Country- and product-specific searches were used to verify government participation, resulting in a final database of 24 verified CLs in 17 nations. We coded CL episodes in terms of outcome, national income, and disease group over three distinct periods of CL activity. Most CL episodes occurred between 2003 and 2005, involved drugs for HIV/AIDS, and occurred in upper-middle-income countries (UMICs). Aside from HIV/AIDS, few CL episodes involved communicable disease, and none occurred in least-developed or low-income countries. Given skepticism about the Doha Declaration's likely impact, we note the relatively high occurrence of CLs, yet CL activity has diminished markedly since 2006. While UMICs have high CL activity and strong incentives to use CLs compared to other countries, we note considerable countervailing pressures against CL use even in UMICs. We conclude that there is a low probability of continued CL activity. We highlight the need for further systematic evaluation of global health governance actions. Please see later in the article for the Editors' Summary.

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

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 13 2012-01-01 2012-01-01 false 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...

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

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 13 2011-01-01 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...

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

Code of Federal Regulations, 2010 CFR

2010-01-01

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

Action potentials recorded from bundles of very thin, gray matter axons in rat cerebellar slices using a grease-gap method.

PubMed

Palani, Damodharan; Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna; Raastad, Morten

2012-07-15

We investigated the ability of a grease-gap method to record fast and slow changes of the membrane potential from bundles of gray matter axons. Their membrane potentials are of particular interest because these axons are different from most axons that have been investigated using intra-axonal or gap techniques. One of the main differences is that gray matter axons typically have closely spaced presynaptic specializations, called boutons or varicosities, distributed along their entire paths. In response to electrical activation of bundles of parallel fiber axons we were able to record small (128-416μV) but stable signals that we show most likely represented a fraction of the trans-membrane action potentials. A less-than 100% fraction prevents measurements of absolute values for membrane potentials, but the good signal-to-noise ratio (typically 10-16) allows detection of changes in resting membrane potential, action potentials and their after-potentials. Because very little is known about the shape of action potentials and after-potentials in these axons we used several independent methods to make it likely that the grease-gap signal was of intra-axonal origin. We demonstrate the utility of the method by showing that the action potentials in cerebellar parallel fibers and hippocampal Schaffer collaterals had a slowly decaying, depolarized after-potential. The method is ideal for pharmacological tests, which we demonstrate by showing that the slow after-potential was sensitive to 4-AP, and that the membrane potential was reduced by 200μM Ba(2+). Copyright © 2012 Elsevier B.V. All rights reserved.

Sexual Harassment on Campus: Are Your Actions Actionable?

ERIC Educational Resources Information Center

Perry, Nancy Walker

1993-01-01

Addresses issue of sexual harassment on academic campus. Includes definitions of sexual harassment; guidelines for determining when sexual harassment has occurred; explanation of employer/employee responsibility in cases of sexual harassment; and strategies designed to prevent or remedy sexual harassment. (Author)

Generating Phenotypical Erroneous Human Behavior to Evaluate Human-automation Interaction Using Model Checking

PubMed Central

Bolton, Matthew L.; Bass, Ellen J.; Siminiceanu, Radu I.

2012-01-01

Breakdowns in complex systems often occur as a result of system elements interacting in unanticipated ways. In systems with human operators, human-automation interaction associated with both normative and erroneous human behavior can contribute to such failures. Model-driven design and analysis techniques provide engineers with formal methods tools and techniques capable of evaluating how human behavior can contribute to system failures. This paper presents a novel method for automatically generating task analytic models encompassing both normative and erroneous human behavior from normative task models. The generated erroneous behavior is capable of replicating Hollnagel’s zero-order phenotypes of erroneous action for omissions, jumps, repetitions, and intrusions. Multiple phenotypical acts can occur in sequence, thus allowing for the generation of higher order phenotypes. The task behavior model pattern capable of generating erroneous behavior can be integrated into a formal system model so that system safety properties can be formally verified with a model checker. This allows analysts to prove that a human-automation interactive system (as represented by the model) will or will not satisfy safety properties with both normative and generated erroneous human behavior. We present benchmarks related to the size of the statespace and verification time of models to show how the erroneous human behavior generation process scales. We demonstrate the method with a case study: the operation of a radiation therapy machine. A potential problem resulting from a generated erroneous human action is discovered. A design intervention is presented which prevents this problem from occurring. We discuss how our method could be used to evaluate larger applications and recommend future paths of development. PMID:23105914

Neurotransmitter Release Can Be Stabilized by a Mechanism That Prevents Voltage Changes Near the End of Action Potentials from Affecting Calcium Currents

PubMed Central

Clarke, Stephen G.; Scarnati, Matthew S.

