Basis for the Induction of Tissue-Level Phase-2 Reentry as a Repolarization Disorder in the Brugada Syndrome

PubMed Central

Bueno-Orovio, Alfonso; Cherry, Elizabeth M.; Evans, Steven J.; Fenton, Flavio H.

2015-01-01

Aims. Human action potentials in the Brugada syndrome have been characterized by delayed or even complete loss of dome formation, especially in the right ventricular epicardial layers. Such a repolarization pattern is believed to trigger phase-2 reentry (P2R); however, little is known about the conditions necessary for its initiation. This study aims to determine the specific mechanisms that facilitate P2R induction in Brugada-affected cardiac tissue in humans. Methods. Ionic models for Brugada syndrome in human epicardial cells were developed and used to study the induction of P2R in cables, sheets, and a three-dimensional model of the right ventricular free wall. Results. In one-dimensional cables, P2R can be induced by adjoining lost-dome and delayed-dome regions, as mediated by tissue excitability and transmembrane voltage profiles, and reduced coupling facilitates its induction. In two and three dimensions, sustained reentry can arise when three regions (delayed-dome, lost-dome, and normal epicardium) are present. Conclusions. Not only does P2R induction by Brugada syndrome require regions of action potential with delayed-dome and lost-dome, but in order to generate a sustained reentry from a triggered waveback multiple factors are necessary, including heterogeneity in action potential distribution, tissue coupling, direction of stimulation, the shape of the late plateau, the duration of lost-dome action potentials, and recovery of tissue excitability, which is predominantly modulated by tissue coupling. PMID:26583094

Electrical signaling and photosynthesis: can they co-exist together?

PubMed

Pavlovič, Andrej; Mancuso, Stefano

2011-06-01

Mechanical irritation of trigger hairs and subsequent generation of action potentials have significant impact on photosynthesis and respiration in carnivorous Venus flytrap (Dionaea muscipula). Action potential-mediated inhibition of photosynthesis and stimulation of respiration is confined only to the trap and was not recorded in adjacent photosynthetic lamina. We showed that the main primary target of electrical signals on assimilation is in the dark enzymatic reaction of photosynthesis. Without doubt, the electrical signaling is costly, and the possible co-existence of such type of signals and photosynthesis in plant cell is discussed.

Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells.

PubMed

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

2011-06-01

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

From damage response to action potentials: early evolution of neural and contractile modules in stem eukaryotes.

PubMed

Brunet, Thibaut; Arendt, Detlev

2016-01-05

Eukaryotic cells convert external stimuli into membrane depolarization, which in turn triggers effector responses such as secretion and contraction. Here, we put forward an evolutionary hypothesis for the origin of the depolarization-contraction-secretion (DCS) coupling, the functional core of animal neuromuscular circuits. We propose that DCS coupling evolved in unicellular stem eukaryotes as part of an 'emergency response' to calcium influx upon membrane rupture. We detail how this initial response was subsequently modified into an ancient mechanosensory-effector arc, present in the last eukaryotic common ancestor, which enabled contractile amoeboid movement that is widespread in extant eukaryotes. Elaborating on calcium-triggered membrane depolarization, we reason that the first action potentials evolved alongside the membrane of sensory-motile cilia, with the first voltage-sensitive sodium/calcium channels (Nav/Cav) enabling a fast and coordinated response of the entire cilium to mechanosensory stimuli. From the cilium, action potentials then spread across the entire cell, enabling global cellular responses such as concerted contraction in several independent eukaryote lineages. In animals, this process led to the invention of mechanosensory contractile cells. These gave rise to mechanosensory receptor cells, neurons and muscle cells by division of labour and can be regarded as the founder cell type of the nervous system. © 2015 The Authors.

From damage response to action potentials: early evolution of neural and contractile modules in stem eukaryotes

PubMed Central

Brunet, Thibaut; Arendt, Detlev

2016-01-01

Eukaryotic cells convert external stimuli into membrane depolarization, which in turn triggers effector responses such as secretion and contraction. Here, we put forward an evolutionary hypothesis for the origin of the depolarization–contraction–secretion (DCS) coupling, the functional core of animal neuromuscular circuits. We propose that DCS coupling evolved in unicellular stem eukaryotes as part of an ‘emergency response’ to calcium influx upon membrane rupture. We detail how this initial response was subsequently modified into an ancient mechanosensory–effector arc, present in the last eukaryotic common ancestor, which enabled contractile amoeboid movement that is widespread in extant eukaryotes. Elaborating on calcium-triggered membrane depolarization, we reason that the first action potentials evolved alongside the membrane of sensory-motile cilia, with the first voltage-sensitive sodium/calcium channels (Nav/Cav) enabling a fast and coordinated response of the entire cilium to mechanosensory stimuli. From the cilium, action potentials then spread across the entire cell, enabling global cellular responses such as concerted contraction in several independent eukaryote lineages. In animals, this process led to the invention of mechanosensory contractile cells. These gave rise to mechanosensory receptor cells, neurons and muscle cells by division of labour and can be regarded as the founder cell type of the nervous system. PMID:26598726

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.

Basolateral Amygdala to Orbitofrontal Cortex Projections Enable Cue-Triggered Reward Expectations.

PubMed

Lichtenberg, Nina T; Pennington, Zachary T; Holley, Sandra M; Greenfield, Venuz Y; Cepeda, Carlos; Levine, Michael S; Wassum, Kate M

2017-08-30

To make an appropriate decision, one must anticipate potential future rewarding events, even when they are not readily observable. These expectations are generated by using observable information (e.g., stimuli or available actions) to retrieve often quite detailed memories of available rewards. The basolateral amygdala (BLA) and orbitofrontal cortex (OFC) are two reciprocally connected key nodes in the circuitry supporting such outcome-guided behaviors. But there is much unknown about the contribution of this circuit to decision making, and almost nothing known about the whether any contribution is via direct, monosynaptic projections, or the direction of information transfer. Therefore, here we used designer receptor-mediated inactivation of OFC→BLA or BLA→OFC projections to evaluate their respective contributions to outcome-guided behaviors in rats. Inactivation of BLA terminals in the OFC, but not OFC terminals in the BLA, disrupted the selective motivating influence of cue-triggered reward representations over reward-seeking decisions as assayed by Pavlovian-to-instrumental transfer. BLA→OFC projections were also required when a cued reward representation was used to modify Pavlovian conditional goal-approach responses according to the reward's current value. These projections were not necessary when actions were guided by reward expectations generated based on learned action-reward contingencies, or when rewards themselves, rather than stored memories, directed action. These data demonstrate that BLA→OFC projections enable the cue-triggered reward expectations that can motivate the execution of specific action plans and allow adaptive conditional responding. SIGNIFICANCE STATEMENT Deficits anticipating potential future rewarding events are associated with many psychiatric diseases. Presently, we know little about the neural circuits supporting such reward expectation. Here we show that basolateral amygdala to orbitofrontal cortex projections are required for expectations of specific available rewards to influence reward seeking and decision making. The necessity of these projections was limited to situations in which expectations were elicited by reward-predictive cues. These projections therefore facilitate adaptive behavior by enabling the orbitofrontal cortex to use environmental stimuli to generate expectations of potential future rewarding events. Copyright © 2017 the authors 0270-6474/17/378374-11$15.00/0.

Basolateral Amygdala to Orbitofrontal Cortex Projections Enable Cue-Triggered Reward Expectations

PubMed Central

Lichtenberg, Nina T.; Pennington, Zachary T.; Holley, Sandra M.; Greenfield, Venuz Y.; Levine, Michael S.

2017-01-01

To make an appropriate decision, one must anticipate potential future rewarding events, even when they are not readily observable. These expectations are generated by using observable information (e.g., stimuli or available actions) to retrieve often quite detailed memories of available rewards. The basolateral amygdala (BLA) and orbitofrontal cortex (OFC) are two reciprocally connected key nodes in the circuitry supporting such outcome-guided behaviors. But there is much unknown about the contribution of this circuit to decision making, and almost nothing known about the whether any contribution is via direct, monosynaptic projections, or the direction of information transfer. Therefore, here we used designer receptor-mediated inactivation of OFC→BLA or BLA→OFC projections to evaluate their respective contributions to outcome-guided behaviors in rats. Inactivation of BLA terminals in the OFC, but not OFC terminals in the BLA, disrupted the selective motivating influence of cue-triggered reward representations over reward-seeking decisions as assayed by Pavlovian-to-instrumental transfer. BLA→OFC projections were also required when a cued reward representation was used to modify Pavlovian conditional goal-approach responses according to the reward's current value. These projections were not necessary when actions were guided by reward expectations generated based on learned action-reward contingencies, or when rewards themselves, rather than stored memories, directed action. These data demonstrate that BLA→OFC projections enable the cue-triggered reward expectations that can motivate the execution of specific action plans and allow adaptive conditional responding. SIGNIFICANCE STATEMENT Deficits anticipating potential future rewarding events are associated with many psychiatric diseases. Presently, we know little about the neural circuits supporting such reward expectation. Here we show that basolateral amygdala to orbitofrontal cortex projections are required for expectations of specific available rewards to influence reward seeking and decision making. The necessity of these projections was limited to situations in which expectations were elicited by reward-predictive cues. These projections therefore facilitate adaptive behavior by enabling the orbitofrontal cortex to use environmental stimuli to generate expectations of potential future rewarding events. PMID:28743727

Dendritic Na+ spikes enable cortical input to drive action potential output from hippocampal CA2 pyramidal neurons

PubMed Central

Sun, Qian; Srinivas, Kalyan V; Sotayo, Alaba; Siegelbaum, Steven A

2014-01-01

Synaptic inputs from different brain areas are often targeted to distinct regions of neuronal dendritic arbors. Inputs to proximal dendrites usually produce large somatic EPSPs that efficiently trigger action potential (AP) output, whereas inputs to distal dendrites are greatly attenuated and may largely modulate AP output. In contrast to most other cortical and hippocampal neurons, hippocampal CA2 pyramidal neurons show unusually strong excitation by their distal dendritic inputs from entorhinal cortex (EC). In this study, we demonstrate that the ability of these EC inputs to drive CA2 AP output requires the firing of local dendritic Na+ spikes. Furthermore, we find that CA2 dendritic geometry contributes to the efficient coupling of dendritic Na+ spikes to AP output. These results provide a striking example of how dendritic spikes enable direct cortical inputs to overcome unfavorable distal synaptic locale to trigger axonal AP output and thereby enable efficient cortico-hippocampal information flow. DOI: http://dx.doi.org/10.7554/eLife.04551.001 PMID:25390033

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.

Cooperative Drought Adaptation: Integrating Infrastructure Development, Conservation, and Water Transfers into Adaptive Policy Pathways

NASA Astrophysics Data System (ADS)

Zeff, H. B.; Characklis, G. W.; Reed, P. M.; Herman, J. D.

2015-12-01

Water supply policies that integrate portfolios of short-term management decisions with long-term infrastructure development enable utilities to adapt to a range of future scenarios. An effective mix of short-term management actions can augment existing infrastructure, potentially forestalling new development. Likewise, coordinated expansion of infrastructure such as regional interconnections and shared treatment capacity can increase the effectiveness of some management actions like water transfers. Highly adaptable decision pathways that mix long-term infrastructure options and short-term management actions require decision triggers capable of incorporating the impact of these time-evolving decisions on growing water supply needs. Here, we adapt risk-based triggers to sequence a set of potential infrastructure options in combination with utility-specific conservation actions and inter-utility water transfers. Individual infrastructure pathways can be augmented with conservation or water transfers to reduce the cost of meeting utility objectives, but they can also include cooperatively developed, shared infrastructure that expands regional capacity to transfer water. This analysis explores the role of cooperation among four water utilities in the 'Research Triangle' region of North Carolina by formulating three distinct categories of adaptive policy pathways: independent action (utility-specific conservation and supply infrastructure only), weak cooperation (utility-specific conservation and infrastructure development with regional transfers), and strong cooperation (utility specific conservation and jointly developed of regional infrastructure that supports transfers). Results suggest that strong cooperation aids the utilities in meeting their individual objections at substantially lower costs and with fewer irreversible infrastructure options.

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.

Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach.

PubMed

Blazquez-Navarro, Arturo; Schachtner, Thomas; Stervbo, Ulrik; Sefrin, Anett; Stein, Maik; Westhoff, Timm H; Reinke, Petra; Klipp, Edda; Babel, Nina; Neumann, Avidan U; Or-Guil, Michal

2018-05-01

BK virus (BKV) associated nephropathy affects 1-10% of kidney transplant recipients, leading to graft failure in about 50% of cases. Immune responses against different BKV antigens have been shown to have a prognostic value for disease development. Data currently suggest that the structural antigens and regulatory antigens of BKV might each trigger a different mode of action of the immune response. To study the influence of different modes of action of the cellular immune response on BKV clearance dynamics, we have analysed the kinetics of BKV plasma load and anti-BKV T cell response (Elispot) in six patients with BKV associated nephropathy using ODE modelling. The results show that only a small number of hypotheses on the mode of action are compatible with the empirical data. The hypothesis with the highest empirical support is that structural antigens trigger blocking of virus production from infected cells, whereas regulatory antigens trigger an acceleration of death of infected cells. These differential modes of action could be important for our understanding of BKV resolution, as according to the hypothesis, only regulatory antigens would trigger a fast and continuous clearance of the viral load. Other hypotheses showed a lower degree of empirical support, but could potentially explain the clearing mechanisms of individual patients. Our results highlight the heterogeneity of the dynamics, including the delay between immune response against structural versus regulatory antigens, and its relevance for BKV clearance. Our modelling approach is the first that studies the process of BKV clearance by bringing together viral and immune kinetics and can provide a framework for personalised hypotheses generation on the interrelations between cellular immunity and viral dynamics.

Modeling cardiac action potential shortening driven by oxidative stress-induced mitochondrial oscillations in guinea pig cardiomyocytes.

PubMed

Zhou, Lufang; Cortassa, Sonia; Wei, An-Chi; Aon, Miguel A; Winslow, Raimond L; O'Rourke, Brian

2009-10-07

Ischemia-induced shortening of the cardiac action potential and its heterogeneous recovery upon reperfusion are thought to set the stage for reentrant arrhythmias and sudden cardiac death. We have recently reported that the collapse of mitochondrial membrane potential (DeltaPsi(m)) through a mechanism triggered by reactive oxygen species (ROS), coupled to the opening of sarcolemmal ATP-sensitive potassium (K(ATP)) channels, contributes to electrical dysfunction during ischemia-reperfusion. Here we present a computational model of excitation-contraction coupling linked to mitochondrial bioenergetics that incorporates mitochondrial ROS-induced ROS release with coupling between the mitochondrial energy state and electrical excitability mediated by the sarcolemmal K(ATP) current (I(K,ATP)). Whole-cell model simulations demonstrate that increasing the fraction of oxygen diverted from the respiratory chain to ROS production triggers limit-cycle oscillations of DeltaPsi(m), redox potential, and mitochondrial respiration through the activation of a ROS-sensitive inner membrane anion channel. The periods of transient mitochondrial uncoupling decrease the cytosolic ATP/ADP ratio and activate I(K,ATP), consequently shortening the cellular action potential duration and ultimately suppressing electrical excitability. The model simulates emergent behavior observed in cardiomyocytes subjected to metabolic stress and provides a new tool for examining how alterations in mitochondrial oxidative phosphorylation will impact the electrophysiological, contractile, and Ca(2+) handling properties of the cardiac cell. Moreover, the model is an important step toward building multiscale models that will permit investigation of the role of spatiotemporal heterogeneity of mitochondrial metabolism in the mechanisms of arrhythmogenesis and contractile dysfunction in cardiac muscle.

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.

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

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.

Decoding spike timing: the differential reverse correlation method

PubMed Central

Tkačik, Gašper; Magnasco, Marcelo O.

2009-01-01

It is widely acknowledged that detailed timing of action potentials is used to encode information, for example in auditory pathways; however the computational tools required to analyze encoding through timing are still in their infancy. We present a simple example of encoding, based on a recent model of time-frequency analysis, in which units fire action potentials when a certain condition is met, but the timing of the action potential depends also on other features of the stimulus. We show that, as a result, spike-triggered averages are smoothed so much they do not represent the true features of the encoding. Inspired by this example, we present a simple method, differential reverse correlations, that can separate an analysis of what causes a neuron to spike, and what controls its timing. We analyze with this method the leaky integrate-and-fire neuron and show the method accurately reconstructs the model's kernel. PMID:18597928

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

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.

Single mechanically-gated cation channel currents can trigger action potentials in neocortical and hippocampal pyramidal neurons.

PubMed

Nikolaev, Yury A; Dosen, Peter J; Laver, Derek R; van Helden, Dirk F; Hamill, Owen P

2015-05-22

The mammalian brain is a mechanosensitive organ that responds to different mechanical forces ranging from intrinsic forces implicated in brain morphogenesis to extrinsic forces that can cause concussion and traumatic brain injury. However, little is known of the mechanosensors that transduce these forces. In this study we use cell-attached patch recording to measure single mechanically-gated (MG) channel currents and their affects on spike activity in identified neurons in neonatal mouse brain slices. We demonstrate that both neocortical and hippocampal pyramidal neurons express stretch-activated MG cation channels that are activated by suctions of ~25mm Hg, have a single channel conductance for inward current of 50-70pS and show weak selectivity for alkali metal cations (i.e., Na(+)

Method for triggering an action

DOEpatents

Hall, David R.; Bartholomew, David B.; Johnson, Monte L.; Moon, Justin; Koehler, Roger O.

2006-10-17

A method for triggering an action of at least one downhole device on a downhole network integrated into a downhole tool string synchronized to an event comprises determining latency, sending a latency adjusted signal, and performing the action. The latency is determined between a control device and the at least one downhole device. The latency adjusted signal for triggering an action is sent to the downhole device. The action is performed downhole synchronized to the event. A preferred method for determining latency comprises the steps: a control device sends a first signal to the downhole device; after receiving the signal, the downhole device sends a response signal to the control device; and the control device analyzes the time from sending the signal to receiving the response signal.

Warning Triggers in Environmental Hazards: Who Should Be Warned to Do What and When?

PubMed

Cova, Thomas J; Dennison, Philip E; Li, Dapeng; Drews, Frank A; Siebeneck, Laura K; Lindell, Michael K

2017-04-01

Determining the most effective public warnings to issue during a hazardous environmental event is a complex problem. Three primary questions need to be answered: Who should take protective action? What is the best action? and When should this action be initiated? Warning triggers provide a proactive means for emergency managers to simultaneously answer these questions by recommending that a target group take a specified protective action if a preset environmental trigger condition occurs (e.g., warn a community to evacuate if a wildfire crosses a proximal ridgeline). Triggers are used to warn the public across a wide variety of environmental hazards, and an improved understanding of their nature and role promises to: (1) advance protective action theory by unifying the natural, built, and social themes in hazards research into one framework, (2) reveal important information about emergency managers' risk perception, situational awareness, and threat assessment regarding threat behavior and public response, and (3) advance spatiotemporal models for representing the geography and timing of disaster warning and response (i.e., a coupled natural-built-social system). We provide an overview and research agenda designed to advance our understanding and modeling of warning triggers. © 2016 Society for Risk Analysis.

On the Masking and Disclosure of Unconscious Elaborate Processing. A Reply to Van Opstal, Reynvoet, and Verguts (2005)

ERIC Educational Resources Information Center

Kunde, Wilfried; Kiesel, Andrea; Hoffmann, Joachim

2005-01-01

We have recently argued that unconscious numerical stimuli might activate responses by a match with prespecified action trigger codes (action trigger account) rather than by semantic prime processing (elaborate processing account). [Van Opstal, F., Reynvoet, B., and Verguts, T. (2005). How to trigger elaborate processing? A comment on Kunde,…

Action-projection in Japanese conversation: topic particles wa, mo, and tte for triggering categorization activities

PubMed Central

Tanaka, Hiroko

2015-01-01

Conversation analytic work has revealed how anticipatory completions and preemptive actions can offer invaluable glimpses into the cognitive, contextual, grammatical, and temporal bases of projectability in turn-taking, by virtue of their potential not only as a display of participants' online prediction of roughly what it might take to complete a turn-in-progress but also to plan the next move. While the predicate-final word order and the incremental transformability of turns in Japanese generally lead to delayed projectability of turn-endings, this may be partially offset by the capacity of certain postpositional particles to trigger and propel prospective action trajectories. This article engages in a case study of the topic particle wa (and related particles mo and tte), by demonstrating how its grammatical affordances, the categorization activities, and cognitive processing it can set in motion, coupled with the immediate contextual, and temporal-productional features may coalesce to a point of critical mass, thereby enhancing the projectability of the not-yet-produced trajectory of the current turn. The discussion attempts to contribute to recent debates on ways language-specific lexicogrammatical resources are deeply interlinked with the types of opportunities that are provided for social action. PMID:26379565

Accelerating Progress in Eating Disorders Prevention: A Call for Policy Translation Research and Training.

PubMed

Austin, S Bryn

2016-01-01

The public health burden of eating disorders is well documented, and over the past several decades, researchers have made important advances in the prevention of eating disorders and related problems with body image. Despite these advances, however, several critical limitations to the approaches developed to date leave the field far from achieving the large-scale impact that is needed. This commentary provides a brief review of what achievements in prevention have been made and identifies the gaps that limit the potential for greater impact on population health. A plan is then offered with specific action steps to accelerate progress in high-impact prevention, most compellingly by promoting a shift in priorities to policy translation research and training for scholars through the adoption of a triggers-to-action framework. Finally, the commentary provides an example of the application of the triggers-to-action framework as practiced at the Strategic Training Initiative for the Prevention of Eating Disorders, a program based at the Harvard T. H. Chan School of Public Health and Boston Children's Hospital. Much has been achieved in the nearly 30 years of research carried out for the prevention of eating disorders and body image problems, but several critical limitations undermine the field's potential for meaningful impact. Through a shift in the field's priorities to policy translation research and training with an emphasis on macro-environmental influences, the pace of progress in prevention can be accelerated and the potential for large-scale impact substantially improved.

Activation of cannabinoid CB1 receptors modulates evoked action potentials in rat retinal ganglion cells.

PubMed

Jiang, Shu-Xia; Li, Qian; Wang, Xiao-Han; Li, Fang; Wang, Zhong-Feng

2013-08-25

Activation of cannabinoid CB1 receptors (CB1Rs) regulates a variety of physiological functions in the vertebrate retina through modulating various types of ion channels. The aim of the present study was to investigate the effects of this receptor on cell excitability of rat retinal ganglion cells (RGCs) in retinal slices using whole-cell patch-clamp techniques. The results showed that under current-clamped condition perfusing WIN55212-2 (WIN, 5 μmol/L), a CB1R agonist, did not significantly change the spontaneous firing frequency and resting membrane potential of RGCs. In the presence of cocktail synaptic blockers, including excitatory postsynaptic receptor blockers CNQX and D-APV, and inhibitory receptor blockers bicuculline and strychnine, perfusion of WIN (5 μmol/L) hardly changed the frequencies of evoked action potentials by a series of positive current injection (from +10 to +100 pA). Phase-plane plot analysis showed that both average threshold voltage for triggering action potential and delay time to reach threshold voltage were not affected by WIN. However, WIN significantly decreased +dV/dtmax and -dV/dtmax of action potentials, suggestive of reduced rising and descending velocities of action potentials. The effects of WIN were reversed by co-application of SR141716, a CB1R selective antagonist. Moreover, WIN did not influence resting membrane potential of RGCs with synaptic inputs being blocked. These results suggest that activation of CB1Rs may regulate intrinsic excitability of rat RGCs through modulating evoked action potentials.

Bidirectional Hebbian Plasticity Induced by Low-Frequency Stimulation in Basal Dendrites of Rat Barrel Cortex Layer 5 Pyramidal Neurons.

PubMed

Díez-García, Andrea; Barros-Zulaica, Natali; Núñez, Ángel; Buño, Washington; Fernández de Sevilla, David

2017-01-01

According to Hebb's original hypothesis (Hebb, 1949), synapses are reinforced when presynaptic activity triggers postsynaptic firing, resulting in long-term potentiation (LTP) of synaptic efficacy. Long-term depression (LTD) is a use-dependent decrease in synaptic strength that is thought to be due to synaptic input causing a weak postsynaptic effect. Although the mechanisms that mediate long-term synaptic plasticity have been investigated for at least three decades not all question have as yet been answered. Therefore, we aimed at determining the mechanisms that generate LTP or LTD with the simplest possible protocol. Low-frequency stimulation of basal dendrite inputs in Layer 5 pyramidal neurons of the rat barrel cortex induces LTP. This stimulation triggered an EPSP, an action potential (AP) burst, and a Ca 2+ spike. The same stimulation induced LTD following manipulations that reduced the Ca 2+ spike and Ca 2+ signal or the AP burst. Low-frequency whisker deflections induced similar bidirectional plasticity of action potential evoked responses in anesthetized rats. These results suggest that both in vitro and in vivo similar mechanisms regulate the balance between LTP and LTD. This simple induction form of bidirectional hebbian plasticity could be present in the natural conditions to regulate the detection, flow, and storage of sensorimotor information.

Bidirectional Hebbian Plasticity Induced by Low-Frequency Stimulation in Basal Dendrites of Rat Barrel Cortex Layer 5 Pyramidal Neurons

PubMed Central

Díez-García, Andrea; Barros-Zulaica, Natali; Núñez, Ángel; Buño, Washington; Fernández de Sevilla, David

2017-01-01

According to Hebb's original hypothesis (Hebb, 1949), synapses are reinforced when presynaptic activity triggers postsynaptic firing, resulting in long-term potentiation (LTP) of synaptic efficacy. Long-term depression (LTD) is a use-dependent decrease in synaptic strength that is thought to be due to synaptic input causing a weak postsynaptic effect. Although the mechanisms that mediate long-term synaptic plasticity have been investigated for at least three decades not all question have as yet been answered. Therefore, we aimed at determining the mechanisms that generate LTP or LTD with the simplest possible protocol. Low-frequency stimulation of basal dendrite inputs in Layer 5 pyramidal neurons of the rat barrel cortex induces LTP. This stimulation triggered an EPSP, an action potential (AP) burst, and a Ca2+ spike. The same stimulation induced LTD following manipulations that reduced the Ca2+ spike and Ca2+ signal or the AP burst. Low-frequency whisker deflections induced similar bidirectional plasticity of action potential evoked responses in anesthetized rats. These results suggest that both in vitro and in vivo similar mechanisms regulate the balance between LTP and LTD. This simple induction form of bidirectional hebbian plasticity could be present in the natural conditions to regulate the detection, flow, and storage of sensorimotor information. PMID:28203145

Spontaneous Release Regulates Synaptic Scaling in the Embryonic Spinal Network In Vivo

PubMed Central

Garcia-Bereguiain, Miguel Angel; Gonzalez-Islas, Carlos; Lindsly, Casie

2016-01-01

Homeostatic plasticity mechanisms maintain cellular or network spiking activity within a physiologically functional range through compensatory changes in synaptic strength or intrinsic cellular excitability. Synaptic scaling is one form of homeostatic plasticity that is triggered after blockade of spiking or neurotransmission in which the strengths of all synaptic inputs to a cell are multiplicatively scaled upward or downward in a compensatory fashion. We have shown previously that synaptic upscaling could be triggered in chick embryo spinal motoneurons by complete blockade of spiking or GABAA receptor (GABAAR) activation for 2 d in vivo. Here, we alter GABAAR activation in a more physiologically relevant manner by chronically adjusting presynaptic GABA release in vivo using nicotinic modulators or an mGluR2 agonist. Manipulating GABAAR activation in this way triggered scaling in a mechanistically similar manner to scaling induced by complete blockade of GABAARs. Remarkably, we find that altering action-potential (AP)-independent spontaneous release was able to fully account for the observed bidirectional scaling, whereas dramatic changes in spiking activity associated with spontaneous network activity had little effect on quantal amplitude. The reliance of scaling on an AP-independent process challenges the plasticity's relatedness to spiking in the living embryonic spinal network. Our findings have implications for the trigger and function of synaptic scaling and suggest that spontaneous release functions to regulate synaptic strength homeostatically in vivo. SIGNIFICANCE STATEMENT Homeostatic synaptic scaling is thought to prevent inappropriate levels of spiking activity through compensatory adjustments in the strength of synaptic inputs. Therefore, it is thought that perturbations in spike rate trigger scaling. Here, we find that dramatic changes in spiking activity in the embryonic spinal cord have little effect on synaptic scaling; conversely, alterations in GABAA receptor activation due to action-potential-independent GABA vesicle release can trigger scaling. The findings suggest that scaling in the living embryonic spinal cord functions to maintain synaptic strength and challenge the view that scaling acts to regulate spiking activity homeostatically. Finally, the results indicate that fetal exposure to drugs that influence GABA spontaneous release, such as nicotine, could profoundly affect synaptic maturation. PMID:27383600

Fipronil is a powerful uncoupler of oxidative phosphorylation that triggers apoptosis in human neuronal cell line SHSY5Y.

PubMed

Vidau, Cyril; González-Polo, Rosa A; Niso-Santano, Mireia; Gómez-Sánchez, Rubén; Bravo-San Pedro, José M; Pizarro-Estrella, Elisa; Blasco, Rafael; Brunet, Jean-Luc; Belzunces, Luc P; Fuentes, José M

2011-12-01

Fipronil is a phenylpyrazole insecticide known to elicit neurotoxicity via an interaction with ionotropic receptors, namely GABA and glutamate receptors. Recently, we showed that fipronil and other phenylpyrazole compounds trigger cell death in Caco-2 cells. In this study, we investigated the mode of action and the type of cell death induced by fipronil in SH-SY5Y human neuroblastoma cells. Flow cytometric and western blot analyses demonstrated that fipronil induces cellular events belonging to the apoptosis process, such as mitochondrial potential collapse, cytochrome c release, caspase-3 activation, nuclear condensation and phosphatidylserine externalization. In addition, fipronil induces a rapid ATP depletion with concomitant activation of anaerobic glycolysis. This cellular response is characteristic of mitochondrial injury associated with a defect of the respiration process. Therefore, we also investigated the effect of fipronil on the oxygen consumption in isolated mitochondria. Interestingly, we show for the first time that fipronil is a strong uncoupler of oxidative phosphorylation at relative low concentrations. Thus in this study, we report a new mode of action by which the insecticide fipronil could triggers apoptosis. Copyright © 2011 Elsevier Inc. All rights reserved.

Epstein-Barr virus and rheumatoid arthritis: is there a link?

PubMed

Costenbader, Karen H; Karlson, Elizabeth W

2006-01-01

Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic, destructive, debilitating arthritis. Its etiology is unknown; it is presumed that environmental factors trigger development in the genetically predisposed. Epstein-Barr virus, a nearly ubiquitous virus in the human population, has generated great interest as a potential trigger. This virus stimulates polyclonal lymphocyte expansion and persists within B lymphocytes for the host's life, inhibited from reactivating by the immune response. In latent and replicating forms, it has immunomodulating actions that could play a role in the development of this autoimmune disease. The evidence linking Epstein-Barr virus and rheumatoid arthritis is reviewed.

Epstein–Barr virus and rheumatoid arthritis: is there a link?

PubMed Central

Costenbader, Karen H; Karlson, Elizabeth W

2006-01-01

Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic, destructive, debilitating arthritis. Its etiology is unknown; it is presumed that environmental factors trigger development in the genetically predisposed. Epstein–Barr virus, a nearly ubiquitous virus in the human population, has generated great interest as a potential trigger. This virus stimulates polyclonal lymphocyte expansion and persists within B lymphocytes for the host's life, inhibited from reactivating by the immune response. In latent and replicating forms, it has immunomodulating actions that could play a role in the development of this autoimmune disease. The evidence linking Epstein–Barr virus and rheumatoid arthritis is reviewed. PMID:16542469

Single-Pixel Optical Fluctuation Analysis of Calcium Channel Function in Active Zones of Motor Nerve Terminals

PubMed Central

Luo, Fujun; Dittrich, Markus; Stiles, Joel R.; Meriney, Stephen D.

2011-01-01

We used high-resolution fluorescence imaging and single-pixel optical fluctuation analysis to estimate the opening probability of individual voltage-gated calcium (Ca2+) channels during an action potential and the number of such Ca2+ channels within active zones of frog neuromuscular junctions. Analysis revealed ~36 Ca2+ channels within each active zone, similar to the number of docked synaptic vesicles but far less than the total number of transmembrane particles reported based on freeze-fracture analysis (~200–250). The probability that each channel opened during an action potential was only ~0.2. These results suggest why each active zone averages only one quantal release event during every other action potential, despite a substantial number of docked vesicles. With sparse Ca2+ channels and low opening probability, triggering of fusion for each vesicle is primarily controlled by Ca2+ influx through individual Ca2+ channels. In contrast, the entire synapse is highly reliable because it contains hundreds of active zones. PMID:21813687

So little source, so much sink: requirements for afterdepolarizations to propagate in tissue.

PubMed

Xie, Yuanfang; Sato, Daisuke; Garfinkel, Alan; Qu, Zhilin; Weiss, James N

2010-09-08

How early (EADs) and delayed afterdepolarizations (DADs) overcome electrotonic source-sink mismatches in tissue to trigger premature ventricular complexes remains incompletely understood. To study this question, we used a rabbit ventricular action potential model to simulate tissues in which a central area of contiguous myocytes susceptible to EADs or DADs was surrounded by unsusceptible tissue. In 1D tissue with normal longitudinal conduction velocity (0.55 m/s), the numbers of contiguous susceptible myocytes required for an EAD and a barely suprathreshold DAD to trigger a propagating action potential were 70 and 80, respectively. In 2D tissue, these numbers increased to 6940 and 7854, and in 3D tissue to 696,910 and 817,280. These numbers were significantly decreased by reduced gap junction conductance, simulated fibrosis, reduced repolarization reserve and heart failure electrical remodeling. In conclusion, the source-sink mismatch in well-coupled cardiac tissue powerfully protects the heart from arrhythmias due to sporadic afterdepolarizations. Structural and electrophysiological remodeling decrease these numbers significantly but still require synchronization mechanisms for EADs and DADs to overcome the robust protective effects of source-sink mismatch. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Intrinsic and integrative properties of substantia nigra pars reticulata neurons

PubMed Central

Zhou, Fu-Ming; Lee, Christian R.

2011-01-01

The GABA projection neurons of the substantia nigra pars reticulata (SNr) are output neurons for the basal ganglia and thus critical for movement control. Their most striking neurophysiological feature is sustained, spontaneous high frequency spike firing. A fundamental question is: what are the key ion channels supporting the remarkable firing capability in these neurons? Recent studies indicate that these neurons express tonically active TRPC3 channels that conduct a Na-dependent inward current even at hyperpolarized membrane potentials. When the membrane potential reaches −60 mV, a voltage-gated persistent sodium current (INaP) starts to activate, further depolarizing the membrane potential. At or slightly below −50 mV, the large transient voltage-activated sodium current (INaT) starts to activate and eventually triggers the rapid rising phase of action potentials. SNr GABA neurons have a higher density of (INaT), contributing to the faster rise and larger amplitude of action potentials, compared with the slow-spiking dopamine neurons. INaT also recovers from inactivation more quickly in SNr GABA neurons than in nigral dopamine neurons. In SNr GABA neurons, the rising phase of the action potential triggers the activation of high-threshold, inactivation-resistant Kv3-like channels that can rapidly repolarize the membrane. These intrinsic ion channels provide SNr GABA neurons with the ability to fire spontaneous and sustained high frequency spikes. Additionally, robust GABA inputs from direct pathway medium spiny neurons in the striatum and GABA neurons in the globus pallidus may inhibit and silence SNr GABA neurons, whereas glutamate synaptic input from the subthalamic nucleus may induce burst firing in SNr GABA neurons. Thus, afferent GABA and glutamate synaptic inputs sculpt the tonic high frequency firing of SNr GABA neurons and the consequent inhibition of their targets into an integrated motor control signal that is further fine-tuned by neuromodulators including dopamine, serotonin, endocannabinoids, and H2O2. PMID:21839148

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.

Action-based flood forecasting for triggering humanitarian action

NASA Astrophysics Data System (ADS)

Coughlan de Perez, Erin; van den Hurk, Bart; van Aalst, Maarten K.; Amuron, Irene; Bamanya, Deus; Hauser, Tristan; Jongma, Brenden; Lopez, Ana; Mason, Simon; Mendler de Suarez, Janot; Pappenberger, Florian; Rueth, Alexandra; Stephens, Elisabeth; Suarez, Pablo; Wagemaker, Jurjen; Zsoter, Ervin

2016-09-01

Too often, credible scientific early warning information of increased disaster risk does not result in humanitarian action. With financial resources tilted heavily towards response after a disaster, disaster managers have limited incentive and ability to process complex scientific data, including uncertainties. These incentives are beginning to change, with the advent of several new forecast-based financing systems that provide funding based on a forecast of an extreme event. Given the changing landscape, here we demonstrate a method to select and use appropriate forecasts for specific humanitarian disaster prevention actions, even in a data-scarce location. This action-based forecasting methodology takes into account the parameters of each action, such as action lifetime, when verifying a forecast. Forecasts are linked with action based on an understanding of (1) the magnitude of previous flooding events and (2) the willingness to act "in vain" for specific actions. This is applied in the context of the Uganda Red Cross Society forecast-based financing pilot project, with forecasts from the Global Flood Awareness System (GloFAS). Using this method, we define the "danger level" of flooding, and we select the probabilistic forecast triggers that are appropriate for specific actions. Results from this methodology can be applied globally across hazards and fed into a financing system that ensures that automatic, pre-funded early action will be triggered by forecasts.

Differential calcium sensitivity in NaV 1.5 mixed syndrome mutants.

PubMed

Abdelsayed, Mena; Baruteau, Alban-Elouen; Gibbs, Karen; Sanatani, Shubhayan; Krahn, Andrew D; Probst, Vincent; Ruben, Peter C

2017-09-15

SCN5a mutations may express gain-of-function (Long QT Syndrome-3), loss-of-function (Brugada Syndrome 1) or both (mixed syndromes), depending on the mutation and environmental triggers. One such trigger may be an increase in cytosolic calcium, accompanying exercise. Many mixed syndromes mutants, including ∆KPQ, E1784K, 1795insD and Q1909R, are found in calcium-sensitive regions. Elevated cytosolic calcium attenuates gain-of-function properties in ∆KPQ, 1795insD and Q1909R, but not in E1784K. By contrast, elevated cytosolic calcium further exacerbates gain-of-function in E1784K by destabilizing slow inactivation. Action potential modelling, using a modified O'Hara Rudy model, suggests that elevated heart rate rescues action potential duration in ∆KPQ, 1795insD and Q1909R, but not in E1784K. Action potential simulations suggest that E1784K carriers have an increased intracellular sodium-to-calcium ratio under bradycardia and tachycardia conditions. Elevated cytosolic calcium, which is common during high heart rates, ameliorates or exacerbates the mixed syndrome phenotype depending on the genetic signature. Inherited arrhythmias may arise from mutations in the gene for SCN5a, which encodes the cardiac voltage-gated sodium channel, Na V 1.5. Mutants in Na V 1.5 result in Brugada Syndrome (BrS1), Long-QT Syndrome (LQT3) or mixed syndromes (an overlap of BrS1/LQT3). Exercise is a potential arrhythmogenic trigger in mixed syndromes. We aimed to determine the effects of elevated cytosolic calcium, which is common during exercise, in mixed syndrome Na V 1.5 mutants. We used whole-cell patch clamp to assess the biophysical properties of Na V 1.5 wild-type (WT), ∆KPQ, E1784K, 1795insD and Q1909R mutants in human embryonic kidney 293 cells transiently transfected with the Na V 1.5 α subunit (WT or mutants), β1 subunit and enhanced green fluorescent protein. Voltage-dependence and kinetics were measured at cytosolic calcium levels of approximately 0, 500 and 2500 nm. In silico, action potential (AP) model simulations were performed using a modified O'Hara Rudy model. Elevated cytosolic calcium attenuates the late sodium current in ∆KPQ, 1795insD and Q1909R, but not in E1784K. Elevated cytosolic calcium restores steady-state slow inactivation (SSSI) to the WT-form in Q1909R, but depolarized SSSI in E1784K. Our AP simulations showed a frequency-dependent reduction of AP duration in ∆KPQ, 1795insD and Q1909R carriers. In E1784K, AP duration is relatively prolonged at both low and high heart rates, resulting in a sodium overload. Cellular perturbations during exercise may affect BrS1/LQT3 patients differently depending on their individual genetic signature. Thus, exercise may be therapeutic or may be an arrhythmogenic trigger in some SCN5a patients. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Firearm trigger assembly

DOEpatents

Crandall, David L.; Watson, Richard W.

2010-02-16

A firearm trigger assembly for use with a firearm includes a trigger mounted to a forestock of the firearm so that the trigger is movable between a rest position and a triggering position by a forwardly placed support hand of a user. An elongated trigger member operatively associated with the trigger operates a sear assembly of the firearm when the trigger is moved to the triggering position. An action release assembly operatively associated with the firearm trigger assembly and a movable assembly of the firearm prevents the trigger from being moved to the triggering position when the movable assembly is not in the locked position.

Hypoxia triggers short term potentiation of phrenic motoneuron discharge after chronic cervical spinal cord injury

PubMed Central

Lee, Kun-Ze; Sandhu, Milapjit S.; Dougherty, Brendan J.; Reier, Paul J.; Fuller, David D.

2014-01-01

Repeated exposure to hypoxia can induce spinal neuroplasticity as well as respiratory and somatic motor recovery after spinal cord injury (SCI). The purpose of the present study was to define the capacity for a single bout of hypoxia to trigger short-term plasticity in phrenic output after cervical SCI, and to determine the phrenic motoneuron (PhrMN) bursting and recruitment patterns underlying the response. Hypoxia-induced short term potentiation (STP) of phrenic motor output was quantified in anesthetized rats 11 wks following lateral spinal hemisection at C2 (C2Hx). A 3-min hypoxic episode (12–14% O2) always triggered STP of inspiratory burst amplitude, the magnitude of which was greater in phrenic bursting ipsilateral vs. contralateral to C2Hx. We next determined if STP could be evoked in recruited (silent) PhrMNs ipsilateral to C2Hx. Individual PhrMN action potentials were recorded during and following hypoxia using a “single fiber” approach. STP of bursting activity did not occur in cells initiating bursting at inspiratory onset, but was robust in recruited PhrMNs as well as previously active cells initiating bursting later in the inspiratory effort. We conclude that following chronic C2Hx, a single bout of hypoxia triggers recruitment of PhrMNs in the ipsilateral spinal cord with bursting that persists beyond the hypoxic exposure. The results provide further support for the use of short bouts of hypoxia as a neurorehabilitative training modality following SCI. PMID:25448009

Ethanol exposure in early adolescence inhibits intrinsic neuronal plasticity via sigma-1 receptor activation in hippocampal CA1 neurons

PubMed Central

Sabeti, Jilla

2011-01-01

Background We demonstrated previously that rats exposed to chronic intermittent ethanol (CIE) vapors in early adolescence show increased magnitudes of long-term potentiation (LTP) of excitatory transmission when recorded at dendritic synapses in hippocampus. Large amplitude LTP following CIE exposure is mediated by sigma-1 receptors; however, not yet addressed is the role of sigma-1 receptors in modulating the intrinsic properties of neurons to alter their action potential firing during LTP. Methods Activity-induced plasticity of spike firing was investigated using rat hippocampal slice recordings to measure changes in both field excitatory postsynaptic potentials (fEPSPs) and population spikes (pop. spikes) concomitantly at dendritic inputs and soma of CA1 pyramidal neurons, respectively. Results We observed unique modifications in plasticity of action potential firing in hippocampal slices from CIE exposed adolescent rats, where the induction of large amplitude LTP by 100 Hz stimulations was accompanied by reduced CA1 neuronal excitability—reflected as decreased pop. spike efficacy and impaired activity-induced fEPSP-to-spike (E-S) potentiation. By contrast, LTP induction in ethanol-naïve control slices resulted in increased spike efficacy and robust E-S potentiation. E-S potentiation impairments emerged at 24 hr after CIE treatment cessation, but not before the alcohol withdrawal period, and were restored with bath-application of the sigma-1 receptor selective antagonist BD1047, but not the NMDA receptor antagonist D-AP5. Further evidence revealed a significantly shortened somatic fEPSP time course in adolescent CIE-withdrawn hippocampal slices during LTP; however, paired-pulse data show no apparent correspondence between E-S dissociation and altered recurrent feedback inhibition. Conclusions Results here suggest that acute withdrawal from adolescent CIE exposure triggers sigma-1 receptors that act to depress the efficacy of excitatory inputs in triggering action potentials during LTP. Such withdrawal-induced depression of E-S plasticity in hippocampus likely entails sigma-1 receptor modulation of one or several voltage-gated ion channels controlling the neuronal input-output dynamics. PMID:21314692

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

Sub-millisecond closed-loop feedback stimulation between arbitrary sets of individual neurons

PubMed Central

Müller, Jan; Bakkum, Douglas J.; Hierlemann, Andreas

2012-01-01

We present a system to artificially correlate the spike timing between sets of arbitrary neurons that were interfaced to a complementary metal–oxide–semiconductor (CMOS) high-density microelectrode array (MEA). The system features a novel reprogrammable and flexible event engine unit to detect arbitrary spatio-temporal patterns of recorded action potentials and is capable of delivering sub-millisecond closed-loop feedback of electrical stimulation upon trigger events in real-time. The relative timing between action potentials of individual neurons as well as the temporal pattern among multiple neurons, or neuronal assemblies, is considered an important factor governing memory and learning in the brain. Artificially changing timings between arbitrary sets of spiking neurons with our system could provide a “knob” to tune information processing in the network. PMID:23335887

Light-evoked hyperpolarization and silencing of neurons by conjugated polymers.

PubMed

Feyen, Paul; Colombo, Elisabetta; Endeman, Duco; Nova, Mattia; Laudato, Lucia; Martino, Nicola; Antognazza, Maria Rosa; Lanzani, Guglielmo; Benfenati, Fabio; Ghezzi, Diego

2016-03-04

The ability to control and modulate the action potential firing in neurons represents a powerful tool for neuroscience research and clinical applications. While neuronal excitation has been achieved with many tools, including electrical and optical stimulation, hyperpolarization and neuronal inhibition are typically obtained through patch-clamp or optogenetic manipulations. Here we report the use of conjugated polymer films interfaced with neurons for inducing a light-mediated inhibition of their electrical activity. We show that prolonged illumination of the interface triggers a sustained hyperpolarization of the neuronal membrane that significantly reduces both spontaneous and evoked action potential firing. We demonstrate that the polymeric interface can be activated by either visible or infrared light and is capable of modulating neuronal activity in brain slices and explanted retinas. These findings prove the ability of conjugated polymers to tune neuronal firing and suggest their potential application for the in-vivo modulation of neuronal activity.

Light-evoked hyperpolarization and silencing of neurons by conjugated polymers

PubMed Central

Feyen, Paul; Colombo, Elisabetta; Endeman, Duco; Nova, Mattia; Laudato, Lucia; Martino, Nicola; Antognazza, Maria Rosa; Lanzani, Guglielmo; Benfenati, Fabio; Ghezzi, Diego

2016-01-01

The ability to control and modulate the action potential firing in neurons represents a powerful tool for neuroscience research and clinical applications. While neuronal excitation has been achieved with many tools, including electrical and optical stimulation, hyperpolarization and neuronal inhibition are typically obtained through patch-clamp or optogenetic manipulations. Here we report the use of conjugated polymer films interfaced with neurons for inducing a light-mediated inhibition of their electrical activity. We show that prolonged illumination of the interface triggers a sustained hyperpolarization of the neuronal membrane that significantly reduces both spontaneous and evoked action potential firing. We demonstrate that the polymeric interface can be activated by either visible or infrared light and is capable of modulating neuronal activity in brain slices and explanted retinas. These findings prove the ability of conjugated polymers to tune neuronal firing and suggest their potential application for the in-vivo modulation of neuronal activity. PMID:26940513

Simulation of Arrhythmogenic Effect of Rogue RyRs in Failing Heart by Using a Coupled Model

PubMed Central

Lu, Luyao; Xia, Ling; Zhu, Xiuwei

2012-01-01

Cardiac cells with heart failure are usually characterized by impairment of Ca2+ handling with smaller SR Ca2+ store and high risk of triggered activities. In this study, we developed a coupled model by integrating the spatiotemporal Ca2+ reaction-diffusion system into the cellular electrophysiological model. With the coupled model, the subcellular Ca2+ dynamics and global cellular electrophysiology could be simultaneously traced. The proposed coupled model was then applied to study the effects of rogue RyRs on Ca2+ cycling and membrane potential in failing heart. The simulation results suggested that, in the presence of rogue RyRs, Ca2+ dynamics is unstable and Ca2+ waves are prone to be initiated spontaneously. These release events would elevate the membrane potential substantially which might induce delayed afterdepolarizations or triggered action potentials. Moreover, the variation of membrane potential depolarization is indicated to be dependent on the distribution density of rogue RyR channels. This study provides a new possible arrhythmogenic mechanism for heart failure from subcellular to cellular level. PMID:23056145

76 FR 30027 - National Oil and Hazardous Substance Pollution Contingency Plan; National Priorities List

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-24

... (dust, paint and water). These trigger criteria were used by the KF work group to identify and.... The KF work group developed and approved all action and no-action determinations. The property owners... remediation When one or more of the trigger criteria were exceeded, a work group evaluated a range of...

Mode of action of leucocin K7 produced by Leuconostoc mesenteroides K7 against Listeria monocytogenes and its potential in milk preservation.

PubMed

Shi, Feng; Wang, Yanwei; Li, Yongfu; Wang, Xiaoyuan

2016-09-01

To investigate the mode of action of leucocin K7 against Listeria monocytogenes and to assess its inhibitory effect on Lis. monocytogenes in refrigerated milk. A bacteriocin-producing strain, Leuconostoc mesenteroides K7, was isolated from a fermented pickle. The bacteriocin, leucocin K7, exhibited antagonistic activity against Lis. monocytogenes with an MIC of 28 µg/ml. It was sensitive to proteaseS and displayed good thermal stability and broad active pH range. Leucocin K7 had no effect on the efflux of ATP from Lis. monocytogenes but triggered the efflux of K(+) and the intracellular hydrolysis of ATP. It also dissipated the transmembrane electrical potential completely and transmembrane pH gradient partially. It 80 AU/ml inhibited the growth of Lis. monocytogenes by 2.3-3.9 log units in milk; when combined with glycine (5 mg/ml), it completely eliminated viable Lis. monocytogenes over 7 days Leucocin K7 shows different mode of action from nisin and may have potential application in milk preservation.

The Mechanism of Extracellular Stimulation of Nerve Cells on an Electrolyte-Oxide-Semiconductor Capacitor

PubMed Central

Schoen, Ingmar; Fromherz, Peter

2007-01-01

Extracellular excitation of neurons is applied in studies of cultured networks and brain tissue, as well as in neuroprosthetics. We elucidate its mechanism in an electrophysiological approach by comparing voltage-clamp and current-clamp recordings of individual neurons on an insulated planar electrode. Noninvasive stimulation of neurons from pedal ganglia of Lymnaea stagnalis is achieved by defined voltage ramps applied to an electrolyte/HfO2/silicon capacitor. Effects on the smaller attached cell membrane and the larger free membrane are distinguished in a two-domain-stimulation model. Under current-clamp, we study the polarization that is induced for closed ion channels. Under voltage-clamp, we determine the capacitive gating of ion channels in the attached membrane by falling voltage ramps and for comparison also the gating of all channels by conventional variation of the intracellular voltage. Neuronal excitation is elicited under current-clamp by two mechanisms: Rising voltage ramps depolarize the free membrane such that an action potential is triggered. Falling voltage ramps depolarize the attached membrane such that local ion currents are activated that depolarize the free membrane and trigger an action potential. The electrophysiological analysis of extracellular stimulation in the simple model system is a basis for its systematic optimization in neuronal networks and brain tissue. PMID:17098803

Unravelling ``off-target'' effects of redox-active polymers and polymer multilayered capsules in prostate cancer cells

NASA Astrophysics Data System (ADS)

Beretta, Giovanni L.; Folini, Marco; Cavalieri, Francesca; Yan, Yan; Fresch, Enrico; Kaliappan, Subramanian; Hasenöhrl, Christoph; Richardson, Joseph J.; Tinelli, Stella; Fery, Andreas; Caruso, Frank; Zaffaroni, Nadia

2015-03-01

Redox-active polymers and carriers are oxidizing nanoagents that can potentially trigger intracellular off-target effects. In the present study, we investigated the occurrence of off-target effects in prostate cancer cells following exposure to redox-active polymer and thin multilayer capsules with different chemical properties. We show that, depending on the intracellular antioxidant capacity, thiol-functionalized poly(methacrylic acid), PMASH triggers cell defense responses/perturbations that result in off-target effects (i.e., induction of autophagy and down-regulation of survivin). Importantly, the conversion of the carboxyl groups of PMASH into the neutral amides of poly(hydroxypropylmetacrylamide) (pHPMASH) nullified the off-target effects and cytotoxicity in tested cell lines. This suggests that the simultaneous action of carboxyl and disulfide groups in PMASH polymer or capsules may play a role in mediating the intracellular off-target effects. Our work provides evidence that the rational design of redox-active carriers for therapeutic-related application should be guided by a careful investigation on potential disturbance of the cellular machineries related to the carrier association.Redox-active polymers and carriers are oxidizing nanoagents that can potentially trigger intracellular off-target effects. In the present study, we investigated the occurrence of off-target effects in prostate cancer cells following exposure to redox-active polymer and thin multilayer capsules with different chemical properties. We show that, depending on the intracellular antioxidant capacity, thiol-functionalized poly(methacrylic acid), PMASH triggers cell defense responses/perturbations that result in off-target effects (i.e., induction of autophagy and down-regulation of survivin). Importantly, the conversion of the carboxyl groups of PMASH into the neutral amides of poly(hydroxypropylmetacrylamide) (pHPMASH) nullified the off-target effects and cytotoxicity in tested cell lines. This suggests that the simultaneous action of carboxyl and disulfide groups in PMASH polymer or capsules may play a role in mediating the intracellular off-target effects. Our work provides evidence that the rational design of redox-active carriers for therapeutic-related application should be guided by a careful investigation on potential disturbance of the cellular machineries related to the carrier association. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07240e

Protective Action Guides (PAGs)

EPA Pesticide Factsheets

The Protective Action Guide (PAG) manual contains radiation dose guidelines that would trigger public safety measures. EPA developed Protective Action Guides to help responders plan for radiation emergencies.

Voltage-gated currents in identified rat olfactory receptor neurons.

PubMed

Trombley, P Q; Westbrook, G L

1991-02-01

Whole-cell recording techniques were used to characterize voltage-gated membrane currents in neonatal rat olfactory receptor neurons (ORNs) in cell culture. Mature ORNs were identified in culture by their characteristic bipolar morphology, by retrograde labeling techniques, and by olfactory marker protein (OMP) immunoreactivity. ORNs did not have spontaneous activity, but fired action potentials to depolarizing current pulses. Action potentials were blocked by tetrodotoxin (TTX), which contrasts with the TTX-resistant action potentials in salamander olfactory receptor cells (e.g., Firestein and Werblin, 1987). Prolonged, suprathreshold current pulses evoked only a single action potential; however, repetitive firing up to 35 Hz could be elicited by a series of brief depolarizing pulses. Under voltage clamp, the TTX-sensitive sodium current had activation and inactivation properties similar to other excitable cells. In TTX and 20 mM barium, sustained inward current were evoked by voltage steps positive to -30 mV. This current was blocked by Cd (100 microM) and by nifedipine (IC50 = 368 nM) consistent with L-type calcium channels in other neurons. No T-type calcium current was observed. Voltage steps positive to -20 mV also evoked an outward current that did not inactivate during 100-msec depolarizations. Tail current analysis of this current was consistent with a selective potassium conductance. The outward current was blocked by external tetraethylammonium but was unaffected by Cd or 4-aminopyridine (4-AP) or by removal of external calcium. A transient outward current was not observed. The 3 voltage-dependent conductances in cultured rat ORNs appear to be sufficient for 2 essential functions: action potential generation and transmitter release. As a single odorant-activated channel can trigger an action potential (e.g., Lynch and Barry, 1989), the repetitive firing seen with brief depolarizing pulses suggests that ORNs do not integrate sensory input, but rather act as high-fidelity relays such that each opening of an odorant-activated channel reaches the olfactory bulb glomeruli as an action potential.

Precursor processes of human self-initiated action.

PubMed

Khalighinejad, Nima; Schurger, Aaron; Desantis, Andrea; Zmigrod, Leor; Haggard, Patrick

2018-01-15

A gradual buildup of electrical potential over motor areas precedes self-initiated movements. Recently, such "readiness potentials" (RPs) were attributed to stochastic fluctuations in neural activity. We developed a new experimental paradigm that operationalized self-initiated actions as endogenous 'skip' responses while waiting for target stimuli in a perceptual decision task. We compared these to a block of trials where participants could not choose when to skip, but were instead instructed to skip. Frequency and timing of motor action were therefore balanced across blocks, so that conditions differed only in how the timing of skip decisions was generated. We reasoned that across-trial variability of EEG could carry as much information about the source of skip decisions as the mean RP. EEG variability decreased more markedly prior to self-initiated compared to externally-triggered skip actions. This convergence suggests a consistent preparatory process prior to self-initiated action. A leaky stochastic accumulator model could reproduce this convergence given the additional assumption of a systematic decrease in input noise prior to self-initiated actions. Our results may provide a novel neurophysiological perspective on the topical debate regarding whether self-initiated actions arise from a deterministic neurocognitive process, or from neural stochasticity. We suggest that the key precursor of self-initiated action may manifest as a reduction in neural noise. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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.

Low K+-induced hyperpolarizations trigger transient depolarizations and action potentials in rabbit ventricular myocytes

PubMed Central

Akuzawa-Tateyama, M; Tateyama, M; Ochi, R

1998-01-01

The effects of large reductions of [K+]o on membrane potential were studied in isolated rabbit ventricular myocytes using the whole-cell patch clamp technique.Decreasing [K+]o from the normal level of 5.4 mm to 0.1 mm increased resting membrane potential (Vrest) from −75.6 ± 0.3 to −140.3 ± 1.9 mV (means ± s.e.m; n = 127), induced irregular, transient depolarizations with mean maximal amplitudes of 19.5 ± 1.5 mV and elicited action potentials in 56.7 % of trials. The action potentials exhibited overshoots of 37.9 ± 1.5 mV (n = 72) and sustained plateaux.Addition of 0.1 mm La3+ in the presence of 0.1 mm[K+]o significantly increased Vrest but decreased the amplitude of transient depolarizations and suppressed the firing of action potentials.Replacement of external Na+ or Cl− with N-methyl-D-glucamine or aspartate, respectively, or internal dialysis with 10 mm EGTA or BAPTA had little effect on low [K+]o-induced membrane potential changes.Hyperpolarizing voltage clamp pulses to potentials between −110 and −200 mV activated irregular inward currents that increased in amplitude and frequency with increasing hyperpolarization and were depressed by 0.1 mm La3+.The generation of transient depolarizations by low [K+]o can be explained as being a consequence of decreasing the inward rectifier K+ current (IK1) and the appearance of inward currents reflecting electroporation resulting from strong electric fields across the membrane. PMID:9824717

Resident-to-resident violence triggers in nursing homes.

PubMed

Snellgrove, Susan; Beck, Cornelia; Green, Angela; McSweeney, Jean C

2013-11-01

Certified nurses' assistants (CNAs) employed by a rural nursing home in Northeast Arkansas described their perceptions of resident-to-resident violence in order to provide insight on factors, including unmet needs, that may trigger the phenomenon. Semistructured interviews were conducted with 11 CNAs. Data were analyzed using content analysis and constant comparison. Two categories of triggers emerged from the data-active and passive. Active triggers involved the actions of other residents that were intrusive in nature, such as wandering into a residents' personal space, taking a resident's belongings, and so forth. Passive triggers did not involve the actions of residents but related to the internal and external environment of the residents. Examples were factors such as boredom, competition for attention and communication difficulties. Results indicate that there are factors, including unmet needs within the nursing home environment that may be identified and altered to prevent violence between residents.

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

PubMed

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

2018-01-01

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

Specialized Binary Analysis for Vetting Android APPS Using GUI Logic

DTIC Science & Technology

2016-04-01

the use of high- level reasoning based on the GUI design logic of an app to enable a security analyst to diagnose and triage the potentially sensitive...execution paths of an app. Levels of Inconsistency We have identified three- levels of logical inconsistencies: Event- level inconsistency A sensitive...operation (e.g., taking a picture) is not trigged by user action on a GUI component. Layout- level inconsistency A sensitive operation is triggered by

Spike detection, characterization, and discrimination using feature analysis software written in LabVIEW.

PubMed

Stewart, C M; Newlands, S D; Perachio, A A

2004-12-01

Rapid and accurate discrimination of single units from extracellular recordings is a fundamental process for the analysis and interpretation of electrophysiological recordings. We present an algorithm that performs detection, characterization, discrimination, and analysis of action potentials from extracellular recording sessions. The program was entirely written in LabVIEW (National Instruments), and requires no external hardware devices or a priori information about action potential shapes. Waveform events are detected by scanning the digital record for voltages that exceed a user-adjustable trigger. Detected events are characterized to determine nine different time and voltage levels for each event. Various algebraic combinations of these waveform features are used as axis choices for 2-D Cartesian plots of events. The user selects axis choices that generate distinct clusters. Multiple clusters may be defined as action potentials by manually generating boundaries of arbitrary shape. Events defined as action potentials are validated by visual inspection of overlain waveforms. Stimulus-response relationships may be identified by selecting any recorded channel for comparison to continuous and average cycle histograms of binned unit data. The algorithm includes novel aspects of feature analysis and acquisition, including higher acquisition rates for electrophysiological data compared to other channels. The program confirms that electrophysiological data may be discriminated with high-speed and efficiency using algebraic combinations of waveform features derived from high-speed digital records.

Effects of communication on the performance of nursing students during the simulation of an emergency situation.

PubMed

Chapelain, Pascal; Morineau, Thierry; Gautier, Claudie

2015-11-01

To explore how nursing performance is impacted by different forms of team communication including a message transmitted through an earpiece which triggers reflective thinking in the simulation of a deteriorating patient situation. Communication can either support team performance or produce interruptions potentially leading to error. Today, technology offers the opportunity to use devices that can permit communication. An experimental protocol was used with quantitative and qualitative analyses. Pairs of nursing students (N = 26) were dispatched to either an experimental group having to wear an earpiece priming reflective thinking, or to a control group. The study was conducted between October 2013-April 2014. The number of spontaneous information exchanges between pairs of participants was positively correlated with overall performance (actions performed and physician call) and with actions performed at the right moment. The number of questions in the team was positively correlated with overall action performance. No quantitative effect of the earpiece message on the performance indicators was found. But, a qualitative observation showed that this message can allow for error avoidance. Subjective evaluation of the earpiece as an aid was negatively correlated with overall action performance. Its evaluation as a disturbance was also negatively correlated with the measurement of actions performed at the right moment. The ability to exchange information and to ask questions seems to contribute to performance in care delivery. The use of communication devices to trigger reflective thinking must be studied in more depth to assess their capacity to improve performance. © 2015 John Wiley & Sons Ltd.

Act quickly, decide later: long-latency visual processing underlies perceptual decisions but not reflexive behavior.

PubMed

Jolij, Jacob; Scholte, H Steven; van Gaal, Simon; Hodgson, Timothy L; Lamme, Victor A F

2011-12-01

Humans largely guide their behavior by their visual representation of the world. Recent studies have shown that visual information can trigger behavior within 150 msec, suggesting that visually guided responses to external events, in fact, precede conscious awareness of those events. However, is such a view correct? By using a texture discrimination task, we show that the brain relies on long-latency visual processing in order to guide perceptual decisions. Decreasing stimulus saliency leads to selective changes in long-latency visually evoked potential components reflecting scene segmentation. These latency changes are accompanied by almost equal changes in simple RTs and points of subjective simultaneity. Furthermore, we find a strong correlation between individual RTs and the latencies of scene segmentation related components in the visually evoked potentials, showing that the processes underlying these late brain potentials are critical in triggering a response. However, using the same texture stimuli in an antisaccade task, we found that reflexive, but erroneous, prosaccades, but not antisaccades, can be triggered by earlier visual processes. In other words: The brain can act quickly, but decides late. Differences between our study and earlier findings suggesting that action precedes conscious awareness can be explained by assuming that task demands determine whether a fast and unconscious, or a slower and conscious, representation is used to initiate a visually guided response.

Trigger Finger

MedlinePlus

... in a bent position. People whose work or hobbies require repetitive gripping actions are at higher risk ... developing trigger finger include: Repeated gripping. Occupations and hobbies that involve repetitive hand use and prolonged gripping ...

Linking Science of Flood Forecasts to Humanitarian Actions for Improved Preparedness and Effective Response

NASA Astrophysics Data System (ADS)

Uprety, M.; Dugar, S.; Gautam, D.; Kanel, D.; Kshetri, M.; Kharbuja, R. G.; Acharya, S. H.

2017-12-01

Advances in flood forecasting have provided opportunities for humanitarian responders to employ a range of preparedness activities at different forecast time horizons. Yet, the science of prediction is less understood and realized across the humanitarian landscape, and often preparedness plans are based upon average level of flood risk. Working under the remit of Forecast Based Financing (FbF), we present a pilot from Nepal on how available flood and weather forecast products are informing specific pre-emptive actions in the local preparedness and response plans, thereby supporting government stakeholders and humanitarian agencies to take early actions before an impending flood event. In Nepal, forecasting capabilities are limited but in a state of positive flux. Whilst local flood forecasts based upon rainfall-runoff models are yet to be operationalized, streamflow predictions from Global Flood Awareness System (GLoFAS) can be utilized to plan and implement preparedness activities several days in advance. Likewise, 3-day rainfall forecasts from Nepal Department of Hydrology and Meteorology (DHM) can further inform specific set of early actions for potential flash floods due to heavy precipitation. Existing community based early warning systems in the major river basins of Nepal are utilizing real time monitoring of water levels and rainfall together with localised probabilistic flood forecasts which has increased warning lead time from 2-3 hours to 7-8 hours. Based on these available forecast products, thresholds and trigger levels have been determined for different flood scenarios. Matching these trigger levels and assigning responsibilities to relevant actors for early actions, a set of standard operating procedures (SOPs) are being developed, broadly covering general preparedness activities and science informed anticipatory actions for different forecast lead times followed by the immediate response activities. These SOPs are currently being rolled out and tested by the Ministry of Home Affairs (MoHA) through its district emergency operation centres in West Nepal. Potential scale up and successful implementation of this science based approach would be instrumental to take forward global commitments on disaster risk reduction, climate change adaptation and sustainable goals in Nepal.

Drug-sensing hydrogels for the inducible release of biopharmaceuticals

NASA Astrophysics Data System (ADS)

Ehrbar, Martin; Schoenmakers, Ronald; Christen, Erik H.; Fussenegger, Martin; Weber, Wilfried

2008-10-01

Drug-dependent dissociation or association of cellular receptors represents a potent pharmacologic mode of action for regulating cell fate and function. Transferring the knowledge of pharmacologically triggered protein-protein interactions to materials science will enable novel design concepts for stimuli-sensing smart hydrogels. Here, we show the design and validation of an antibiotic-sensing hydrogel for the trigger-inducible release of human vascular endothelial growth factor. Genetically engineered bacterial gyrase subunit B (GyrB) (ref. 4) coupled to polyacrylamide was dimerized by the addition of the aminocoumarin antibiotic coumermycin, resulting in hydrogel formation. Addition of increasing concentrations of clinically validated novobiocin (Albamycin) dissociated the GyrB subunits, thereby resulting in dissociation of the hydrogel and dose- and time-dependent liberation of the entrapped protein pharmaceutical VEGF121 for triggering proliferation of human umbilical vein endothelial cells. Pharmacologically controlled hydrogels have the potential to fulfil the promises of stimuli-sensing materials as smart devices for spatiotemporally controlled delivery of drugs within the patient.

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

PubMed

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

2017-04-01

Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias. Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information-rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re-parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K + current and a drastic decrease in the slow delayed rectifier K + current, and this prediction was validated experimentally. Subsequent simulations with the adjusted model generated the clinically relevant prediction that the slow delayed rectifier is better able to stabilize the action potential and suppress pro-arrhythmic events than the rapid delayed rectifier. In summary, iterative coupling of simulations and experiments enabled novel insight into how the balance between cardiac K + currents influences ventricular arrhythmia susceptibility. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

On the Inclusion of Externally Controlled Actions in Action Planning

ERIC Educational Resources Information Center

Tsai, Jessica Chia-Chin; Knoblich, Gunther; Sebanz, Natalie

2011-01-01

According to ideomotor theories, perceiving action effects produced by others triggers corresponding action representations in the observer. We tested whether this principle extends to actions performed by externally controlled limbs and tools. Participants performed a go-no-go version of a spatial compatibility task in which their own actions…

Pulling the Religious Trigger: Iran’s End-Times Beliefs and Divine Justifications for Potential Action Against the United States

DTIC Science & Technology

2014-09-01

current government. Moving to the regime’s current leadership , the literature survey mostly includes primary sources from Iran’s Supreme Leader, Ali...Office of the Secretary of Defense, published Mullahs, Guards, and Bonyads38: An Exploration of Iranian Leadership Dynamics. The book’s objective is...to provide a “framework to help policymakers and analysts better understand existing and evolving leadership dynamics driving Iranian decisionmaking

Avoiding nerve stimulation in irreversible electroporation: a numerical modeling study

NASA Astrophysics Data System (ADS)

Mercadal, Borja; Arena, Christopher B.; Davalos, Rafael V.; Ivorra, Antoni

2017-10-01

Electroporation based treatments consist in applying one or multiple high voltage pulses to the tissues to be treated. As an undesired side effect, these pulses cause electrical stimulation of excitable tissues such as nerves and muscles. This increases the complexity of the treatments and may pose a risk to the patient. To minimize electrical stimulation during electroporation based treatments, it has been proposed to replace the commonly used monopolar pulses by bursts of short bipolar pulses. In the present study, we have numerically analyzed the rationale for such approach. We have compared different pulsing protocols in terms of their electroporation efficacy and their capability of triggering action potentials in nerves. For that, we have developed a modeling framework that combines numerical models of nerve fibers and experimental data on irreversible electroporation. Our results indicate that, by replacing the conventional relatively long monopolar pulses by bursts of short bipolar pulses, it is possible to ablate a large tissue region without triggering action potentials in a nearby nerve. Our models indicate that this is possible because, as the pulse length of these bipolar pulses is reduced, the stimulation thresholds raise faster than the irreversible electroporation thresholds. We propose that this different dependence on the pulse length is due to the fact that transmembrane charging for nerve fibers is much slower than that of cells treated by electroporation because of their geometrical differences.

Electrotonic and action potentials in the Venus flytrap.

PubMed

Volkov, Alexander G; Vilfranc, Chrystelle L; Murphy, Veronica A; Mitchell, Colee M; Volkova, Maia I; O'Neal, Lawrence; Markin, Vladislav S

2013-06-15

The electrical phenomena and morphing structures in the Venus flytrap have attracted researchers since the nineteenth century. We have observed that mechanical stimulation of trigger hairs on the lobes of the Venus flytrap induces electrotonic potentials in the lower leaf. Electrostimulation of electrical circuits in the Venus flytrap can induce electrotonic potentials propagating along the upper and lower leaves. The instantaneous increase or decrease in voltage of stimulating potential generates a nonlinear electrical response in plant tissues. Any electrostimulation that is not instantaneous, such as sinusoidal or triangular functions, results in linear responses in the form of small electrotonic potentials. The amplitude and sign of electrotonic potentials depend on the polarity and the amplitude of the applied voltage. Electrical stimulation of the lower leaf induces electrical signals, which resemble action potentials, in the trap between the lobes and the midrib. The trap closes if the stimulating voltage is above the threshold level of 4.4V. Electrical responses in the Venus flytrap were analyzed and reproduced in the discrete electrical circuit. The information gained from this study can be used to elucidate the coupling of intracellular and intercellular communications in the form of electrical signals within plants. Copyright © 2013 Elsevier GmbH. All rights reserved.

Electrophysiological and neuromuscular stability of persons with chronic inflammatory demyelinating polyneuropathy.

PubMed

Gilmore, Kevin J; Allen, Matti D; Doherty, Timothy J; Kimpinski, Kurt; Rice, Charles L

2017-09-01

We assessed motor unit (MU) properties and neuromuscular stability in the tibialis anterior (TA) of chronic inflammatory demyelinating polyneuropathy (CIDP) patients using decomposition-based quantitative electromyography. Dorsiflexion strength was assessed, and surface and concentric needle electromyography were sampled from the TA. Estimates of MU numbers were derived using decomposition-based quantitative electromyography and spike-triggered averaging. Neuromuscular transmission stability was assessed from concentric needle-detected MU potentials. CIDP patients had 43% lower compound muscle action potential amplitude than controls, and despite near-maximum voluntary activation, were 37% weaker. CIDP had 27% fewer functioning MUs in the TA, and had 90% and 44% higher jiggle and jitter values, respectively compared with controls. CIDP had lower strength and compound muscle action potential values, moderately fewer numbers of MUs, and significant neuromuscular instability compared with controls. Thus, in addition to muscle atrophy, voluntary weakness is also due to limitations of peripheral neural transmission consistent with demyelination. Muscle Nerve 56: 413-420, 2017. © 2016 Wiley Periodicals, Inc.

Automated vision occlusion-timing instrument for perception-action research.

PubMed

Brenton, John; Müller, Sean; Rhodes, Robbie; Finch, Brad

2018-02-01

Vision occlusion spectacles are a highly valuable instrument for visual-perception-action research in a variety of disciplines. In sports, occlusion spectacles have enabled invaluable knowledge to be obtained about the superior capability of experts to use visual information to guide actions within in-situ settings. Triggering the spectacles to occlude a performer's vision at a precise time in an opponent's action or object flight has been problematic, due to experimenter error in using a manual buttonpress approach. This article describes a new laser curtain wireless trigger for vision occlusion spectacles that is portable and fast in terms of its transmission time. The laser curtain can be positioned in a variety of orientations to accept a motion trigger, such as a cricket bowler's arm that distorts the lasers, which then activates a wireless signal for the occlusion spectacles to change from transparent to opaque, which occurs in only 8 ms. Results are reported from calculations done in an electronics laboratory, as well as from tests in a performance laboratory with a cricket bowler and a baseball pitcher, which verified this short time delay before vision occlusion. In addition, our results show that occlusion consistently occurred when it was intended-that is, near ball release and during mid-ball-flight. Only 8% of the collected data trials were unusable. The laser curtain improves upon the limitations of existing vision occlusion spectacle triggers, indicating that it is a valuable instrument for perception-action research in a variety of disciplines.

Fast, temperature-sensitive and clathrin-independent endocytosis at central synapses

PubMed Central

Delvendahl, Igor; Vyleta, Nicholas P.; von Gersdorff, Henrique; Hallermann, Stefan

2016-01-01

The fusion of neurotransmitter-filled vesicles during synaptic transmission is balanced by endocytotic membrane retrieval. Despite extensive research, the speed and mechanisms of synaptic vesicle endocytosis have remained controversial. Here, we establish low-noise time-resolved membrane capacitance measurements that allow monitoring changes in surface membrane area elicited by single action potentials and stronger stimuli with high-temporal resolution at physiological temperature in individual bonafide mature central synapses. We show that single action potentials trigger very rapid endocytosis, retrieving presynaptic membrane with a time constant of 470 ms. This fast endocytosis is independent of clathrin, but mediated by dynamin and actin. In contrast, stronger stimuli evoke a slower mode of endocytosis that is clathrin-, dynamin-, and actin-dependent. Furthermore, the speed of endocytosis is highly temperature-dependent with a Q10 of ~3.5. These results demonstrate that distinct molecular modes of endocytosis with markedly different kinetics operate at central synapses. PMID:27146271

Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

PubMed Central

Pashut, Tamar; Magidov, Dafna; Ben-Porat, Hana; Wolfus, Shuki; Friedman, Alex; Perel, Eli; Lavidor, Michal; Bar-Gad, Izhar; Yeshurun, Yosef; Korngreen, Alon

2014-01-01

Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies. PMID:24917788

Improving Robot Motor Learning with Negatively Valenced Reinforcement Signals

PubMed Central

Navarro-Guerrero, Nicolás; Lowe, Robert J.; Wermter, Stefan

2017-01-01

Both nociception and punishment signals have been used in robotics. However, the potential for using these negatively valenced types of reinforcement learning signals for robot learning has not been exploited in detail yet. Nociceptive signals are primarily used as triggers of preprogrammed action sequences. Punishment signals are typically disembodied, i.e., with no or little relation to the agent-intrinsic limitations, and they are often used to impose behavioral constraints. Here, we provide an alternative approach for nociceptive signals as drivers of learning rather than simple triggers of preprogrammed behavior. Explicitly, we use nociception to expand the state space while we use punishment as a negative reinforcement learning signal. We compare the performance—in terms of task error, the amount of perceived nociception, and length of learned action sequences—of different neural networks imbued with punishment-based reinforcement signals for inverse kinematic learning. We contrast the performance of a version of the neural network that receives nociceptive inputs to that without such a process. Furthermore, we provide evidence that nociception can improve learning—making the algorithm more robust against network initializations—as well as behavioral performance by reducing the task error, perceived nociception, and length of learned action sequences. Moreover, we provide evidence that punishment, at least as typically used within reinforcement learning applications, may be detrimental in all relevant metrics. PMID:28420976

Hybrid Markov-mass action law model for cell activation by rare binding events: Application to calcium induced vesicular release at neuronal synapses.

PubMed

Guerrier, Claire; Holcman, David

2016-10-18

Binding of molecules, ions or proteins to small target sites is a generic step of cell activation. This process relies on rare stochastic events where a particle located in a large bulk has to find small and often hidden targets. We present here a hybrid discrete-continuum model that takes into account a stochastic regime governed by rare events and a continuous regime in the bulk. The rare discrete binding events are modeled by a Markov chain for the encounter of small targets by few Brownian particles, for which the arrival time is Poissonian. The large ensemble of particles is described by mass action laws. We use this novel model to predict the time distribution of vesicular release at neuronal synapses. Vesicular release is triggered by the binding of few calcium ions that can originate either from the synaptic bulk or from the entry through calcium channels. We report here that the distribution of release time is bimodal although it is triggered by a single fast action potential. While the first peak follows a stimulation, the second corresponds to the random arrival over much longer time of ions located in the synaptic terminal to small binding vesicular targets. To conclude, the present multiscale stochastic modeling approach allows studying cellular events based on integrating discrete molecular events over several time scales.

Mast cells in atherosclerotic cardiovascular disease - Activators and actions.

PubMed

Kovanen, Petri T; Bot, Ilze

2017-12-05

Mast cells are potent actors involved in inflammatory reactions in various tissues, including both in the intimal and the adventitial layers of atherosclerotic arteries. In the arterial intima, the site of atherogenesis, mast cells are activated to degranulate, and thereby triggered to release an abundance of preformed inflammatory mediators, notably histamine, heparin, neutral proteases and cytokines stored in their cytoplasmic secretory granules. Depending on the stimulus, mast cell activation may also launch prolonged synthesis and secretion of single bioactive molecules, such as cytokines and derivatives of arachidonic acid. The mast cell-derived mediators may impede the functions of different types of cells present in atherosclerotic lesions, and also compromise the structural and functional integrity of the intimal extracellular matrix. In the adventitial layer of atherosclerotic coronary arteries, mast cells locate next to peptidergic sensory nerve fibers, which, by releasing neuropeptides may activate mast cells to release vasoactive compounds capable of triggering local vasoconstriction. The concerted actions of arterial mast cells have the potential to contribute to the initiation and progression of atherosclerosis, and ultimately to destabilization and rupture of an advanced atherosclerotic plaque with ensuing atherothrombotic complications. Copyright © 2017 Elsevier B.V. All rights reserved.

Polymeric micelles with stimuli-triggering systems for advanced cancer drug targeting.

PubMed

Nakayama, Masamichi; Akimoto, Jun; Okano, Teruo

2014-08-01

Since the 1990s, nanoscale drug carriers have played a pivotal role in cancer chemotherapy, acting through passive drug delivery mechanisms and subsequent pharmaceutical action at tumor tissues with reduction of adverse effects. Polymeric micelles, as supramolecular assemblies of amphiphilic polymers, have been considerably developed as promising drug carrier candidates, and a number of clinical studies of anticancer drug-loaded polymeric micelle carriers for cancer chemotherapy applications are now in progress. However, these systems still face several issues; at present, the simultaneous control of target-selective delivery and release of incorporated drugs remains difficult. To resolve these points, the introduction of stimuli-responsive mechanisms to drug carrier systems is believed to be a promising approach to provide better solutions for future tumor drug targeting strategies. As possible trigger signals, biological acidic pH, light, heating/cooling and ultrasound actively play significant roles in signal-triggering drug release and carrier interaction with target cells. This review article summarizes several molecular designs for stimuli-responsive polymeric micelles in response to variation of pH, light and temperature and discusses their potentials as next-generation tumor drug targeting systems.