2016-01-01

At chemical synapses, presynaptic action potentials (APs) activate voltage-gated calcium channels, allowing calcium to enter and trigger neurotransmitter release. The duration, peak amplitude, and shape of the AP falling phase alter calcium entry, which can affect neurotransmitter release significantly. In many neurons, APs do not immediately return to the resting potential, but instead exhibit a period of depolarization or hyperpolarization referred to as an afterpotential. We hypothesized that presynaptic afterpotentials should alter neurotransmitter release by affecting the electrical driving force for calcium entry and calcium channel gating. In support of this, presynaptic calcium entry is affected by afterpotentials after standard instant voltage jumps. Here, we used the mouse calyx of Held synapse, which allows simultaneous presynaptic and postsynaptic patch-clamp recording, to show that the postsynaptic response is affected significantly by presynaptic afterpotentials after voltage jumps. We therefore tested the effects of presynaptic afterpotentials using simultaneous presynaptic and postsynaptic recordings and AP waveforms or real APs. Surprisingly, presynaptic afterpotentials after AP stimuli did not alter calcium channel responses or neurotransmitter release appreciably. We show that the AP repolarization time course causes afterpotential-induced changes in calcium driving force and changes in calcium channel gating to effectively cancel each other out. This mechanism, in which electrical driving force is balanced by channel gating, prevents changes in calcium influx from occurring at the end of the AP and therefore acts to stabilize synaptic transmission. In addition, this mechanism can act to stabilize neurotransmitter release when the presynaptic resting potential changes. SIGNIFICANCE STATEMENT The shape of presynaptic action potentials (APs), particularly the falling phase, affects calcium entry and small changes in calcium influx can produce large changes in postsynaptic responses. We hypothesized that afterpotentials, which often follow APs, affect calcium entry and neurotransmitter release. We tested this in calyx of Held nerve terminals, which allow simultaneous recording of presynaptic calcium currents and postsynaptic responses. Surprisingly, presynaptic afterpotentials did not alter calcium current or neurotransmitter release. We show that the AP falling phase causes afterpotential-induced changes in electrical driving force and calcium channel gating to cancel each other out. This mechanism regulates calcium entry at the end of APs and therefore stabilizes synaptic transmission. This also stabilizes responses when the presynaptic resting potential changes. PMID:27911759

Neurotransmitter Release Can Be Stabilized by a Mechanism That Prevents Voltage Changes Near the End of Action Potentials from Affecting Calcium Currents.

PubMed

Clarke, Stephen G; Scarnati, Matthew S; Paradiso, Kenneth G

2016-11-09

At chemical synapses, presynaptic action potentials (APs) activate voltage-gated calcium channels, allowing calcium to enter and trigger neurotransmitter release. The duration, peak amplitude, and shape of the AP falling phase alter calcium entry, which can affect neurotransmitter release significantly. In many neurons, APs do not immediately return to the resting potential, but instead exhibit a period of depolarization or hyperpolarization referred to as an afterpotential. We hypothesized that presynaptic afterpotentials should alter neurotransmitter release by affecting the electrical driving force for calcium entry and calcium channel gating. In support of this, presynaptic calcium entry is affected by afterpotentials after standard instant voltage jumps. Here, we used the mouse calyx of Held synapse, which allows simultaneous presynaptic and postsynaptic patch-clamp recording, to show that the postsynaptic response is affected significantly by presynaptic afterpotentials after voltage jumps. We therefore tested the effects of presynaptic afterpotentials using simultaneous presynaptic and postsynaptic recordings and AP waveforms or real APs. Surprisingly, presynaptic afterpotentials after AP stimuli did not alter calcium channel responses or neurotransmitter release appreciably. We show that the AP repolarization time course causes afterpotential-induced changes in calcium driving force and changes in calcium channel gating to effectively cancel each other out. This mechanism, in which electrical driving force is balanced by channel gating, prevents changes in calcium influx from occurring at the end of the AP and therefore acts to stabilize synaptic transmission. In addition, this mechanism can act to stabilize neurotransmitter release when the presynaptic resting potential changes. The shape of presynaptic action potentials (APs), particularly the falling phase, affects calcium entry and small changes in calcium influx can produce large changes in postsynaptic responses. We hypothesized that afterpotentials, which often follow APs, affect calcium entry and neurotransmitter release. We tested this in calyx of Held nerve terminals, which allow simultaneous recording of presynaptic calcium currents and postsynaptic responses. Surprisingly, presynaptic afterpotentials did not alter calcium current or neurotransmitter release. We show that the AP falling phase causes afterpotential-induced changes in electrical driving force and calcium channel gating to cancel each other out. This mechanism regulates calcium entry at the end of APs and therefore stabilizes synaptic transmission. This also stabilizes responses when the presynaptic resting potential changes. Copyright © 2016 the authors 0270-6474/16/3611559-14$15.00/0.

Nerve Impulses in Plants

ERIC Educational Resources Information Center

Blatt, F. J.

1974-01-01

Summarizes research done on the resting and action potential of nerve impulses, electrical excitation of nerve cells, electrical properties of Nitella, and temperature effects on action potential. (GS)

Central Nervous System-Toxic Lidocaine Concentrations Unmask L-Type Ca²⁺ Current-Mediated Action Potentials in Rat Thalamocortical Neurons: An In Vitro Mechanism of Action Study.

PubMed

Putrenko, Igor; Ghavanini, Amer A; Meyer Schöniger, Katrin S; Schwarz, Stephan K W

2016-05-01

High systemic lidocaine concentrations exert well-known toxic effects on the central nervous system (CNS), including seizures, coma, and death. The underlying mechanisms are still largely obscure, and the actions of lidocaine on supraspinal neurons have received comparatively little study. We recently found that lidocaine at clinically neurotoxic concentrations increases excitability mediated by Na-independent, high-threshold (HT) action potential spikes in rat thalamocortical neurons. Our goal in this study was to characterize these spikes and test the hypothesis that they are generated by HT Ca currents, previously implicated in neurotoxicity. We also sought to identify and isolate the specific underlying subtype of Ca current. We investigated the actions of lidocaine in the CNS-toxic concentration range (100 μM-1 mM) on ventrobasal thalamocortical neurons in rat brain slices in vitro, using whole-cell patch-clamp recordings aided by differential interference contrast infrared videomicroscopy. Drugs were bath applied; action potentials were generated using current clamp protocols, and underlying currents were identified and isolated with ion channel blockers and electrolyte substitution. Lidocaine (100 μM-1 mM) abolished Na-dependent tonic firing in all neurons tested (n = 46). However, in 39 of 46 (85%) neurons, lidocaine unmasked evoked HT action potentials with lower amplitudes and rates of de-/repolarization compared with control. These HT action potentials remained during the application of tetrodotoxin (600 nM), were blocked by Cd (50 μM), and disappeared after superfusion with an extracellular solution deprived of Ca. These features implied that the unmasked potentials were generated by high-voltage-activated Ca channels and not by Na channels. Application of the L-type Ca channel blocker, nifedipine (5 μM), completely blocked the HT potentials, whereas the N-type Ca channel blocker, ω-conotoxin GVIA (1 μM), had little effect. At clinically CNS-toxic concentrations, lidocaine unmasked in thalamocortical neurons evoked HT action potentials mediated by the L-type Ca current while substantially suppressing Na-dependent excitability. On the basis of the known role of an increase in intracellular Ca in the pathogenesis of local anesthetic neurotoxicity, this novel action represents a plausible contributing candidate mechanism for lidocaine's CNS toxicity in vivo.

An intracellular analysis of the visual responses of neurones in cat visual cortex.

PubMed Central

Douglas, R J; Martin, K A; Whitteridge, D

1991-01-01

1. Extracellular and intracellular recordings were made from neurones in the visual cortex of the cat in order to compare the subthreshold membrane potentials, reflecting the input to the neurone, with the output from the neurone seen as action potentials. 2. Moving bars and edges, generated under computer control, were used to stimulate the neurones. The membrane potential was digitized and averaged for a number of trials after stripping the action potentials. Comparison of extracellular and intracellular discharge patterns indicated that the intracellular impalement did not alter the neurones' properties. Input resistance of the neurone altered little during stable intracellular recordings (30 min-2 h 50 min). 3. Intracellular recordings showed two distinct patterns of membrane potential changes during optimal visual stimulation. The patterns corresponded closely to the division of S-type (simple) and C-type (complex) receptive fields. Simple cells had a complex pattern of membrane potential fluctuations, involving depolarizations alternating with hyperpolarizations. Complex cells had a simple single sustained plateau of depolarization that was often followed but not preceded by a hyperpolarization. In both simple and complex cells the depolarizations led to action potential discharges. The hyperpolarizations were associated with inhibition of action potential discharge. 4. Stimulating simple cells with non-optimal directions of motion produced little or no hyperpolarization of the membrane in most cases, despite a lack of action potential output. Directional complex cells always produced a single plateau of depolarization leading to action potential discharge in both the optimal and non-optimal directions of motion. The directionality could not be predicted on the basis of the position of the hyperpolarizing inhibitory potentials found in the optimal direction. 5. Stimulation of simple cells with non-optimal orientations occasionally produced slight hyperpolarizations and inhibition of action potential discharge. Complex cells, which had broader orientation tuning than simple cells, could show marked hyperpolarization for non-optimal orientations, but this was not generally the case. 6. The data do not support models of directionality and orientation that rely solely on strong inhibitory mechanisms to produce stimulus selectivity. PMID:1804981

Relationships between resting conductances, excitability, and t-system ionic homeostasis in skeletal muscle.