(2R,3S,2”R,3”R)-manniflavanone, a new gastrointestinal smooth muscle L-type calcium channel inhibitor, which underlies the spasmolytic properties of Garcinia buchananii stem bark extract

PubMed Central

Balemba, Onesmo B.; Stark, Timo D.; Lösch, Sofie; Patterson, Savannah; McMillan, John S.; Mawe, Gary M.; Hofmann, Thomas

2014-01-01

Garcinia buchananii Baker stem bark extract (GBB) is a traditional medication of diarrhea and dysentery in sub-Saharan Africa. It is believed that GBB causes gastrointestinal smooth muscle relaxation. The aim of this study was to determine whether GBB has spasmolytic actions and identify compounds underlying these actions. Calcium (Ca2+) imaging was used to analyze the effect of GBB on Ca2+ flashes and Ca2+ waves in guinea pig gallbladder and distal colon smooth muscle. Intracellular microelectrode recording was used to determine the effect of GBB, six fractions of GBB, M1–5 and M7, and (2R,3S,2”R,3”R)-manniflavanone, a compound isolated from M3 on action potentials in gallbladder smooth muscle. The technique was also used to analyze the effect of GBB, M3, and (2R,3S,2”R,3”R)-manniflavanone on action potentials in the circular muscle of mouse and guinea pig distal colons, and the effect of GBB and (2R,3S,2”R,3”R)-manniflavanone on slow waves in porcine ileum. GBB inhibited Ca2+ flashes and Ca2+ waves. GBB, M3 and (2R,3S,2”R,3”R)-manniflavanone inhibited action potentials. L-type Ca2+ channel activator Bay K 8644 increased the discharge of action potentials in mouse colon but did not trigger or increase action potentials in the presence of GBB and (2R,3S,2”R,3”R)-manniflavanone. GBB and (2R,3S,2”R,3”R)-manniflavanone inhibited action potentials in the presence of Bay K 8644. GBB and (2R,3S,2”R,3”R)-manniflavanone reduced the amplitude but did not alter the frequency of slow waves in the porcine ileum. In conclusion, GBB and (2R,3S,2”R,3”R)-manniflavanone relax smooth muscle by inhibiting L-type Ca2+ channels, thus have potential for use as therapies of gastrointestinal smooth muscle spasms, and arrhythmias. PMID:26081368

Triggered Firing and Atrial Fibrillation in Transgenic Mice With Selective Atrial Fibrosis Induced by Overexpression of TGF-β1

PubMed Central

Choi, Eue-Keun; Chang, Po-Cheng; Lee, Young-Soo; Lin, Shien-Fong; Zhu, Wuqiang; Maruyama, Mitsunori; Fishbein, Michael C.; Chen, Zhenhui; der Lohe, Michael Rubart-von; Field, Loren J.; Chen, Peng-Sheng

2013-01-01

Background Calcium transient triggered firing (CTTF) is induced by large intracellular calcium (Cai) transient and short action potential duration (APD). We hypothesized that CTTF underlies the mechanisms of early afterdepolarization (EAD) and spontaneous recurrent atrial fibrillation (AF) in transgenic (Tx) mice with overexpression of transforming growth factor β1 (TGF-β1). Methods and Results MHC-TGFcys33ser Tx mice develop atrial fibrosis because of elevated levels of TGF-β1. We studied membrane potential and Cai transients of isolated superfused atria from Tx and wild-type (Wt) littermates. Short APD and persistently elevated Cai transients promoted spontaneous repetitive EADs, triggered activity and spontaneous AF after cessation of burst pacing in Tx but not Wt atria (39% vs. 0%, P=0.008). We were able to map optically 4 episodes of spontaneous AF re-initiation. All first and second beats of spontaneous AF originated from the right atrium (4/4, 100%), which is more severely fibrotic than the left atrium. Ryanodine and thapsigargin inhibited spontaneous re-initiation of AF in all 7 Tx atria tested. Western blotting showed no significant changes of calsequestrin or sarco/endoplasmic reticulum Ca2+-ATPase 2a. Conclusions Spontaneous AF may occur in the Tx atrium because of CTTF, characterized by APD shortening, prolonged Cai transient, EAD and triggered activity. Inhibition of Ca2+ release from the sarcoplasmic reticulum suppressed spontaneous AF. Our results indicate that CTTF is an important arrhythmogenic mechanism in TGF-β1 Tx atria. PMID:22447020

Translational Research on Habit and Alcohol.

PubMed

McKim, Theresa H; Shnitko, Tatiana A; Robinson, Donita L; Boettiger, Charlotte A

2016-03-01

Habitual actions enable efficient daily living, but they can also contribute to pathological behaviors that resistant change, such as alcoholism. Habitual behaviors are learned actions that appear goal-directed but are in fact no longer under the control of the action's outcome. Instead, these actions are triggered by stimuli, which may be exogenous or interoceptive, discrete or contextual. A major hallmark characteristic of alcoholism is continued alcohol use despite serious negative consequences. In essence, although the outcome of alcohol seeking and drinking is dramatically devalued, these actions persist, often triggered by environmental cues associated with alcohol use. Thus, alcoholism meets the definition of an initially goal-directed behavior that converts to a habit-based process. Habit and alcohol have been well investigated in rodent models, with comparatively less research in non-human primates and people. This review focuses on translational research on habit and alcohol with an emphasis on cross-species methodology and neural circuitry.

Aspirin-triggered lipoxin A4 and lipoxin A4 up-regulate transcriptional corepressor NAB1 in human neutrophils.

PubMed

Qiu, F H; Devchand, P R; Wada, K; Serhan, C N

2001-12-01

Aspirin-triggered 15-epi-lipoxin A4 (ATL) is an endogenous lipid mediator that mimics the actions of native lipoxin A4, a putative "stop signal" involved in regulating resolution of inflammation. A metabolically more stable analog of ATL, 15-epi-16-(para-fluoro)-phenoxy-lipoxin A4 analog (ATLa), inhibits neutrophil recruitment in vitro and in vivo and displays potent anti-inflammatory actions. ATLa binds with high affinity to the lipoxin A4 receptor, a G protein-coupled receptor on the surface of leukocytes. In this study, we used freshly isolated human neutrophils to examine ATLa's potential for initiating rapid nuclear responses. Using differential display reverse transcription polymerase chain reaction, we identified a subset of genes that was selectively up-regulated upon short exposure of polymorphonuclear leukocytes to ATLa but not to the chemoattractant leukotriene B4 or vehicle alone. We further investigated ATLa regulation of one of the genes, NAB1, a transcriptional corepressor identified previously as a glucocorticoid-responsive gene in hamster smooth muscle cells. Treatment of human neutrophils with pertussis toxin blocked ATLa up-regulation of NAB1. In addition, ATLa stimulated NAB1 gene expression in murine lung vascular smooth muscle in vivo. These findings provide evidence for rapid transcriptional induction of a cassette of genes via an ATLa-stimulated G protein-coupled receptor pathway that is potentially protective and overlaps with the anti-inflammatory glucocorticoid regulatory circuit.

Nuclear accumulation of the Arabidopsis immune receptor RPS4 is necessary for triggering EDS1-dependent defense.

PubMed

Wirthmueller, Lennart; Zhang, Yan; Jones, Jonathan D G; Parker, Jane E

2007-12-04

Recognition of specific pathogen molecules inside the cell by nucleotide-binding domain and leucine-rich repeat (NB-LRR) receptors constitutes an important layer of innate immunity in plants. Receptor activation triggers host cellular reprogramming involving transcriptional potentiation of basal defenses and localized programmed cell death. The sites and modes of action of NB-LRR receptors are, however, poorly understood. Arabidopsis Toll/Interleukin-1 (TIR) type NB-LRR receptor RPS4 recognizes the bacterial type III effector AvrRps4. We show that epitope-tagged RPS4 expressed under its native regulatory sequences distributes between endomembranes and nuclei in healthy and AvrRps4-triggered tissues. RPS4 accumulation in the nucleus, mediated by a bipartite nuclear localization sequence (NLS) at its C terminus, is necessary for triggering immunity through authentic activation by AvrRps4 in Arabidopsis or as an effector-independent "deregulated" receptor in tobacco. A strikingly conserved feature of TIR-NB-LRR receptors is their recruitment of the nucleocytoplasmic basal-defense regulator EDS1 in resistance to diverse pathogens. We find that EDS1 is an indispensable component of RPS4 signaling and that it functions downstream of RPS4 activation but upstream of RPS4-mediated transcriptional reprogramming in the nucleus.

Recent development in antihyperalgesic effect of phytochemicals: anti-inflammatory and neuro-modulatory actions.

PubMed

Singh, Ajeet Kumar; Kumar, Sanjay; Vinayak, Manjula

2018-05-16

Pain is an unpleasant sensation triggered by noxious stimulation. It is one of the most prevalent conditions, limiting productivity and diminishing quality of life. Non steroidal anti inflammatory drugs (NSAIDs) are widely used as pain relievers in present day practice as pain is mostly initiated due to inflammation. However, due to potentially serious side effects, long term use of these antihyperalgesic drugs raises concern. Therefore there is a demand to search novel medicines with least side effects. Herbal products have been used for centuries to reduce pain and inflammation, and phytochemicals are known to cause fewer side effects. However, identification of active phytochemicals of herbal medicines and clear understanding of the molecular mechanism of their action is needed for clinical acceptance. In this review, we have briefly discussed the cellular and molecular changes during hyperalgesia via inflammatory mediators and neuro-modulatory action involved therein. The review includes 54 recently reported phytochemicals with antihyperalgesic action, as per the literature available with PubMed, Google Scholar and Scopus. Compounds of high interest as potential antihyperalgesic agents are: curcumin, resveratrol, capsaicin, quercetin, eugenol, naringenin and epigallocatechin gallate (EGCG). Current knowledge about molecular targets of pain and their regulation by these phytochemicals is elaborated and the scope of further research is discussed.

LTP-triggered cholesterol redistribution activates Cdc42 and drives AMPA receptor synaptic delivery

PubMed Central

Brachet, Anna; Norwood, Stephanie; Brouwers, Jos F.; Palomer, Ernest; Helms, J. Bernd

2015-01-01

Neurotransmitter receptor trafficking during synaptic plasticity requires the concerted action of multiple signaling pathways and the protein transport machinery. However, little is known about the contribution of lipid metabolism during these processes. In this paper, we addressed the question of the role of cholesterol in synaptic changes during long-term potentiation (LTP). We found that N-methyl-d-aspartate–type glutamate receptor (NMDAR) activation during LTP induction leads to a rapid and sustained loss or redistribution of intracellular cholesterol in the neuron. A reduction in cholesterol, in turn, leads to the activation of Cdc42 and the mobilization of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid–type glutamate receptors (AMPARs) from Rab11-recycling endosomes into the synaptic membrane, leading to synaptic potentiation. This process is accompanied by an increase of NMDAR function and an enhancement of LTP. These results imply that cholesterol acts as a sensor of NMDAR activation and as a trigger of downstream signaling to engage small GTPase (guanosine triphosphatase) activation and AMPAR synaptic delivery during LTP. PMID:25753037

Single CA3 pyramidal cells trigger sharp waves in vitro by exciting interneurones.

PubMed

Bazelot, Michaël; Teleńczuk, Maria T; Miles, Richard

2016-05-15

The CA3 hippocampal region generates sharp waves (SPW), a population activity associated with neuronal representations. The synaptic mechanisms responsible for the generation of these events still require clarification. Using slices maintained in an interface chamber, we found that the firing of single CA3 pyramidal cells triggers SPW like events at short latencies, similar to those for the induction of firing in interneurons. Multi-electrode records from the CA3 stratum pyramidale showed that pyramidal cells triggered events consisting of putative interneuron spikes followed by field IPSPs. SPW fields consisted of a repetition of these events at intervals of 4-8 ms. Although many properties of induced and spontaneous SPWs were similar, the triggered events tended to be initiated close to the stimulated cell. These data show that the initiation of SPWs in vitro is mediated via pyramidal cell synapses that excite interneurons. They do not indicate why interneuron firing is repeated during a SPW. Sharp waves (SPWs) are a hippocampal population activity that has been linked to neuronal representations. We show that SPWs in the CA3 region of rat hippocampal slices can be triggered by the firing of single pyramidal cells. Single action potentials in almost one-third of pyramidal cells initiated SPWs at latencies of 2-5 ms with probabilities of 0.07-0.76. Initiating pyramidal cells evoked field IPSPs (fIPSPs) at similar latencies when SPWs were not initiated. Similar spatial profiles for fIPSPs and middle components of SPWs suggested that SPW fields reflect repeated fIPSPs. Multiple extracellular records showed that the initiated SPWs tended to start near the stimulated pyramidal cell, whereas spontaneous SPWs could emerge at multiple sites. Single pyramidal cells could initiate two to six field IPSPs with distinct amplitude distributions, typically preceeded by a short-duration extracellular action potential. Comparison of these initiated fields with spontaneously occurring inhibitory field motifs allowed us to identify firing in different interneurones during the spread of SPWs. Propagation away from an initiating pyramidal cell was typically associated with the recruitment of interneurones and field IPSPs that were not activated by the stimulated pyramidal cell. SPW fields initiated by single cells were less variable than spontaneous events, suggesting that more stereotyped neuronal ensembles were activated, although neither the spatial profiles of fields, nor the identities of interneurone firing were identical for initiated events. The effects of single pyramidal cell on network events are thus mediated by different sequences of interneurone firing. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Humic Substances: Determining Potential Molecular Regulatory Processes in Plants

PubMed Central

Shah, Zahid Hussain; Rehman, Hafiz M.; Akhtar, Tasneem; Alsamadany, Hameed; Hamooh, Bahget T.; Mujtaba, Tahir; Daur, Ihsanullah; Al Zahrani, Yahya; Alzahrani, Hind A. S.; Ali, Shawkat; Yang, Seung H.; Chung, Gyuhwa

2018-01-01

Humic substances (HSs) have considerable effects on soil fertility and crop productivity owing to their unique physiochemical and biochemical properties, and play a vital role in establishing biotic and abiotic interactions within the plant rhizosphere. A comprehensive understanding of the mode of action and tissue distribution of HS is, however, required, as this knowledge could be useful for devising advanced rhizospheric management practices. These substances trigger various molecular processes in plant cells, and can strengthen the plant’s tolerance to various kinds of abiotic stresses. HS manifest their effects in cells through genetic, post-transcriptional, and post-translational modifications of signaling entities that trigger different molecular, biochemical, and physiological processes. Understanding of such fundamental mechanisms will provide a better perspective for defining the cues and signaling crosstalk of HS that mediate various metabolic and hormonal networks operating in plant systems. Various regulatory activities and distribution strategies of HS have been discussed in this review. PMID:29593751

Webinar: Know the Drill for Healthy IAQ: Training School Staff and Occupants to Reduce Indoor Asthma Triggers

EPA Pesticide Factsheets

A page to register to view the first webinar in the IAQ Knowledge-to-Action Professional Training Webinar Series: Know the Drill for Healthy IAQ: Training School Staff and Occupants to Reduce Indoor Asthma Triggers

Role of AMPA and NMDA receptors and back-propagating action potentials in spike timing-dependent plasticity.

PubMed

Fuenzalida, Marco; Fernández de Sevilla, David; Couve, Alejandro; Buño, Washington

2010-01-01

The cellular mechanisms that mediate spike timing-dependent plasticity (STDP) are largely unknown. We studied in vitro in CA1 pyramidal neurons the contribution of AMPA and N-methyl-d-aspartate (NMDA) components of Schaffer collateral (SC) excitatory postsynaptic potentials (EPSPs; EPSP(AMPA) and EPSP(NMDA)) and of the back-propagating action potential (BAP) to the long-term potentiation (LTP) induced by a STDP protocol that consisted in pairing an EPSP and a BAP. Transient blockade of EPSP(AMPA) with 7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile (CNQX) during the STDP protocol prevented LTP. Contrastingly LTP was induced under transient inhibition of EPSP(AMPA) by combining SC stimulation, an imposed EPSP(AMPA)-like depolarization, and BAP or by coupling the EPSP(NMDA) evoked under sustained depolarization (approximately -40 mV) and BAP. In Mg(2+)-free solution EPSP(NMDA) and BAP also produced LTP. Suppression of EPSP(NMDA) or BAP always prevented LTP. Thus activation of NMDA receptors and BAPs are needed but not sufficient because AMPA receptor activation is also obligatory for STDP. However, a transient depolarization of another origin that unblocks NMDA receptors and a BAP may also trigger LTP.

Role of voltage-gated K(+) channels in regulating Ca(2+) entry in rat cortical astrocytes.

PubMed

Wu, King-Chuen; Kuo, Chang-Shin; Chao, Chia-Chia; Huang, Chieh-Chen; Tu, Yuan-Kun; Chan, Paul; Leung, Yuk-Man

2015-03-01

Astrocytes have multiple functions such as provision of nourishment and mechanical support to the nervous system, helping to clear extracellular metabolites of neurons and modulating synaptic transmission by releasing gliotransmitters. In excitable cells, voltage-gated K(+) (Kv) channels serve to repolarize during action potentials. Astrocytes are considered non-excitable cells since they are not able to generate action potentials. There is an abundant expression of various Kv channels in astrocytes but the functions of these Kv channels remain unclear. We examined whether these astrocyte Kv channels regulate astrocyte "excitability" in the form of cytosolic Ca(2+) signaling. Electrophysiological examination revealed that neonatal rat cortical astrocytes possessed both delayed rectifier type and A-type Kv channels. Pharmacological blockade of both delayed rectifier Kv channels by TEA and A-type Kv channels by quinidine significantly suppressed store-operated Ca(2+) influx; however, TEA alone or quinidine alone did not suffice to cause such suppression. TEA and quinidine together dramatically enhanced current injection-triggered membrane potential overshoot (depolarization); either drug alone caused much smaller enhancements. Taken together, the results suggest both delayed rectifier and A-type Kv channels regulate astrocyte Ca(2+) signaling via controlling membrane potential.

Early assessment of proarrhythmic risk of drugs using the in vitro data and single-cell-based in silico models: proof of concept.

PubMed

Abbasi, Mitra; Small, Ben G; Patel, Nikunjkumar; Jamei, Masoud; Polak, Sebastian

2017-02-01

To determine the predictive performance of in silico models using drug-specific preclinical cardiac electrophysiology data to investigate drug-induced arrhythmia risk (e.g. Torsade de pointes (TdP)) in virtual human subjects. To assess drug proarrhythmic risk, we used a set of in vitro electrophysiological measurements describing ion channel inhibition triggered by the investigated drugs. The Cardiac Safety Simulator version 2.0 (CSS; Simcyp, Sheffield, UK) platform was used to simulate human left ventricular cardiac myocyte action potential models. This study shows the impact of drug concentration changes on particular ionic currents by using available experimental data. The simulation results display safety threshold according to drug concentration threshold and log (threshold concentration/ effective therapeutic plasma concentration (ETPC)). We reproduced the underlying biophysical characteristics of cardiac cells resulted in effects of drugs associated with cardiac arrhythmias (action potential duration (APD) and QT prolongation and TdP) which were observed in published 3D simulations, yet with much less computational burden.

Fast, Temperature-Sensitive and Clathrin-Independent Endocytosis at Central Synapses.

PubMed

Delvendahl, Igor; Vyleta, Nicholas P; von Gersdorff, Henrique; Hallermann, Stefan

2016-05-04

The fusion of neurotransmitter-filled vesicles during synaptic transmission is balanced by endocytotic membrane retrieval. Despite extensive research, the speed and mechanisms of synaptic vesicle endocytosis have remained controversial. Here, we establish low-noise time-resolved membrane capacitance measurements that allow monitoring changes in surface membrane area elicited by single action potentials and stronger stimuli with high-temporal resolution at physiological temperature in individual bona-fide mature central synapses. We show that single action potentials trigger very rapid endocytosis, retrieving presynaptic membrane with a time constant of 470 ms. This fast endocytosis is independent of clathrin but mediated by dynamin and actin. In contrast, stronger stimuli evoke a slower mode of endocytosis that is clathrin, dynamin, and actin dependent. Furthermore, the speed of endocytosis is highly temperature dependent with a Q10 of ∼3.5. These results demonstrate that distinct molecular modes of endocytosis with markedly different kinetics operate at central synapses. Copyright © 2016 Elsevier Inc. All rights reserved.

Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP.

PubMed

Zhang, Li; Rajbhandari, Prashant; Priest, Christina; Sandhu, Jaspreet; Wu, Xiaohui; Temel, Ryan; Castrillo, Antonio; de Aguiar Vallim, Thomas Q; Sallam, Tamer; Tontonoz, Peter

2017-10-25

Cholesterol homeostasis is maintained through concerted action of the SREBPs and LXRs. Here, we report that RNF145, a previously uncharacterized ER membrane ubiquitin ligase, participates in crosstalk between these critical signaling pathways. RNF145 expression is induced in response to LXR activation and high-cholesterol diet feeding. Transduction of RNF145 into mouse liver inhibits the expression of genes involved in cholesterol biosynthesis and reduces plasma cholesterol levels. Conversely, acute suppression of RNF145 via shRNA-mediated knockdown, or chronic inactivation of RNF145 by genetic deletion, potentiates the expression of cholesterol biosynthetic genes and increases cholesterol levels both in liver and plasma. Mechanistic studies show that RNF145 triggers ubiquitination of SCAP on lysine residues within a cytoplasmic loop essential for COPII binding, potentially inhibiting its transport to Golgi and subsequent processing of SREBP-2. These findings define an additional mechanism linking hepatic sterol levels to the reciprocal actions of the SREBP-2 and LXR pathways.

[Methods of brain stimulation based on weak electric current--future tool for the clinician?].

PubMed

Kotilainen, Tuukka; Lehto, Soili M

2016-01-01

Methods of brain stimulation based on a weak electric current are non-invasive neuromodulation techniques. They include transcranial direct current, alternating current and random noise stimulation. These methods modify the membrane potential of neurons without triggering the action potential, and have been successfully utilized to influence cognition and regulation of emotions in healthy experimental subjects. In clinical studies, indications of the efficacy of these techniques have been obtained in the treatment of depression, schizophrenia, memory disorders and pain as well as in stroke rehabilitation. It is hoped that these techniques will become established as part of the care and rehabilitation of psychiatric and neurologic patients in the future.

A Dynamical Threshold for Cardiac Delayed Afterdepolarization-Mediated Triggered Activity.

PubMed

Liu, Michael B; Ko, Christopher Y; Song, Zhen; Garfinkel, Alan; Weiss, James N; Qu, Zhilin

2016-12-06

Ventricular myocytes are excitable cells whose voltage threshold for action potential (AP) excitation is ∼-60 mV at which I Na is activated to give rise to a fast upstroke. Therefore, for a short stimulus pulse to elicit an AP, a stronger stimulus is needed if the resting potential lies further away from the I Na threshold, such as in hypokalemia. However, for an AP elicited by a long duration stimulus or a diastolic spontaneous calcium release, we observed that the stimulus needed was lower in hypokalemia than in normokalemia in both computer simulations and experiments of rabbit ventricular myocytes. This observation provides insight into why hypokalemia promotes calcium-mediated triggered activity, despite the resting potential lying further away from the I Na threshold. To understand the underlying mechanisms, we performed bifurcation analyses and demonstrated that there is a dynamical threshold, resulting from a saddle-node bifurcation mainly determined by I K1 and I NCX . This threshold is close to the voltage at which I K1 is maximum, and lower than the I Na threshold. After exceeding this dynamical threshold, the membrane voltage will automatically depolarize above the I Na threshold due to the large negative slope of the I K1 -V curve. This dynamical threshold becomes much lower in hypokalemia, especially with respect to calcium, as predicted by our theory. Because of the saddle-node bifurcation, the system can automatically depolarize even in the absence of I Na to voltages higher than the I Ca,L threshold, allowing for triggered APs in single myocytes with complete I Na block. However, because I Na is important for AP propagation in tissue, blocking I Na can still suppress premature ventricular excitations in cardiac tissue caused by calcium-mediated triggered activity. This suppression is more effective in normokalemia than in hypokalemia due to the difference in dynamical thresholds. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Potential Environmental Triggers of Myositis

DTIC Science & Technology

2012-10-01

Myositis PRINCIPAL INVESTIGATOR: Robert Goldberg CONTRACTING ORGANIZATION: The...TYPE Annual Report 3. DATES COVERED 12September2011-11September2012 4. TITLE AND SUBTITLE Potential Environmental Triggers of Myositis 5a...10 INTRODUCTION: The Potential Environmental Triggers of Myositis

Advancing complex explanatory conceptualizations of daily negative and positive affect: trigger and maintenance coping action patterns.

PubMed

Dunkley, David M; Ma, Denise; Lee, Ihno A; Preacher, Kristopher J; Zuroff, David C

2014-01-01

The present study addressed a fundamental gap between research and clinical work by advancing complex explanatory conceptualizations of coping action patterns that trigger and maintain daily negative affect and (low) positive affect. One hundred ninety-six community adults completed measures of perfectionism, and then 6 months later completed questionnaires at the end of the day for 14 consecutive days to provide simultaneous assessments of appraisals, coping, and affect across different stressful situations in everyday life. Multilevel structural equation modeling (MSEM) supported complex explanatory conceptualizations that demonstrated (a) disengagement trigger patterns consisting of several distinct appraisals (e.g., event stress) and coping strategies (e.g., avoidant coping) that commonly operate together across many different stressors when the typical individual experiences daily increases in negative affect and drops in positive affect; and (b) disengagement maintenance patterns composed of different appraisal and coping maintenance factors that, in combination, can explain why individuals with higher levels of self-critical perfectionism have persistent daily negative affect and low positive mood 6 months later. In parallel, engagement patterns (triggers and maintenance) composed of distinct appraisals (e.g., perceived social support) and coping strategies (e.g., problem-focused coping) were linked to compensatory experiences of daily positive affect. These findings demonstrate the promise of using daily diary methodologies and MSEM to promote a shared understanding between therapists and clients of trigger and maintenance coping action patterns that explain what precipitates and perpetuates clients' difficulties, which, in turn, can help achieve the 2 overarching therapy goals of reducing clients' distress and bolstering resilience. (c) 2014 APA, all rights reserved.

ADHD patients fail to maintain task goals in face of subliminally and consciously induced cognitive conflicts.

PubMed

Gohil, K; Bluschke, A; Roessner, V; Stock, A-K; Beste, C

2017-07-01

Attention deficit hyperactivity disorder (ADHD) patients have been reported to display deficits in action control processes. While it is known that subliminally and consciously induced conflicts interact and conjointly modulate action control in healthy subjects, this has never been investigated for ADHD. We investigated the (potential) interaction of subliminally and consciously triggered response conflicts in children with ADHD and matched healthy controls using neuropsychological methods (event-related potentials; ERPs) to identify the involved cognitive sub-processes. Unlike healthy controls, ADHD patients showed no interaction of subliminally and consciously triggered response conflicts. Instead, they only showed additive effects as their behavioural performance (accuracy) was equally impaired by each conflict and they showed no signs of task-goal shielding even in cases of low conflict load. Of note, this difference between ADHD and controls was not rooted in early bottom-up attentional stimulus processing as reflected by the P1 and N1 ERPs. Instead, ADHD showed either no or reversed modulations of conflict-related processes and response selection as reflected by the N2 and P3 ERPs. There are fundamental differences in the architecture of cognitive control which might be of use for future diagnostic procedures. Unlike healthy controls, ADHD patients do not seem to be endowed with a threshold which allows them to maintain high behavioural performance in the face of low conflict load. ADHD patients seem to lack sufficient top-down attentional resources to maintain correct response selection in the face of conflicts by shielding the response selection process from response tendencies evoked by any kind of distractor.

Three types of membrane excitations in the marine diatom Coscinodiscus wailesii.

PubMed

Gradmann, D; Boyd, C M

2000-05-15

Three types of electrical excitation have been investigated in the marine diatom Coscinodiscus wailesii. I: Depolarization-triggered, transient Cl(-) conductance, G(Cl)(t), followed by a transient, voltage-gated K(+) conductance, G(K), with an active state a and two inactive states i(1) and i(2) in series (a-i(1)-i(2)). II: Similar G(Cl)(t) as in Type-I but triggered by hyperpolarization; a subsequent increase of G(K) in this type is indicated but not analyzed in detail. III: Hyperpolarization-induced transient of a voltage-gated activity of an electrogenic pump (i(2)-a-i(2)), followed by G(Cl)(t) as in Type-II excitations. Type-III with pump gating is novel as such. G(Cl)(t) in all types seems to reflect the mechanism of InsP(-)(3) and Ca(2+)-mediated G(Cl)(t) in the action potential in Chara (Biskup et al., 1999). The nonlinear current-voltage-time relationships of Type-I and Type-III excitations have been recorded under voltage-clamp using single saw-tooth command voltages (voltage range: -200 to +50 mV, typical slope: +/-1 Vs(-1)). Fits of the corresponding models to the experimental data provided numerical values of the model parameters. The statistical significance of these solutions is investigated. We suggest that the original function of electrical excitability of biological membranes is related to osmoregulation which has persisted through evolution in plants, whereas the familiar and osmotically neutral action potentials in animals have evolved later towards the novel function of rapid transmission of information over long distances.

Depolarizing actions of GABA in immature neurons depend neither on ketone bodies nor on pyruvate.

PubMed

Tyzio, Roman; Allene, Camille; Nardou, Romain; Picardo, Michel A; Yamamoto, Sumii; Sivakumaran, Sudhir; Caiati, Maddalena D; Rheims, Sylvain; Minlebaev, Marat; Milh, Mathieu; Ferré, Pascal; Khazipov, Rustem; Romette, Jean-Louis; Lorquin, Jean; Cossart, Rosa; Khalilov, Ilgam; Nehlig, Astrid; Cherubini, Enrico; Ben-Ari, Yehezkel

2011-01-05

GABA depolarizes immature neurons because of a high [Cl(-)](i) and orchestrates giant depolarizing potential (GDP) generation. Zilberter and coworkers (Rheims et al., 2009; Holmgren et al., 2010) showed recently that the ketone body metabolite DL-3-hydroxybutyrate (DL-BHB) (4 mM), lactate (4 mM), or pyruvate (5 mM) shifted GABA actions to hyperpolarizing, suggesting that the depolarizing effects of GABA are attributable to inadequate energy supply when glucose is the sole energy source. We now report that, in rat pups (postnatal days 4-7), plasma D-BHB, lactate, and pyruvate levels are 0.9, 1.5, and 0.12 mM, respectively. Then, we show that DL-BHB (4 mM) and pyruvate (200 μM) do not affect (i) the driving force for GABA(A) receptor-mediated currents (DF(GABA)) in cell-attached single-channel recordings, (2) the resting membrane potential and reversal potential of synaptic GABA(A) receptor-mediated responses in perforated patch recordings, (3) the action potentials triggered by focal GABA applications, or (4) the GDPs determined with electrophysiological recordings and dynamic two-photon calcium imaging. Only very high nonphysiological concentrations of pyruvate (5 mM) reduced DF(GABA) and blocked GDPs. Therefore, DL-BHB does not alter GABA signals even at the high concentrations used by Zilberter and colleagues, whereas pyruvate requires exceedingly high nonphysiological concentrations to exert an effect. There is no need to alter conventional glucose enriched artificial CSF to investigate GABA signals in the developing brain.

Identification of a vacuolar proton channel that triggers the bioluminescent flash in dinoflagellates.

PubMed

Rodriguez, Juan D; Haq, Saddef; Bachvaroff, Tsvetan; Nowak, Kristine F; Nowak, Scott J; Morgan, Deri; Cherny, Vladimir V; Sapp, Maredith M; Bernstein, Steven; Bolt, Andrew; DeCoursey, Thomas E; Place, Allen R; Smith, Susan M E

2017-01-01

In 1972, J. Woodland Hastings and colleagues predicted the existence of a proton selective channel (HV1) that opens in response to depolarizing voltage across the vacuole membrane of bioluminescent dinoflagellates and conducts protons into specialized luminescence compartments (scintillons), thereby causing a pH drop that triggers light emission. HV1 channels were subsequently identified and demonstrated to have important functions in a multitude of eukaryotic cells. Here we report a predicted protein from Lingulodinium polyedrum that displays hallmark properties of bona fide HV1, including time-dependent opening with depolarization, perfect proton selectivity, and characteristic ΔpH dependent gating. Western blotting and fluorescence confocal microscopy of isolated L. polyedrum scintillons immunostained with antibody to LpHV1 confirm LpHV1's predicted organellar location. Proteomics analysis demonstrates that isolated scintillon preparations contain peptides that map to LpHV1. Finally, Zn2+ inhibits both LpHV1 proton current and the acid-induced flash in isolated scintillons. These results implicate LpHV1 as the voltage gated proton channel that triggers bioluminescence in L. polyedrum, confirming Hastings' hypothesis. The same channel likely mediates the action potential that communicates the signal along the tonoplast to the scintillon.

Key Physiological Parameters Dictate Triggering of Activity-Dependent Bulk Endocytosis in Hippocampal Synapses

PubMed Central

Wenzel, Eva M.; Morton, Andrew; Ebert, Katrin; Welzel, Oliver; Kornhuber, Johannes; Cousin, Michael A.; Groemer, Teja W.

2012-01-01

To maintain neurotransmission in central neurons, several mechanisms are employed to retrieve synaptically exocytosed membrane. The two major modes of synaptic vesicle (SV) retrieval are clathrin-mediated endocytosis and activity-dependent bulk endocytosis (ADBE). ADBE is the dominant SV retrieval mode during intense stimulation, however the precise physiological conditions that trigger this mode are not resolved. To determine these parameters we manipulated rat hippocampal neurons using a wide spectrum of stimuli by varying both the pattern and duration of stimulation. Using live-cell fluorescence imaging and electron microscopy approaches, we established that stimulation frequency, rather than the stimulation load, was critical in the triggering of ADBE. Thus two hundred action potentials, when delivered at high frequency, were sufficient to induce near maximal bulk formation. Furthermore we observed a strong correlation between SV pool size and ability to perform ADBE. We also identified that inhibitory nerve terminals were more likely to utilize ADBE and had a larger SV recycling pool. Thus ADBE in hippocampal synaptic terminals is tightly coupled to stimulation frequency and is more likely to occur in terminals with large SV pools. These results implicate ADBE as a key modulator of both hippocampal neurotransmission and plasticity. PMID:22675521

Coupling of pulsed electromagnetic fields (PEMF) therapy to molecular grounds of the cell

PubMed Central

Funk, Richard HW

2018-01-01

In this review we compile results cited in reliable journals that show a ratio for the use of pulsed electromagnetic fields (PEMF) in therapy, indeed. This is true especially for chronically inflamed joints. Furthermore, we try to link this therapeutic approach to the molecular background of chronic inflammation and arthritis. At first we start with the clinical outcome of PEMF therapy. Then, we look for possible triggers and an electromagnetic counterpart that is endogenously inherent in cell biology and in the tissues of interest. Finally, we want to investigate causal molecular and cellular mechanisms of possible PEMF actions. It shows that there are endogenous mechanisms, indeed, which can act as triggers for PEMF like the resting membrane potential as well as resonance mechanisms in charged moieties like membrane transporters. Especially voltage-gated calcium channels can be triggered. These may lead into specific signaling pathways and also may elicit nitric oxide as well as moderate radical reactions, which can ultimately lead to e.g. NFκB-like reactions. Concerted in the right way, these reactions can cause a kind of cell protection and ultimately lead to a dampening of inflammatory signals like interleukins. PMID:29887943

Launch Vehicle Failure Dynamics and Abort Triggering Analysis

NASA Technical Reports Server (NTRS)

Hanson, John M.; Hill, Ashely D.; Beard, Bernard B.

2011-01-01

Launch vehicle ascent is a time of high risk for an on-board crew. There are many types of failures that can kill the crew if the crew is still on-board when the failure becomes catastrophic. For some failure scenarios, there is plenty of time for the crew to be warned and to depart, whereas in some there is insufficient time for the crew to escape. There is a large fraction of possible failures for which time is of the essence and a successful abort is possible if the detection and action happens quickly enough. This paper focuses on abort determination based primarily on data already available from the GN&C system. This work is the result of failure analysis efforts performed during the Ares I launch vehicle development program. Derivation of attitude and attitude rate abort triggers to ensure that abort occurs as quickly as possible when needed, but that false positives are avoided, forms a major portion of the paper. Some of the potential failure modes requiring use of these triggers are described, along with analysis used to determine the success rate of getting the crew off prior to vehicle demise.

Identification of a vacuolar proton channel that triggers the bioluminescent flash in dinoflagellates

PubMed Central

Rodriguez, Juan D.; Haq, Saddef; Bachvaroff, Tsvetan; Nowak, Kristine F.; Nowak, Scott J.; Morgan, Deri; Cherny, Vladimir V.; Sapp, Maredith M.; Bernstein, Steven; Bolt, Andrew; DeCoursey, Thomas E.; Place, Allen R.; Smith, Susan M. E.

2017-01-01

In 1972, J. Woodland Hastings and colleagues predicted the existence of a proton selective channel (HV1) that opens in response to depolarizing voltage across the vacuole membrane of bioluminescent dinoflagellates and conducts protons into specialized luminescence compartments (scintillons), thereby causing a pH drop that triggers light emission. HV1 channels were subsequently identified and demonstrated to have important functions in a multitude of eukaryotic cells. Here we report a predicted protein from Lingulodinium polyedrum that displays hallmark properties of bona fide HV1, including time-dependent opening with depolarization, perfect proton selectivity, and characteristic ΔpH dependent gating. Western blotting and fluorescence confocal microscopy of isolated L. polyedrum scintillons immunostained with antibody to LpHV1 confirm LpHV1’s predicted organellar location. Proteomics analysis demonstrates that isolated scintillon preparations contain peptides that map to LpHV1. Finally, Zn2+ inhibits both LpHV1 proton current and the acid-induced flash in isolated scintillons. These results implicate LpHV1 as the voltage gated proton channel that triggers bioluminescence in L. polyedrum, confirming Hastings’ hypothesis. The same channel likely mediates the action potential that communicates the signal along the tonoplast to the scintillon. PMID:28178296

Enhancing patient freedom in rehabilitation robotics using gaze-based intention detection.

PubMed

Novak, Domen; Riener, Robert

2013-06-01

Several design strategies for rehabilitation robotics have aimed to improve patients' experiences using motivating and engaging virtual environments. This paper presents a new design strategy: enhancing patient freedom with a complex virtual environment that intelligently detects patients' intentions and supports the intended actions. A 'virtual kitchen' scenario has been developed in which many possible actions can be performed at any time, allowing patients to experiment and giving them more freedom. Remote eye tracking is used to detect the intended action and trigger appropriate support by a rehabilitation robot. This approach requires no additional equipment attached to the patient and has a calibration time of less than a minute. The system was tested on healthy subjects using the ARMin III arm rehabilitation robot. It was found to be technically feasible and usable by healthy subjects. However, the intention detection algorithm should be improved using better sensor fusion, and clinical tests with patients are needed to evaluate the system's usability and potential therapeutic benefits.

Bootstrapping agency: How control-relevant information affects motivation.

PubMed

Karsh, Noam; Eitam, Baruch; Mark, Ilya; Higgins, E Tory

2016-10-01

How does information about one's control over the environment (e.g., having an own-action effect) influence motivation? The control-based response selection framework was proposed to predict and explain such findings. Its key tenant is that control relevant information modulates both the frequency and speed of responses by determining whether a perceptual event is an outcome of one's actions or not. To test this framework empirically, the current study examines whether and how temporal and spatial contiguity/predictability-previously established as being important for one's sense of agency-modulate motivation from control. In 5 experiments, participants responded to a cue, potentially triggering a perceptual effect. Temporal (Experiments 1a-c) and spatial (Experiments 2a and b) contiguity/predictability between actions and their potential effects were experimentally manipulated. The influence of these control-relevant factors was measured, both indirectly (through their effect on explicit judgments of agency) and directly on response time and response frequency. The pattern of results was highly consistent with the control-based response selection framework in suggesting that control relevant information reliably modulates the impact of "having an effect" on different levels of action selection. We discuss the implications of this study for the notion of motivation from control and for the empirical work on the sense of agency. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Too Good to be True? Ideomotor Theory from a Computational Perspective

PubMed Central

Herbort, Oliver; Butz, Martin V.