PubMed

Fraser, James A; Huang, Christopher L-H; Pedersen, Thomas H

2011-07-01

Activation of skeletal muscle fibers requires rapid sarcolemmal action potential (AP) conduction to ensure uniform excitation along the fiber length, as well as successful tubular excitation to initiate excitation-contraction coupling. In our companion paper in this issue, Pedersen et al. (2011. J. Gen. Physiol. doi:10.1085/jgp.201010510) quantify, for subthreshold stimuli, the influence upon both surface conduction velocity and tubular (t)-system excitation of the large changes in resting membrane conductance (G(M)) that occur during repetitive AP firing. The present work extends the analysis by developing a multi-compartment modification of the charge-difference model of Fraser and Huang to provide a quantitative description of the conduction velocity of actively propagated APs; the influence of voltage-gated ion channels within the t-system; the influence of t-system APs on ionic homeostasis within the t-system; the influence of t-system ion concentration changes on membrane potentials; and the influence of Phase I and Phase II G(M) changes on these relationships. Passive conduction properties of the novel model agreed with established linear circuit analysis and previous experimental results, while key simulations of AP firing were tested against focused experimental microelectrode measurements of membrane potential. This study thereby first quantified the effects of the t-system luminal resistance and voltage-gated Na(+) channel density on surface AP propagation and the resultant electrical response of the t-system. Second, it demonstrated the influence of G(M) changes during repetitive AP firing upon surface and t-system excitability. Third, it showed that significant K(+) accumulation occurs within the t-system during repetitive AP firing and produces a baseline depolarization of the surface membrane potential. Finally, it indicated that G(M) changes during repetitive AP firing significantly influence both t-system K(+) accumulation and its influence on the resting membrane potential. Thus, the present study emerges with a quantitative description of the changes in membrane potential, excitability, and t-system ionic homeostasis that occur during repetitive AP firing in skeletal muscle.

Selective Algicidal Action of Peptides against Harmful Algal Bloom Species

PubMed Central

Park, Seong-Cheol; Lee, Jong-Kook; Kim, Si Wouk; Park, Yoonkyung

2011-01-01

Recently, harmful algal bloom (HAB), also termed “red tide”, has been recognized as a serious problem in marine environments according to climate changes worldwide. Many novel materials or methods to prevent HAB have not yet been employed except for clay dispersion, in which can the resulting sedimentation on the seafloor can also cause alteration in marine ecology or secondary environmental pollution. In the current study, we investigated that antimicrobial peptide have a potential in controlling HAB without cytotoxicity to harmless marine organisms. Here, antimicrobial peptides are proposed as new algicidal compounds in combating HAB cells. HPA3 and HPA3NT3 peptides which exert potent antimicrobial activity via pore forming action in plasma membrane showed that HPA3NT3 reduced the motility of algal cells, disrupted their plasma membrane, and induced the efflux of intracellular components. Against raphidoflagellate such as Heterosigma akashiwo, Chattonella sp., and C. marina, it displayed a rapid lysing action in cell membranes at 1∼4 µM within 2 min. Comparatively, its lysing effects occurred at 8 µM within 1 h in dinoflagellate such as Cochlodium polykrikoides, Prorocentrum micans, and P. minimum. Moreover, its lysing action induced the lysis of chloroplasts and loss of chlorophyll a. In the contrary, this peptide was not effective against Skeletonema costatum, harmless algal cell, even at 256 µM, moreover, it killed only H. akashiwo or C. marina in co-cultivation with S. costatum, indicating to its selective algicidal activity between harmful and harmless algal cells. The peptide was non-hemolytic against red blood cells of Sebastes schlegeli, the black rockfish, at 120 µM. HAB cells were quickly and selectively lysed following treatment of antimicrobial peptides without cytotoxicity to harmless marine organisms. Thus, the antibiotic peptides examined in our study appear to have much potential in effectively controlling HAB with minimal impact on marine ecology. PMID:22046341

Selective algicidal action of peptides against harmful algal bloom species.

PubMed

Park, Seong-Cheol; Lee, Jong-Kook; Kim, Si Wouk; Park, Yoonkyung

2011-01-01

Recently, harmful algal bloom (HAB), also termed "red tide", has been recognized as a serious problem in marine environments according to climate changes worldwide. Many novel materials or methods to prevent HAB have not yet been employed except for clay dispersion, in which can the resulting sedimentation on the seafloor can also cause alteration in marine ecology or secondary environmental pollution. In the current study, we investigated that antimicrobial peptide have a potential in controlling HAB without cytotoxicity to harmless marine organisms. Here, antimicrobial peptides are proposed as new algicidal compounds in combating HAB cells. HPA3 and HPA3NT3 peptides which exert potent antimicrobial activity via pore forming action in plasma membrane showed that HPA3NT3 reduced the motility of algal cells, disrupted their plasma membrane, and induced the efflux of intracellular components. Against raphidoflagellate such as Heterosigma akashiwo, Chattonella sp., and C. marina, it displayed a rapid lysing action in cell membranes at 1~4 µM within 2 min. Comparatively, its lysing effects occurred at 8 µM within 1 h in dinoflagellate such as Cochlodium polykrikoides, Prorocentrum micans, and P. minimum. Moreover, its lysing action induced the lysis of chloroplasts and loss of chlorophyll a. In the contrary, this peptide was not effective against Skeletonema costatum, harmless algal cell, even at 256 µM, moreover, it killed only H. akashiwo or C. marina in co-cultivation with S. costatum, indicating to its selective algicidal activity between harmful and harmless algal cells. The peptide was non-hemolytic against red blood cells of Sebastes schlegeli, the black rockfish, at 120 µM. HAB cells were quickly and selectively lysed following treatment of antimicrobial peptides without cytotoxicity to harmless marine organisms. Thus, the antibiotic peptides examined in our study appear to have much potential in effectively controlling HAB with minimal impact on marine ecology.

Escherichia coli Cell Surface Perturbation and Disruption Induced by Antimicrobial Peptides BP100 and pepR*

PubMed Central

Alves, Carla S.; Melo, Manuel N.; Franquelim, Henri G.; Ferre, Rafael; Planas, Marta; Feliu, Lidia; Bardají, Eduard; Kowalczyk, Wioleta; Andreu, David; Santos, Nuno C.; Fernandes, Miguel X.; Castanho, Miguel A. R. B.

2010-01-01

The potential of antimicrobial peptides (AMPs) as an alternative to conventional therapies is well recognized. Insights into the biological and biophysical properties of AMPs are thus key to understanding their mode of action. In this study, the mechanisms adopted by two AMPs in disrupting the Gram-negative Escherichia coli bacterial envelope were explored. BP100 is a short cecropin A-melittin hybrid peptide known to inhibit the growth of phytopathogenic Gram-negative bacteria. pepR, on the other hand, is a novel AMP derived from the dengue virus capsid protein. Both BP100 and pepR were found to inhibit the growth of E. coli at micromolar concentrations. Zeta potential measurements of E. coli incubated with increasing peptide concentrations allowed for the establishment of a correlation between the minimal inhibitory concentration (MIC) of each AMP and membrane surface charge neutralization. While a neutralization-mediated killing mechanism adopted by either AMP is not necessarily implied, the hypothesis that surface neutralization occurs close to MIC values was confirmed. Atomic force microscopy (AFM) was then employed to visualize the structural effect of the interaction of each AMP with the E. coli cell envelope. At their MICs, BP100 and pepR progressively destroyed the bacterial envelope, with extensive damage already occurring 2 h after peptide addition to the bacteria. A similar effect was observed for each AMP in the concentration-dependent studies. At peptide concentrations below MIC values, only minor disruptions of the bacterial surface occurred. PMID:20566635

Hospital-acquired listeriosis associated with sandwiches in the UK: a cause for concern.

PubMed

Little, C L; Amar, C F L; Awofisayo, A; Grant, K A

2012-09-01

Hospital-acquired outbreaks of listeriosis are not commonly reported but remain a significant public health problem. To raise awareness of listeriosis outbreaks that have occurred in hospitals and describe actions that can be taken to minimize the risk of foodborne listeriosis to vulnerable patients. Foodborne outbreaks and incidents of Listeria monocytogenes reported to the Health Protection Agency national surveillance systems were investigated and those linked to hospitals were extracted. The data were analysed to identify the outbreak/incident setting, the food vehicle, outbreak contributory factors and origin of problem. Most (8/11, 73%) foodborne outbreaks of listeriosis that occurred in the UK between 1999 and 2011 were associated with sandwiches purchased from or provided in hospitals. Recurrently in the outbreaks the infecting subtype of L. monocytogenes was detected in supplied prepacked sandwiches and sandwich manufacturing environments. In five of the outbreaks breaches in cold chain controls of food also occurred at hospital level. The outbreaks highlight the potential for sandwiches contaminated with L. monocytogenes to cause severe infection in vulnerable people. Control of L. monocytogenes in sandwich manufacturing and within hospitals is essential to minimize the potential for consumption of this bacterium at levels hazardous to health. Manufacturers supplying sandwiches to hospitals should aim to ensure absence of L. monocytogenes in sandwiches at the point of production and hospital-documented food safety management systems should ensure the integrity of the food cold chain. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Role of insects in the transmission of bovine leukosis virus: potential for transmission by stable flies, horn flies, and tabanids.

PubMed

Buxton, B A; Hinkle, N C; Schultz, R D

1985-01-01

The ability of stable flies (Stomoxys calcitrans), horn flies (Haematobia irritans), and tabanids (Diptera: Tabanidae) to transmit bovine leukosis virus (BLV) was investigated. Stable flies and horn flies were fed on blood collected from an infected cow, and the flies' mouthparts were immediately removed, placed in RPMI-1640 medium, ground, and inoculated into sheep and calves. Infection of sheep occurred with mouthparts from as few as 25 stable flies or 25 horn flies. However, sheep were not infected when removal of stable fly mouthparts was delayed greater than or equal to 1 hour after blood feeding. Infection of calves occurred after inoculation of mouthparts removed immediately after feeding from as few as 50 stable flies or 100 horn flies. Infected blood, applied by capillary action to the mouthparts (labella) of 15 deer flies (Chrysops sp) and a single horse fly (Tabanus atratus) caused infection in each of 2 sheep. Infection did not occur in 2 calves inoculated daily for 5 days with mouthparts from 50 horn flies collected after feeding on a BLV-infected steer. Four calves receiving bites from 75 stable flies interrupted from feeding on a BLV-positive cow also were not infected. Seronegative cattle held for 1 to 4 months in a screened enclosure with positive cattle in the presence of biting flies were not infected with BLV. The feeding behavior of each insect is discussed to assess their potential as vectors of BLV.

Orientation priming of grasping decision for drawings of objects and blocks, and words.