2012-01-01

In recent years, Ideomotor Theory has regained widespread attention and sparked the development of a number of theories on goal-directed behavior and learning. However, there are two issues with previous studies’ use of Ideomotor Theory. Although Ideomotor Theory is seen as very general, it is often studied in settings that are considerably more simplistic than most natural situations. Moreover, Ideomotor Theory’s claim that effect anticipations directly trigger actions and that action-effect learning is based on the formation of direct action-effect associations is hard to address empirically. We address these points from a computational perspective. A simple computational model of Ideomotor Theory was tested in tasks with different degrees of complexity. The model evaluation showed that Ideomotor Theory is a computationally feasible approach for understanding efficient action-effect learning for goal-directed behavior if the following preconditions are met: (1) The range of potential actions and effects has to be restricted. (2) Effects have to follow actions within a short time window. (3) Actions have to be simple and may not require sequencing. The first two preconditions also limit human performance and thus support Ideomotor Theory. The last precondition can be circumvented by extending the model with more complex, indirect action generation processes. In conclusion, we suggest that Ideomotor Theory offers a comprehensive framework to understand action-effect learning. However, we also suggest that additional processes may mediate the conversion of effect anticipations into actions in many situations. PMID:23162524

Destabilization of mitochondrial functions as a target against breast cancer progression: Role of TPP{sup +}-linked-polyhydroxybenzoates

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

Sandoval-Acuña, Cristian

Mitochondrion is an accepted molecular target in cancer treatment since it exhibits a higher transmembrane potential in cancer cells, making it susceptible to be targeted by lipophilic-delocalized cations of triphenylphosphonium (TPP{sup +}). Thus, we evaluated five TPP{sup +}-linked decyl polyhydroxybenzoates as potential cytotoxic agents in several human breast cancer cell lines that differ in estrogen receptor and HER2/neu expression, and in metabolic profile. Results showed that all cell lines tested were sensitive to the cytotoxic action of these compounds. The mechanism underlying the cytotoxicity would be triggered by their weak uncoupling effect on the oxidative phosphorylation system, while having amore » wider and safer therapeutic range than other uncouplers and a significant lowering in transmembrane potential. Noteworthy, while the TPP{sup +}-derivatives alone led to almost negligible losses of ATP, when these were added in the presence of an AMP-activated protein kinase inhibitor, the levels of ATP fell greatly. Overall, data presented suggest that decyl polyhydroxybenzoates-TPP{sup +} and its derivatives warrant future investigation as potential anti-tumor agents. - Highlights: • TPP{sup +}-polyhydroxybenzoates are cytotoxic to various subtypes of breast cancer cells. • Cytotoxicity is not-dependent on the expression of estrogen/growth factor receptors. • Cytotoxicity appears to be triggered by a weak mitochondrial uncoupling effect. • Effects include loss of transmembrane potential and apoptosis was detected. • TPP{sup +}-polyhydroxybenzoates inhibit migration of highly metastatic cells.« less

Selenium suppresses leukemia through the action of endogenous eicosanoids

PubMed Central

Gandhi, Ujjawal H.; Kaushal, Naveen; Hegde, Shailaja; Finch, Emily R.; Kudva, Avinash K.; Kennett, Mary J.; Jordan, Craig T.; Paulson, Robert F.; Prabhu, K. Sandeep

2014-01-01

Eradicating cancer stem-like cells (CSC) may be essential to fully eradicate cancer. Metabolic changes in CSC could hold a key to their targeting. Here we report that the dietary micronutrient selenium can trigger apoptosis of CSC derived from chronic or acute myelogenous leukemias when administered at supraphysiological but non-toxic doses. In leukemia CSC, selenium treatment activated ATM-p53-dependent apoptosis accompanied by increased intracellular levels of reactive oxygen species. Importantly, the same treatment did not trigger apoptosis in hematopoietic stem cells. Serial transplantation studies with BCR-ABL-expressing CSC revealed that the selenium status in mice was a key determinant of CSC survival. Selenium action relied upon the endogenous production of the cyclooxygenase-derived prostaglandins Δ12-PGJ2 and 15d-PGJ2. Accordingly, non-steroidal anti-inflammatory drugs and NADPH oxidase inhibitors abrogated the ability of selenium to trigger apoptosis in leukemia CSC. Our results reveal how selenium-dependent modulation of arachidonic acid metabolism can be directed to trigger apoptosis of primary human and murine CSC in leukemia. PMID:24872387

The role of research and development on safety regulation

DOT National Transportation Integrated Search

1995-10-01

A review of regulatory actions taken by the Federal Aviation Administration (FAA) over approximately the past thirty years was made to identify which of these actions were preceded by or triggered by research and development (R&D) programs. The focus...

Robust Water Supply Infrastructure Development Pathways: What, When and Where Matters the Most? (INVITED)

NASA Astrophysics Data System (ADS)

Reed, Patrick; Zeff, Harrison; Characklis, Gregory

2017-04-01

Water supply adaptation frameworks that seek robustness must adaptively trigger actions that are contextually appropriate to emerging system observations and avoid long term high regret lock-ins. As an example, emerging water scarcity concerns in southeastern United States are associated with several deeply uncertain factors, including rapid population growth, limited coordination across adjacent municipalities and the increasing risks for sustained regional droughts. Managing these uncertainties will require that regional water utilities identify regionally coordinated, scarcity-mitigating infrastructure development pathways that trigger time appropriate actions. Mistakes can lead to water shortages, overbuilt stranded assets and possibly financial failures. This presentation uses the Research Triangle area of North Carolina to illustrate the key concerns and challenges that emerged when helping Raleigh, Durham, Cary and Chapel Hill develop their long term water supply infrastructure pathways through 2060. This example shows how the region's water utilities' long term infrastructure pathways are strongly shaped by their short term conservation policies (i.e., reacting to evolving demands) and their ability to consider regional water transfers (i.e., reacting to supply imbalances). Cooperatively developed, shared investments across the four municipalities expand their capacity to use short term transfers to better manage severe droughts with fewer investments in irreversible infrastructure options. Cooperative pathways are also important for avoiding regional robustness conflicts, where one party benefits strongly at the expense of one or more the others. A significant innovation of this work is the exploitation of weekly and annual dynamic risk-of-failure action triggers that exploit evolving feedbacks between co-evolving human demands and regional supplies. These dynamic action triggers provide high levels of adaptivity, tailor actions to their specific context, and motivate the value of joint human—natural system observation systems. The insights from this work have general merit globally for urban regions where adjacent municipalities can benefit from cooperative planning.

Acute Effect of Pore-Forming Clostridium perfringens ε-Toxin on Compound Action Potentials of Optic Nerve of Mouse.

PubMed

Cases, Mercè; Llobet, Artur; Terni, Beatrice; Gómez de Aranda, Inmaculada; Blanch, Marta; Doohan, Briain; Revill, Alexander; Brown, Angus M; Blasi, Juan; Solsona, Carles

2017-01-01

ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood-brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system. We also investigated the effect of the toxin on compound action potentials (CAPs) in isolated mice optic nerves. When nerves were stimulated at 100 Hz during 200 ms, the decrease of the amplitude and the area of the CAPs was attenuated in the presence of ε-toxin. The computational modelling of myelinated fibers of mouse optic nerve revealed that the experimental results can be mimicked by an increase of the conductance of myelin and agrees with the pore forming activity of the toxin which binds to myelin and could drill it by making pores. The intimate ultrastructure of myelin was not modified during the periods of time investigated. In summary, the acute action of the toxin produces a subtle functional impact on the propagation of the nerve action potential in myelinated fibers of the central nervous system with an eventual desynchronization of the information. These results may agree with the hypothesis that the toxin could be an environmental trigger of multiple sclerosis (MS).

Acute Effect of Pore-Forming Clostridium perfringens ε-Toxin on Compound Action Potentials of Optic Nerve of Mouse

PubMed Central

Terni, Beatrice; Gómez de Aranda, Inmaculada; Blanch, Marta; Brown, Angus M.

2017-01-01

ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood–brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system. We also investigated the effect of the toxin on compound action potentials (CAPs) in isolated mice optic nerves. When nerves were stimulated at 100 Hz during 200 ms, the decrease of the amplitude and the area of the CAPs was attenuated in the presence of ε-toxin. The computational modelling of myelinated fibers of mouse optic nerve revealed that the experimental results can be mimicked by an increase of the conductance of myelin and agrees with the pore forming activity of the toxin which binds to myelin and could drill it by making pores. The intimate ultrastructure of myelin was not modified during the periods of time investigated. In summary, the acute action of the toxin produces a subtle functional impact on the propagation of the nerve action potential in myelinated fibers of the central nervous system with an eventual desynchronization of the information. These results may agree with the hypothesis that the toxin could be an environmental trigger of multiple sclerosis (MS). PMID:28798954

Triggers of oral lichen planus flares and the potential role of trigger avoidance in disease management.

PubMed

Chen, Hannah X; Blasiak, Rachel; Kim, Edwin; Padilla, Ricardo; Culton, Donna A

2017-09-01

Many patients with oral lichen planus (OLP) report triggers of flares, some of which overlap with triggers of other oral diseases, including oral allergy syndrome and oral contact dermatitis. The purpose of this study was to evaluate the prevalence of commonly reported triggers of OLP flares, their overlap with triggers of other oral diseases, and the potential role of trigger avoidance as a management strategy. Questionnaire-based survey of 51 patients with biopsy-proven lichen planus with oral involvement seen in an academic dermatology specialty clinic and/or oral pathology clinic between June 2014 and June 2015. Of the participants, 94% identified at least one trigger of their OLP flares. Approximately half of the participants (51%) reported at least one trigger that overlapped with known triggers of oral allergy syndrome, and 63% identified at least one trigger that overlapped with known triggers of oral contact dermatitis. Emotional stress was the most commonly reported trigger (77%). Regarding avoidance, 79% of the study participants reported avoiding their known triggers in daily life. Of those who actively avoided triggers, 89% reported an improvement in symptoms and 70% reported a decrease in the frequency of flares. Trigger identification and avoidance can play a potentially effective role in the management of OLP. Copyright © 2017 Elsevier Inc. All rights reserved.

Carbon monoxide – physiology, detection and controlled release

PubMed Central

Heinemann, Stefan H.; Hoshi, Toshinori; Westerhausen, Matthias

2014-01-01

Carbon monoxide (CO) is increasingly recognized as a cell-signalling molecule akin to nitric oxide (NO). CO has attracted particular attention as a potential therapeutic agent because of its reported anti-hypertensive, anti-inflammatory and cell-protective effects. We discuss recent progress in identifying new effector systems and elucidating the mechanisms of action of CO on, e.g., ion channels, as well as the design of novel methods to monitor CO in cellular environments. We also report on recent developments in the area of CO-releasing molecules (CORMs) and materials for controlled CO application. Novel triggers for CO release, metal carbonyls and degradation mechanisms of CORMs, are highlighted. In addition, potential formulations of CORMs for targeted CO release are discussed. PMID:24556640

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.

Acute suppression of spontaneous neurotransmission drives synaptic potentiation.

PubMed

Nosyreva, Elena; Szabla, Kristen; Autry, Anita E; Ryazanov, Alexey G; Monteggia, Lisa M; Kavalali, Ege T

2013-04-17

The impact of spontaneous neurotransmission on neuronal plasticity remains poorly understood. Here, we show that acute suppression of spontaneous NMDA receptor-mediated (NMDAR-mediated) neurotransmission potentiates synaptic responses in the CA1 regions of rat and mouse hippocampus. This potentiation requires protein synthesis, brain-derived neurotrophic factor expression, eukaryotic elongation factor-2 kinase function, and increased surface expression of AMPA receptors. Our behavioral studies link this same synaptic signaling pathway to the fast-acting antidepressant responses elicited by ketamine. We also show that selective neurotransmitter depletion from spontaneously recycling vesicles triggers synaptic potentiation via the same pathway as NMDAR blockade, demonstrating that presynaptic impairment of spontaneous release, without manipulation of evoked neurotransmission, is sufficient to elicit postsynaptic plasticity. These findings uncover an unexpectedly dynamic impact of spontaneous glutamate release on synaptic efficacy and provide new insight into a key synaptic substrate for rapid antidepressant action.

Music and epilepsy: a critical review.

PubMed

Maguire, Melissa Jane

2012-06-01

The effect of music on patients with epileptic seizures is complex and at present poorly understood. Clinical studies suggest that the processing of music within the human brain involves numerous cortical areas, extending beyond Heschl's gyrus and working within connected networks. These networks could be recruited during a seizure manifesting as musical phenomena. Similarly, if certain areas within the network are hyperexcitable, then there is a potential that particular sounds or certain music could act as epileptogenic triggers. This occurs in the case of musicogenic epilepsy, whereby seizures are triggered by music. Although it appears that this condition is rare, the exact prevalence is unknown, as often patients do not implicate music as an epileptogenic trigger and routine electroencephalography does not use sound in seizure provocation. Music therapy for refractory epilepsy remains controversial, and further research is needed to explore the potential anticonvulsant role of music. Dopaminergic system modulation and the ambivalent action of cognitive and sensory input in ictogenesis may provide possible theories for the dichotomous proconvulsant and anticonvulsant role of music in epilepsy. The effect of antiepileptic drugs and surgery on musicality should not be underestimated. Altered pitch perception in relation to carbamazepine is rare, but health care professionals should discuss this risk or consider alternative medication particularly if the patient is a professional musician or native-born Japanese. Studies observing the effect of epilepsy surgery on musicality suggest a risk with right temporal lobectomy, although the extent of this risk and correlation to size and area of resection need further delineation. This potential risk may bring into question whether tests on musical perception and memory should form part of the preoperative neuropsychological workup for patients embarking on surgery, particularly that of the right temporal lobe. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

A novel approach to periodic event-triggered control: Design and application to the inverted pendulum.

PubMed

Aranda-Escolástico, Ernesto; Guinaldo, María; Gordillo, Francisco; Dormido, Sebastián

2016-11-01

In this paper, periodic event-triggered controllers are proposed for the rotary inverted pendulum. The control strategy is divided in two steps: swing-up and stabilization. In both cases, the system is sampled periodically but the control actions are only computed at certain instances of time (based on events), which are a subset of the sampling times. For the stabilization control, the asymptotic stability is guaranteed applying the Lyapunov-Razumikhin theorem for systems with delays. This result is applicable to general linear systems and not only to the inverted pendulum. For the swing-up control, a trigger function is provided from the derivative of the Lyapunov function for the swing-up control law. Experimental results show a significant improvement with respect to periodic control in the number of control actions. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Immediate increase in food intake following exercise messages.

PubMed

Albarracin, Dolores; Wang, Wei; Leeper, Joshua

2009-07-01

Communications to stimulate weight loss include exercise-promotion messages that often produce unsatisfactory results due to compensatory behavioral and metabolic mechanisms triggered by physical activity. This research investigated potential automatic facilitation of eating immediately after exercise messages in the absence of actual exercise. Two controlled experiments demonstrated greater than control food intake following exposure to print messages typical of exercise campaigns as well as subliminal presentation of action words associated with exercise (e.g., "active"). These inadvertent effects may explain the limited efficacy of exercise-promotion programs for weight loss, particularly when systematic dietary guidelines are absent.

Functions of external cues in prospective memory.

DOT National Transportation Integrated Search

1995-02-01

A simulation of an air traffic control task was the setting for an investigation of the functions of external cues in prospective memory. External cues can support the triggering of an action or memory for the content of the action. : We focused on m...

Mechanisms of Intentional Binding and Sensory Attenuation: The Role of Temporal Prediction, Temporal Control, Identity Prediction, and Motor Prediction

ERIC Educational Resources Information Center

Hughes, Gethin; Desantis, Andrea; Waszak, Florian

2013-01-01

Sensory processing of action effects has been shown to differ from that of externally triggered stimuli, with respect both to the perceived timing of their occurrence (intentional binding) and to their intensity (sensory attenuation). These phenomena are normally attributed to forward action models, such that when action prediction is consistent…

Storyboard method of end-user programming with natural language configuration

DOEpatents

Bouchard, Ann M; Osbourn, Gordon C

2013-11-19

A technique for end-user programming includes populating a template with graphically illustrated actions and then invoking a command to generate a screen element based on the template. The screen element is rendered within a computing environment and provides a mechanism for triggering execution of a sequence of user actions. The sequence of user actions is based at least in part on the graphically illustrated actions populated into the template.

The therapeutic potential of iron-targeting gallium compounds in human disease: From basic research to clinical application.

PubMed

Chitambar, Christopher R

2017-01-01

Gallium, group IIIa metal, shares certain chemical characteristics with iron which enable it to function as an iron mimetic that can disrupt iron-dependent tumor cell growth. Gallium may also display antimicrobial activity by disrupting iron homeostasis in certain bacteria and fungi. Gallium's action on iron homeostasis leads to inhibition of ribonucleotide reductase, mitochondrial function, and changes in proteins of iron transport and storage. In addition, gallium induces an increase in mitochondrial reactive oxygen species in cells which triggers downstream upregulation of metallothionein and hemoxygenase-1. Early clinical trials evaluated the efficacy of the simple gallium salts, gallium nitrate and gallium chloride. However, newer gallium-ligands such as Tris(8-quinolinolato)gallium(III) (KP46) and gallium maltolate have been developed and are undergoing clinical evaluation. Additional gallium-ligands that demonstrate antitumor activity in preclinical studies have emerged. Their mechanisms of action and their spectrum of antitumor activity may extend beyond the earlier generations of gallium compounds and warrant further investigation. This review will focus on the evolution and potential of gallium-based therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nonlinear physics of electrical wave propagation in the heart: a review

NASA Astrophysics Data System (ADS)

Alonso, Sergio; Bär, Markus; Echebarria, Blas

2016-09-01

The beating of the heart is a synchronized contraction of muscle cells (myocytes) that is triggered by a periodic sequence of electrical waves (action potentials) originating in the sino-atrial node and propagating over the atria and the ventricles. Cardiac arrhythmias like atrial and ventricular fibrillation (AF,VF) or ventricular tachycardia (VT) are caused by disruptions and instabilities of these electrical excitations, that lead to the emergence of rotating waves (VT) and turbulent wave patterns (AF,VF). Numerous simulation and experimental studies during the last 20 years have addressed these topics. In this review we focus on the nonlinear dynamics of wave propagation in the heart with an emphasis on the theory of pulses, spirals and scroll waves and their instabilities in excitable media with applications to cardiac modeling. After an introduction into electrophysiological models for action potential propagation, the modeling and analysis of spatiotemporal alternans, spiral and scroll meandering, spiral breakup and scroll wave instabilities like negative line tension and sproing are reviewed in depth and discussed with emphasis on their impact for cardiac arrhythmias.

Activity-Dependent Exocytosis of Lysosomes Regulates the Structural Plasticity of Dendritic Spines.

PubMed

Padamsey, Zahid; McGuinness, Lindsay; Bardo, Scott J; Reinhart, Marcia; Tong, Rudi; Hedegaard, Anne; Hart, Michael L; Emptage, Nigel J

2017-01-04

Lysosomes have traditionally been viewed as degradative organelles, although a growing body of evidence suggests that they can function as Ca 2+ stores. Here we examined the function of these stores in hippocampal pyramidal neurons. We found that back-propagating action potentials (bpAPs) could elicit Ca 2+ release from lysosomes in the dendrites. This Ca 2+ release triggered the fusion of lysosomes with the plasma membrane, resulting in the release of Cathepsin B. Cathepsin B increased the activity of matrix metalloproteinase 9 (MMP-9), an enzyme involved in extracellular matrix (ECM) remodelling and synaptic plasticity. Inhibition of either lysosomal Ca 2+ signaling or Cathepsin B release prevented the maintenance of dendritic spine growth induced by Hebbian activity. This impairment could be rescued by exogenous application of active MMP-9. Our findings suggest that activity-dependent exocytosis of Cathepsin B from lysosomes regulates the long-term structural plasticity of dendritic spines by triggering MMP-9 activation and ECM remodelling. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Emotion triggers executive attention: anterior cingulate cortex and amygdala responses to emotional words in a conflict task.

PubMed

Kanske, Philipp; Kotz, Sonja A

2011-02-01

Coherent behavior depends on attentional control that detects and resolves conflict between opposing actions. The current functional magnetic resonance imaging study tested the hypothesis that emotion triggers attentional control to speed up conflict processing in particularly salient situations. Therefore, we presented emotionally negative and neutral words in a version of the flanker task. In response to conflict, we found activation of the dorsal anterior cingulate cortex (ACC) and of the amygdala for emotional stimuli. When emotion and conflict coincided, a region in the ventral ACC was activated, which resulted in faster conflict processing in reaction times. Emotion also increased functional connectivity between the ventral ACC and activation of the dorsal ACC and the amygdala in conflict trials. These data suggest that the ventral ACC integrates emotion and conflict and prioritizes the processing of conflict in emotional trials. This adaptive mechanism ensures rapid detection and resolution of conflict in potentially threatening situations signaled by emotional stimuli. Copyright © 2010 Wiley-Liss, Inc.

Effects of in vitro lactoferricin and lactoferrin on the head kidney cells of European sea bass (Dicentrarchus labrax, L.).

PubMed

Henry, Morgane A; Alexis, Maria N

2009-08-15

Antimicrobial, anti-inflammatory and immunomodulating properties of lactoferrin have been demonstrated in mammals and in fish. However, in vivo, lactoferrin is digested by gastric pepsin treatment into the N-terminal derived peptide named lactoferricin. This has been so far overlooked in fish in vitro studies. The aim of the present study was to assess in vitro the effects of both lactoferricin and lactoferrin on the head kidney cells of European sea bass (Dicentrarchus labrax, L.) in order to determine their potential as dietary additives and to get some insight into their mode of action. In vitro lactoferricin decreased significantly the chemiluminescent response of head kidney cells but did not affect the zymosan-triggered chemiluminescence activity. On the other hand, a high concentration of lactoferrin directly stimulated chemiluminescence but reduced the zymosan-triggered chemiluminescence. The bactericidal activity of head kidney cells was also significantly diminished by pre-incubation with lactoferrin in a dose-dependent manner. Although no significant effect of lactoferricin or lactoferrin was evidenced on head kidney cellular viability, absent or negative effect on the priming of respiratory burst activity suggested that care should be taken when using lactoferrin in the diet of sea bass and high doses should be avoided. Hypotheses about the mechanisms of action of lactoferricin and lactoferrin are presented.

Curcumin induces the apoptotic intrinsic pathway via upregulation of reactive oxygen species and JNKs in H9c2 cardiac myoblasts.

PubMed

Zikaki, Kyriaki; Aggeli, Ioanna-Katerina; Gaitanaki, Catherine; Beis, Isidoros

2014-06-01

Curcumin derived from the rhizome of turmeric (Curcuma longa L.), is a well known coloring culinary agent, that has therapeutic properties against diverse pathologies such as cancer, atherosclerosis and heart failure. Given the salutary potential of curcumin, deciphering its mode of action particularly in cardiac cells, is of outstanding value. Accumulating evidence implicates curcumin in the regulation of multiple signaling pathways leading to cell survival or apoptosis. Therefore, the present study aimed at elucidating the molecular mechanisms triggered by curcumin in H9c2 cells. Curcumin was found to activate p38-mitogen-activated protein kinase (p38-MAPK) as well as c-jun NH2 terminal kinases (JNKs), in a dose- and time-dependent manner. We also observed curcumin to impair cell survival by promoting apoptosis, evidenced by chromatin condensation, poly(ADP-ribose) polymerase (PARP) and caspase-3 cleavage, as well as Bax translocation and cytochrome c release into the cytosol. Curcumin-induced apoptosis was ascribed to JNKs, since hindering their activity abolished PARP fragmentation. Furthermore, we identified curcumin to exert a pro-oxidative activity, with 2',7'-dichlorofluorescin diacetate (DCFH-DA) staining revealing up-regulation of reactive oxygen species (ROS) levels and anti-oxidants found to abrogate PARP cleavage. In conclusion, curcumin was found to stimulate the apoptotic cell death of H9c2 cells by upregulating ROS generation and triggering activation of JNKs. With reports underscoring the capacity of curcumin to perturb the cellular redox balance ensuring survival or enhancing apoptosis, determination of its mode of action appears to be critical. Future studies should assess the appropriate administration conditions of curcumin, so as to optimize its therapeutic potential against cardiovascular pathologies.

Cues that Trigger Social Transmission of Disinhibition in Young Children

ERIC Educational Resources Information Center

Moriguchi, Yusuke; Minato, Takashi; Ishiguro, Hiroshi; Shinohara, Ikuko; Itakura, Shoji

2010-01-01

Previous studies have shown that observing a human model's actions, but not a robot's actions, could induce young children's perseverative behaviors and suggested that children's sociocognitive abilities can lead to perseverative errors ("social transmission of disinhibition"). This study investigated how the social transmission of disinhibition…

Insect haptoelectrical stimulation of Venus flytrap triggers exocytosis in gland cells.

PubMed

Scherzer, Sönke; Shabala, Lana; Hedrich, Benjamin; Fromm, Jörg; Bauer, Hubert; Munz, Eberhard; Jakob, Peter; Al-Rascheid, Khaled A S; Kreuzer, Ines; Becker, Dirk; Eiblmeier, Monika; Rennenberg, Heinz; Shabala, Sergey; Bennett, Malcolm; Neher, Erwin; Hedrich, Rainer

2017-05-02

The Venus flytrap Dionaea muscipula captures insects and consumes their flesh. Prey contacting touch-sensitive hairs trigger traveling electrical waves. These action potentials (APs) cause rapid closure of the trap and activate secretory functions of glands, which cover its inner surface. Such prey-induced haptoelectric stimulation activates the touch hormone jasmonate (JA) signaling pathway, which initiates secretion of an acidic hydrolase mixture to decompose the victim and acquire the animal nutrients. Although postulated since Darwin's pioneering studies, these secretory events have not been recorded so far. Using advanced analytical and imaging techniques, such as vibrating ion-selective electrodes, carbon fiber amperometry, and magnetic resonance imaging, we monitored stimulus-coupled glandular secretion into the flytrap. Trigger-hair bending or direct application of JA caused a quantal release of oxidizable material from gland cells monitored as distinct amperometric spikes. Spikes reminiscent of exocytotic events in secretory animal cells progressively increased in frequency, reaching steady state 1 d after stimulation. Our data indicate that trigger-hair mechanical stimulation evokes APs. Gland cells translate APs into touch-inducible JA signaling that promotes the formation of secretory vesicles. Early vesicles loaded with H + and Cl - fuse with the plasma membrane, hyperacidifying the "green stomach"-like digestive organ, whereas subsequent ones carry hydrolases and nutrient transporters, together with a glutathione redox moiety, which is likely to act as the major detected compound in amperometry. Hence, when glands perceive the haptoelectrical stimulation, secretory vesicles are tailored to be released in a sequence that optimizes digestion of the captured animal.

Stress, habits, and drug addiction: a psychoneuroendocrinological perspective.

PubMed

Schwabe, Lars; Dickinson, Anthony; Wolf, Oliver T

2011-02-01

It is well known that stress is a significant risk factor for the development of drug addiction and addiction relapse. Remarkably, the cognitive processes involved in the effects of stress on addictive behavior remain poorly understood. Here it is proposed that stress-induced changes in the neural circuits controlling instrumental action provide a potential mechanism by which stress affects the development of addiction and relapse vulnerability. Instrumental action can be controlled by two anatomically distinct systems: a goal-directed system that involves learning of action-outcome associations, and a habit system that learns stimulus-response associations. The transition from initial voluntary drug use to subsequent involuntary, compulsive drug use represents a switch from goal-directed to habitual control of action. Recent evidence indicates that this switch from goal-directed to habit action can be prompted by stress and stress hormones. We argue (i) that acute stressors reinstate habitual responding to drug-related cues and thus trigger relapse to addictive behavior, and (ii) that prolonged or repeated stress may accelerate the transition from voluntary to involuntary drug use and thus promote the development of addiction. The suggested mechanism encompasses cognitive processes that may contribute to the effects of stress on addictive behavior and could have important implications for the treatment of addiction and the prevention of relapse. (c) 2011 APA, all rights reserved

The essence of helping: significant others and nurses in action draw men into nursing.

PubMed

Juliff, Dianne; Russell, Kylie; Bulsara, Caroline

2017-04-01

Nurses are ageing placing nursing workforce sustainability under threat. An untapped potential resource of men in nursing exists within Australia. The aim of the first phase of this longitudinal study was to investigate why men choose nursing. Qualitative methodological approach used interpretative phenomenological analysis (IPA). "What are the experiences of male graduate nurses regarding their career choice?" The IPA method focused on personal subjective experience where the participants' own sense-making is important. Discussions were audio-recorded, transcribed verbatim and analysed using a format relevant to IPA. Purposeful snowball sampling recruited nine nurses. The "essence of helping" permeated the key theme through significant others and career choice triggers impacting on their decision to enter nursing. Exposure to nurses in action is purported to enhance the awareness of nursing as a career option for men that may contribute to increased recruitment of men into nursing.

Differential Effects of Systemic Cholinergic Receptor Blockade on Pavlovian Incentive Motivation and Goal-Directed Action Selection

PubMed Central

Ostlund, Sean B; Kosheleff, Alisa R; Maidment, Nigel T

2014-01-01

Reward-seeking actions can be guided by external cues that signal reward availability. For instance, when confronted with a stimulus that signals sugar, rats will prefer an action that produces sugar over a second action that produces grain pellets. Action selection is also sensitive to changes in the incentive value of potential rewards. Thus, rats that have been prefed a large meal of sucrose will prefer a grain-seeking action to a sucrose-seeking action. The current study investigated the dependence of these different aspects of action selection on cholinergic transmission. Hungry rats were given differential training with two unique stimulus-outcome (S1-O1 and S2-O2) and action-outcome (A1-O1 and A2-O2) contingencies during separate training phases. Rats were then given a series of Pavlovian-to-instrumental transfer tests, an assay of cue-triggered responding. Before each test, rats were injected with scopolamine (0, 0.03, or 0.1 mg/kg, intraperitoneally), a muscarinic receptor antagonist, or mecamylamine (0, 0.75, or 2.25 mg/kg, intraperitoneally), a nicotinic receptor antagonist. Although the reward-paired cues were capable of biasing action selection when rats were tested off-drug, both anticholinergic treatments were effective in disrupting this effect. During a subsequent round of outcome devaluation testing—used to assess the sensitivity of action selection to a change in reward value—we found no effect of either scopolamine or mecamylamine. These results reveal that cholinergic signaling at both muscarinic and nicotinic receptors mediates action selection based on Pavlovian reward expectations, but is not critical for flexibly selecting actions using current reward values. PMID:24370780

Action-outcome learning and prediction shape the window of simultaneity of audiovisual outcomes.

PubMed

Desantis, Andrea; Haggard, Patrick

2016-08-01

To form a coherent representation of the objects around us, the brain must group the different sensory features composing these objects. Here, we investigated whether actions contribute in this grouping process. In particular, we assessed whether action-outcome learning and prediction contribute to audiovisual temporal binding. Participants were presented with two audiovisual pairs: one pair was triggered by a left action, and the other by a right action. In a later test phase, the audio and visual components of these pairs were presented at different onset times. Participants judged whether they were simultaneous or not. To assess the role of action-outcome prediction on audiovisual simultaneity, each action triggered either the same audiovisual pair as in the learning phase ('predicted' pair), or the pair that had previously been associated with the other action ('unpredicted' pair). We found the time window within which auditory and visual events appeared simultaneous increased for predicted compared to unpredicted pairs. However, no change in audiovisual simultaneity was observed when audiovisual pairs followed visual cues, rather than voluntary actions. This suggests that only action-outcome learning promotes temporal grouping of audio and visual effects. In a second experiment we observed that changes in audiovisual simultaneity do not only depend on our ability to predict what outcomes our actions generate, but also on learning the delay between the action and the multisensory outcome. When participants learned that the delay between action and audiovisual pair was variable, the window of audiovisual simultaneity for predicted pairs increased, relative to a fixed action-outcome pair delay. This suggests that participants learn action-based predictions of audiovisual outcome, and adapt their temporal perception of outcome events based on such predictions. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

The Influence of Glutamate on Axonal Compound Action Potential In Vitro.

PubMed

Abouelela, Ahmed; Wieraszko, Andrzej

2016-01-01

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

Antioxidants in dermatology*

PubMed Central

Addor, Flavia Alvim Sant'anna

2017-01-01

The skin cells continuously produce, through cellular respiration, metabolic processes or under external aggressions, highly reactive molecules oxidation products, generally called free radicals. These molecules are immediately neutralized by enzymatic and non-enzymatic systems in a physiological and dynamic balance. In situations where this balance is broken, various cellular structures, such as the cell membrane, nuclear or mitochondrial DNA may suffer structural modifications, triggering or worsening skin diseases. several substances with alleged antioxidant effects has been offered for topical or oral use, but little is known about their safety, possible associations and especially their mechanism of action. The management of topical and oral antioxidants can help dermatologist to intervene in the oxidative processes safely and effectively, since they know the mechanisms, limitations and potential risks of using these molecules as well as the potential benefits of available associations. PMID:29186248

Targeting Inflammation in Heart Failure with Histone Deacetylase Inhibitors

PubMed Central

McKinsey, Timothy A

2011-01-01

Cardiovascular insults such as myocardial infarction and chronic hypertension can trigger the heart to undergo a remodeling process characterized by myocyte hypertrophy, myocyte death and fibrosis, often resulting in impaired cardiac function and heart failure. Pathological cardiac remodeling is associated with inflammation, and therapeutic approaches targeting inflammatory cascades have shown promise in patients with heart failure. Small molecule histone deacetylase (HDAC) inhibitors block adverse cardiac remodeling in animal models, suggesting unforeseen potential for this class of compounds for the treatment of heart failure. In addition to their beneficial effects on myocardial cells, HDAC inhibitors have potent antiinflammatory actions. This review highlights the roles of HDACs in the heart and the potential for using HDAC inhibitors as broad-based immunomodulators for the treatment of human heart failure. PMID:21267510

Vicarious Group-Based Rejection: Creating a Potentially Dangerous Mix of Humiliation, Powerlessness, and Anger

PubMed Central

Veldhuis, Tinka M.; Gordijn, Ernestine H.; Veenstra, René; Lindenberg, Siegwart

2014-01-01

Rejection can convey that one is seen as inferior and not worth bothering with. Is it possible for people to feel vicariously rejected in this sense and have reactions that are similar to those following personal rejection, such as feeling humiliated, powerless, and angry? A study on personal rejection was followed by two main studies on vicarious group-based rejection. It was found that merely observing rejection of ingroup members can trigger feelings of humiliation that are equally intense as those experienced in response to personal rejection. Moreover, given that the rejection is explicit, vicariously experienced feelings of humiliation can be accompanied by powerlessness and anger. Potentially, this combination of emotions could be an important source of offensive action against rejecters. PMID:24759901

Contextual Predictors of Self-Determined Actions in Students with and without Intellectual Disability

ERIC Educational Resources Information Center

Mumbardó-Adam, Cristina; Shogren, Karrie A.; Guàrdia-olmos, Joan; Giné, Climent

2017-01-01

Research in the field of intellectual disability suggests that promotion of self-determination triggers positive transition outcomes for youth with intellectual disability. This article examines the contributions of personal and environmental variables in predicting self-determined action in students with and without intellectual disability. The…

Triggered intracellular calcium waves in dog and human left atrial myocytes from normal and failing hearts.

PubMed

Aistrup, Gary L; Arora, Rishi; Grubb, Søren; Yoo, Shin; Toren, Benjamin; Kumar, Manvinder; Kunamalla, Aaron; Marszalec, William; Motiwala, Tej; Tai, Shannon; Yamakawa, Sean; Yerrabolu, Satya; Alvarado, Francisco J; Valdivia, Hector H; Cordeiro, Jonathan M; Shiferaw, Yohannes; Wasserstrom, John Andrew

2017-11-01

Abnormal intracellular Ca2+ cycling contributes to triggered activity and arrhythmias in the heart. We investigated the properties and underlying mechanisms for systolic triggered Ca2+ waves in left atria from normal and failing dog hearts. Intracellular Ca2+ cycling was studied using confocal microscopy during rapid pacing of atrial myocytes (36 °C) isolated from normal and failing canine hearts (ventricular tachypacing model). In normal atrial myocytes (NAMs), Ca2+ waves developed during rapid pacing at rates ≥ 3.3 Hz and immediately disappeared upon cessation of pacing despite high sarcoplasmic reticulum (SR) load. In heart failure atrial myocytes (HFAMs), triggered Ca2+ waves (TCWs) developed at a higher incidence at slower rates. Because of their timing, TCW development relies upon action potential (AP)-evoked Ca2+ entry. The distribution of Ca2+ wave latencies indicated two populations of waves, with early events representing TCWs and late events representing conventional spontaneous Ca2+ waves. Latency analysis also demonstrated that TCWs arise after junctional Ca2+ release has occurred and spread to non-junctional (cell core) SR. TCWs also occurred in intact dog atrium and in myocytes from humans and pigs. β-adrenergic stimulation increased Ca2+ release and abolished TCWs in NAMs but was ineffective in HFAMs making this a potentially effective adaptive mechanism in normals but potentially arrhythmogenic in HF. Block of Ca-calmodulin kinase II also abolished TCWs, suggesting a role in TCW formation. Pharmacological manoeuvres that increased Ca2+ release suppressed TCWs as did interventions that decreased Ca2+ release but these also severely reduced excitation-contraction coupling. TCWs develop during the atrial AP and thus could affect AP duration, producing repolarization gradients and creating a substrate for reentry, particularly in HF where they develop at slower rates and a higher incidence. TCWs may represent a mechanism for the initiation of atrial fibrillation particularly in HF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

Threat prompts defensive brain responses independently of attentional control.

PubMed

Pichon, Swann; de Gelder, Beatrice; Grèzes, Julie

2012-02-01

Negative emotional signals are known to influence task performance, but so far, investigations have focused on how emotion interacts with perceptual processes by mobilizing attentional resources. The attention-independent effects of negative emotional signals are less well understood. Here, we show that threat signals trigger defensive responses independently of what observers pay attention to. Participants were scanned using functional magnetic resonance imaging while watching short video clips of threatening actions and performed either color or emotion judgments. Seeing threatening actions interfered with performance in both tasks. Amygdala activation reflected both stimulus and task conditions. In contrast, threat stimuli prompted a constant activity in a network underlying reflexive defensive behavior (periaqueductal gray, hypothalamus, and premotor cortex). Threat stimuli also disrupted ongoing behavior and provoked motor conflict in prefrontal regions during both tasks. The present results are consistent with the view that emotions trigger adaptive action tendencies independently of task settings.

A path model of different forms of impulsivity with externalizing and internalizing psychopathology: Towards greater specificity.

PubMed

Johnson, Sheri L; Tharp, Jordan A; Peckham, Andrew D; Carver, Charles S; Haase, Claudia M

2017-09-01

A growing empirical literature indicates that emotion-related impulsivity (compared to impulsivity that is unrelated to emotion) is particularly relevant for understanding a broad range of psychopathologies. Recent work, however, has differentiated two forms of emotion-related impulsivity: A factor termed Pervasive Influence of Feelings captures tendencies for emotions (mostly negative emotions) to quickly shape thoughts, and a factor termed Feelings Trigger Action captures tendencies for positive and negative emotions to quickly and reflexively shape behaviour and speech. This study used path modelling to consider links from emotion-related and non-emotion-related impulsivity to a broad range of psychopathologies. Undergraduates completed self-report measures of impulsivity, depression, anxiety, aggression, and substance use symptoms. A path model (N = 261) indicated specificity of these forms of impulsivity. Pervasive Influence of Feelings was related to anxiety and depression, whereas Feelings Trigger Action and non-emotion-related impulsivity were related to aggression and substance use. The findings of this study suggest that emotion-relevant impulsivity could be a potentially important treatment target for a set of psychopathologies. Recent work has differentiated two forms of emotion-related impulsivity. This study tests a multivariate path model linking emotion-related and non-emotion-related impulsivity with multiple forms of psychopathology. Impulsive thoughts in response to negative emotions were related to anxiety and depression. Impulsive actions in response to emotions were related to aggression and substance use, as did non-emotion-related impulsivity. The study was limited by the reliance on self-report measures of impulsivity and psychopathology. There is a need for longitudinal work on how these forms of impulsivity predict the onset and course of psychopathology. © 2017 The British Psychological Society.

Novel Activity of a Synthetic Decapeptide Against Toxoplasma gondii Tachyzoites.