PubMed

Chainay, Hanna; Naouri, Lucie; Pavec, Alice

2011-05-01

This study tested the influence of orientation priming on grasping decisions. Two groups of 20 healthy participants had to select a preferred grasping orientation (horizontal, vertical) based on drawings of everyday objects, geometric blocks or object names. Three priming conditions were used: congruent, incongruent and neutral. The facilitating effects of priming were observed in the grasping decision task for drawings of objects and blocks but not object names. The visual information about congruent orientation in the prime quickened participants' responses but had no effect on response accuracy. The results are discussed in the context of the hypothesis that an object automatically potentiates grasping associated with it, and that the on-line visual information is necessary for grasping potentiation to occur. The possibility that the most frequent orientation of familiar objects might be included in object-action representation is also discussed.

Ellagic Acid: A Logical Lead for Drug Development?

PubMed

Shakeri, Abolfazl; Zirak, Mohammad Reza; Sahebkar, Amirhossein

2018-01-01

Naturally occurring polyphenols are the subject of increasing attention due to their potent antioxidant activity and their marked effects on the prevention of various oxidative stress-associated diseases such as cancer. Ellagic acid (EA) is an herbal polyphenol that is structurally a condensed dimer of gallic acid. This review aims to provide a comprehensive and updated overview on the biological activities of EA and potential therapeutic applications. EA is found in fruits and nuts, either in the combined form with hexahydroxydiphenic acid or in the bound form (ellagitannins). EA exhibits many biological properties such as antioxidant, anti-diabetic, anticancer and apoptosis-inducing activities. These biological and pharmacological properties are relevant to the treatment of several human diseases. Owing to its multiple mechanisms of action, EA represents a potential therapeutic agent against human diseases particularly cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Neuroprotective effects of resveratrol in Alzheimer disease pathology

PubMed Central

Rege, Shraddha D.; Geetha, Thangiah; Griffin, Gerald D.; Broderick, Tom L.; Babu, Jeganathan Ramesh

2014-01-01

Alzheimer’s disease is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and behavioral abilities. Extracellular senile plaques and intracellular neurofibrillary tangles are hallmarks of AD. Researchers aim to analyze the molecular mechanisms underlying AD pathogenesis; however, the therapeutic options available to treat this disease are inadequate. In the past few years, several studies have reported interesting insights about the neuroprotective properties of the polyphenolic compound resveratrol (3, 5, 4′-trihydroxy-trans-stilbene) when used with in vitro and in vivo models of AD. The aim of this review is to focus on the neuroprotective and antioxidant effects of resveratrol on AD and its multiple potential mechanisms of action. In addition, because the naturally occurring forms of resveratrol have a very limited half-life in plasma, a description of potential analogs aimed at increasing the bioavailability in plasma is also discussed. PMID:25309423

Early detection of ecosystem regime shifts: a multiple method evaluation for management application.

PubMed

Lindegren, Martin; Dakos, Vasilis; Gröger, Joachim P; Gårdmark, Anna; Kornilovs, Georgs; Otto, Saskia A; Möllmann, Christian

2012-01-01

Critical transitions between alternative stable states have been shown to occur across an array of complex systems. While our ability to identify abrupt regime shifts in natural ecosystems has improved, detection of potential early-warning signals previous to such shifts is still very limited. Using real monitoring data of a key ecosystem component, we here apply multiple early-warning indicators in order to assess their ability to forewarn a major ecosystem regime shift in the Central Baltic Sea. We show that some indicators and methods can result in clear early-warning signals, while other methods may have limited utility in ecosystem-based management as they show no or weak potential for early-warning. We therefore propose a multiple method approach for early detection of ecosystem regime shifts in monitoring data that may be useful in informing timely management actions in the face of ecosystem change.

Early Detection of Ecosystem Regime Shifts: A Multiple Method Evaluation for Management Application

PubMed Central

Lindegren, Martin; Dakos, Vasilis; Gröger, Joachim P.; Gårdmark, Anna; Kornilovs, Georgs; Otto, Saskia A.; Möllmann, Christian

2012-01-01

Critical transitions between alternative stable states have been shown to occur across an array of complex systems. While our ability to identify abrupt regime shifts in natural ecosystems has improved, detection of potential early-warning signals previous to such shifts is still very limited. Using real monitoring data of a key ecosystem component, we here apply multiple early-warning indicators in order to assess their ability to forewarn a major ecosystem regime shift in the Central Baltic Sea. We show that some indicators and methods can result in clear early-warning signals, while other methods may have limited utility in ecosystem-based management as they show no or weak potential for early-warning. We therefore propose a multiple method approach for early detection of ecosystem regime shifts in monitoring data that may be useful in informing timely management actions in the face of ecosystem change. PMID:22808007

Exploring cellular uptake of iron oxide nanoparticles associated with rhodium citrate in breast cancer cells

PubMed Central

Chaves, Natalia L; Estrela-Lopis, Irina; Böttner, Julia; Lopes, Cláudio AP; Guido, Bruna C; de Sousa, Aparecido R; Báo, Sônia N

2017-01-01

Nanocarriers have the potential to improve the therapeutic index of currently available drugs by improving their efficacy and achieving therapeutic steady-state levels over an extended period. The association of maghemite–rhodium citrate (MRC) nanoparticles (NPs) has the potential to increase specificity of the cytotoxic action. However, the interaction of these NPs with cells, their uptake mechanism, and subcellular localization need to be elucidated. This work evaluates the uptake mechanism of MRC NPs in metastatic and nonmetastatic breast cancer-cell models, comparing them to a nontumor cell line. MRC NPs uptake in breast cancer cells was more effective than in normal cells, with regard to both the amount of internalized material and the achievement of more strategic intracellular distribution. Moreover, this process occurred through a clathrin-dependent endocytosis pathway with different basal expression levels of this protein in the cell lines tested. PMID:28814867

Exploring cellular uptake of iron oxide nanoparticles associated with rhodium citrate in breast cancer cells.