PubMed

Giovati, Laura; Santinoli, Claudia; Mangia, Carlo; Vismarra, Alice; Belletti, Silvana; D'Adda, Tiziana; Fumarola, Claudia; Ciociola, Tecla; Bacci, Cristina; Magliani, Walter; Polonelli, Luciano; Conti, Stefania; Kramer, Laura H

2018-01-01

The killer peptide KP is a synthetic decapeptide derived from the sequence of the variable region of a recombinant yeast killer toxin-like microbicidal single-chain antibody. KP proved to exert significant activities against diverse microbial and viral pathogens through different mechanisms of action, but little is known of its effect on apicomplexan protozoa. The aim of the present study was to evaluate the in vitro activity of KP against Toxoplasma gondii , a globally widespread protozoan parasite of great medical interest. The effect of KP treatment and its potential mechanism of action on T. gondii were evaluated by various methods, including light microscopy, quantitative PCR, flow cytometry, confocal microscopy, and transmission electron microscopy. In the presence of KP, the number of T. gondii tachyzoites able to invade Vero cells and the parasite intracellular proliferation were significantly reduced. Morphological observation and analysis of apoptotic markers suggested that KP is able to trigger an apoptosis-like cell death in T. gondii . Overall, our results indicate that KP could be a promising candidate for the development of new anti- Toxoplasma drugs with a novel mechanism of action.

Imaging when acting: picture but not word cues induce action-related biases of visual attention.

PubMed

Wykowska, Agnieszka; Hommel, Bernhard; Schubö, Anna

2012-01-01

In line with the Theory of Event Coding (Hommel et al., 2001a), action planning has been shown to affect perceptual processing - an effect that has been attributed to a so-called intentional weighting mechanism (Wykowska et al., 2009; Memelink and Hommel, 2012), whose functional role is to provide information for open parameters of online action adjustment (Hommel, 2010). The aim of this study was to test whether different types of action representations induce intentional weighting to various degrees. To meet this aim, we introduced a paradigm in which participants performed a visual search task while preparing to grasp or to point. The to-be performed movement was signaled either by a picture of a required action or a word cue. We reasoned that picture cues might trigger a more concrete action representation that would be more likely to activate the intentional weighting of perceptual dimensions that provide information for online action control. In contrast, word cues were expected to trigger a more abstract action representation that would be less likely to induce intentional weighting. In two experiments, preparing for an action facilitated the processing of targets in an unrelated search task if they differed from distractors on a dimension that provided information for online action control. As predicted, however, this effect was observed only if action preparation was signaled by picture cues but not if it was signaled by word cues. We conclude that picture cues are more efficient than word cues in activating the intentional weighting of perceptual dimensions, presumably by specifying not only invariant characteristics of the planned action but also the dimensions of action-specific parameters.

Imaging When Acting: Picture but Not Word Cues Induce Action-Related Biases of Visual Attention

PubMed Central

Wykowska, Agnieszka; Hommel, Bernhard; Schubö, Anna

2012-01-01

In line with the Theory of Event Coding (Hommel et al., 2001a), action planning has been shown to affect perceptual processing – an effect that has been attributed to a so-called intentional weighting mechanism (Wykowska et al., 2009; Memelink and Hommel, 2012), whose functional role is to provide information for open parameters of online action adjustment (Hommel, 2010). The aim of this study was to test whether different types of action representations induce intentional weighting to various degrees. To meet this aim, we introduced a paradigm in which participants performed a visual search task while preparing to grasp or to point. The to-be performed movement was signaled either by a picture of a required action or a word cue. We reasoned that picture cues might trigger a more concrete action representation that would be more likely to activate the intentional weighting of perceptual dimensions that provide information for online action control. In contrast, word cues were expected to trigger a more abstract action representation that would be less likely to induce intentional weighting. In two experiments, preparing for an action facilitated the processing of targets in an unrelated search task if they differed from distractors on a dimension that provided information for online action control. As predicted, however, this effect was observed only if action preparation was signaled by picture cues but not if it was signaled by word cues. We conclude that picture cues are more efficient than word cues in activating the intentional weighting of perceptual dimensions, presumably by specifying not only invariant characteristics of the planned action but also the dimensions of action-specific parameters. PMID:23087656

Damming the rivers of the Amazon basin

NASA Astrophysics Data System (ADS)

Latrubesse, Edgardo M.; Arima, Eugenio Y.; Dunne, Thomas; Park, Edward; Baker, Victor R.; D'Horta, Fernando M.; Wight, Charles; Wittmann, Florian; Zuanon, Jansen; Baker, Paul A.; Ribas, Camila C.; Norgaard, Richard B.; Filizola, Naziano; Ansar, Atif; Flyvbjerg, Bent; Stevaux, Jose C.

2017-06-01

More than a hundred hydropower dams have already been built in the Amazon basin and numerous proposals for further dam constructions are under consideration. The accumulated negative environmental effects of existing dams and proposed dams, if constructed, will trigger massive hydrophysical and biotic disturbances that will affect the Amazon basin’s floodplains, estuary and sediment plume. We introduce a Dam Environmental Vulnerability Index to quantify the current and potential impacts of dams in the basin. The scale of foreseeable environmental degradation indicates the need for collective action among nations and states to avoid cumulative, far-reaching impacts. We suggest institutional innovations to assess and avoid the likely impoverishment of Amazon rivers.

Damming the rivers of the Amazon basin.

PubMed

Latrubesse, Edgardo M; Arima, Eugenio Y; Dunne, Thomas; Park, Edward; Baker, Victor R; d'Horta, Fernando M; Wight, Charles; Wittmann, Florian; Zuanon, Jansen; Baker, Paul A; Ribas, Camila C; Norgaard, Richard B; Filizola, Naziano; Ansar, Atif; Flyvbjerg, Bent; Stevaux, Jose C

2017-06-14

More than a hundred hydropower dams have already been built in the Amazon basin and numerous proposals for further dam constructions are under consideration. The accumulated negative environmental effects of existing dams and proposed dams, if constructed, will trigger massive hydrophysical and biotic disturbances that will affect the Amazon basin's floodplains, estuary and sediment plume. We introduce a Dam Environmental Vulnerability Index to quantify the current and potential impacts of dams in the basin. The scale of foreseeable environmental degradation indicates the need for collective action among nations and states to avoid cumulative, far-reaching impacts. We suggest institutional innovations to assess and avoid the likely impoverishment of Amazon rivers.

Thinking Outside of the Detained Box: A Guide to Temporary Seizures of Property Under the Fourth Amendment

DTIC Science & Technology

2009-12-01

reasonable suspicion, this action triggers a responsibility to diligently develop probable cause with regard to the seized property.17 Once...Amendment prohibits only ‘meaningful interference’ with a person’s possessory interests, not Government action which is reasonable under the...tempered this standard by observing that while the police could have acted more expeditiously, their actions were reasonably diligent, because they

A Novel Task for the Investigation of Action Acquisition

PubMed Central

Stafford, Tom; Thirkettle, Martin; Walton, Tom; Vautrelle, Nicolas; Hetherington, Len; Port, Michael; Gurney, Kevin; Redgrave, Pete

2012-01-01

We present a behavioural task designed for the investigation of how novel instrumental actions are discovered and learnt. The task consists of free movement with a manipulandum, during which the full range of possible movements can be explored by the participant and recorded. A subset of these movements, the ‘target’, is set to trigger a reinforcing signal. The task is to discover what movements of the manipulandum evoke the reinforcement signal. Targets can be defined in spatial, temporal, or kinematic terms, can be a combination of these aspects, or can represent the concatenation of actions into a larger gesture. The task allows the study of how the specific elements of behaviour which cause the reinforcing signal are identified, refined and stored by the participant. The task provides a paradigm where the exploratory motive drives learning and as such we view it as in the tradition of Thorndike [1]. Most importantly it allows for repeated measures, since when a novel action is acquired the criterion for triggering reinforcement can be changed requiring a new action to be discovered. Here, we present data using both humans and rats as subjects, showing that our task is easily scalable in difficulty, adaptable across species, and produces a rich set of behavioural measures offering new and valuable insight into the action learning process. PMID:22675490

A BMI-based occupational therapy assist suit: asynchronous control by SSVEP

PubMed Central

Sakurada, Takeshi; Kawase, Toshihiro; Takano, Kouji; Komatsu, Tomoaki; Kansaku, Kenji

2013-01-01

A brain-machine interface (BMI) is an interface technology that uses neurophysiological signals from the brain to control external machines. Recent invasive BMI technologies have succeeded in the asynchronous control of robot arms for a useful series of actions, such as reaching and grasping. In this study, we developed non-invasive BMI technologies aiming to make such useful movements using the subject's own hands by preparing a BMI-based occupational therapy assist suit (BOTAS). We prepared a pre-recorded series of useful actions—a grasping-a-ball movement and a carrying-the-ball movement—and added asynchronous control using steady-state visual evoked potential (SSVEP) signals. A SSVEP signal was used to trigger the grasping-a-ball movement and another SSVEP signal was used to trigger the carrying-the-ball movement. A support vector machine was used to classify EEG signals recorded from the visual cortex (Oz) in real time. Untrained, able-bodied participants (n = 12) operated the system successfully. Classification accuracy and time required for SSVEP detection were ~88% and 3 s, respectively. We further recruited three patients with upper cervical spinal cord injuries (SCIs); they also succeeded in operating the system without training. These data suggest that our BOTAS system is potentially useful in terms of rehabilitation of patients with upper limb disabilities. PMID:24068982

Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence.

PubMed

Rohleder, Cathrin; Müller, Juliane K; Lange, Bettina; Leweke, F M

2016-01-01

There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ 9 -THC), cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although, results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in both rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial demonstrated that in acute schizophrenia cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug amisulpride while being accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. Although, a plethora of mechanisms of action has been suggested, their potential relevance for the antipsychotic effects of cannabidiol still needs to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol's antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials.

40 CFR 430.03 - Best management practices (BMPs) for spent pulping liquor, soap, and turpentine management, spill...

Code of Federal Regulations, 2010 CFR

2010-07-01

... triggers investigative or corrective action. Mills determine action levels by a statistical analysis of six... exchanger, recovery furnace or boiler, pipeline, valve, fitting, or other device that contains, processes... gases from the cooking of softwoods by the kraft pulping process. Sometimes referred to as sulfate...

Transcriptional profile of diurnon-induces toxicity on the urinary bladder of male wistar rats to inform mode of action

EPA Science Inventory

Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that induces rat urinary bladder urothelial tumors at high dietary levels (2500 ppm). The specific mode of action and molecular alterations triggered by diuron, however, have not been clarified. Th...

Simulating an Enactment Effect: Pronouns Guide Action Simulation during Narrative Comprehension

ERIC Educational Resources Information Center

Ditman, Tali; Brunye, Tad T.; Mahoney, Caroline R.; Taylor, Holly A.

2010-01-01

Recent research has suggested that reading involves the mental simulation of events and actions described in a text. It is possible however that previous findings did not tap into processes engaged during natural reading but rather those triggered by task demands. The present study examined whether readers spontaneously mentally simulate the…

Responding In-the-Moment: Learning to Prepare for the Unexpected

ERIC Educational Resources Information Center

Mason, John

2015-01-01

Becoming aware of something unexpected can be a form of awakening: sharpening attention, enriching noticing, opening up fresh possibilities of action, and educating awareness so as to enable a sensitive response to similar situations in the future. However it can also trigger tunnel vision (few if any actions available) or freezing (no actions…

Sirtuin 1 Mediates the Actions of Peroxisome Proliferator-Activated Receptor δ on the Oxidized Low-Density Lipoprotein-Triggered Migration and Proliferation of Vascular Smooth Muscle Cells.

PubMed

Hwang, Jung Seok; Ham, Sun Ah; Yoo, Taesik; Lee, Won Jin; Paek, Kyung Shin; Lee, Chi-Ho; Seo, Han Geuk

2016-11-01

Peroxisome proliferator-activated receptor δ (PPARδ) has been implicated in vascular pathophysiology. However, its functions in atherogenic changes of the vascular wall have not been fully elucidated. PPARδ activated by GW501516 (2-[2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid) significantly inhibited the migration and proliferation of vascular smooth muscle cells (VSMCs) triggered by oxidized low-density lipoprotein (oxLDL). These GW501516-mediated effects were significantly reversed by PPARδ-targeting small-interfering RNA (siRNA), indicating that PPARδ is involved in the action of GW501516. The antiproliferative effect of GW501516 was directly linked to cell cycle arrest at the G 0 /G 1 to S phase transition, which was followed by the down-regulation of cyclin-dependent kinase 4 along with increased levels of p21 and p53. In VSMCs treated with GW501516, the expression of sirtuin 1 (SIRT1) mRNA and protein was time-dependently increased. This GW501516-mediated up-regulation of SIRT1 expression was also demonstrated even in the presence of oxLDL. In addition, GW501516-dependent inhibition of oxLDL-triggered migration and proliferation of VSMCs was almost completely abolished in the presence of SIRT1-targeting siRNA. These effects of GW501516 on oxLDL-triggered phenotypic changes of VSMCs were also demonstrated via activation or inhibition of SIRT1 activity by resveratrol or sirtinol, respectively. Finally, gain or loss of SIRT1 function imitated the action of PPARδ on oxLDL-triggered migration and proliferation of VSMCs. Taken together, these observations indicate that PPARδ-dependent up-regulation of SIRT1 contributes to the antiatherogenic activities of PPARδ by suppressing the migration and proliferation of VSMCs linked to vascular diseases such as restenosis and atherosclerosis. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Visual Stimuli Evoked Action Potentials Trigger Rapidly Propagating Dendritic Calcium Transients in the Frog Optic Tectum Layer 6 Neurons.

PubMed

Svirskis, Gytis; Baranauskas, Gytis; Svirskiene, Natasa; Tkatch, Tatiana

2015-01-01

The superior colliculus in mammals or the optic tectum in amphibians is a major visual information processing center responsible for generation of orientating responses such as saccades in monkeys or prey catching avoidance behavior in frogs. The conserved structure function of the superior colliculus the optic tectum across distant species such as frogs, birds monkeys permits to draw rather general conclusions after studying a single species. We chose the frog optic tectum because we are able to perform whole-cell voltage-clamp recordings fluorescence imaging of tectal neurons while they respond to a visual stimulus. In the optic tectum of amphibians most visual information is processed by pear-shaped neurons possessing long dendritic branches, which receive the majority of synapses originating from the retinal ganglion cells. Since the first step of the retinal input integration is performed on these dendrites, it is important to know whether this integration is enhanced by active dendritic properties. We demonstrate that rapid calcium transients coinciding with the visual stimulus evoked action potentials in the somatic recordings can be readily detected up to the fine branches of these dendrites. These transients were blocked by calcium channel blockers nifedipine CdCl2 indicating that calcium entered dendrites via voltage-activated L-type calcium channels. The high speed of calcium transient propagation, >300 μm in <10 ms, is consistent with the notion that action potentials, actively propagating along dendrites, open voltage-gated L-type calcium channels causing rapid calcium concentration transients in the dendrites. We conclude that such activation by somatic action potentials of the dendritic voltage gated calcium channels in the close vicinity to the synapses formed by axons of the retinal ganglion cells may facilitate visual information processing in the principal neurons of the frog optic tectum.

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.

Asthma Quiz

MedlinePlus

... Asthma is a chronic disease that requires ongoing management. Personalized plans for treatment may include medications, an asthma action plan, and environmental control measures to avoid your child's asthma triggers. ...

Insect haptoelectrical stimulation of Venus flytrap triggers exocytosis in gland cells

PubMed Central

Scherzer, Sönke; Shabala, Lana; Hedrich, Benjamin; Fromm, Jörg; Bauer, Hubert; Munz, Eberhard; Jakob, Peter; Al-Rascheid, Khaled A. S.; Kreuzer, Ines; Becker, Dirk; Eiblmeier, Monika; Rennenberg, Heinz; Shabala, Sergey; Neher, Erwin; Hedrich, Rainer

2017-01-01

The Venus flytrap Dionaea muscipula captures insects and consumes their flesh. Prey contacting touch-sensitive hairs trigger traveling electrical waves. These action potentials (APs) cause rapid closure of the trap and activate secretory functions of glands, which cover its inner surface. Such prey-induced haptoelectric stimulation activates the touch hormone jasmonate (JA) signaling pathway, which initiates secretion of an acidic hydrolase mixture to decompose the victim and acquire the animal nutrients. Although postulated since Darwin’s pioneering studies, these secretory events have not been recorded so far. Using advanced analytical and imaging techniques, such as vibrating ion-selective electrodes, carbon fiber amperometry, and magnetic resonance imaging, we monitored stimulus-coupled glandular secretion into the flytrap. Trigger-hair bending or direct application of JA caused a quantal release of oxidizable material from gland cells monitored as distinct amperometric spikes. Spikes reminiscent of exocytotic events in secretory animal cells progressively increased in frequency, reaching steady state 1 d after stimulation. Our data indicate that trigger-hair mechanical stimulation evokes APs. Gland cells translate APs into touch-inducible JA signaling that promotes the formation of secretory vesicles. Early vesicles loaded with H+ and Cl− fuse with the plasma membrane, hyperacidifying the “green stomach”-like digestive organ, whereas subsequent ones carry hydrolases and nutrient transporters, together with a glutathione redox moiety, which is likely to act as the major detected compound in amperometry. Hence, when glands perceive the haptoelectrical stimulation, secretory vesicles are tailored to be released in a sequence that optimizes digestion of the captured animal. PMID:28416693

Event-Triggered Adaptive Dynamic Programming for Continuous-Time Systems With Control Constraints.

PubMed

Dong, Lu; Zhong, Xiangnan; Sun, Changyin; He, Haibo

2016-08-31

In this paper, an event-triggered near optimal control structure is developed for nonlinear continuous-time systems with control constraints. Due to the saturating actuators, a nonquadratic cost function is introduced and the Hamilton-Jacobi-Bellman (HJB) equation for constrained nonlinear continuous-time systems is formulated. In order to solve the HJB equation, an actor-critic framework is presented. The critic network is used to approximate the cost function and the action network is used to estimate the optimal control law. In addition, in the proposed method, the control signal is transmitted in an aperiodic manner to reduce the computational and the transmission cost. Both the networks are only updated at the trigger instants decided by the event-triggered condition. Detailed Lyapunov analysis is provided to guarantee that the closed-loop event-triggered system is ultimately bounded. Three case studies are used to demonstrate the effectiveness of the proposed method.

Design and Characterization of a Multifunctional pH-Triggered Peptide C8 for Selective Anticancer Activity.

PubMed

Lu, Sheng; Bennett, W F Drew; Ding, Yong; Zhang, Lei; Fan, Helen Y; Zhao, Danyang; Zheng, Tao; Ouyang, Ping-Kai; Li, Jason; Wu, Yan; Xu, Wen; Chu, Dafeng; Yuan, Yongfang; Heerklotz, Heiko; Karttunen, Mikko; Chen, P

2015-12-09

Most drug delivery systems have been developed for efficient delivery to tumor sites via targeting and on-demand strategies, but the carriers rarely execute synergistic therapeutic actions. In this work, C8, a cationic, pH-triggered anticancer peptide, is developed by incorporating histidine-mediated pH-sensitivity, amphipathic helix, and amino acid pairing self-assembly design. We designed C8 to function as a pH-responsive nanostructure whose cytotoxicity can be switched on and off by its self-assembly: Noncytotoxic β-sheet fibers at high pH with neutral histidines, and positively charged monomers with membrane lytic activity at low pH. The selective activity of C8, tested for three different cancer cell lines and two noncancerous cell lines, is shown. Based on liposome leakage assays and multiscale computer simulations, its physical mechanisms of pore-forming action and selectivity are proposed, which originate from differences in the lipid composition of the cellular membrane and changes in hydrogen bonding. C8 is then investigated for its potential as a drug carrier. C8 forms a nanocomplex with ellipticine, a nonselective model anticancer drug. It selectively targets cancer cells in a pH-responsive manner, demonstrating enhanced efficacy and selectivity. This study provides a novel powerful strategy for the design and development of multifunctional self-assembling peptides for therapeutic and drug delivery applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Metabolic control of female puberty: potential therapeutic targets.

PubMed

Castellano, Juan M; Tena-Sempere, Manuel

2016-10-01

The onset of puberty in females is highly sensitive to the nutritional status and the amount of energy reserves of the organism. This metabolic information is sensed and transmitted to hypothalamic GnRH neurons, considered to be ultimately responsible for triggering puberty through the coordinated action of different peripheral hormones, central neurotransmitters, and molecular mediators. This article will review and discuss (i) the relevant actions of the adipose hormone leptin, as a stimulatory/permissive signal, and the gut hormone ghrelin, as an inhibitory factor, in the metabolic control of female puberty; (ii) the crucial role of the hypothalamic kisspeptin neurons, recently emerged as essential gatekeepers of puberty, in transmitting this metabolic information to GnRH neurons; and (iii) the potential involvement of key cellular energy sensors, such as mTOR, as molecular mediators in this setting. The thorough characterization of the physiological roles of the above elements in the metabolic control of female puberty, along with the discovery of novel factors, pathways, and mechanisms involved, will promote our understanding of the complex networks connecting metabolism and puberty and, ultimately, will aid in the design of target-specific treatments for female pubertal disorders linked to conditions of metabolic stress.

Oxymatrine extracted from Sophora flavescens inhibited cell growth and induced apoptosis in human osteosarcoma MG-63 cells in vitro.

PubMed

Wei, Jianghua; Zhu, Yin; Xu, Gang; Yang, Fan; Guan, Zhe; Wang, Mao; Fang, Yonghong

2014-11-01

Oxymatrine, one of the most active components of the ethanol extracts from Sophora flavescens, is known for its potent antitumor activity both in vitro and in vivo. However, the mechanism of its action in mediating the cell apoptosis remains elusive. In this study, we investigated the proliferation inhibitory and apoptotic activities of oxymatrine against human osteosarcoma MG-63 cells. The compound was found to markedly and dose-dependently inhibit the cell proliferation determined by 5-bromo-2-deoxyuridine incorporation. Oxymatrine also induced the cell apoptosis in a dose- and time-dependent manner as showed by the annexin V-FITC/PI double staining and TUNEL assay. Furthermore, a disruption of mitochondrial membrane potential and an up-regulation of cleaved caspases-3, and-9 and downregulation of Bax/Bcl-2 was evidenced in the oxymatrine-treated cells. These proteins have been known to play a pivotal role in the regulation of apoptosis. In conclusion, these observations indicate of the oxymatrine potential as an effective antitumor agent against osteosarcoma. Moreover, the compound appears to exert its anti-tumor action by stimulating the caspase-triggered signaling pathway.

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

PubMed

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

2015-01-01

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

Positive Education for School Leaders: Exploring the Effects of Emotion-Gratitude and Action-Gratitude

ERIC Educational Resources Information Center

Waters, Lea; Stokes, Helen

2015-01-01

This qualitative study describes the effect of two gratitude interventions designed to trigger emotion-gratitude (gratitude diary) and action-gratitude (gratitude letter) in school leaders. Case study methodology was applied to analyse reflective journals of 27 school leaders. The gratitude diary served to foster a more balanced view of the…

Screening for Biologically Annotated Drugs That Trigger Triacylglycerol Accumulation in the Diatom Phaeodactylum.

PubMed

Conte, Melissa; Lupette, Josselin; Seddiki, Khawla; Meï, Coline; Dolch, Lina-Juana; Gros, Valérie; Barette, Caroline; Rébeillé, Fabrice; Jouhet, Juliette; Maréchal, Eric

2018-06-01

Microalgae are a promising feedstock for the production of triacylglycerol (TAG) for a variety of potential applications, ranging from food and human health to biofuels and green chemistry. However, obtaining high TAG yields is challenging. A phenotypic assay for the accumulation of oil droplets was developed to screen a library of 1,200 drugs, annotated with pharmacology information, to select compounds that trigger TAG accumulation in the diatom Phaeodactylum tricornutum Using this screen, we identified 34 molecules acting in a dose-dependent manner. Previously characterized targets of these compounds include cell division and cell signaling effectors, membrane receptors and transporters, and sterol metabolism. Among the five compounds possibly acting on sterol metabolism, we focused our study on ethynylestradiol, a synthetic form of estrogen that is used in contraceptive pills and known for its ecological impact as an endocrine disruptor. Ethynylestradiol impaired the production of very-long-chain polyunsaturated fatty acids, destabilized the galactolipid versus phospholipid balance, and triggered the recycling of fatty acids from membrane lipids to TAG. The P. tricornutum transcriptomic response to treatment with ethynylestradiol was consistent with the reallocation of carbon from sterols to acetyl-coenzyme A and TAG. The mode of action and catabolism of ethynylestradiol are unknown but might involve several up-regulated cytochrome P450 proteins. A fatty acid elongase, Δ6-ELO-B1, might be involved in the impairment of very-long-chain polyunsaturated fatty acids and fatty acid turnover. This phenotypic screen opens new perspectives for the exploration of novel bioactive molecules, potential target genes, and pathways controlling TAG biosynthesis. It also unraveled the sensitivity of diatoms to endocrine disruptors, highlighting an impact of anthropogenic pollution on phytoplankton. © 2018 American Society of Plant Biologists. All Rights Reserved.

Presynaptic strontium dynamics and synaptic transmission.

PubMed Central

Xu-Friedman, M A; Regehr, W G

1999-01-01

Strontium can replace calcium in triggering neurotransmitter release, although peak release is reduced and the duration of release is prolonged. Strontium has therefore become useful in probing release, but its mechanism of action is not well understood. Here we study the action of strontium at the granule cell to Purkinje cell synapse in mouse cerebellar slices. Presynaptic residual strontium levels were monitored with fluorescent indicators, which all responded to strontium (fura-2, calcium orange, fura-2FF, magnesium green, and mag-fura-5). When calcium was replaced by equimolar concentrations of strontium in the external bath, strontium and calcium both entered presynaptic terminals. Contaminating calcium was eliminated by including EGTA in the extracellular bath, or by loading parallel fibers with EGTA, enabling the actions of strontium to be studied in isolation. After a single stimulus, strontium reached higher peak free levels than did calcium (approximately 1.7 times greater), and decayed more slowly (half-decay time 189 ms for strontium and 32 ms for calcium). These differences in calcium and strontium dynamics are likely a consequence of greater strontium permeability through calcium channels, lower affinity of the endogenous buffer for strontium, and less efficient extrusion of strontium. Measurements of presynaptic divalent levels help to explain properties of release evoked by strontium. Parallel fiber synaptic currents triggered by strontium are smaller in amplitude and longer in duration than those triggered by calcium. In both calcium and strontium, release consists of two components, one more steeply dependent on divalent levels than the other. Strontium drives both components less effectively than does calcium, suggesting that the affinities of the sensors involved in both phases of release are lower for strontium than for calcium. Thus, the larger and slower strontium transients account for the prominent slow component of release triggered by strontium. PMID:10096899

Hypertension management: rationale for triple therapy based on mechanisms of action.

PubMed

Neutel, Joel M; Smith, David H G

2013-10-01

An estimated 25% of patients will require 3 antihypertensive agents to achieve blood pressure (BP) control; combination therapy is thus an important strategy in hypertension treatment. This review discusses the triple-therapy combination of an angiotensin receptor blocker (ARB) or direct renin antagonist (DRI) with a calcium channel blocker (CCB) and a diuretic, with a focus on mechanisms of action. Multiple physiologic pathways contribute to hypertension. Combining antihypertensive agents not only better targets the underlying pathways, but also helps blunt compensatory responses that may be triggered by single-agent therapy. DRIs and ARBs target the renin-angiotensin-aldosterone system (RAAS) at the initial and final steps, respectively, and both classes lower BP by reducing the effects of angiotensin-2; however, ARBs may trigger a compensatory increase in renin activity. Dihydropyridine CCBs target L-type calcium channels and lower BP through potent vasodilation, but can trigger compensatory activation of the sympathetic nervous system (SNS) and RAAS. Thiazide diuretics lower BP initially through sodium depletion and plasma volume reduction, followed by total peripheral resistance reduction, but can also trigger compensatory activation of the SNS and RAAS. The combination of an agent targeting the RAAS with a CCB and diuretic is rational, and triple combinations of valsartan/amlodipine/hydrochlorothiazide, olmesartan/amlodipine/hydrochlorothiazide, and aliskiren/amlodipine/hydrochlorothiazide have demonstrated greater effectiveness compared with their respective dual-component combinations. In addition, single-pill, fixed-dose combinations can address barriers to BP control including clinical inertia and poor adherence. Fixed-dose antihypertensive combination products capitalize on complementary mechanisms of action and have been shown to result in improved BP control. © 2012 John Wiley & Sons Ltd.

The thalamic low-threshold Ca2+ potential: a key determinant of the local and global dynamics of the slow (<1 Hz) sleep oscillation in thalamocortical networks

PubMed Central

Crunelli, Vincenzo; Errington, Adam C.; Hughes, Stuart W.; Tóth, Tibor I.

2011-01-01

During non-rapid eye movement sleep and certain types of anaesthesia, neurons in the neocortex and thalamus exhibit a distinctive slow (<1 Hz) oscillation that consists of alternating UP and DOWN membrane potential states and which correlates with a pronounced slow (<1 Hz) rhythm in the electroencephalogram. While several studies have claimed that the slow oscillation is generated exclusively in neocortical networks and then transmitted to other brain areas, substantial evidence exists to suggest that the full expression of the slow oscillation in an intact thalamocortical (TC) network requires the balanced interaction of oscillator systems in both the neocortex and thalamus. Within such a scenario, we have previously argued that the powerful low-threshold Ca2+ potential (LTCP)-mediated burst of action potentials that initiates the UP states in individual TC neurons may be a vital signal for instigating UP states in related cortical areas. To investigate these issues we constructed a computational model of the TC network which encompasses the important known aspects of the slow oscillation that have been garnered from earlier in vivo and in vitro experiments. Using this model we confirm that the overall expression of the slow oscillation is intricately reliant on intact connections between the thalamus and the cortex. In particular, we demonstrate that UP state-related LTCP-mediated bursts in TC neurons are proficient in triggering synchronous UP states in cortical networks, thereby bringing about a synchronous slow oscillation in the whole network. The importance of LTCP-mediated action potential bursts in the slow oscillation is also underlined by the observation that their associated dendritic Ca2+ signals are the only ones that inform corticothalamic synapses of the TC neuron output, since they, but not those elicited by tonic action potential firing, reach the distal dendritic sites where these synapses are located. PMID:21893530

Role of calcium stores and membrane voltage in the generation of slow wave action potentials in guinea-pig gastric pylorus

PubMed Central

Van Helden, D F; Imtiaz, M S; Nurgaliyeva, K; von der Weid, P-Y; Dosen, P J

2000-01-01

Intracellular recordings made in single bundle strips of a visceral smooth muscle revealed rhythmic spontaneous membrane depolarizations termed slow waves (SWs). These exhibited ‘pacemaker’ and ‘regenerative’ components composed of summations of more elementary events termed spontaneous transient depolarizations (STDs). STDs and SWs persisted in the presence of tetrodotoxin, nifedipine and ryanodine, and upon brief exposure to Ca2+-free Cd2+-containing solutions; they were enhanced by ACh and blocked by BAPTA AM, cyclopiazonic acid and caffeine. SWs were also inhibited in heparin-loaded strips. SWs were observed over a wide range of membrane potentials (e.g. −80 to −45 mV) with increased frequencies at more depolarized potentials. Regular spontaneous SW activity in this preparation began after 1–3 h superfusion of the tissue with physiological saline following the dissection procedure. Membrane depolarization applied before the onset of this activity induced bursts of STD-like events (termed the ‘initial’ response) which, when larger than threshold levels initiated regenerative responses. The combined initial-regenerative waveform was termed the SW-like action potential. Voltage-induced responses exhibited large variable latencies (typical range 0.3–4 s), refractory periods of ≈11 s and a pharmacology that was indistinguishable from those of STDs and spontaneous SWs. The data indicate that SWs arise through more elementary inositol 1,4,5-trisphosphate (IP3) receptor-induced Ca2+ release events which rhythmically synchronize to trigger regenerative Ca2+ release and induce inward current across the plasmalemma. The finding that action potentials, which were indistinguishable from SWs, could be evoked by depolarization suggests that membrane potential modulates IP3 production. Voltage feedback on intracellular IP3-sensitive Ca2+ release is likely to have a major influence on the generation and propagation of SWs. PMID:10747196

The antihypertensive drug hydralazine activates the intrinsic pathway of apoptosis and causes DNA damage in leukemic T cells

PubMed Central

Ruiz-Magaña, María J.; Martínez-Aguilar, Rocío; Lucendo, Estefanía; Campillo-Davo, Diana; Schulze-Osthoff, Klaus; Ruiz-Ruiz, Carmen

2016-01-01

Epigenetic therapies have emerged as promising anticancer approaches, since epigenetic modifications play a major role in tumor initiation and progression. Hydralazine, an approved vasodilator and antihypertensive drug, has been recently shown to act as a DNA methylation inhibitor. Even though hydralazine is already tested in clinical cancer trials, its mechanism of antitumor action remains undefined. Here, we show that hydralazine induced caspase-dependent apoptotic cell death in human p53-mutant leukemic T cells. Moreover, we demonstrate that hydralazine triggered the mitochondrial pathway of apoptosis by inducing Bak activation and loss of the mitochondrial membrane potential. Hydralazine treatment further resulted in the accumulation of reactive oxygen species, whereas a superoxide dismutase mimetic inhibited hydralazine-induced cell death. Interestingly, caspase-9-deficient Jurkat cells or Bcl-2- and Bcl-xL-overexpressing cells were strongly resistant to hydralazine treatment, thereby demonstrating the dependence of hydralazine-induced apoptosis on the mitochondrial death pathway. Furthermore, we demonstrate that hydralazine treatment triggered DNA damage which might contribute to its antitumor effect. PMID:26942461

Bifurcation theory and cardiac arrhythmias

PubMed Central

Karagueuzian, Hrayr S; Stepanyan, Hayk; Mandel, William J

2013-01-01

In this paper we review two types of dynamic behaviors defined by the bifurcation theory that are found to be particularly useful in describing two forms of cardiac electrical instabilities that are of considerable importance in cardiac arrhythmogenesis. The first is action potential duration (APD) alternans with an underlying dynamics consistent with the period doubling bifurcation theory. This form of electrical instability could lead to spatially discordant APD alternans leading to wavebreak and reentrant form of tachyarrhythmias. Factors that modulate the APD alternans are discussed. The second form of bifurcation of importance to cardiac arrhythmogenesis is the Hopf-homoclinic bifurcation that adequately describes the dynamics of the onset of early afterdepolarization (EAD)-mediated triggered activity (Hopf) that may cause ventricular tachycardia and ventricular fibrillation (VT/VF respectively). The self-termination of the triggered activity is compatible with the homoclinic bifurcation. Ionic and intracellular calcium dynamics underlying these dynamics are discussed using available experimental and simulation data. The dynamic analysis provides novel insights into the mechanisms of VT/VF, a major cause of sudden cardiac death in the US. PMID:23459417

Development and Content Validation of Crisis Response Training Package Red Cape: Crisis Action Planning and Execution

DTIC Science & Technology

2007-08-01

example, the topic of massively multiplayer online role playing games ( MMORPGs ). (A related class of first person multiplayer shooters includes...key and measurable indicators that require immediate action. They develop plans of action for these trigger points to avoid premature commitment of...recognize that the cause of the incident may be an accident or act of nature, or it may be either criminal or terrorist activity. They avoid the

Global Examination of Triggered Tectonic Tremor following the 2017 Mw8.1 Tehuantepec Earthquake in Mexico

NASA Astrophysics Data System (ADS)

Chao, K.; Gonzalez-Huizar, H.; Tang, V.; Klaeser, R. D.; Mattia, M.; Van der Lee, S.

2017-12-01

Triggered tremor is one type of slow earthquake that activated by teleseismic surfaces waves of large magnitude earthquake. Observations of triggered tremor can help to evaluate the background ambient tremor rate and slow slip events in the surrounding region. The Mw 8.1 Tehuantepec earthquake in Mexico is an ideal tremor-triggering candidate for a global search for triggered tremor. Here, we examine triggered tremor globally following the M8.1 event and model the tremor-triggering potential. We examine 7,000 seismic traces and found a widely spread triggered tremor along the western coast of the North America occur during the surface waves of the Mw 8.1 event. Triggered tremor appeared in the San Jacinto Fault, San Andreas Fault around Parkfield, and Calaveras Fault in California, in Vancouver Island in Cascadia subduction zone, in Queen Charlotte Margin and Eastern Denali Fault in Canada, and in Alaska and Aleutian Arc. In addition, we observe a newly found triggered tremor source in Mt. Etna in Sicily Island, Italy. However, we do not find clear triggered tremor evidences in the tremor active regions in Japan, Taiwan, and in New Zealand. We model tremor-triggering potential at the triggering earthquake source and triggered tremor sources. Our modeling results suggest the source parameters of the M8.1 triggering events and the stress at the triggered fault zone are two critical factors to control tremor-triggering threshold.

At Least I Tried: The Relationship between Regulatory Focus and Regret Following Action vs. Inaction

PubMed Central

Itzkin, Adi; Van Dijk, Dina; Azar, Ofer H.

2016-01-01

Regret is an unpleasant feeling that may arise following decisions that ended poorly, and may affect the decision-maker's well-being and future decision making. Some studies show that a decision to act leads to greater regret than a decision not to act when both resulted in failure, because the latter is usually the norm. In some cases, when the norm is to act, this pattern is reversed. We suggest that the decision maker's regulatory focus, affects regret after action or inaction. Specifically, promotion-focused individuals, who tend to be more proactive, view action as more normal than prevention-focused individuals, and therefore experience regulatory fit when an action decision is made. Hence, we hypothesized that promotion-focused individuals will feel less regret than prevention-focused individuals when a decision to act ended poorly. In addition, we hypothesized that a trigger for change implied in the situation, decreases the level of regret following action. We tested our hypotheses on a sample of 330 participants enrolled in an online survey. The participants received six decision scenarios, in which they were asked to evaluate the level of regret following action and inaction. Individual regulatory focus was measured by two different scales. Promotion-focused individuals attributed less regret than prevention-focused individuals to action decisions. Regret following inaction was not affected by regulatory focus. In addition, a trigger for change decreases regret following action. Orthodox people tend to attribute more regret than non-orthodox to a person who made an action decision. The results contribute to the literature by showing that not only the situation but also the decision maker's orientation affects the regret after action vs. inaction. PMID:27833581

Stereotyped responses of Drosophila peptidergic neuronal ensemble depend on downstream neuromodulators

PubMed Central

Mena, Wilson; Diegelmann, Sören; Wegener, Christian; Ewer, John

2016-01-01

Neuropeptides play a key role in the regulation of behaviors and physiological responses including alertness, social recognition, and hunger, yet, their mechanism of action is poorly understood. Here, we focus on the endocrine control ecdysis behavior, which is used by arthropods to shed their cuticle at the end of every molt. Ecdysis is triggered by ETH (Ecdysis triggering hormone), and we show that the response of peptidergic neurons that produce CCAP (crustacean cardioactive peptide), which are key targets of ETH and control the onset of ecdysis behavior, depends fundamentally on the actions of neuropeptides produced by other direct targets of ETH and released in a broad paracrine manner within the CNS; by autocrine influences from the CCAP neurons themselves; and by inhibitory actions mediated by GABA. Our findings provide insights into how this critical insect behavior is controlled and general principles for understanding how neuropeptides organize neuronal activity and behaviors. DOI: http://dx.doi.org/10.7554/eLife.19686.001 PMID:27976997

Covering the optical spectrum through collective rare-earth doping of NaGdF4 nanoparticles: 806 and 980 nm excitation routes.

PubMed

Skripka, A; Marin, R; Benayas, A; Canton, P; Hemmer, E; Vetrone, F

2017-05-17

Today, at the frontier of biomedical research, the need has been clearly established for integrating disease detection and therapeutic function in one single theranostic system. Light-emitting nanoparticles are being intensively investigated to fulfil this demand, by continuously developing nanoparticle systems simultaneously emitting in both the UV/visible (light-triggered release and activation of drugs) and the near-infrared (imaging and tracking) spectral regions. In this work, rare-earth (RE) doped nanoparticles (RENPs) were synthesized via a thermal decomposition process and spectroscopically investigated as potential candidates as all-in-one optical imaging, diagnostic and therapeutic agents. These core/shell/shell nanoparticles (NaGdF 4 :Er 3+ ,Ho 3+ ,Yb 3+ /NaGdF 4 :Nd 3+ ,Yb 3+ /NaGdF 4 ) are optically excited by heating-free 806 nm light that, aside from minimizing the local thermal load, also allows to obtain a deeper sub-tissue penetration with respect to the still widely used 980 nm light. Moreover, these water-dispersed nanoplatforms offer interesting assets as triggers/probes for biomedical applications, by virtue of a plethora of emission bands (spanning the 380-1600 nm range). Our results pave the way to use these RENPs for UV/visible-triggered photodynamic therapy/drug release, while simultaneously tracking the nanoparticle biodistribution and monitoring their therapeutic action through the near-infrared signal that overlaps with biological transparency windows.

Autoimmunity and the Gut

PubMed Central

Campbell, Andrew W.

2014-01-01

Autoimmune diseases have increased dramatically worldwide since World War II. This is coincidental with the increased production and use of chemicals both in industrial countries and agriculture, as well as the ease of travel from region to region and continent to continent, making the transfer of a pathogen or pathogens from one part of the world to another much easier than ever before. In this review, triggers of autoimmunity are examined, principally environmental. The number of possible environmental triggers is vast and includes chemicals, bacteria, viruses, and molds. Examples of these triggers are given and include the mechanism of action and method by which they bring about autoimmunity. PMID:24900918

Dynamic and diverse sugar signaling

PubMed Central

Li, Lei; Sheen, Jen

2016-01-01

Sugars fuel life and exert numerous regulatory actions that are fundamental to all life forms. There are two principal mechanisms underlie sugar “perception and signal transduction” in biological systems. Direct sensing and signaling is triggered via sugar-binding sensors with a broad range of affinity and specificity, whereas sugar-derived bioenergetic molecules and metabolites modulate signaling proteins and indirectly relay sugar signals. This review discusses the emerging sugar signals and potential sugar sensors discovered in plant systems. The findings leading to informative understanding of physiological regulation by sugars are considered and assessed. Comparative transcriptome analyses highlight the primary and dynamic sugar responses and reveal the convergent and specific regulators of key biological processes in the sugar-signaling network. PMID:27423125

Networked event-triggered control: an introduction and research trends

NASA Astrophysics Data System (ADS)

Mahmoud, Magdi S.; Sabih, Muhammad

2014-11-01

A physical system can be studied as either continuous time or discrete-time system depending upon the control objectives. Discrete-time control systems can be further classified into two categories based on the sampling: (1) time-triggered control systems and (2) event-triggered control systems. Time-triggered systems sample states and calculate controls at every sampling instant in a periodic fashion, even in cases when states and calculated control do not change much. This indicates unnecessary and useless data transmission and computation efforts of a time-triggered system, thus inefficiency. For networked systems, the transmission of measurement and control signals, thus, cause unnecessary network traffic. Event-triggered systems, on the other hand, have potential to reduce the communication burden in addition to reducing the computation of control signals. This paper provides an up-to-date survey on the event-triggered methods for control systems and highlights the potential research directions.

Potentiation of kinin analogues by ramiprilat is exclusively related to their degradation.

PubMed

Dendorfer, A; Reibetamann, S; Wolfrum, S; Raasch, W; Dominiak, P

2001-07-01

The potentiation of kinin actions represents a cardioprotective property of ACE inhibitors. Although a clear contribution to this effect is related to the inhibition of bradykinin (BK) breakdown, the high efficacy of potentiation and the ability of ACE inhibitors to provoke a B(2)-receptor-mediated response even after receptor desensitization has also triggered hypotheses concerning additional mechanisms of kinin potentiation. The application of kinin analogues with enhanced metabolic stability for the demonstration of degradation-independent mechanisms of potentiation, however, has yielded inconsistent results. Therefore, the relation between the susceptibility of B(2)-agonists to ACE and the potentiation of their actions by ACE inhibitors was investigated with the use of minimally modified kinin derivatives that varied in their degree of ACE resistance. The B(2)-agonists BK, D-Arg-[Hyp(3)]-BK, [Hyp,(3) Tyr(Me)(8)]-BK, [DeltaPhe(5)]-BK, [D-NMF(7)]-BK, and [Phe(8)psi(CH(2)-NH)Arg(9)]-BK were tested for degradation by purified rabbit ACE and for their potency in contracting the endothelium-denuded rabbit jugular vein in the absence and presence of ramiprilat. Purified ACE degraded D-Arg-[Hyp(3)]-BK and [Hyp,(3) Tyr(Me)(8)]-BK at 81% and 71% of BK degradation activity, respectively, whereas other peptides were highly ([DeltaPhe(5)]-BK) or completely ([D-NMF(7)]-BK, [Phe(8)psi(CH(2)-NH)Arg(9)]-BK) resistant. The EC(50) of BK-induced venoconstriction (1.15+/-0.2 nmol/L) was reduced by a factor of 5.7 in the presence of ramiprilat. Likewise, D-Arg-[Hyp(3)]-BK and [Hyp,(3) Tyr(Me)(8)]-BK were both significantly potentiated by a factor of 4.4, whereas the activities of the other agonists were not affected. Ramiprilat exerted no influence on the maximum contraction induced by any of the agonists. It is concluded that the potentiation of kinin analogues during ACE inhibition correlates quantitatively with the susceptibility of each substance to degradation by ACE. As such, no evidence of degradation-independent potentiating actions of ACE inhibitors could be obtained.

Fatty acid synthase inhibition triggers apoptosis during S phase in human cancer cells.

PubMed

Zhou, Weibo; Simpson, P Jeanette; McFadden, Jill M; Townsend, Craig A; Medghalchi, Susan M; Vadlamudi, Aravinda; Pinn, Michael L; Ronnett, Gabriele V; Kuhajda, Francis P

2003-11-01

C75, an inhibitor of fatty acid synthase (FAS), induces apoptosis in cultured human cancer cells. Its proposed mechanism of action linked high levels of malonyl-CoA after FAS inhibition to potential downstream effects including inhibition of carnitine palmitoyltransferase-1 (CPT-1) with resultant inhibition of fatty acid oxidation. Recent data has shown that C75 directly stimulates CPT-1 increasing fatty acid oxidation in MCF-7 human breast cancer cells despite inhibitory concentrations of malonyl-CoA. In light of these findings, we have studied fatty acid metabolism in MCF7 human breast cancer cells to elucidate the mechanism of action of C75. We now report that: (a) in the setting of increased fatty acid oxidation, C75 inhibits fatty acid synthesis; (b) C273, a reduced form of C75, is unable to inhibit fatty acid synthesis and is nontoxic to MCF7 cells; (c) C75 and 5-(tetradecyloxy)-2-furoic acid (TOFA), an inhibitor of acetyl-CoA carboxylase, both cause a significant reduction of fatty acid incorporation into phosphatidylcholine, the major membrane phospholipid, within 2 h; (d) pulse chase studies with [(14)C]acetate labeling of membrane lipids show that both C75 and TOFA accelerate the decay of (14)C-labeled lipid from membranes within 2 h; (e) C75 also promotes a 2-3-fold increase in oxidation of membrane lipids within 2 h; and (f) because interference with phospholipid synthesis during S phase is known to trigger apoptosis in cycling cells, we performed double-labeled terminal deoxynucleotidyltransferase-mediated nick end labeling and BrdUrd analysis with both TOFA and C75. C75 triggered apoptosis during S phase, whereas TOFA did not. Moreover, application of TOFA 2 h before C75 blocked the C75 induced apoptosis, whereas etomoxir did not. Taken together these data indicate that FAS inhibition and its downstream inhibition of phospholipid production is a necessary part of the mechanism of action of C75. CPT-1 stimulation does not likely play a role in the cytotoxic response. The continued ability of TOFA to rescue cancer cells from C75 cytotoxicity implies a proapoptotic role for malonyl-CoA independent of CPT-1 that selectively targets cancer cells as they progress into S phase.

Gallium and its competing roles with iron in biological systems.

PubMed

Chitambar, Christopher R

2016-08-01

Gallium, a group IIIa metal, shares chemical properties with iron. Studies have shown that gallium-based compounds have potential therapeutic activity against certain cancers and infectious microorganisms. By functioning as an iron mimetic, gallium perturbs iron-dependent proliferation processes in tumor cells. Gallium's action on iron homeostasis leads to disruption of ribonucleotide reductase, mitochondrial function, and the regulation of transferrin receptor and ferritin. In addition, gallium nitrate stimulates an increase in mitochondrial reactive oxygen species in cells which triggers downstream upregulation of metallothionein and hemoxygenase-1. Gallium's anti-infective activity against bacteria and fungi results from disruption of microbial iron utilization through mechanisms which include gallium binding to siderophores and downregulation of bacterial iron uptake. Gallium compounds lack cross-resistance to conventional chemotherapeutic drugs and antibiotics thus making them attractive agents for drug development. This review will focus on the mechanisms of action of gallium with emphasis on its interaction with iron and iron proteins. Copyright © 2016 Elsevier B.V. All rights reserved.

Business Simulation Exercises in Small Business Management Education: Using Principles and Ideas from Action Learning

ERIC Educational Resources Information Center

Gabrielsson, Jonas; Tell, Joakim; Politis, Diamanto

2010-01-01

Recent calls to close the rigour-relevance gap in business school education have suggested incorporating principles and ideas from action learning in small business management education. In this paper we discuss how business simulation exercises can be used as a platform to trigger students' learning by providing them with a platform where they…

Willingness to Engage in Open Educational Practices among Academics in Rwandan Public Higher Education and Responsive Actions

ERIC Educational Resources Information Center

Nkuyubwatsi, Bernard

2017-01-01

Academics' engagement in Open Educational Practices (OEPs) is critical for opening up higher education. It is in this perspective that the willingness to engage in such practices among academics in Rwandan public higher education was investigated with an agenda to trigger responsive actions. Via convenience/availability and volunteer sampling, 170…

TRPV1: ON THE ROAD TO PAIN RELIEF

PubMed Central

Jara-Oseguera, Andrés; Simon, Sidney A.

2009-01-01

Historically, drug research targeted to pain treatment has focused on trying to prevent the propagation of action potentials in the periphery from reaching the brain rather than pinpointing the molecular basis underlying the initial detection of the nociceptive stimulus: the receptor itself. This has now changed, given that many receptors of nociceptive stimuli have been identified and/or cloned. Transient Receptor Potential (TRP) channels have been implicated in several physiological processes such as mechanical, chemical and thermal stimuli detection. Ten years after the cloning of TRPV1, compelling data has been gathered on the role of this channel in inflammatory and neuropathic states. TRPV1 activation in nociceptive neurons, where it is normally expressed, triggers the release of neuropeptides and transmitters resulting in the generation of action potentials that will be sent to higher CNS areas where they will often be perceived as pain. Its activation also will evoke the peripheral release of pro-inflammatory compounds that may sensitize other neurons to physical, thermal or chemical stimuli. For these reasons as well as because its continuous activation causes analgesia, TRPV1 has become a viable drug target for clinical use in the management of pain. This review will provide a general picture of the physiological and pathophysiological roles of the TRPV1 channel and of its structural, pharmacological and biophysical properties. Finally, it will provide the reader with an overall view of the status of the discovery of potential therapeutic agents for the management of chronic and neuropathic pain. PMID:20021438

SHOCK-EXCITED OSCILLATOR

DOEpatents

Creveling, R.

1957-12-17

S> A shock-excited quartz crystal oscillator is described. The circuit was specifically designed for application in micro-time measuring work to provide an oscillator which immediately goes into oscillation upon receipt of a trigger pulse and abruptly ceases oscillation when a second pulse is received. To achieve the instant action, the crystal has a prestressing voltage applied across it. A monostable multivibrator receives the on and off trigger pulses and discharges a pulse through the crystal to initiate or terminate oscillation instantly.

Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells.

PubMed

Mármol, Inés; Virumbrales-Muñoz, María; Quero, Javier; Sánchez-de-Diego, Cristina; Fernández, Luis; Ochoa, Ignacio; Cerrada, Elena; Yoldi, Mª Jesús Rodríguez

2017-11-01

Given the rise of apoptosis-resistant tumors, there exist a growing interest in developing new drugs capable of inducing different types of cell death to reduce colorectal cancer-related death rates. As apoptosis and necroptosis do not share cellular machinery, necroptosis induction may have a great therapeutic potential on those apoptosis-resistant cancers, despite the inflammatory effects associated with it. We have synthesized an alkynyl gold(I) complex [Au(CC-2-NC 5 H 4 )(PTA)] whose anticancer effect was tested on the colorectal adenocarcinoma Caco-2 cell line. With regard to its mechanism of action, this gold complex enters the mitochondria and disrupts its normal function, leading to an increase in ROS production, which triggers necroptosis. Necroptosis induction has been found dependent of TNF-α (Tumor necrosisfactor α) and TNFR1(Tumor necrosisfactor receptor 1) binding, RIP1(Receptor-Interacting Protein 1) activation and NF-κB (Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells) signaling. Moreover, the antitumor potential of [Au(CC-2-NC 5 H 4 )(PTA)] has also been confirmed on the 3D cancer model spheroid. Overall, the obtained data show firstly that gold complexes might have the ability of inducing necroptosis, and secondarily that our compound [Au(CC-2-NC 5 H 4 )(PTA)] is an interesting alternative to current chemotherapy drugs in cases of apoptosis resistance. Copyright © 2017. Published by Elsevier Inc.

Kicking the (barking) dog effect: the moderating role of target attributes on triggered displaced aggression.

PubMed

Pedersen, William C; Bushman, Brad J; Vasquez, Eduardo A; Miller, Norman

2008-10-01

Sometimes aggression is displaced onto a target who is not totally innocent but emits a mildly irritating behavior called a triggering event. In three experiments, the authors examine stable personal attributes of targets that can impact such triggered displaced aggression (TDA). Lower levels of TDA were directed to targets whose attitudes were similar as compared to dissimilar to those of the actor (Experiment 1) and to targets who were ingroup as compared to out-group members (Experiment 2). Conceptually replicating the findings of Experiments 1 and 2, the manipulated valence of the target (viz., liked, neutral, and disliked) functioned in a similar manner, with positive valence serving a buffering function against a triggering action that followed an initial provocation (Experiment 3). The results from all three experiments are consistent with cognitive neoassociationist theory.

Bio-effects of non-ionizing electromagnetic fields in context of cancer therapy.

PubMed

Saliev, Timur; Tachibana, Katsuro; Bulanin, Denis; Mikhalovsky, Sergey; Whitby, Ray D L

2014-01-01

Bio-effects mediated by non-ionizing electromagnetic fields (EMF) have become a hot topic of research in the last decades. This interest has been triggered by a growing public concern about the rapid expansion of telecommunication devices and possible consequences of their use on human health. Despite a feasibility study of potential negative impacts, the therapeutic advantages of EMF could be effectively harnessed for the treatment of cancer and other diseases. This review aims to examine recent findings relating to the mechanisms of action underlying the bio-effects induced by non-ionizing EMF. The potential of non-thermal and thermal effects is discussed in the context of possible applications for the induction of apoptosis, formation of reactive oxygen species, and increase of membrane permeability in malignant cells. A special emphasis has been put on the combination of EMF with magnetic nano-particles and ultrasound for cancer treatment. The review encompasses both human and animal studies.

A perspective on modern pesticides, pelagic fish declines, and unknown ecological resilience in highly managed ecosystems

USGS Publications Warehouse

Scholz, Nathaniel L.; Fleishman, Erica; Brown, Larry; Werner, Inge; Johnson, Michael L.; Brooks, Marjorie L.; Mitchelmore, Carys L.; Schlenk, Daniel

2012-01-01

Pesticides applied on land are commonly transported by runoff or spray drift to aquatic ecosystems, where they are potentially toxic to fishes and other nontarget organisms. Pesticides add to and interact with other stressors of ecosystem processes, including surface-water diversions, losses of spawning and rearing habitats, nonnative species, and harmful algal blooms. Assessing the cumulative effects of pesticides on species or ecological functions has been difficult for historical, legal, conceptual, and practical reasons. To explore these challenges, we examine current-use (modern) pesticides and their potential connections to the abundances of fishes in the San Francisco Estuary (California). Declines in delta smelt (Hypomesus transpacificus), Chinook salmon (Oncorhynchus tshawytscha), and other species have triggered mandatory and expensive management actions in the urbanizing estuary and agriculturally productive Central Valley. Our inferences are transferable to other situations in which toxics may drive changes in ecological status and trends.

Vesicular glutamate release from central axons contributes to myelin damage.

PubMed

Doyle, Sean; Hansen, Daniel Bloch; Vella, Jasmine; Bond, Peter; Harper, Glenn; Zammit, Christian; Valentino, Mario; Fern, Robert

2018-03-12

The axon myelin sheath is prone to injury associated with N-methyl-D-aspartate (NMDA)-type glutamate receptor activation but the source of glutamate in this context is unknown. Myelin damage results in permanent action potential loss and severe functional deficit in the white matter of the CNS, for example in ischemic stroke. Here, we show that in rats and mice, ischemic conditions trigger activation of myelinic NMDA receptors incorporating GluN2C/D subunits following release of axonal vesicular glutamate into the peri-axonal space under the myelin sheath. Glial sources of glutamate such as reverse transport did not contribute significantly to this phenomenon. We demonstrate selective myelin uptake and retention of a GluN2C/D NMDA receptor negative allosteric modulator that shields myelin from ischemic injury. The findings potentially support a rational approach toward a low-impact prophylactic therapy to protect patients at risk of stroke and other forms of excitotoxic injury.

Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: potential therapeutic relevance.

PubMed

Martirosyan, Anna; Clendening, James W; Goard, Carolyn A; Penn, Linda Z

2010-03-18

Ovarian carcinoma is a rarely curable disease, for which new treatment options are required. As agents that block HMG-CoA reductase and the mevalonate pathway, the statin family of drugs are used in the treatment of hypercholesterolemia and have been shown to trigger apoptosis in a tumor-specific manner. Recent clinical trials show that the addition of statins to traditional chemotherapeutic strategies can increase efficacy of targeting statin-sensitive tumors. Our goal was to assess statin-induced apoptosis of ovarian cancer cells, either alone or in combination with chemotherapeutics, and then determine these mechanisms of action. The effect of lovastatin on ovarian cancer cell lines was evaluated alone and in combination with cisplatin and doxorubicin using several assays (MTT, TUNEL, fixed PI, PARP cleavage) and synergy determined by evaluating the combination index. The mechanisms of action were evaluated using functional, molecular, and pharmacologic approaches. We demonstrate that lovastatin induces apoptosis of ovarian cancer cells in a p53-independent manner and synergizes with doxorubicin, a chemotherapeutic agent used to treat recurrent cases of ovarian cancer. Lovastatin drives ovarian tumor cell death by two mechanisms: first, by blocking HMG-CoA reductase activity, and second, by sensitizing multi-drug resistant cells to doxorubicin by a novel mevalonate-independent mechanism. This inhibition of drug transport, likely through inhibition of P-glycoprotein, potentiates both DNA damage and tumor cell apoptosis. The results of this research provide pre-clinical data to warrant further evaluation of statins as potential anti-cancer agents to treat ovarian carcinoma. Many statins are inexpensive, off-patent generic drugs that are immediately available for use as anti-cancer agents. We provide evidence that lovastatin triggers apoptosis of ovarian cancer cells as a single agent by a mevalonate-dependent mechanism. Moreover, we also show lovastatin synergizes with doxorubicin, an agent administered for recurrent disease. This synergy occurs by a novel mevalonate-independent mechanism that antagonizes drug resistance, likely by inhibiting P-glycoprotein. These data raise important issues that may impact how statins can best be included in chemotherapy regimens.

Responses of Withdrawal Interneurons to Serotonin Applications in Naïve and Learned Snails Are Different

PubMed Central

Bogodvid, Tatiana K.; Andrianov, Vyatcheslav V.; Deryabina, Irina B.; Muranova, Lyudmila N.; Silantyeva, Dinara I.; Vinarskaya, Aliya; Balaban, Pavel M.; Gainutdinov, Khalil L.

2017-01-01

Long-term changes in membrane potential after associative training were described previously in identified premotor interneurons for withdrawal of the terrestrial snail Helix. Serotonin was shown to be a major transmitter involved in triggering the long-term changes in mollusks. In the present study we compared the changes in electrophysiological characteristics of identifiable premotor interneurons for withdrawal in response to bath applications of serotonin (5-HT) or serotonin precursor 5-hydroxytryptophan (5-HTP) in preparations from naïve, neurotoxin-injected or associatively trained snails. It was found that 5-HT or 5-HTP applications caused a significant decrease of membrane potential in premotor interneurons of naïve snails, associatively trained snails and snails with impaired serotonergic system by injection of a selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) 1 week before the experiments. Applications of 5-HT or 5-HTP did not cause significant changes in the action potential (AP) threshold potential of these neurons in naïve snails. Conversely, applications of 5-HT or 5-HTP to the premotor interneurons of previously trained or 5,7-DHT-injected snails caused a significant increase in the firing threshold potential in spite of a depolarizing shift of the resting membrane potential. Results demonstrate that responsiveness of premotor interneurons to extracellularly applied 5-HT or 5-HTP changes for days after the associative training or serotonin depletion. Similarity of the effects in trained and 5,7-DHT-injected animals may be due to massive release of serotonin elicited by 5,7-DHT injection. Our results suggest that serotonin release due to aversive conditionining or elicited by the neurotoxin administration triggers similar changes in resting membrane potential and AP threshold in response to bath applications of 5-HT or its precursor 5-HTP. PMID:29311833

Sterile Inflammation of Brain, due to Activation of Innate Immunity, as a Culprit in Psychiatric Disorders

PubMed Central

Ratajczak, Mariusz Z.; Pedziwiatr, Daniel; Cymer, Monika; Kucia, Magda; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy

2018-01-01

Evidence has accumulated that the occurrence of psychiatric disorders is related to chronic inflammation. In support of this linkage, changes in the levels of circulating pro-inflammatory cytokines and chemokines in the peripheral blood (PB) of psychiatric patients as well as correlations between chronic inflammatory processes and psychiatric disorders have been described. Furthermore, an inflammatory process known as “sterile inflammation” when initiated directly in brain tissue may trigger the onset of psychoses. In this review, we will present the hypothesis that prolonged or chronic activation of the complement cascade (ComC) directly triggers inflammation in the brain and affects the proper function of this organ. Based on the current literature and our own work on mechanisms activating the ComC we hypothesize that inflammation in the brain is initiated by the mannan-binding lectin pathway of ComC activation. This activation is triggered by an increase in brain tissue of danger-associated molecular pattern (DAMP) mediators, including extracellular ATP and high-mobility group box 1 (HMGB1) protein, which are recognized by circulating pattern-recognition receptors, including mannan-binding lectin (MBL), that activate the ComC. On the other hand, this process is controlled by the anti-inflammatory action of heme oxygenase 1 (HO-1). In this review, we will try to connect changes in the release of DAMPs in the brain with inflammatory processes triggered by the innate immunity involving activation of the ComC as well as the inflammation-limiting effects of the anti-inflammatory HO-1 pathway. We will also discuss parallel observations that during ComC activation subsets of stem cells are mobilized into PB from bone marrow that are potentially involved in repair mechanisms. PMID:29541038

Sterile Inflammation of Brain, due to Activation of Innate Immunity, as a Culprit in Psychiatric Disorders.

PubMed

Ratajczak, Mariusz Z; Pedziwiatr, Daniel; Cymer, Monika; Kucia, Magda; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy

2018-01-01

Evidence has accumulated that the occurrence of psychiatric disorders is related to chronic inflammation. In support of this linkage, changes in the levels of circulating pro-inflammatory cytokines and chemokines in the peripheral blood (PB) of psychiatric patients as well as correlations between chronic inflammatory processes and psychiatric disorders have been described. Furthermore, an inflammatory process known as "sterile inflammation" when initiated directly in brain tissue may trigger the onset of psychoses. In this review, we will present the hypothesis that prolonged or chronic activation of the complement cascade (ComC) directly triggers inflammation in the brain and affects the proper function of this organ. Based on the current literature and our own work on mechanisms activating the ComC we hypothesize that inflammation in the brain is initiated by the mannan-binding lectin pathway of ComC activation. This activation is triggered by an increase in brain tissue of danger-associated molecular pattern (DAMP) mediators, including extracellular ATP and high-mobility group box 1 (HMGB1) protein, which are recognized by circulating pattern-recognition receptors, including mannan-binding lectin (MBL), that activate the ComC. On the other hand, this process is controlled by the anti-inflammatory action of heme oxygenase 1 (HO-1). In this review, we will try to connect changes in the release of DAMPs in the brain with inflammatory processes triggered by the innate immunity involving activation of the ComC as well as the inflammation-limiting effects of the anti-inflammatory HO-1 pathway. We will also discuss parallel observations that during ComC activation subsets of stem cells are mobilized into PB from bone marrow that are potentially involved in repair mechanisms.

Triggering Mechanism for Neutron Induced Single-Event Burnout in Power Devices

NASA Astrophysics Data System (ADS)

Shoji, Tomoyuki; Nishida, Shuichi; Hamada, Kimimori

2013-04-01

Cosmic ray neutrons can trigger catastrophic failures in power devices. It has been reported that parasitic transistor action causes single-event burnout (SEB) in power metal-oxide-semiconductor field-effect transistors (MOSFETs) and insulated gate bipolar transistors (IGBTs). However, power diodes do not have an inherent parasitic transistor. In this paper, we describe the mechanism triggering SEB in power diodes for the first time using transient device simulation. Initially, generated electron-hole pairs created by incident recoil ions generate transient current, which increases the electron density in the vicinity of the n-/n+ boundary. The space charge effect of the carriers leads to an increase in the strength of the electric field at the n-/n+ boundary. Finally, the onset of impact ionization at the n-/n+ boundary can trigger SEB. Furthermore, this failure is closely related to diode secondary breakdown. It was clarified that the impact ionization at the n-/n+ boundary is a key point of the mechanism triggering SEB in power devices.

National Environmental Leadership Award in Asthma Management

EPA Pesticide Factsheets

The National Asthma Awards recognizes health plans, healthcare providers and communities in action that demonstrate an environmental component to address asthma triggers, collaborate with others and save healthcare dollars with their programming.

Asthma Home Environment Checklist

EPA Pesticide Factsheets

This checklist guides home care visitors in identifying environmental asthma triggers most commonly found in homes. It includes sections on the building, home interior and room interior and provides low-cost action steps for remediation.

Handgun Trigger Safety Act of 2014

THOMAS, 113th Congress

Sen. Markey, Edward J. [D-MA

2014-02-27

Senate - 02/27/2014 Read twice and referred to the Committee on Commerce, Science, and Transportation. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Thyroid hormone activation of retinoic acid synthesis in hypothalamic tanycytes.

PubMed

Stoney, Patrick N; Helfer, Gisela; Rodrigues, Diana; Morgan, Peter J; McCaffery, Peter

2016-03-01

Thyroid hormone (TH) is essential for adult brain function and its actions include several key roles in the hypothalamus. Although TH controls gene expression via specific TH receptors of the nuclear receptor class, surprisingly few genes have been demonstrated to be directly regulated by TH in the hypothalamus, or the adult brain as a whole. This study explored the rapid induction by TH of retinaldehyde dehydrogenase 1 (Raldh1), encoding a retinoic acid (RA)-synthesizing enzyme, as a gene specifically expressed in hypothalamic tanycytes, cells that mediate a number of actions of TH in the hypothalamus. The resulting increase in RA may then regulate gene expression via the RA receptors, also of the nuclear receptor class. In vivo exposure of the rat to TH led to a significant and rapid increase in hypothalamic Raldh1 within 4 hours. That this may lead to an in vivo increase in RA is suggested by the later induction by TH of the RA-responsive gene Cyp26b1. To explore the actions of RA in the hypothalamus as a potential mediator of TH control of gene regulation, an ex vivo hypothalamic rat slice culture method was developed in which the Raldh1-expressing tanycytes were maintained. These slice cultures confirmed that TH did not act on genes regulating energy balance but could induce Raldh1. RA has the potential to upregulate expression of genes involved in growth and appetite, Ghrh and Agrp. This regulation is acutely sensitive to epigenetic changes, as has been shown for TH action in vivo. These results indicate that sequential triggering of two nuclear receptor signalling systems has the capability to mediate some of the functions of TH in the hypothalamus. © 2015 Wiley Periodicals, Inc.

Novel inhibitors of the Pseudomonas aeruginosa virulence factor LasB: a potential therapeutic approach for the attenuation of virulence mechanisms in pseudomonal infection.

PubMed

Cathcart, George R A; Quinn, Derek; Greer, Brett; Harriott, Pat; Lynas, John F; Gilmore, Brendan F; Walker, Brian

2011-06-01

Pseudomonas elastase (LasB), a metalloprotease virulence factor, is known to play a pivotal role in pseudomonal infection. LasB is secreted at the site of infection, where it exerts a proteolytic action that spans from broad tissue destruction to subtle action on components of the host immune system. The former enhances invasiveness by liberating nutrients for continued growth, while the latter exerts an immunomodulatory effect, manipulating the normal immune response. In addition to the extracellular effects of secreted LasB, it also acts within the bacterial cell to trigger the intracellular pathway that initiates growth as a bacterial biofilm. The key role of LasB in pseudomonal virulence makes it a potential target for the development of an inhibitor as an antimicrobial agent. The concept of inhibition of virulence is a recently established antimicrobial strategy, and such agents have been termed "second-generation" antibiotics. This approach holds promise in that it seeks to attenuate virulence processes without bactericidal action and, hence, without selection pressure for the emergence of resistant strains. A potent inhibitor of LasB, N-mercaptoacetyl-Phe-Tyr-amide (K(i) = 41 nM) has been developed, and its ability to block these virulence processes has been assessed. It has been demonstrated that thes compound can completely block the action of LasB on protein targets that are instrumental in biofilm formation and immunomodulation. The novel LasB inhibitor has also been employed in bacterial-cell-based assays, to reduce the growth of pseudomonal biofilms, and to eradicate biofilm completely when used in combination with conventional antibiotics.

Serotonin increases synaptic activity in olfactory bulb glomeruli

PubMed Central

Brill, Julia; Shao, Zuoyi; Puche, Adam C.; Wachowiak, Matt

2016-01-01

Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range. PMID:26655822

Serotonin increases synaptic activity in olfactory bulb glomeruli.

PubMed

Brill, Julia; Shao, Zuoyi; Puche, Adam C; Wachowiak, Matt; Shipley, Michael T

2016-03-01

Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range. Copyright © 2016 the American Physiological Society.

Effect of acute stretch injury on action potential and network activity of rat neocortical neurons in culture.

PubMed

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

2015-10-22

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

Functional role of ambient GABA in refining neuronal circuits early in postnatal development

PubMed Central

Cellot, Giada; Cherubini, Enrico

2013-01-01

Early in development, γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the mature brain, depolarizes and excites targeted neurons by an outwardly directed flux of chloride, resulting from the peculiar balance between the cation-chloride importer NKCC1 and the extruder KCC2. The low expression of KCC2 at birth leads to accumulation of chloride inside the cell and to the equilibrium potential for chloride positive respect to the resting membrane potential. GABA exerts its action via synaptic and extrasynaptic GABAA receptors mediating phasic and tonic inhibition, respectively. Here, recent data on the contribution of “ambient” GABA to the refinement of neuronal circuits in the immature brain have been reviewed. In particular, we focus on the hippocampus, where, prior to the formation of conventional synapses, GABA released from growth cones and astrocytes in a calcium- and SNARE (soluble N-ethylmaleimide-sensitive-factor attachment protein receptor)-independent way, diffuses away to activate in a paracrine fashion extrasynaptic receptors localized on distal neurons. The transient increase in intracellular calcium following the depolarizing action of GABA leads to inhibition of DNA synthesis and cell proliferation. Tonic GABA exerts also a chemotropic action on cell migration. Later on, when synapses are formed, GABA spilled out from neighboring synapses, acting mainly on extrasynaptic α5, β2, β3, and γ containing GABAA receptor subunits, provides the membrane depolarization necessary for principal cells to reach the window where intrinsic bursts are generated. These are instrumental in triggering calcium transients associated with network-driven giant depolarizing potentials which act as coincident detector signals to enhance synaptic efficacy at emerging GABAergic and glutamatergic synapses. PMID:23964205

76 FR 9987 - Protection of Stratospheric Ozone: Amendments to the Section 608 Leak Repair Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-23

... trigger rates for comfort cooling, commercial refrigeration, and industrial process refrigeration and air..., commercial refrigeration, and industrial process refrigeration appliances. This action also proposes to...

Influence of verbal instructions on effect-based action control.

PubMed

Eder, Andreas B; Dignath, David

2017-03-01

According to ideomotor theory, people use bidirectional associations between movements and their effects for action selection and initiation. Our experiments examined how verbal instructions of action effects influence response selection without prior experience of action effects in a separate acquisition phase. Instructions for different groups of participants specified whether they should ignore, attend, learn, or intentionally produce acoustic effects produced by button presses. Results showed that explicit instructions of action-effect relations trigger effect-congruent action tendencies in the first trials following the instruction; in contrast, no evidence for effect-based action control was observed in these trials when instructions were to ignore or to attend to the action effects. These findings show that action-effect knowledge acquired through verbal instruction and direct experience is similarly effective for effect-based action control as long as the relation between the movement and the effect is clearly spelled out in the instruction.

Reflective Practice in the Clinical Setting: A Multi-Institutional Qualitative Study of Pediatric Faculty and Residents.

PubMed

Plant, Jennifer; Li, Su-Ting T; Blankenburg, Rebecca; Bogetz, Alyssa L; Long, Michele; Butani, Lavjay

2017-11-01

To explore when and in what form pediatric faculty and residents practice reflection. From February to June 2015, the authors conducted focus groups of pediatric faculty and residents at the University of California, Davis; Stanford University; and the University of California, San Francisco, until thematic saturation occurred. Transcripts were analyzed based on Mezirow's and Schon's models of reflection, using the constant comparative method associated with grounded theory. Two investigators independently coded transcripts and reconciled codes to develop themes. All investigators reviewed the codes and developed a final list of themes through consensus. Through iterative discussions, investigators developed a conceptual model of reflection in the clinical setting. Seventeen faculty and 20 residents from three institutions participated in six focus groups. Five themes emerged: triggers of reflection, intrinsic factors, extrinsic factors, timing, and outcome of reflection. Various triggers led to reflection; whether a specific trigger led to reflection depended on intrinsic and extrinsic factors. When reflection occurred, it happened in action or on action. Under optimal conditions, this reflection was goal and action directed and became critical reflection. In other instances, this process resulted in unproductive rumination or acted as an emotional release or supportive therapy. Participants reflected in clinical settings, but did not always explicitly identify it as reflection or reflect in growth-promoting ways. Strategies to enhance critical reflection include developing knowledge and skills in reflection, providing performance data to inform reflection, creating time and space for safe reflection, and providing mentorship to guide the process.

Cardiovascular effects of air pollution.

PubMed

Brook, Robert D

2008-09-01

Air pollution is a heterogeneous mixture of gases, liquids and PM (particulate matter). In the modern urban world, PM is principally derived from fossil fuel combustion with individual constituents varying in size from a few nanometres to 10 microm in diameter. In addition to the ambient concentration, the pollution source and chemical composition may play roles in determining the biological toxicity and subsequent health effects. Nevertheless, studies from across the world have consistently shown that both short- and long-term exposures to PM are associated with a host of cardiovascular diseases, including myocardial ischaemia and infarctions, heart failure, arrhythmias, strokes and increased cardiovascular mortality. Evidence from cellular/toxicological experiments, controlled animal and human exposures and human panel studies have demonstrated several mechanisms by which particle exposure may both trigger acute events as well as prompt the chronic development of cardiovascular diseases. PM inhaled into the pulmonary tree may instigate remote cardiovascular health effects via three general pathways: instigation of systemic inflammation and/or oxidative stress, alterations in autonomic balance, and potentially by direct actions upon the vasculature of particle constituents capable of reaching the systemic circulation. In turn, these responses have been shown to trigger acute arterial vasoconstriction, endothelial dysfunction, arrhythmias and pro-coagulant/thrombotic actions. Finally, long-term exposure has been shown to enhance the chronic genesis of atherosclerosis. Although the risk to one individual at any single time point is small, given the prodigious number of people continuously exposed, PM air pollution imparts a tremendous burden to the global public health, ranking it as the 13th leading cause of morality (approx. 800,000 annual deaths).

Towards improved migraine management: Determining potential trigger factors in individual patients.

PubMed

Peris, Francesc; Donoghue, Stephen; Torres, Ferran; Mian, Alec; Wöber, Christian

2017-04-01

Background Certain chronic diseases such as migraine result in episodic, debilitating attacks for which neither cause nor timing is well understood. Historically, possible triggers were identified through analysis of aggregated data from populations of patients. However, triggers common in populations may not be wholly responsible for an individual's attacks. To explore this hypothesis we developed a method to identify individual 'potential trigger' profiles and analysed the degree of inter-individual variation. Methods We applied N = 1 statistical analysis to a 326-migraine-patient database from a study in which patients used paper-based diaries for 90 days to track 33 factors (potential triggers or premonitory symptoms) associated with their migraine attacks. For each patient, univariate associations between factors and migraine events were analysed using Cox proportional hazards models. Results We generated individual factor-attack association profiles for 87% of the patients. The average number of factors associated with attacks was four per patient: Factor profiles were highly individual and were unique in 85% of patients with at least one identified association. Conclusion Accurate identification of individual factor-attack profiles is a prerequisite for testing which are true triggers and for development of trigger avoidance or desensitisation strategies. Our methodology represents a necessary development toward this goal.

A public health approach to eating disorders prevention: it's time for public health professionals to take a seat at the table.

PubMed

Austin, S Bryn

2012-10-09

The societal burden of eating disorders is clear, and though there is a compelling need for a public health approach to eating disorders prevention, public health professionals have yet to take up the challenge. The article lays out an argument for what steps need to be taken to bring a public health approach to eating disorders prevention. First, stock is taken of what the field has achieved so far, using tools from the prevention science literature, and, second, a research plan of action is offered that plays to the unique strengths of public health, drawing on a triggers-to-action framework from public health law. Minimal participation was found from public health professionals in eating disorders prevention research, and the vast majority of prevention research to date was found to be concentrated within the disciplines of psychology and psychiatry. Extreme disciplinary concentration of the research has led to a preponderance of individually targeted prevention strategies with little research focused on environmental targets, particularly at the macro level. New environmental initiatives are now emerging, such as a government-sponsored mass media anti-dieting campaign, and legal bans on extremely thin models in advertising, but for the most part, they have yet to be evaluated. A triggers-to-action framework, which focuses on evidentiary base, practical considerations, and political will, developed in public health law provides a basis for a strategic research plan for a public health approach to eating disorders prevention. There is enormous potential for growth in the scope and diversity of eating disorder prevention research strategies, particularly those targeting the macro environment. A public health approach will require a strategic plan for research that leverages the macro environment for prevention. The full engagement of public health professionals will bring to the field the much broader range of preventive strategies and perspectives needed to tackle the problem of eating disorders.

A public health approach to eating disorders prevention: It’s time for public health professionals to take a seat at the table

PubMed Central

2012-01-01

Background The societal burden of eating disorders is clear, and though there is a compelling need for a public health approach to eating disorders prevention, public health professionals have yet to take up the challenge. Discussion The article lays out an argument for what steps need to be taken to bring a public health approach to eating disorders prevention. First, stock is taken of what the field has achieved so far, using tools from the prevention science literature, and, second, a research plan of action is offered that plays to the unique strengths of public health, drawing on a triggers-to-action framework from public health law. Minimal participation was found from public health professionals in eating disorders prevention research, and the vast majority of prevention research to date was found to be concentrated within the disciplines of psychology and psychiatry. Extreme disciplinary concentration of the research has led to a preponderance of individually targeted prevention strategies with little research focused on environmental targets, particularly at the macro level. New environmental initiatives are now emerging, such as a government-sponsored mass media anti-dieting campaign, and legal bans on extremely thin models in advertising, but for the most part, they have yet to be evaluated. A triggers-to-action framework, which focuses on evidentiary base, practical considerations, and political will, developed in public health law provides a basis for a strategic research plan for a public health approach to eating disorders prevention. Summary There is enormous potential for growth in the scope and diversity of eating disorder prevention research strategies, particularly those targeting the macro environment. A public health approach will require a strategic plan for research that leverages the macro environment for prevention. The full engagement of public health professionals will bring to the field the much broader range of preventive strategies and perspectives needed to tackle the problem of eating disorders. PMID:23043459

Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell-matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis.