PubMed

Chaves, Natalia L; Estrela-Lopis, Irina; Böttner, Julia; Lopes, Cláudio Ap; Guido, Bruna C; de Sousa, Aparecido R; Báo, Sônia N

2017-01-01

Nanocarriers have the potential to improve the therapeutic index of currently available drugs by improving their efficacy and achieving therapeutic steady-state levels over an extended period. The association of maghemite-rhodium citrate (MRC) nanoparticles (NPs) has the potential to increase specificity of the cytotoxic action. However, the interaction of these NPs with cells, their uptake mechanism, and subcellular localization need to be elucidated. This work evaluates the uptake mechanism of MRC NPs in metastatic and nonmetastatic breast cancer-cell models, comparing them to a nontumor cell line. MRC NPs uptake in breast cancer cells was more effective than in normal cells, with regard to both the amount of internalized material and the achievement of more strategic intracellular distribution. Moreover, this process occurred through a clathrin-dependent endocytosis pathway with different basal expression levels of this protein in the cell lines tested.

A Compartmentalized Mathematical Model of the β1-Adrenergic Signaling System in Mouse Ventricular Myocytes

PubMed Central

Bondarenko, Vladimir E.

2014-01-01

The β1-adrenergic signaling system plays an important role in the functioning of cardiac cells. Experimental data shows that the activation of this system produces inotropy, lusitropy, and chronotropy in the heart, such as increased magnitude and relaxation rates of [Ca2+]i transients and contraction force, and increased heart rhythm. However, excessive stimulation of β1-adrenergic receptors leads to heart dysfunction and heart failure. In this paper, a comprehensive, experimentally based mathematical model of the β1-adrenergic signaling system for mouse ventricular myocytes is developed, which includes major subcellular functional compartments (caveolae, extracaveolae, and cytosol). The model describes biochemical reactions that occur during stimulation of β1-adrenoceptors, changes in ionic currents, and modifications of Ca2+ handling system. Simulations describe the dynamics of major signaling molecules, such as cyclic AMP and protein kinase A, in different subcellular compartments; the effects of inhibition of phosphodiesterases on cAMP production; kinetics and magnitudes of phosphorylation of ion channels, transporters, and Ca2+ handling proteins; modifications of action potential shape and duration; magnitudes and relaxation rates of [Ca2+]i transients; changes in intracellular and transmembrane Ca2+ fluxes; and [Na+]i fluxes and dynamics. The model elucidates complex interactions of ionic currents upon activation of β1-adrenoceptors at different stimulation frequencies, which ultimately lead to a relatively modest increase in action potential duration and significant increase in [Ca2+]i transients. In particular, the model includes two subpopulations of the L-type Ca2+ channels, in caveolae and extracaveolae compartments, and their effects on the action potential and [Ca2+]i transients are investigated. The presented model can be used by researchers for the interpretation of experimental data and for the developments of mathematical models for other species or for pathological conditions. PMID:24586529

Twitch and tetanic force responses and longitudinal propagation of action potentials in skinned skeletal muscle fibres of the rat

PubMed Central

Posterino, G S; Lamb, G D; Stephenson, D G

2000-01-01

Transverse electrical field stimulation (50 V cm−1, 2 ms duration) of mechanically skinned skeletal muscle fibres of the rat elicited twitch and tetanic force responses (36 ± 4 and 83 ± 4 % of maximum Ca2+-activated force, respectively; n = 23) closely resembling those in intact fibres. The responses were steeply dependent on the field strength and were eliminated by inclusion of 10 μm tetrodotoxin (TTX) in the (sealed) transverse tubular (T-) system of the skinned fibres and by chronic depolarisation of the T-system. Spontaneous twitch-like activity occurred sporadically in many fibres, producing near maximal force in some instances (mean time to peak: 190 ± 40 ms; n = 4). Such responses propagated as a wave of contraction longitudinally along the fibre at a velocity of 13 ± 3 mm s−1 (n = 7). These spontaneous contractions were also inhibited by inclusion of TTX in the T-system and by chronic depolarisation. We examined whether the T-tubular network was interconnected longitudinally using fibre segments that were skinned for only ∼2/3 of their length, leaving the remainder of each segment intact with its T-system open to the bathing solution. After such fibres were exposed to TTX (60 μm), the adjacent skinned region (with its T-system not open to the solution) became unresponsive to subsequent electrical stimulation in ∼50 % of cases (7/15), indicating that TTX was able to diffuse longitudinally inside the fibre via the tubular network over hundreds of sarcomeres. These experiments show that excitation–contraction coupling in mammalian muscle fibres involves action potential propagation both transversally and longitudinally within the tubular system. Longitudinal propagation of action potentials inside skeletal muscle fibres is likely to be an important safety mechanism for reducing conduction failure during fatigue and explains why, in developing skeletal muscle, the T-system first develops as an internal longitudinal network. PMID:10944176

Staff Handbook on Natural Gas.