PubMed

Chen, Yan; Li, Zheng; He, Yan; Shang, Dandan; Pan, Jigang; Wang, Hongmei; Chen, Huamei; Zhu, Zhuxia; Wan, Lei; Wang, Xudong

2014-03-01

Fulvestrant (ICI 182 780, ICI) has been used in treating patients with hormone-sensitive breast cancer, yet initial or acquired resistance to endocrine therapies frequently arises and, in particular, cancer recurs as metastasis. We demonstrate here that both 17-beta-estradiol (E2) and ICI enhance cell adhesion to matrigel in MCF-7 breast cancer cells, with increased autolysis of calpain 1 (large subunit) and proteolysis of focal adhesion kinase (FAK), indicating calpain activation. Additionally, either E2 or ICI induced down-regulation of estrogen receptor α without affecting G protein coupled estrogen receptor 30 (GPR30) expression. Interestingly, GPR30 agonist G1 triggered calpain 1 autolysis but not calpain 2, whereas ER agonist diethylstilbestrol caused no apparent calpain autolysis. Furthermore, the actions of E2 and ICI on calpain and cell adhesion were tremendously suppressed by G15, or knockdown of GPR30. E2 and ICI also induced phosphorylation of extracellular regulated protein kinases 1 and 2 (ERK1/2), and suppression of ERK1/2 phosphorylation by U0126 profoundly impeded calpain activation triggered by estrogenic and antiestrogenic stimulations indicating implication of ERK1/2 in the GPR30-mediated action. Lastly, the E2- or ICI-induced cell adhesion was dramatically impaired by calpain-specific inhibitors, ALLN or calpeptin, suggesting requirement of calpain in the GPR30-associated action. These data show that enhanced cell adhesion by E2 and ICI occurs via a novel GPR30-ERK1/2-calpain pathway. Our results indicate that targeting the GPR30 signaling may be a potential strategy to reduce metastasis and improve the efficacy of antiestrogens in treatment of advanced breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise

PubMed Central

2015-01-01

Enhanced skeletal muscle and whole body insulin sensitivity can persist for up to 24–48 h after one exercise session. This review focuses on potential mechanisms for greater postexercise and insulin-stimulated glucose uptake (ISGU) by muscle in individuals with normal or reduced insulin sensitivity. A model is proposed for the processes underlying this improvement; i.e., triggers initiate events that activate subsequent memory elements, which store information that is relayed to mediators, which translate memory into action by controlling an end effector that directly executes increased insulin-stimulated glucose transport. Several candidates are potential triggers or memory elements, but none have been conclusively verified. Regarding potential mediators in both normal and insulin-resistant individuals, elevated postexercise ISGU with a physiological insulin dose coincides with greater Akt substrate of 160 kDa (AS160) phosphorylation without improved proximal insulin signaling at steps from insulin receptor binding to Akt activity. Causality remains to be established between greater AS160 phosphorylation and improved ISGU. The end effector for normal individuals is increased GLUT4 translocation, but this remains untested for insulin-resistant individuals postexercise. Following exercise, insulin-resistant individuals can attain ISGU values similar to nonexercising healthy controls, but after a comparable exercise protocol performed by both groups, ISGU for the insulin-resistant group has been consistently reported to be below postexercise values for the healthy group. Further research is required to fully understand the mechanisms underlying the improved postexercise ISGU in individuals with normal or subnormal insulin sensitivity and to explain the disparity between these groups after similar exercise. PMID:26487009

Temporally Shaped Current Pulses on a Two-Cavity Linear Transformer Driver System

DTIC Science & Technology

2011-06-01

essentially at a fraction of the total switch voltage. Non-uniform corona current characteristics of the different corona needles could cause imperfect...withstand twice the capacitor voltage. A pulse applied to the switch trigger electrodes initiate closure of each switch. We have arranged triggering in...internal cavity potential to ground, allows the trigger electrode of the spark gaps to be at ground potential during charging, and eliminates a

Relationship between auditory thresholds, central spontaneous activity and hair cell loss after acoustic trauma

PubMed Central

Mulders, W.H.A.M.; Ding, D.; Salvi, R.; Robertson, D.

2011-01-01

Acoustic trauma caused by exposure to a very loud sound increases spontaneous activity in central auditory structures such as the inferior colliculus. This hyperactivity has been suggested as a neural substrate for tinnitus, a phantom hearing sensation. In previous studies we have described a tentative link between the frequency region of hearing impairment and the corresponding tonotopic regions in the inferior colliculus showing hyperactivity. In this study we further investigated the relationship between cochlear compound action potential threshold loss, cochlear outer and inner hair cell loss and central hyperactivity in inferior colliculus of guinea pigs. Two weeks after a 10 kHz pure tone acoustic trauma, a tight relationship was demonstrated between the frequency region of compound action potential threshold loss and frequency regions in the inferior colliculus showing hyperactivity. Extending the duration of the acoustic trauma from 1 to 2 h did not result in significant increases in final cochlear threshold loss, but did result in a further increase of spontaneous firing rates in the inferior colliculus. Interestingly, hair cell loss was not present in the frequency regions where elevated cochlear thresholds and central hyperactivity were measured, suggesting that subtle changes in hair cell or primary afferent neural function are sufficient for central hyperactivity to be triggered and maintained. PMID:21491427

Simulation of Ectopic Pacemakers in the Heart: Multiple Ectopic Beats Generated by Reentry inside Fibrotic Regions

PubMed Central

Gouvêa de Barros, Bruno; Weber dos Santos, Rodrigo; Alonso, Sergio

2015-01-01

The inclusion of nonconducting media, mimicking cardiac fibrosis, in two models of cardiac tissue produces the formation of ectopic beats. The fraction of nonconducting media in comparison with the fraction of healthy myocytes and the topological distribution of cells determines the probability of ectopic beat generation. First, a detailed subcellular microscopic model that accounts for the microstructure of the cardiac tissue is constructed and employed for the numerical simulation of action potential propagation. Next, an equivalent discrete model is implemented, which permits a faster integration of the equations. This discrete model is a simplified version of the microscopic model that maintains the distribution of connections between cells. Both models produce similar results when describing action potential propagation in homogeneous tissue; however, they slightly differ in the generation of ectopic beats in heterogeneous tissue. Nevertheless, both models present the generation of reentry inside fibrotic tissues. This kind of reentry restricted to microfibrosis regions can result in the formation of ectopic pacemakers, that is, regions that will generate a series of ectopic stimulus at a fast pacing rate. In turn, such activity has been related to trigger fibrillation in the atria and in the ventricles in clinical and animal studies. PMID:26583127

Tympanal mechanics and neural responses in the ears of a noctuid moth

NASA Astrophysics Data System (ADS)

Ter Hofstede, Hannah M.; Goerlitz, Holger R.; Montealegre-Z, Fernando; Robert, Daniel; Holderied, Marc W.

2011-12-01

Ears evolved in many groups of moths to detect the echolocation calls of predatory bats. Although the neurophysiology of bat detection has been intensively studied in moths for decades, the relationship between sound-induced movement of the noctuid tympanic membrane and action potentials in the auditory sensory cells (A1 and A2) has received little attention. Using laser Doppler vibrometry, we measured the velocity and displacement of the tympanum in response to pure tone pulses for moths that were intact or prepared for neural recording. When recording from the auditory nerve, the displacement of the tympanum at the neural threshold remained constant across frequencies, whereas velocity varied with frequency. This suggests that the key biophysical parameter for triggering action potentials in the sensory cells of noctuid moths is tympanum displacement, not velocity. The validity of studies on the neurophysiology of moth hearing rests on the assumption that the dissection and recording procedures do not affect the biomechanics of the ear. There were no consistent differences in tympanal velocity or displacement when moths were intact or prepared for neural recordings for sound levels close to neural threshold, indicating that this and other neurophysiological studies provide good estimates of what intact moths hear at threshold.

Estrogen's Place in the Family of Synaptic Modulators.

PubMed

Kramár, Enikö A; Chen, Lulu Y; Rex, Christopher S; Gall, Christine M; Lynch, Gary

2009-01-01

Estrogen, in addition to its genomic effects, triggers rapid synaptic changes in hippocampus and cortex. Here we summarize evidence that the acute actions of the steroid arise from actin signaling cascades centrally involved in long-term potentiation (LTP). A 10-min infusion of E2 reversibly increased fast EPSPs and promoted theta burst-induced LTP within adult hippocampal slices. The latter effect reflected a lowered threshold and an elevated ceiling for the potentiation effect. E2's actions on transmission and plasticity were completely blocked by latrunculin, a toxin that prevents actin polymerization. E2 also caused a reversible increase in spine concentrations of filamentous (F-) actin and markedly enhanced polymerization caused by theta burst stimulation (TBS). Estrogen activated the small GTPase RhoA, but not the related GTPase Rac, and phosphorylated (inactivated) synaptic cofilin, an actin severing protein targeted by RhoA. An inhibitor of RhoA kinase (ROCK) thoroughly suppressed the synaptic effects of E2. Collectively, these results indicate that E2 engages a RhoA >ROCK> cofilin> actin pathway also used by brain-derived neurotrophic factor and adenosine, and therefore belongs to a family of 'synaptic modulators' that regulate plasticity. Finally, we describe evidence that the acute signaling cascade is critical to the depression of LTP produced by ovariectomy.

Adhesion to Carbon Nanotube Conductive Scaffolds Forces Action-Potential Appearance in Immature Rat Spinal Neurons

PubMed Central

Toma, Francesca Maria; Calura, Enrica; Rizzetto, Lisa; Carrieri, Claudia; Roncaglia, Paola; Martinelli, Valentina; Scaini, Denis; Masten, Lara; Turco, Antonio; Gustincich, Stefano; Prato, Maurizio; Ballerini, Laura

2013-01-01

In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies. PMID:23951361

Spontaneous activity of isolated dopaminergic periglomerular cells of the main olfactory bulb.

PubMed

Puopolo, Michelino; Bean, Bruce P; Raviola, Elio

2005-11-01

We examined the electrophysiological properties of a population of identified dopaminergic periglomerular cells of the main olfactory bulb using transgenic mice in which catecholaminergic neurons expressed human placental alkaline phosphatase (PLAP) on the outer surface of the plasma membrane. After acute dissociation, living dopaminergic periglomerular cells were identified by a fluorescently labeled monoclonal antibody to PLAP. In current-clamp mode, dopaminergic periglomerular cells spontaneously generated action potentials in a rhythmic fashion with an average frequency of 8 Hz. The hyperpolarization-activated cation current (Ih) did not seem important for pacemaking because blocking the current with ZD 7288 or Cs+ had little effect on spontaneous firing. To investigate what ionic currents do drive pacemaking, we performed action-potential-clamp experiments using records of pacemaking as voltage command in voltage-clamp experiments. We found that substantial TTX-sensitive Na+ current flows during the interspike depolarization. In addition, substantial Ca2+ current flowed during the interspike interval, and blocking Ca2+ current hyperpolarized the neurons and stopped spontaneous firing. These results show that dopaminergic periglomerular cells have intrinsic pacemaking activity, supporting the possibility that they can maintain a tonic release of dopamine to modulate the sensitivity of the olfactory system during odor detection. Calcium entry into these neurons provides electrical drive for pacemaking as well as triggering transmitter release.

Evaluation of a Workplace-Based Migraine Education Program.

PubMed

Burton, Wayne N; Chen, Chin-Yu; Li, Xingquan; McCluskey, Maureen; Erickson, Denise; Schultz, Alyssa B

2016-08-01

Migraine affects approximately 10% of working-age adults and is associated with increased health care costs, absenteeism, and presenteeism in the workplace. A migraine education program was offered to United States employees of a global financial services organization. Two hundred forty three employees (46% response rate) completed both a baseline and 6-month follow-up migraine questionnaire. The program included webinars, E-mailed educational tips, and intranet-based resources. No change was found in the frequency of migraines but improvements were observed in the severity, workdays missed, effectiveness at work during migraine, and work/activity limitations. Participants reported taking action to identify and reduce migraine triggers. A worksite disease education program for migraine headache has the potential to significantly impact lost productivity and absenteeism for migraineurs.

ER-stress and apoptosis: molecular mechanisms and potential relevance in infection.

PubMed

Häcker, Georg

2014-10-01

During ER-stress, one of the responses a cell can choose is apoptosis. Apoptosis generally is a cell's preferred response when other control mechanisms are overwhelmed. We now have a reasonably clear molecular picture what is happening once the apoptotic apparatus has been started. Unclear however are the majority of the upstream pathways that connect other signalling to apoptosis. During ER-stress, confirmed apoptosis-regulating targets are pro- and anti-apoptotic proteins of the Bcl-2-family, whose concerted action induces apoptosis. I will here discuss how mitochondrial apoptosis is triggered, how this is linked to the ER-stress response and in what way this may be relevant during microbial infections. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

More Than a Text Message: Dismantling Digital Triggers to Curate Behavior Change in Patient-Centered Health Interventions.

PubMed

Muench, Frederick; Baumel, Amit

2017-05-26

Digital triggers such as text messages, emails, and push alerts are designed to focus an individual on a desired goal by prompting an internal or external reaction at the appropriate time. Triggers therefore have an essential role in engaging individuals with digital interventions delivered outside of traditional health care settings, where other events in daily lives and fluctuating motivation to engage in effortful behavior exist. There is an emerging body of literature examining the use of digital triggers for short-term action and longer-term behavior change. However, little attention has been given to understanding the components of digital triggers. Using tailoring as an overarching framework, we separated digital triggers into 5 primary components: (1) who (sender), (2) how (stimulus type, delivery medium, heterogeneity), (3) when (delivered), (4) how much (frequency, intensity), and (5) what (trigger's target, trigger's structure, trigger's narrative). We highlighted key considerations when tailoring each component and the pitfalls of ignoring common mistakes, such as alert fatigue and habituation. As evidenced throughout the paper, there is a broad literature base from which to draw when tailoring triggers to curate behavior change in health interventions. More research is needed, however, to examine differences in efficacy based on component tailoring, to best use triggers to facilitate behavior change over time, and to keep individuals engaged in physical and mental health behavior change efforts. Dismantling digital triggers into their component parts and reassembling them according to the gestalt of one's change goals is the first step in this development work. ©Frederick Muench, Amit Baumel. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 26.05.2017.

Omission P3 after voluntary action indexes the formation of action-driven prediction.

PubMed

Kimura, Motohiro; Takeda, Yuji

2018-02-01

When humans frequently experience a certain sensory effect after a certain action, a bidirectional association between neural representations of the action and the sensory effect is rapidly acquired, which enables action-driven prediction of the sensory effect. The present study aimed to test whether or not omission P3, an event-related brain potential (ERP) elicited by the sudden omission of a sensory effect, is sensitive to the formation of action-driven prediction. For this purpose, we examined how omission P3 is affected by the number of possible visual effects. In four separate blocks (1-, 2-, 4-, and 8-stimulus blocks), participants successively pressed a right button at an interval of about 1s. In all blocks, each button press triggered a bar on a display (a bar with square edges, 85%; a bar with round edges, 5%), but occasionally did not (sudden omission of a visual effect, 10%). Participants were required to press a left button when a bar with round edges appeared. In the 1-stimulus block, the orientation of the bar was fixed throughout the block; in the 2-, 4-, and 8-stimulus blocks, the orientation was randomly varied among two, four, and eight possibilities, respectively. Omission P3 in the 1-stimulus block was greater than those in the 2-, 4-, and 8-stimulus blocks; there were no significant differences among the 2-, 4-, and 8-stimulus blocks. This binary pattern nicely fits the limitation in the acquisition of action-effect association; although an association between an action and one visual effect is easily acquired, associations between an action and two or more visual effects cannot be acquired concurrently. Taken together, the present results suggest that omission P3 is highly sensitive to the formation of action-driven prediction. Copyright © 2017 Elsevier B.V. All rights reserved.

77 FR 50504 - Clean Air Act Operating Permit Program; Action on Petition for Objection to State Operating...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-21

...) requirements because WDNR erroneously exempted as ``routine maintenance, repair, and replacement'' projects... were triggered through non-exempt fuel switching and WDNR improperly deferred addressing this issue...

Investigation of Potential Triggered Tremor in Latin America and the Caribbean

NASA Astrophysics Data System (ADS)

Gonzalez-Huizar, H.; Velasco, A. A.; Peng, Z.

2012-12-01

Recent observations have shown that seismic waves generate transient stresses capable of triggering earthquakes and tectonic (or non-volcanic) tremor far away from the original earthquake source. However, the mechanisms behind remotely triggered seismicity still remain unclear. Triggered tremor signals can be particularly useful in investigating remote triggering processes, since in many cases, the tremor pulses are very clearly modulated by the passing surface waves. The temporal stress changes (magnitude and orientation) caused by seismic waves at the tremor source region can be calculated and correlated with tremor pulses, which allows for exploring the stresses involved in the triggering process. Some observations suggest that triggered and ambient tremor signals are generated under similar physical conditions; thus, investigating triggered tremor might also provide important clues on how and under what conditions ambient tremor signals generate. In this work we present some of the results and techniques we employ in the research of potential cases of triggered tectonic tremor in Latin America and the Caribbean. This investigation includes: (1) the triggered tremor detection, with the use of specific signal filters; (2) localization of the sources, using uncommon techniques like time reversal signals; (3) and the analysis of the stress conditions under which they are generated, by modeling the triggering waves related dynamic stress. Our results suggest that tremor can be dynamically triggered by both Love and Rayleigh waves and in broad variety of tectonic environments depending strongly on the dynamic stress amplitude and orientation. Investigating remotely triggered seismicity offers the opportunity to improve our knowledge about deformation mechanisms and the physics of rupture.

Behavioral characteristics of Internet gamblers who trigger corporate responsible gambling interventions.

PubMed

Gray, Heather M; LaPlante, Debi A; Shaffer, Howard J

2012-09-01

As the worldwide popularity of Internet gambling increases, concerns about the potential for gambling-related harm also increase. This paper reports the results of a study examining actual Internet gambling behavior during 10 years of play. We examined the electronic gambling records of subscribers (N=2,066) who triggered a responsible gaming alert system at a large international online gaming company. We compared these cases with control subscribers (N=2,066) who had the same amount of exposure to the Internet gambling service provider. We used discriminant function analysis to explore what aspects of gambling behavior distinguish cases from controls. Indices of the intensity of gambling activity (e.g., total number of bets made, number of bets per betting day) best distinguished cases from controls, particularly in the case of live-action sports betting. Control group players evidenced behavior similar to the population of players using this service. These results add to our understanding of behavioral markers for disordered Internet gambling and will aid in the development of behavior-based algorithms capable of predicting the presence and/or the onset of disordered Internet gambling. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Dendritic calcium channels and their activation by synaptic signals in auditory coincidence detector neurons.

PubMed

Blackmer, Trillium; Kuo, Sidney P; Bender, Kevin J; Apostolides, Pierre F; Trussell, Laurence O

2009-08-01

The avian nucleus laminaris (NL) encodes the azimuthal location of low-frequency sound sources by detecting the coincidence of binaural signals. Accurate coincidence detection requires precise developmental regulation of the lengths of the fine, bitufted dendrites that characterize neurons in NL. Such regulation has been suggested to be driven by local, synaptically mediated, dendritic signals such as Ca(2+). We examined Ca(2+) signaling through patch clamp and ion imaging experiments in slices containing nucleus laminaris from embryonic chicks. Voltage-clamp recordings of neurons located in the NL showed the presence of large Ca(2+) currents of two types, a low voltage-activated, fast inactivating Ni(2+) sensitive channel resembling mammalian T-type channels, and a high voltage-activated, slowly inactivating Cd(2+) sensitive channel. Two-photon Ca(2+) imaging showed that both channel types were concentrated on dendrites, even at their distal tips. Single action potentials triggered synaptically or by somatic current injection immediately elevated Ca(2+) throughout the entire cell. Ca(2+) signals triggered by subthreshold synaptic activity were highly localized. Thus when electrical activity is suprathreshold, Ca(2+) channels ensure that Ca(2+) rises in all dendrites, even those that are synaptically inactive.

Effects of diadenosine tetraphosphate on FGF9-induced chloride flux changes in achondroplastic chondrocytes.

PubMed

Huete, Fernando; Guzman-Aranguez, Ana; Ortín, Javier; Hoyle, Charles H V; Pintor, Jesús

2011-06-01

Achondroplasia, the most common type of dwarfism, is characterized by a mutation in the fibroblast growth factor receptor 3 (FGFR3). Achondroplasia is an orphan pathology with no pharmacological treatment so far. However, the possibility of using the dinucleotide diadenosine tetraphosphate (Ap(4)A) with therapeutic purposes in achondroplasia has been previously suggested. The pathogenesis involves the constitutive activation of FGFR3, resulting in altered biochemical and physiological processes in chondrocytes. Some of these altered processes can be influenced by changes in cell volume and ionic currents. In this study, the action of mutant FGFR3 on chondrocyte size and chloride flux in achondroplastic chondrocytes was investigated as well as the effect of the Ap(4)A on these processes triggered by mutant FGFR3. Stimulation with the fibroblast growth factor 9 (FGF9), the preferred ligand for FGFR3, induced an enlarged achondroplastic chondrocyte size and an increase in the intracellular chloride concentration, suggesting the blockade of chloride efflux. Treatment with the Ap(4)A reversed the morphological changes triggered by FGF9 and restored the chloride efflux. These data provide further evidence for the therapeutic potential of this dinucleotide in achondroplasia treatment.

Influence of Bisphenol A on Type 2 Diabetes Mellitus

PubMed Central

Provvisiero, Donatella Paola; Pivonello, Claudia; Muscogiuri, Giovanna; Negri, Mariarosaria; de Angelis, Cristina; Simeoli, Chiara; Pivonello, Rosario; Colao, Annamaria

2016-01-01

Bisphenol A (BPA) is an organic synthetic compound employed to produce plastics and epoxy resins. It is used as a structural component in polycarbonate beverage bottles and as coating for metal surface in food containers and packaging. The adverse effects of BPA on human health are widely disputed. BPA has been recently associated with a wide variety of medical disorders and, in particular, it was identified as potential endocrine-disrupting compound with diabetogenic action. Most of the clinical observational studies in humans reveal a positive link between BPA exposure, evaluated by the measurement of urinary BPA levels, and the risk of developing type 2 diabetes mellitus. Clinical studies on humans and preclinical studies on in vivo, ex vivo, and in vitro models indicate that BPA, mostly at low doses, may have a role in increasing type 2 diabetes mellitus developmental risk, directly acting on pancreatic cells, in which BPA induces the impairment of insulin and glucagon secretion, triggers inhibition of cell growth and apoptosis, and acts on muscle, hepatic, and adipose cell function, triggering an insulin-resistant state. The current review summarizes the available evidences regarding the association between BPA and type 2 diabetes mellitus, focusing on both clinical and preclinical studies. PMID:27782064

Biomolecular Photovoltaics and Artificial Sight

NASA Astrophysics Data System (ADS)

Greenbaum, Elias; Kuritz, Tanya; Lee, Ida; Owens, Elizabeth T.; Humayun, Mark

2004-11-01

The goal of this project is insertion of purified Photosystem I (PSI) reaction centers or other photoactive agents into retinal cells where they will restore photoreceptor function to people who suffer from age-related macular degeneration (AMD) or retinitis pigmentosa (RP), diseases that are the leading causes of blindness world-wide. Although the neural ``wiring'' from eye to brain is intact, these patients lack photoreceptor activity. It is the ultimate goal of this project to restore photoreceptor activity to these patients using PSI as the optical trigger. In principle, the approach should work. PSI is a robust integral membrane molecular photovoltaic device. Depending on orientation, it can depolarize or hyperpolarize the cell membrane with sufficient voltage to trigger an action potential. The first objective of this work, reported here, is to impart photoreceptor activity to mammalian cells using the previously determined molecular photovoltaic properties of isolated Photosystem I reaction centers. Incubation of WERI-Rb-1 retinoblastoma cells with functional PSI reaction centers that were isolated from spinach leaves and reconstituted into proteoliposomes resulted in a light-induced PSI-dependent increase in intracellular Ca^2+. The increase, due to Ca^2+ uptake, was dependent on the presence of extracellular Ca^2+ ions.

Molecular Photovoltaics and Artificial Sight

NASA Astrophysics Data System (ADS)

Greenbaum, Elias

2005-03-01

The goal of this project is insertion of purified Photosystem I (PSI) reaction centers or other photoactive agents into retinal cells where they will restore photoreceptor function to people who suffer from age-related macular degeneration (AMD) or retinitis pigmentosa (RP), diseases that are the leading causes of blindness world-wide. Although the neural ``wiring'' from eye to brain is intact, these patients lack photoreceptor activity. It is the ultimate goal of this project to restore photoreceptor activity to these patients using PSI as the optical trigger. In principle, the approach should work. PSI is a robust integral membrane molecular photovoltaic device. Depending on orientation, it can depolarize or hyperpolarize the cell membrane with sufficient voltage to trigger an action potential. The first objective of this work, reported here, is to impart photoreceptor activity to mammalian cells using the previously determined molecular photovoltaic properties of isolated Photosystem I reaction centers. Incubation of WERI-Rb-1 retinoblastoma cells with functional PSI reaction centers that were isolated from spinach leaves and reconstituted into proteoliposomes resulted in a light-induced PSI-dependent increase in intracellular Ca^2+. The increase, due to Ca^2+ uptake, was dependent on the presence of extracellular Ca^2+ ions.

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

PubMed

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

2008-07-22

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

Redox mechanism of levobupivacaine cytostatic effect on human prostate cancer cells.

PubMed

Jose, Caroline; Hebert-Chatelain, Etienne; Dias Amoedo, Nivea; Roche, Emmanuel; Obre, Emilie; Lacombe, Didier; Rezvani, Hamid Reza; Pourquier, Philippe; Nouette-Gaulain, Karine; Rossignol, Rodrigue

2018-05-31

Anti-cancer effects of local anesthetics have been reported but the mode of action remains elusive. Here, we examined the bioenergetic and REDOX impact of levobupivacaine on human prostate cancer cells (DU145) and corresponding non-cancer primary human prostate cells (BHP). Levobupivacaine induced a combined inhibition of glycolysis and oxidative phosphorylation in cancer cells, resulting in a reduced cellular ATP production and consecutive bioenergetic crisis, along with reactive oxygen species generation. The dose-dependent inhibition of respiratory chain complex I activity by levobupivacaine explained the alteration of mitochondrial energy fluxes. Furthermore, the potency of levobupivacaine varied with glucose and oxygen availability as well as the cellular energy demand, in accordance with a bioenergetic anti-cancer mechanism. The levobupivacaine-induced bioenergetic crisis triggered cytostasis in prostate cancer cells as evidenced by a S-phase cell cycle arrest, without apoptosis induction. In DU145 cells, levobupivacaine also triggered the induction of autophagy and blockade of this process potentialized the anti-cancer effect of the local anesthetic. Therefore, our findings provide a better characterization of the REDOX mechanisms underpinning the anti-effect of levobupivacaine against human prostate cancer cells. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Delivering "Just-In-Time" Smoking Cessation Support Via Mobile Phones: Current Knowledge and Future Directions.

PubMed

Naughton, Felix

2016-05-28

Smoking lapses early on during a quit attempt are highly predictive of failing to quit. A large proportion of these lapses are driven by cravings brought about by situational and environmental cues. Use of cognitive-behavioral lapse prevention strategies to combat cue-induced cravings is associated with a reduced risk of lapse, but evidence is lacking in how these strategies can be effectively promoted. Unlike most traditional methods of delivering behavioral support, mobile phones can in principle deliver automated support, including lapse prevention strategy recommendations, Just-In-Time (JIT) for when a smoker is most vulnerable, and prevent early lapse. JIT support can be activated by smokers themselves (user-triggered), by prespecified rules (server-triggered) or through sensors that dynamically monitor a smoker's context and trigger support when a high risk environment is sensed (context-triggered), also known as a Just-In-Time Adaptive Intervention (JITAI). However, research suggests that user-triggered JIT cessation support is seldom used and existing server-triggered JIT support is likely to lack sufficient accuracy to effectively target high-risk situations in real time. Evaluations of mobile phone cessation interventions that include user and/or server-triggered JIT support have yet to adequately assess whether this improves management of high risk situations. While context-triggered systems have the greatest potential to deliver JIT support, there are, as yet, no impact evaluations of such systems. Although it may soon be feasible to learn about and monitor a smoker's context unobtrusively using their smartphone without burdensome data entry, there are several potential advantages to involving the smoker in data collection. This commentary describes the current knowledge on the potential for mobile phones to deliver automated support to help smokers manage or cope with high risk environments or situations for smoking, known as JIT support. The article categorizes JIT support into three main types: user-triggered, server-triggered, and context-triggered. For each type of JIT support, a description of the evidence and their potential to effectively target specific high risk environments or situations is described. The concept of unobtrusive sensing without user data entry to inform the delivery of JIT support is finally discussed in relation to potential advantages and disadvantages for behavior change. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

77 FR 53189 - Notice of Public Meetings for the Draft Legislative Environmental Impact Statement for the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-31

... and facilitate maintenance of prohibited entry and hazardous area warning signs along the CMAGR... military training. Selection of this alternative would trigger planning and actions to compensate for the...

Effect-based trigger values for in vitro bioassays: Reading across from existing water quality guideline values.

PubMed

Escher, Beate I; Neale, Peta A; Leusch, Frederic D L

2015-09-15

Cell-based bioassays are becoming increasingly popular in water quality assessment. The new generations of reporter-gene assays are very sensitive and effects are often detected in very clean water types such as drinking water and recycled water. For monitoring applications it is therefore imperative to derive trigger values that differentiate between acceptable and unacceptable effect levels. In this proof-of-concept paper, we propose a statistical method to read directly across from chemical guideline values to trigger values without the need to perform in vitro to in vivo extrapolations. The derivation is based on matching effect concentrations with existing chemical guideline values and filtering out appropriate chemicals that are responsive in the given bioassays at concentrations in the range of the guideline values. To account for the mixture effects of many chemicals acting together in a complex water sample, we propose bioanalytical equivalents that integrate the effects of groups of chemicals with the same mode of action that act in a concentration-additive manner. Statistical distribution methods are proposed to derive a specific effect-based trigger bioanalytical equivalent concentration (EBT-BEQ) for each bioassay of environmental interest that targets receptor-mediated toxicity. Even bioassays that are indicative of the same mode of action have slightly different numeric trigger values due to differences in their inherent sensitivity. The algorithm was applied to 18 cell-based bioassays and 11 provisional effect-based trigger bioanalytical equivalents were derived as an illustrative example using the 349 chemical guideline values protective for human health of the Australian Guidelines for Water Recycling. We illustrate the applicability using the example of a diverse set of water samples including recycled water. Most recycled water samples were compliant with the proposed triggers while wastewater effluent would not have been compliant with a few. The approach is readily adaptable to any water type and guideline or regulatory framework and can be expanded from the protection goal of human health to environmental protection targets. While this work constitutes a proof of principle, the applicability remains limited at present due to insufficient experimental bioassay data on individual regulated chemicals and the derived effect-based trigger values are of course only provisional. Once the experimental database is expanded and made more robust, the proposed effect-based trigger values may provide guidance in a regulatory context. Copyright © 2015 Elsevier Ltd. All rights reserved.

Study on Excitation-triggered Damage Mechanism in Perilous Rock

NASA Astrophysics Data System (ADS)

Chen, Hongkai; Wang, Shengjuan

2017-12-01

Chain collapse is easy to happen for perilous rock aggregate locating on steep high slope, and one of the key scientific problems is the damage mechanism of perilous rock under excitation action at perilous rock rupture. This paper studies excitation-triggered damage mechanism in perilous rock by wave mechanics, which gives three conclusions. Firstly, when only the normal incidence attenuation spread of excitation wave is considered, while the energy loss is ignored for excitation wave to spread in perilous rock aggregate, the paper establishes one method to calculate peak velocity when excitation wave passes through boundary between any two perilous rock blocks in perilous rock aggregate. Secondly, following by Sweden and Canmet criteria, the paper provides one wave velocity criterion for excitation-triggered damage in the aggregate. Thirdly, assuming double parameters of volume strain of cracks or fissures in rock meet the Weibull distribution, one method to estimate micro-fissure in excitation-triggered damage zone in perilous rock aggregate is established. The studies solve the mechanical description problem for excitation-triggered damage in perilous rock, which is valuable in studies on profoundly rupture mechanism.

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.

Antimicrobial effect and mode of action of terpeneless cold-pressed Valencia orange essential oil on methicillin-resistant Staphylococcus aureus.

PubMed

Muthaiyan, A; Martin, E M; Natesan, S; Crandall, P G; Wilkinson, B J; Ricke, S C

2012-05-01

The objectives of this study were to evaluate the antistaphylococcal effect and elucidate the mechanism of action of orange essential oil against antibiotic-resistant Staphylococcus aureus strains. The inhibitory effect of commercial orange essential oil (EO) against six Staph. aureus strains was tested using disc diffusion and agar dilution methods. The mechanism of EO action on MRSA was analysed by transcriptional profiling. Morphological changes of EO-treated Staph. aureus were examined using transmission electron microscopy. Results showed that 0·1% of terpeneless cold-pressed Valencia orange oil (CPV) induced the cell wall stress stimulon consistent with the inhibition of cell wall synthesis. Transmission electron microscopic observation revealed cell lysis and suggested a cell wall lysis-related mechanism of CPV. CPV inhibits the growth of Staph. aureus, causes gene expression changes consistent with the inhibition of cell wall synthesis, and triggers cell lysis. Multiple antibiotics resistance is becoming a serious problem in the management of Staph. aureus infections. In this study, the altered expression of cell wall-associated genes and subsequent cell lysis in MRSA caused by CPV suggest that it may be a potential antimicrobial agent to control antibiotic-resistant Staph. aureus. © 2012 The Authors. Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

Human Subject Research Protocol: Computer-Aided Human Centric Cyber Situation Awareness: Understanding Cognitive Processes of Cyber Analysts

DTIC Science & Technology

2013-11-01

by existing cyber-attack detection tools far exceeds the analysts’ cognitive capabilities. Grounded in perceptual and cognitive theory , many visual...Processes Inspired by the sense-making theory discussed earlier, we model the analytical reasoning process of cyber analysts using three key...analyst are called “working hypotheses”); each hypothesis could trigger further actions to confirm or disconfirm it. New actions will lead to new

Proteomics analysis suggests broad functional changes in potato leaves triggered by phosphites and a complex indirect mode of action against Phytophthora infestans.

PubMed

Lim, Sanghyun; Borza, Tudor; Peters, Rick D; Coffin, Robert H; Al-Mughrabi, Khalil I; Pinto, Devanand M; Wang-Pruski, Gefu

2013-11-20

Phosphite (salts of phosphorous acid; Phi)-based fungicides are increasingly used in controlling oomycete pathogens, such as the late blight agent Phytophthora infestans. In plants, low amounts of Phi induce pathogen resistance through an indirect mode of action. We used iTRAQ-based quantitative proteomics to investigate the effects of phosphite on potato plants before and after infection with P. infestans. Ninety-three (62 up-regulated and 31 down-regulated) differentially regulated proteins, from a total of 1172 reproducibly identified proteins, were identified in the leaf proteome of Phi-treated potato plants. Four days post-inoculation with P. infestans, 16 of the 31 down-regulated proteins remained down-regulated and 42 of the 62 up-regulated proteins remained up-regulated, including 90% of the defense proteins. This group includes pathogenesis-related, stress-responsive, and detoxification-related proteins. Callose deposition and ultrastructural analyses of leaf tissues after infection were used to complement the proteomics approach. This study represents the first comprehensive proteomics analysis of the indirect mode of action of Phi, demonstrating broad effects on plant defense and plant metabolism. The proteomics data and the microscopy study suggest that Phi triggers a hypersensitive response that is responsible for induced resistance of potato leaves against P. infestans. Phosphie triggers complex functional changes in potato leaves that are responsible for the induced resistance against Phytophthora infestans. This article is part of a Special Issue entitled: Translational Plant Proteomics. Copyright © 2013 Elsevier B.V. All rights reserved.

Monitoring for a specific management objective: protection of shorebird foraging habitat adjacent to a waste water treatment plant.

PubMed

Morris, Liz; Petch, David; May, David; Steele, William K

2017-05-01

Intertidal invertebrates are often used in environmental monitoring programs as they are good indicators of water quality and an important food source for many species of fish and birds. We present data from a monitoring program where the primary aim is to report on the condition of the potential invertebrate prey abundance, biomass and diversity for migrating shorebirds on mudflats adjacent to a waste water treatment plant in a Ramsar listed wetland in Victoria, Australia. A key threat to the foraging habitat at this site has been assessed as a reduction in potential prey items as a result of the changes to the waste water treatment processes. We use control charts, which summarise data from intertidal mudflats across the whole shoreline of the adjacent waste water treatment plant, to elicit a management response when trigger levels are reached. We then examine data from replicate discharge and control sites to determine the most appropriate management response. The monitoring program sits within an adaptive management framework where management decisions are reviewed and the data is examined at different scales to evaluate and modify our models of the likely outcomes of management actions. This study provides a demonstration of the process undertaken in a year when trigger levels were reached and a management decision was required. This highlights the importance of monitoring data from a range of scales in reducing uncertainty and improving decision making in complex systems.

Toward a rational understanding of migraine trigger factors.

PubMed

Martin, V T; Behbehani, M M

2001-07-01

The typical migraine patient is exposed to a myriad of migraine triggers on a daily basis. These triggers potentially can act at various sites within the cerebral vasculature and the central nervous system to promote the development of migraine headache. The challenge to the physician is in the identification and avoidance of migraine trigger factors within patients suffering from migraine headache. Only through a rational approach to migraine trigger factors can physicians develop an appropriate treatment strategy for migraine patients.

CGRP and Migraine: Could PACAP Play a Role Too?

PubMed Central

Kaiser, Eric A.; Russo, Andrew F.

2013-01-01

Migraine is a debilitating neurological disorder that affects about 12% of the population. In the past decade, the role of the neuropeptide calcitonin gene-related peptide (CGRP) in migraine has been firmly established by clinical studies. CGRP administration can trigger migraines, and CGRP receptor antagonists ameliorate migraine. In this review, we will describe multifunctional activities of CGRP that could potentially contribute to migraine. These include roles in light aversion, neurogenic inflammation, peripheral and central sensitization of nociceptive pathways, cortical spreading depression, and regulation of nitric oxide production. Yet clearly there will be many other contributing genes that could act in concert with CGRP. One candidate is pituitary adenylate cyclase-activating peptide (PACAP), which shares some of the same actions as CGRP, including the ability to induce migraine in migraineurs and light aversive behavior in rodents. Interestingly, both CGRP and PACAP act on receptors that share an accessory subunit called receptor activity modifying protein-1 (RAMP1). Thus, comparisons between the actions of these two migraine-inducing neuropeptides, CGRP and PACAP, may provide new insights into migraine pathophysiology. PMID:24210136

[Social actors in HIV/AIDS prevention: opposition and interests in educational policy in Mexico, 1994-2000].

PubMed

Granados-Cosme, José Arturo; Nasaiya, Kittipong; Brambila, Alberto Torres

2007-03-01

Studies and recommendations by health agencies have emphasized the importance of education in HIV-AIDS prevention. Mexico has included topics on sexuality and HIV-AIDS in school programs, triggering resistance by some social actors. The current study seeks to clarify the various positions and interests and their influence on the textbook content. A literature search was conducted on the period during which the last educational reform was implemented in Mexico. The discourse analysis focused on the ethnography of communication, which identified: the various actors' positions, arguments, actions, economic and political power, and relations to others. The results show that those who oppose the inclusion of these themes in the school curriculum base their position on tradition, contrary to modernization and secularization of social life, and that their positions range from refusal to raising conditions. Networks have been formed that provide such groups with significant economic and political power. Government has given in to some demands by partially modifying the textbook contents. The current analysis proposes to reflect on the potential repercussions of such actions on the control of the epidemic.

Purification, Characterization, and Mode of Action of Plantaricin GZ1-27, a Novel Bacteriocin against Bacillus cereus.

PubMed

Du, Hechao; Yang, Jie; Lu, Xiaohong; Lu, Zhaoxin; Bie, Xiaomei; Zhao, Haizhen; Zhang, Chong; Lu, Fengxia

2018-05-09

Bacillus cereus is an opportunistic pathogen that causes foodborne diseases. We isolated a novel bacteriocin, designated plantaricin GZ1-27, and elucidated its mode of action against B. cereus. Plantaricin GZ1-27 was purified using ammonium sulfate precipitation, gel-filtration chromatography, and RP-HPLC. MALDI-TOF/MS revealed that its molecular mass was 975 Da, and Q-TOF-MS/MS analysis predicted the amino acid sequence as VSGPAGPPGTH. Plantaricin GZ1-27 showed thermostability and pH stability. The antibacterial mechanism was investigated using flow cytometry, confocal laser-scanning microscopy, scanning and transmission electron microscopy, and RT-PCR, which revealed that GZ1-27 increased cell membrane permeability, triggered K + leakage and pore formation, damaged cell membrane integrity, altered cell morphology and intracellular organization, and reduced the expression of genes related to cytotoxin production, peptidoglycan synthesis, and cell division. These results suggest that plantaricin GZ1-27 effectively inhibits B. cereus at both the cellular and the molecular levels and is a potential natural food preservative targeting B. cereus.