ERIC Educational Resources Information Center

Gorges, H. A., Ed.; Raine, L. P., Ed.

The Department of Commerce created a Natural Gas Action Group early in the fall of 1975 to assist industrial firms and the communities they serve to cope with the effects of potentially severe and crippling curtailment situations. This action group was trained to assess a specific local situation, review the potential for remedial action and…

75 FR 43072 - Trichoderma Hamatum Isolate 382; Exemption from the Requirement of a Tolerance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-23

... Information A. Does this Action Apply to Me? You may be potentially affected by this action if you are an agricultural producer, food manufacturer, or pesticide manufacturer. Potentially affected entities may include... exhaustive, but rather provides a guide for readers regarding entities likely to be affected by this action...

Components of action potential repolarization in cerebellar parallel fibres.

PubMed

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

2014-11-15

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

DOUBLE TRACKS Test Site interim corrective action plan

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The DOUBLE TRACKS site is located on Range 71 north of the Nellis Air Force Range, northwest of the Nevada Test Site (NTS). DOUBLE TRACKS was the first of four experiments that constituted Operation ROLLER COASTER. On May 15, 1963, weapons-grade plutonium and depleted uranium were dispersed using 54 kilograms of trinitrotoluene (TNT) explosive. The explosion occurred in the open, 0.3 m above the steel plate. No fission yield was detected from the test, and the total amount of plutonium deposited on the ground surface was estimated to be between 980 and 1,600 grams. The test device was composed primarilymore » of uranium-238 and plutonium-239. The mass ratio of uranium to plutonium was 4.35. The objective of the corrective action is to reduce the potential risk to human health and the environment and to demonstrate technically viable and cost-effective excavation, transportation, and disposal. To achieve these objectives, Bechtel Nevada (BN) will remove soil with a total transuranic activity greater then 200 pCI/g, containerize the soil in ``supersacks,`` transport the filled ``supersacks`` to the NTS, and dispose of them in the Area 3 Radioactive Waste Management Site. During this interim corrective action, BN will also conduct a limited demonstration of an alternative method for excavation of radioactive near-surface soil contamination.« less

Optimal conservation resource allocation under variable economic and ecological time discounting rates in boreal forest.

PubMed

Mazziotta, Adriano; Pouzols, Federico Montesino; Mönkkönen, Mikko; Kotiaho, Janne S; Strandman, Harri; Moilanen, Atte

2016-09-15

Resource allocation to multiple alternative conservation actions is a complex task. A common trade-off occurs between protection of smaller, expensive, high-quality areas versus larger, cheaper, partially degraded areas. We investigate optimal allocation into three actions in boreal forest: current standard forest management rules, setting aside of mature stands, or setting aside of clear-cuts. We first estimated how habitat availability for focal indicator species and economic returns from timber harvesting develop through time as a function of forest type and action chosen. We then developed an optimal resource allocation by accounting for budget size and habitat availability of indicator species in different forest types. We also accounted for the perspective adopted towards sustainability, modeled via temporal preference and economic and ecological time discounting. Controversially, we found that in boreal forest set-aside followed by protection of clear-cuts can become a winning cost-effective strategy when accounting for habitat requirements of multiple species, long planning horizon, and limited budget. It is particularly effective when adopting a long-term sustainability perspective, and accounting for present revenues from timber harvesting. The present analysis assesses the cost-effective conditions to allocate resources into an inexpensive conservation strategy that nevertheless has potential to produce high ecological values in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuroimaging of the joint Simon effect with believed biological and non-biological co-actors

PubMed Central

Wen, Tanya; Hsieh, Shulan

2015-01-01

Performing a task alone or together with another agent can produce different outcomes. The current study used event-related functional magnetic resonance imaging (fMRI) to investigate the neural underpinnings when participants performed a Go/Nogo task alone or complementarily with another co-actor (unseen), whom was believed to be another human or a computer. During both complementary tasks, reaction time data suggested that participants integrated the potential action of their co-actor in their own action planning. Compared to the single-actor task, increased parietal and precentral activity during complementary tasks as shown in the fMRI data further suggested representation of the co-actor’s response. The superior frontal gyrus of the medial prefrontal cortex was differentially activated in the human co-actor condition compared to the computer co-actor condition. The medial prefrontal cortex, involved thinking about the beliefs and intentions of other people, possibly reflects a social-cognitive aspect or self-other discrimination during the joint task when believing a biological co-actor is present. Our results suggest that action co-representation can occur even offline with any agent type given a priori information that they are co-acting; however, additional regions are recruited when participants believe they are task-sharing with another human. PMID:26388760