Intracellular calcium dynamics and acetylcholine-induced triggered activity in the pulmonary veins of dogs with pacing-induced heart failure

PubMed Central

Chou, Chung-Chuan; Nguyen, Bich Lien; Tan, Alex Y.; Chang, Po-Cheng; Lee, Hui-Ling; Lin, Fun-Chung; Yeh, San-Jou; Fishbein, Michael C.; Lin, Shien-Fong; Wu, Delon; Wen, Ming-Shien; Chen, Peng-Sheng

2009-01-01

BACKGROUND Heart failure increases autonomic nerve activities and changes intracellular calcium (Cai) dynamics. OBJECTIVE The purpose of this study was to investigate the hypothesis that abnormal Cai dynamics are responsible for triggered activity in the pulmonary veins (PVs) during acetylcholine infusion in a canine model of heart failure. METHODS Simultaneous optical mapping of and membrane Cai potential was performed in isolated Langendorff-perfused PV–left atrial (LA) preparations from nine dogs with ventricular pacing-induced heart failure. Mapping was performed at baseline, during acetylcholine (1 μmol/L) infusion (N = 9), and during thapsigargin and ryanodine infusion (N = 6). RESULTS Acetylcholine abbreviated the action potential. In four tissues, long pauses were followed by elevated diastolic Cai, late phase 3 early afterdepolarizations, and atrial fibrillation (AF). The incidence of PV focal discharges during AF was increased by acetylcholine from 2.4 ± 0.6 beats/s (N = 4) to 6.5 ± 2.2 beats/s (N = 8; P = .003). PV focal discharge and PV–LA microreentry coexisted in 6 of 9 preparations. The spatial distribution of dominant frequency demonstrated a focal source pattern, with the highest dominant frequency areas colocalized with PV focal discharge sites in 35 (95%) of 37 cholinergic AF episodes (N = 8). Thapsigargin and ryanodine infusion eliminated focal discharges in 6 of 6 preparations and suppressed the inducibility of AF in 4 of 6 preparations. PVs with focal discharge have higher densities of parasympathetic nerves than do PVs without focal discharges (P = .01), and periodic acid–Schiff (PAS)-positive cells were present at the focal discharge sites. CONCLUSION Cai dynamics are important in promoting triggered activity during acetylcholine infusion in PVs from pacing-induced heart failure. PV focal discharge sites have PAS-positive cells and high densities of parasympathetic nerves. PMID:18554987

Surface-wave potential for triggering tectonic (nonvolcanic) tremor

USGS Publications Warehouse

Hill, D.P.

2010-01-01

Source processes commonly posed to explain instances of remote dynamic triggering of tectonic (nonvolcanic) tremor by surface waves include frictional failure and various modes of fluid activation. The relative potential for Love- and Rayleigh-wave dynamic stresses to trigger tectonic tremor through failure on critically stressed thrust and vertical strike-slip faults under the Coulomb-Griffith failure criteria as a function of incidence angle is anticorrelated over the 15- to 30-km-depth range that hosts tectonic tremor. Love-wave potential is high for strike-parallel incidence on low-angle reverse faults and null for strike-normal incidence; the opposite holds for Rayleigh waves. Love-wave potential is high for both strike-parallel and strike-normal incidence on vertical, strike-slip faults and minimal for ~45?? incidence angles. The opposite holds for Rayleigh waves. This pattern is consistent with documented instances of tremor triggered by Love waves incident on the Cascadia mega-thrust and the San Andreas fault (SAF) in central California resulting from shear failure on weak faults (apparent friction, ????? 0.2). However, documented instances of tremor triggered by surface waves with strike-parallel incidence along the Nankai megathrust beneath Shikoku, Japan, is associated primarily with Rayleigh waves. This is consistent with the tremor bursts resulting from mixed-mode failure (crack opening and shear failure) facilitated by near-lithostatic ambient pore pressure, low differential stress, with a moderate friction coefficient (?? ~ 0.6) on the Nankai subduction interface. Rayleigh-wave dilatational stress is relatively weak at tectonic tremor source depths and seems unlikely to contribute significantly to the triggering process, except perhaps for an indirect role on the SAF in sustaining tremor into the Rayleigh-wave coda that was initially triggered by Love waves.

Surface-wave potential for triggering tectonic (nonvolcanic) tremor-corrected

USGS Publications Warehouse

Hill, David P.

2012-01-01

Source processes commonly posed to explain instances of remote dynamic triggering of tectonic (nonvolcanic) tremor by surface waves include frictional failure and various modes of fluid activation. The relative potential for Love- and Rayleigh-wave dynamic stresses to trigger tectonic tremor through failure on critically stressed thrust and vertical strike-slip faults under the Coulomb-Griffith failure criteria as a function of incidence angle are anticorrelated over the 15- to 30-km-depth range that hosts tectonic tremor. Love-wave potential is high for strike-parallel incidence on low-angle reverse faults and null for strike-normal incidence; the opposite holds for Rayleigh waves. Love-wave potential is high for both strike-parallel and strike-normal incidence on vertical, strike-slip faults and minimal for ~45° incidence angles. The opposite holds for Rayleigh waves. This pattern is consistent with documented instances of tremor triggered by Love waves incident on the Cascadia megathrust and the San Andreas fault (SAF) in central California resulting from shear failure on weak faults (apparent friction is μ* ≤ 0:2). Documented instances of tremor triggered by surface waves with strike-parallel incidence along the Nankai megathrust beneath Shikoku, Japan, however, are associated primarily with Rayleigh waves. This is consistent with the tremor bursts resulting from mixed-mode failure (crack opening and shear failure) facilitated by near-lithostatic ambient pore pressure, low differential stress, with a moderate friction coefficient (μ ~ 0:6) on the Nankai subduction interface. Rayleigh-wave dilatational stress is relatively weak at tectonic tremor source depths and seems unlikely to contribute significantly to the triggering process, except perhaps for an indirect role on the SAF in sustaining tremor into the Rayleigh-wave coda that was initially triggered by Love waves.

Lipoxins and novel 15-epi-lipoxin analogs display potent anti-inflammatory actions after oral administration.

PubMed

Bannenberg, Gerard; Moussignac, Rose-Laure; Gronert, Karsten; Devchand, Pallavi R; Schmidt, Birgitta A; Guilford, William J; Bauman, John G; Subramanyam, Babu; Perez, H Daniel; Parkinson, John F; Serhan, Charles N

2004-09-01

1. Lipoxins (LX) and aspirin-triggered 15-epi-lipoxins (ATL) exert potent anti-inflammatory actions. In the present study, we determined the anti-inflammatory efficacy of endogenous LXA(4) and LXB(4), the stable ATL analog ATLa2, and a series of novel 3-oxa-ATL analogs (ZK-996, ZK-990, ZK-994, and ZK-142) after intravenous, oral, and topical administration in mice. 2. LXA(4), LXB(4), ATLa2, and ZK-994 were orally active, exhibiting potent systemic inhibition of zymosan A-induced peritonitis at very low doses (50 ng kg(-1)-50 microg kg(-1)). 3. Intravenous ZK-994 and ZK-142 (500 microg kg(-1)) potently attenuated hind limb ischemia/reperfusion-induced lung injury, with 32+/-12 and 53+/-5% inhibition (P<0.05), respectively, of neutrophil accumulation in lungs. The same dose of ATLa2 had no significant protective action. 4. Topical application of ATLa2, ZK-994, and ZK-142 ( approximately 20 microg cm(-2)) prevented vascular leakage and neutrophil infiltration in LTB(4)/PGE(2)-stimulated ear skin inflammation. While ATLa2 and ZK-142 displayed approximately equal anti-inflammatory efficacy in this model, ZK-994 displayed a slower onset of action. 5. In summary, native LXA(4) and LXB(4), and analogs ATLa2, ZK-142, and ZK-994 retain broad anti-inflammatory effects after intravenous, oral, and topical administration. The 3-oxa-ATL analogs, which have enhanced metabolic and chemical stability and a superior pharmacokinetic profile, provide new opportunities to explore the actions and therapeutic potential for LX and ATL.

Using community level strategies to reduce asthma attacks triggered by outdoor air pollution: a case crossover analysis

PubMed Central

2014-01-01

Background Evidence indicates that asthma attacks can be triggered by exposure to ambient air pollutants, however, detailed pollution information is missing from asthma action plans. Asthma is commonly associated with four criteria pollutants with standards derived by the United States Environmental Protection Agency. Since multiple pollutants trigger attacks and risks depend upon city-specific mixtures of pollutants, there is lack of specific guidance to reduce exposure. Until multi-pollutant statistical modeling fully addresses this gap, some guidance on pollutant attack risk is required. This study examines the risks from exposure to the asthma-related pollutants in a large metropolitan city and defines the city-specific association between attacks and pollutant mixtures. Our goal is that city-specific pollution risks be incorporated into individual asthma action plans as additional guidance to prevent attacks. Methods Case-crossover analysis and conditional logistic regression were used to measure the association between ozone, fine particulate matter, nitrogen dioxide, sulfur dioxide and carbon monoxide pollution and 11,754 emergency medical service ambulance treated asthma attacks in Houston, Texas from 2004-2011. Both single and multi-pollutant models are presented. Results In Houston, ozone and nitrogen dioxide are important triggers (RR = 1.05; 95% CI: 1.00, 1.09), (RR = 1.10; 95% CI: 1.05, 1.15) with 20 and 8 ppb increase in ozone and nitrogen dioxide, respectively, in a multi-pollutant model. Both pollutants are simultaneously high at certain times of the year. The risk attributed to these pollutants differs when they are considered together, especially as concentrations increase. Cumulative exposure for ozone (0-2 day lag) is of concern, whereas for nitrogen dioxide the concern is with single day exposure. Persons at highest risk are aged 46-66, African Americans, and males. Conclusions Accounting for cumulative and concomitant outdoor pollutant exposure is important to effectively attribute risk for triggering of an asthma attack, especially as concentrations increase. Improved asthma action plans for Houston individuals should warn of these pollutants, their trends, correlation and cumulative effects. Our Houston based study identifies nitrogen dioxide levels and the three-day exposure to ozone to be of concern whereas current single pollutant based national standards do not. PMID:25012280

More Than a Text Message: Dismantling Digital Triggers to Curate Behavior Change in Patient-Centered Health Interventions

PubMed Central

2017-01-01

Digital triggers such as text messages, emails, and push alerts are designed to focus an individual on a desired goal by prompting an internal or external reaction at the appropriate time. Triggers therefore have an essential role in engaging individuals with digital interventions delivered outside of traditional health care settings, where other events in daily lives and fluctuating motivation to engage in effortful behavior exist. There is an emerging body of literature examining the use of digital triggers for short-term action and longer-term behavior change. However, little attention has been given to understanding the components of digital triggers. Using tailoring as an overarching framework, we separated digital triggers into 5 primary components: (1) who (sender), (2) how (stimulus type, delivery medium, heterogeneity), (3) when (delivered), (4) how much (frequency, intensity), and (5) what (trigger’s target, trigger’s structure, trigger’s narrative). We highlighted key considerations when tailoring each component and the pitfalls of ignoring common mistakes, such as alert fatigue and habituation. As evidenced throughout the paper, there is a broad literature base from which to draw when tailoring triggers to curate behavior change in health interventions. More research is needed, however, to examine differences in efficacy based on component tailoring, to best use triggers to facilitate behavior change over time, and to keep individuals engaged in physical and mental health behavior change efforts. Dismantling digital triggers into their component parts and reassembling them according to the gestalt of one’s change goals is the first step in this development work. PMID:28550001

Characterization of postsynaptic calcium signals in the pyramidal neurons of anterior cingulate cortex

PubMed Central

Li, Xu-Hui; Song, Qian; Chen, Tao; Zhuo, Min

2017-01-01

Calcium signaling is critical for synaptic transmission and plasticity. N-methyl-D-aspartic acid (NMDA) receptors play a key role in synaptic potentiation in the anterior cingulate cortex. Most previous studies of calcium signaling focus on hippocampal neurons, little is known about the activity-induced calcium signals in the anterior cingulate cortex. In the present study, we show that NMDA receptor-mediated postsynaptic calcium signals induced by different synaptic stimulation in anterior cingulate cortex pyramidal neurons. Single and multi-action potentials evoked significant suprathreshold Ca2+ increases in somas and spines. Both NMDA receptors and voltage-gated calcium channels contributed to this increase. Postsynaptic Ca2+signals were induced by puff-application of glutamate, and a NMDA receptor antagonist AP5 blocked these signals in both somas and spines. Finally, long-term potentiation inducing protocols triggered postsynaptic Ca2+ influx, and these influx were NMDA receptor dependent. Our results provide the first study of calcium signals in the anterior cingulate cortex and demonstrate that NMDA receptors play important roles in postsynaptic calcium signals in anterior cingulate cortex pyramidal neurons. PMID:28726541

Priming of reach trajectory when observing actions: Hand-centred effects

PubMed Central

Griffiths, Debra; Tipper, Steven P.

2009-01-01

When another person's actions are observed it appears that these actions are simulated, such that similar motor processes are triggered in the observer. Much evidence suggests that such simulation concerns the achievement of behavioural goals, such as grasping a particular object, and is less concerned with the specific nature of the action, such as the path the hand takes to reach the goal object. We demonstrate that when observing another person reach around an obstacle, an observer's subsequent reach has an increased curved trajectory, reflecting motor priming of reach path. This priming of reach trajectory via action observation can take place under a variety of circumstances: with or without a shared goal, and when the action is seen from a variety of perspectives. However, of most importance, the reach path priming effect is only evoked if the obstacle avoided by another person is within the action (peripersonal) space of the observer. PMID:19731190

Complementary interactions between command-like interneurons that function to activate and specify motor programs.

PubMed

Wu, Jin-Sheng; Wang, Nan; Siniscalchi, Michael J; Perkins, Matthew H; Zheng, Yu-Tong; Yu, Wei; Chen, Song-an; Jia, Ruo-nan; Gu, Jia-Wei; Qian, Yi-Qing; Ye, Yang; Vilim, Ferdinand S; Cropper, Elizabeth C; Weiss, Klaudiusz R; Jing, Jian

2014-05-07

Motor activity is often initiated by a population of command-like interneurons. Command-like interneurons that reliably drive programs have received the most attention, so little is known about how less reliable command-like interneurons may contribute to program generation. We study two electrically coupled interneurons, cerebral-buccal interneuron-2 (CBI-2) and CBI-11, which activate feeding motor programs in the mollusk Aplysia californica. Earlier work indicated that, in rested preparations, CBI-2, a powerful activator of programs, can trigger ingestive and egestive programs. CBI-2 reliably generated ingestive patterns only when it was repeatedly stimulated. The ability of CBI-2 to trigger motor activity has been attributed to the two program-promoting peptides it contains, FCAP and CP2. Here, we show that CBI-11 differs from CBI-2 in that it contains FCAP but not CP2. Furthermore, it is weak in its ability to drive programs. On its own, CBI-11 is therefore less effective as a program activator. When it is successful, however, CBI-11 is an effective specifier of motor activity; that is, it drives mostly ingestive programs. Importantly, we found that CBI-2 and CBI-11 complement each other's actions. First, prestimulation of CBI-2 enhanced the ability of CBI-11 to drive programs. This effect appears to be partly mediated by CP2. Second, coactivation of CBI-11 with CBI-2 makes CBI-2 programs immediately ingestive. This effect may be mediated by specific actions that CBI-11 exerts on pattern-generating interneurons. Therefore, different classes of command-like neurons in a motor network may make distinct, but potentially complementary, contributions as either activators or specifiers of motor activity.

Physiological Response to Facial Expressions in Peripersonal Space Determines Interpersonal Distance in a Social Interaction Context.

PubMed

Cartaud, Alice; Ruggiero, Gennaro; Ott, Laurent; Iachini, Tina; Coello, Yann

2018-01-01

Accurate control of interpersonal distances in social contexts is an important determinant of effective social interactions. Although comfortable interpersonal distance seems to be dependent on social factors such as the gender, age and activity of the confederates, it also seems to be modulated by the way we represent our peripersonal-action space. To test this hypothesis, the present study investigated the relation between the emotional responses registered through electrodermal activity (EDA) triggered by human-like point-light displays (PLDs) carrying different facial expressions (neutral, angry, happy) when located in the participants peripersonal or extrapersonal space, and the comfort distance with the same PLDs when approaching and crossing the participants fronto-parallel axis on the right or left side. The results show an increase of the phasic EDA for PLDs with angry facial expressions located in the peripersonal space (reachability judgment task), in comparison to the same PLDs located in the extrapersonal space, which was not observed for PLDs with neutral or happy facial expressions. The results also show an increase of the comfort distance for PLDs approaching the participants with an angry facial expression (interpersonal comfort distance judgment task), in comparison to PLDs with happy and neutral ones, which was related to the increase of the physiological response. Overall, the findings indicate that comfort social space can be predicted from the emotional reaction triggered by a confederate when located within the observer's peripersonal space. This suggests that peripersonal-action space and interpersonal-social space are similarly sensitive to the emotional valence of the confederate, which could reflect a common adaptive mechanism in specifying theses spaces to subtend interactions with both the physical and social environment, but also to ensure body protection from potential threats.

Complementary Interactions between Command-Like Interneurons that Function to Activate and Specify Motor Programs

PubMed Central

Wu, Jin-Sheng; Wang, Nan; Siniscalchi, Michael J.; Perkins, Matthew H.; Zheng, Yu-Tong; Yu, Wei; Chen, Song-an; Jia, Ruo-nan; Gu, Jia-Wei; Qian, Yi-Qing; Ye, Yang; Vilim, Ferdinand S.; Cropper, Elizabeth C.; Weiss, Klaudiusz R.

2014-01-01

Motor activity is often initiated by a population of command-like interneurons. Command-like interneurons that reliably drive programs have received the most attention, so little is known about how less reliable command-like interneurons may contribute to program generation. We study two electrically coupled interneurons, cerebral-buccal interneuron-2 (CBI-2) and CBI-11, which activate feeding motor programs in the mollusk Aplysia californica. Earlier work indicated that, in rested preparations, CBI-2, a powerful activator of programs, can trigger ingestive and egestive programs. CBI-2 reliably generated ingestive patterns only when it was repeatedly stimulated. The ability of CBI-2 to trigger motor activity has been attributed to the two program-promoting peptides it contains, FCAP and CP2. Here, we show that CBI-11 differs from CBI-2 in that it contains FCAP but not CP2. Furthermore, it is weak in its ability to drive programs. On its own, CBI-11 is therefore less effective as a program activator. When it is successful, however, CBI-11 is an effective specifier of motor activity; that is, it drives mostly ingestive programs. Importantly, we found that CBI-2 and CBI-11 complement each other's actions. First, prestimulation of CBI-2 enhanced the ability of CBI-11 to drive programs. This effect appears to be partly mediated by CP2. Second, coactivation of CBI-11 with CBI-2 makes CBI-2 programs immediately ingestive. This effect may be mediated by specific actions that CBI-11 exerts on pattern-generating interneurons. Therefore, different classes of command-like neurons in a motor network may make distinct, but potentially complementary, contributions as either activators or specifiers of motor activity. PMID:24806677

Effect of nitric oxide-releasing derivative of indomethacin on Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

PubMed

Choe, So-Hui; Choi, Eun-Young; Hyeon, Jin-Yi; Choi, In Soon; Kim, Sung-Jo

2017-10-14

The purpose of this study was to investigate the influences of NCX 2121, a nitric oxide (NO)-releasing derivative of indomethacin, upon the generation of proinflammatory mediators using murine macrophages activated by lipopolysaccharide (LPS) isolated from Prevotella intermedia, which is one of the pathogens implicated in periodontal diseases. Inducible NO synthase (iNOS)-derived NO, IL-1β and IL-6 as well as their relevant mRNA were significantly attenuated by NCX 2121 in RAW264.7 cells activated by P. intermedia LPS. NCX 2121 was much more effective than the parental compound indomethacin in reducing these proinflammatory mediators. NCX 2121 triggered induction of heme oxygenase-1 (HO-1) in cells exposed to P. intermedia LPS, and its inhibitory influence upon P. intermedia LPS-elicited NO generation was notably blocked by SnPP treatment. NCX 2121 attenuated NF-κB-dependent SEAP release induced by P. intermedia LPS. NCX 2121 did not display inhibitory action towards IκB-α degradation triggered by LPS. Instead, it significantly diminished nuclear translocation as well as DNA-binding action of NF-κB p50 subunit elicited by P. intermedia LPS. Further, NCX 2121 significantly up-regulated SOCS1 mRNA expression in cells challenged with P. intermedia LPS. In summary, NCX 2121 down-regulates P. intermedia LPS-elicited generation of NO, IL-1β and IL-6 in murine macrophages in a mechanism that involves anti-inflammatory HO-1 induction as well as decrement of NF-κB activation, which may be associated with SOCS1 expression. NCX 2121 may have potential benefits as a host immunomodulatory agent for the therapy of periodontal disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Reducing regional drought vulnerabilities and multi-city robustness conflicts using many-objective optimization under deep uncertainty

NASA Astrophysics Data System (ADS)

Trindade, B. C.; Reed, P. M.; Herman, J. D.; Zeff, H. B.; Characklis, G. W.

2017-06-01

Emerging water scarcity concerns in many urban regions are associated with several deeply uncertain factors, including rapid population growth, limited coordination across adjacent municipalities and the increasing risks for sustained regional droughts. Managing these uncertainties will require that regional water utilities identify coordinated, scarcity-mitigating strategies that trigger the appropriate actions needed to avoid water shortages and financial instabilities. This research focuses on the Research Triangle area of North Carolina, seeking to engage the water utilities within Raleigh, Durham, Cary and Chapel Hill in cooperative and robust regional water portfolio planning. Prior analysis of this region through the year 2025 has identified significant regional vulnerabilities to volumetric shortfalls and financial losses. Moreover, efforts to maximize the individual robustness of any of the mentioned utilities also have the potential to strongly degrade the robustness of the others. This research advances a multi-stakeholder Many-Objective Robust Decision Making (MORDM) framework to better account for deeply uncertain factors when identifying cooperative drought management strategies. Our results show that appropriately designing adaptive risk-of-failure action triggers required stressing them with a comprehensive sample of deeply uncertain factors in the computational search phase of MORDM. Search under the new ensemble of states-of-the-world is shown to fundamentally change perceived performance tradeoffs and substantially improve the robustness of individual utilities as well as the overall region to water scarcity. Search under deep uncertainty enhanced the discovery of how cooperative water transfers, financial risk mitigation tools, and coordinated regional demand management must be employed jointly to improve regional robustness and decrease robustness conflicts between the utilities. Insights from this work have general merit for regions where adjacent municipalities can benefit from cooperative regional water portfolio planning.

Perceptions of successful cues to action and opportunities to augment behavioral triggers in diabetes self-management: qualitative analysis of a mobile intervention for low-income Latinos with diabetes.

PubMed

Burner, Elizabeth R; Menchine, Michael D; Kubicek, Katrina; Robles, Marisela; Arora, Sanjay

2014-01-29

The increasing prevalence of diabetes and the associated cost of managing this complicated disease have a significant impact on public health outcomes and health expenditures, especially among resource-poor Latino patients. Mobile health (mHealth) may be the solution to reaching this group and improving their health. In this qualitative study, we examined nuances of motivation, intention, and triggers to action effected by TExT-MED (Trial to Examine Text Messaging for Emergency Department patient with Diabetes), an mHealth intervention tailored to low-income, urban Latinos with diabetes. TExT-MED is a fully-automated, text message-based program designed to increase knowledge, self-efficacy, and subsequent disease management and glycemic control. We conducted 5 focus group interviews with 24 people who participated in TExT-MED. We employed a modified grounded theory analytic approach-an iterative process of coding and immersion in the data used to recognize the patterns and links between concepts voiced by the participants. We coded data to identify themes of participant experiences, motivations, and responses to the program. We organized themes into a theory of TExT-MED's action. Participants enjoyed their experience with TExT-MED and believed it improved their diabetes management. Through analysis of the transcripts, we identified that the strengths of the program were messages that cued specific behaviors such as medication reminders and challenge messages. Our analysis also revealed that increasing personalization of message delivery and content could augment these cues. This in-depth qualitative analysis of TExT-MED shows that low-income Latino patients will accept text messages as a behavioral intervention. This mHealth intervention acts as a behavioral trigger rather than an education platform. Personalization is an opportunity to enhance these cues to action and further research should be conducted on the ideal forms of personalization.

Perceptions of Successful Cues to Action and Opportunities to Augment Behavioral Triggers in Diabetes Self-Management: Qualitative Analysis of a Mobile Intervention for Low-Income Latinos With Diabetes

PubMed Central

Menchine, Michael D; Kubicek, Katrina; Robles, Marisela; Arora, Sanjay

2014-01-01

Background The increasing prevalence of diabetes and the associated cost of managing this complicated disease have a significant impact on public health outcomes and health expenditures, especially among resource-poor Latino patients. Mobile health (mHealth) may be the solution to reaching this group and improving their health. Objective In this qualitative study, we examined nuances of motivation, intention, and triggers to action effected by TExT-MED (Trial to Examine Text Messaging for Emergency Department patient with Diabetes), an mHealth intervention tailored to low-income, urban Latinos with diabetes. TExT-MED is a fully-automated, text message-based program designed to increase knowledge, self-efficacy, and subsequent disease management and glycemic control. Methods We conducted 5 focus group interviews with 24 people who participated in TExT-MED. We employed a modified grounded theory analytic approach—an iterative process of coding and immersion in the data used to recognize the patterns and links between concepts voiced by the participants. We coded data to identify themes of participant experiences, motivations, and responses to the program. We organized themes into a theory of TExT-MED’s action. Results Participants enjoyed their experience with TExT-MED and believed it improved their diabetes management. Through analysis of the transcripts, we identified that the strengths of the program were messages that cued specific behaviors such as medication reminders and challenge messages. Our analysis also revealed that increasing personalization of message delivery and content could augment these cues. Conclusions This in-depth qualitative analysis of TExT-MED shows that low-income Latino patients will accept text messages as a behavioral intervention. This mHealth intervention acts as a behavioral trigger rather than an education platform. Personalization is an opportunity to enhance these cues to action and further research should be conducted on the ideal forms of personalization. PMID:24476784

How to include the variability of TMS responses in simulations: a speech mapping case study

NASA Astrophysics Data System (ADS)

De Geeter, N.; Lioumis, P.; Laakso, A.; Crevecoeur, G.; Dupré, L.

2016-11-01

When delivered over a specific cortical site, TMS can temporarily disrupt the ongoing process in that area. This allows mapping of speech-related areas for preoperative evaluation purposes. We numerically explore the observed variability of TMS responses during a speech mapping experiment performed with a neuronavigation system. We selected four cases with very small perturbations in coil position and orientation. In one case (E) a naming error occurred, while in the other cases (NEA, B, C) the subject appointed the images as smoothly as without TMS. A realistic anisotropic head model was constructed of the subject from T1-weighted and diffusion-weighted MRI. The induced electric field distributions were computed, associated to the coil parameters retrieved from the neuronavigation system. Finally, the membrane potentials along relevant white matter fibre tracts, extracted from DTI-based tractography, were computed using a compartmental cable equation. While only minor differences could be noticed between the induced electric field distributions of the four cases, computing the corresponding membrane potentials revealed different subsets of tracts were activated. A single tract was activated for all coil positions. Another tract was only triggered for case E. NEA induced action potentials in 13 tracts, while NEB stimulated 11 tracts and NEC one. The calculated results are certainly sensitive to the coil specifications, demonstrating the observed variability in this study. However, even though a tract connecting Broca’s with Wernicke’s area is only triggered for the error case, further research is needed on other study cases and on refining the neural model with synapses and network connections. Case- and subject-specific modelling that includes both electromagnetic fields and neuronal activity enables demonstration of the variability in TMS experiments and can capture the interaction with complex neural networks.

Protection against β-amyloid neurotoxicity by a non-toxic endogenous N-terminal β-amyloid fragment and its active hexapeptide core sequence.

PubMed

Forest, Kelly H; Alfulaij, Naghum; Arora, Komal; Taketa, Ruth; Sherrin, Tessi; Todorovic, Cedomir; Lawrence, James L M; Yoshikawa, Gene T; Ng, Ho-Leung; Hruby, Victor J; Nichols, Robert A

2018-01-01

High levels (μM) of beta amyloid (Aβ) oligomers are known to trigger neurotoxic effects, leading to synaptic impairment, behavioral deficits, and apoptotic cell death. The hydrophobic C-terminal domain of Aβ, together with sequences critical for oligomer formation, is essential for this neurotoxicity. However, Aβ at low levels (pM-nM) has been shown to function as a positive neuromodulator and this activity resides in the hydrophilic N-terminal domain of Aβ. An N-terminal Aβ fragment (1-15/16), found in cerebrospinal fluid, was also shown to be a highly active neuromodulator and to reverse Aβ-induced impairments of long-term potentiation. Here, we show the impact of this N-terminal Aβ fragment and a shorter hexapeptide core sequence in the Aβ fragment (Aβcore: 10-15) to protect or reverse Aβ-induced neuronal toxicity, fear memory deficits and apoptotic death. The neuroprotective effects of the N-terminal Aβ fragment and Aβcore on Aβ-induced changes in mitochondrial function, oxidative stress, and apoptotic neuronal death were demonstrated via mitochondrial membrane potential, live reactive oxygen species, DNA fragmentation and cell survival assays using a model neuroblastoma cell line (differentiated NG108-15) and mouse hippocampal neuron cultures. The protective action of the N-terminal Aβ fragment and Aβcore against spatial memory processing deficits in amyloid precursor protein/PSEN1 (5XFAD) mice was demonstrated in contextual fear conditioning. Stabilized derivatives of the N-terminal Aβcore were also shown to be fully protective against Aβ-triggered oxidative stress. Together, these findings indicate an endogenous neuroprotective role for the N-terminal Aβ fragment, while active stabilized N-terminal Aβcore derivatives offer the potential for therapeutic application. © 2017 International Society for Neurochemistry.

Parent Trigger Policies, Representation, and the Public Good

ERIC Educational Resources Information Center

Allen, Ann; Saultz, Andrew

2015-01-01

Using theories of representation and democratic education, this article examines the impetus of parent trigger policies in the United States and their potential effects on public good goals for public education. The article also uses theories of representation and responsible democratic governance to assess the parent trigger policies, or what are…

An event-related visual occlusion method for examining anticipatory skill in natural interceptive tasks.

PubMed

Mann, David L; Abernethy, Bruce; Farrow, Damian; Davis, Mark; Spratford, Wayne

2010-05-01

This article describes a new automated method for the controlled occlusion of vision during natural tasks. The method permits the time course of the presence or absence of visual information to be linked to identifiable events within the task of interest. An example application is presented in which the method is used to examine the ability of cricket batsmen to pick up useful information from the prerelease movement patterns of the opposing bowler. Two key events, separated by a consistent within-action time lag, were identified in the cricket bowling action sequence-namely, the penultimate foot strike prior to ball release (Event 1), and the subsequent moment of ball release (Event 2). Force-plate registration of Event 1 was then used as a trigger to facilitate automated occlusion of vision using liquid crystal occlusion goggles at time points relative to Event 2. Validation demonstrated that, compared with existing approaches that are based on manual triggering, this method of occlusion permitted considerable gains in temporal precision and a reduction in the number of unusable trials. A more efficient and accurate protocol to examine anticipation is produced, while preserving the important natural coupling between perception and action.

Phase-shift, stimuli-responsive drug carriers for targeted delivery

PubMed Central

O’Neill, Brian E; Rapoport, Natalya

2011-01-01

The intersection of particles and directed energy is a rich source of novel and useful technology that is only recently being realized for medicine. One of the most promising applications is directed drug delivery. This review focuses on phase-shift nanoparticles (that is, particles of submicron size) as well as micron-scale particles whose action depends on an external-energy triggered, first-order phase shift from a liquid to gas state of either the particle itself or of the surrounding medium. These particles have tremendous potential for actively disrupting their environment for altering transport properties and unloading drugs. This review covers in detail ultrasound and laser-activated phase-shift nano- and micro-particles and their use in drug delivery. Phase-shift based drug-delivery mechanisms and competing technologies are discussed. PMID:22059114

DNA Nanostructures as Smart Drug-Delivery Vehicles and Molecular Devices.

PubMed

Linko, Veikko; Ora, Ari; Kostiainen, Mauri A

2015-10-01

DNA molecules can be assembled into custom predesigned shapes via hybridization of sequence-complementary domains. The folded structures have high spatial addressability and a tremendous potential to serve as platforms and active components in a plethora of bionanotechnological applications. DNA is a truly programmable material, and its nanoscale engineering thus opens up numerous attractive possibilities to develop novel methods for therapeutics. The tailored molecular devices could be used in targeting cells and triggering the cellular actions in the biological environment. In this review we focus on the DNA-based assemblies - primarily DNA origami nanostructures - that could perform complex tasks in cells and serve as smart drug-delivery vehicles in, for example, cancer therapy, prodrug medication, and enzyme replacement therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Need telomere maintenance? Call 911.

PubMed

Francia, Sofia; Weiss, Robert S; d'Adda di Fagagna, Fabrizio

2007-01-17

"Natura non facit saltum" (nature makes no leap) the Latins used to say, meaning that nature does not like discontinuities. Cells make no exception and indeed any discontinuity in the DNA double helix is promptly detected, triggering an alteration of cell proliferation and an attempt to repair. Yet, linear chromosomes bear DNA ends that are compatible with normal cell proliferation and they escape, under normal conditions, any repair. How telomeres, the chromosomes tips, achieve that is not fully understood. We recently observed that the Rad9/Hus1/Rad1 (911) complex, previously known for its functions in DNA metabolism and DNA damage responses, is constitutively associated with telomeres and plays an important role in their maintenance. Here, we summarize the available data and discuss the potential mechanisms of 911 action at telomeres.

Need telomere maintenance? Call 911

PubMed Central

Francia, Sofia; Weiss, Robert S; d'Adda di Fagagna, Fabrizio

2007-01-01

"Natura non facit saltum" (nature makes no leap) the Latins used to say, meaning that nature does not like discontinuities. Cells make no exception and indeed any discontinuity in the DNA double helix is promptly detected, triggering an alteration of cell proliferation and an attempt to repair. Yet, linear chromosomes bear DNA ends that are compatible with normal cell proliferation and they escape, under normal conditions, any repair. How telomeres, the chromosomes tips, achieve that is not fully understood. We recently observed that the Rad9/Hus1/Rad1 (911) complex, previously known for its functions in DNA metabolism and DNA damage responses, is constitutively associated with telomeres and plays an important role in their maintenance. Here, we summarize the available data and discuss the potential mechanisms of 911 action at telomeres. PMID:17229321

Are there negative CNS impacts of aluminum adjuvants used in vaccines and immunotherapy?

PubMed

Shaw, Christopher A; Li, Dan; Tomljenovic, Lucija

2014-01-01

In spite of a common view that aluminum (Al) salts are inert and therefore harmless as vaccine adjuvants or in immunotherapy, the reality is quite different. In the following article we briefly review the literature on Al neurotoxicity and the use of Al salts as vaccine adjuvants and consider not only direct toxic actions on the nervous system, but also the potential impact for triggering autoimmunity. Autoimmune and inflammatory responses affecting the CNS appear to underlie some forms of neurological disease, including developmental disorders. Al has been demonstrated to impact the CNS at every level, including by changing gene expression. These outcomes should raise concerns about the increasing use of Al salts as vaccine adjuvants and for the application as more general immune stimulants.

78 FR 25236 - Approval and Promulgation of Implementation Plans; New York; Infrastructure SIP for the 1997 8...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-30

... enable the Commissioner to designate air pollution episodes which trigger the action plans. Pursuant to..., posts warnings on the above-referenced Web site and issues press releases to local media outlets if...

Testing for the 'predictability' of dynamically triggered earthquakes in The Geysers geothermal field

NASA Astrophysics Data System (ADS)

Aiken, Chastity; Meng, Xiaofeng; Hardebeck, Jeanne

2018-03-01

The Geysers geothermal field is well known for being susceptible to dynamic triggering of earthquakes by large distant earthquakes, owing to the introduction of fluids for energy production. Yet, it is unknown if dynamic triggering of earthquakes is 'predictable' or whether dynamic triggering could lead to a potential hazard for energy production. In this paper, our goal is to investigate the characteristics of triggering and the physical conditions that promote triggering to determine whether or not triggering is in anyway foreseeable. We find that, at present, triggering in The Geysers is not easily 'predictable' in terms of when and where based on observable physical conditions. However, triggered earthquake magnitude positively correlates with peak imparted dynamic stress, and larger dynamic stresses tend to trigger sequences similar to mainshock-aftershock sequences. Thus, we may be able to 'predict' what size earthquakes to expect at The Geysers following a large distant earthquake.

Testing for the ‘predictability’ of dynamically triggered earthquakes in Geysers Geothermal Field

USGS Publications Warehouse

Aiken, Chastity; Meng, Xiaofeng; Hardebeck, Jeanne L.

2018-01-01

The Geysers geothermal field is well known for being susceptible to dynamic triggering of earthquakes by large distant earthquakes, owing to the introduction of fluids for energy production. Yet, it is unknown if dynamic triggering of earthquakes is ‘predictable’ or whether dynamic triggering could lead to a potential hazard for energy production. In this paper, our goal is to investigate the characteristics of triggering and the physical conditions that promote triggering to determine whether or not triggering is in anyway foreseeable. We find that, at present, triggering in The Geysers is not easily ‘predictable’ in terms of when and where based on observable physical conditions. However, triggered earthquake magnitude positively correlates with peak imparted dynamic stress, and larger dynamic stresses tend to trigger sequences similar to mainshock–aftershock sequences. Thus, we may be able to ‘predict’ what size earthquakes to expect at The Geysers following a large distant earthquake.

Implementation of a custom time-domain firmware trigger for RADAR-based cosmic ray detection

NASA Astrophysics Data System (ADS)

Prohira, S.; Besson, D.; Kunwar, S.; Ratzlaff, K.; Young, R.

2018-05-01

Interest in Radio-based detection schemes for ultra-high energy cosmic rays (UHECR) has surged in recent years, owing to the potentially very low cost/detection ratio. The method of radio-frequency (RF) scatter has been proposed as potentially the most economical detection technology. Though the first dedicated experiment to employ this method, the Telescope Array RADAR experiment (TARA) reported no signal, efforts to develop more robust and sensitive trigger techniques continue. This paper details the development of a time-domain firmware trigger that exploits characteristics of the expected scattered signal from an UHECR extensive-air shower (EAS). The improved sensitivity of this trigger is discussed, as well as implementation in two separate field deployments from 2016 to 2017.

Using WYSIWYG GUI Tools with UML

DTIC Science & Technology

2009-06-01

diagram that shows the ports through which it sends and receives messages to and from other active classes. The behavior is described using a state...software that talks to its environment through ports (specified in the structure diagram), and performs actions as it transitions through a sequence of...used to trigger actions on the state diagram. As a result, the stimulus to these events is pro- vided by the system itself in the case of the timer port

PHASE-SHIFT, STIMULI-RESPONSIVE PERFLUOROCARBON NANODROPLETS FOR DRUG DELIVERY TO CANCER

PubMed Central

2012-01-01

This review focuses on phase-shift perfluorocarbon nanoemulsions whose action depends on an ultrasound-triggered phase shift from a liquid to gas state. For drug-loaded perfluorocarbon nanoemulsions, microbubbles are formed under the action of tumor-directed ultrasound and drug is released locally into tumor volume in this process. This review covers in detail mechanisms involved in the droplet-to-bubble transition as well as mechanisms of ultrasound-mediated drug delivery. PMID:22730185

New operator assistance features in the CMS Run Control System

NASA Astrophysics Data System (ADS)

Andre, J.-M.; Behrens, U.; Branson, J.; Brummer, P.; Chaze, O.; Cittolin, S.; Contescu, C.; Craigs, B. G.; Darlea, G.-L.; Deldicque, C.; Demiragli, Z.; Dobson, M.; Doualot, N.; Erhan, S.; Fulcher, J. R.; Gigi, D.; Gładki, M.; Glege, F.; Gomez-Ceballos, G.; Hegeman, J.; Holzner, A.; Janulis, M.; Jimenez-Estupiñán, R.; Masetti, L.; Meijers, F.; Meschi, E.; Mommsen, R. K.; Morovic, S.; O'Dell, V.; Orsini, L.; Paus, C.; Petrova, P.; Pieri, M.; Racz, A.; Reis, T.; Sakulin, H.; Schwick, C.; Simelevicius, D.; Vougioukas, M.; Zejdl, P.

2017-10-01

During Run-1 of the LHC, many operational procedures have been automated in the run control system of the Compact Muon Solenoid (CMS) experiment. When detector high voltages are ramped up or down or upon certain beam mode changes of the LHC, the DAQ system is automatically partially reconfigured with new parameters. Certain types of errors such as errors caused by single-event upsets may trigger an automatic recovery procedure. Furthermore, the top-level control node continuously performs cross-checks to detect sub-system actions becoming necessary because of changes in configuration keys, changes in the set of included front-end drivers or because of potential clock instabilities. The operator is guided to perform the necessary actions through graphical indicators displayed next to the relevant command buttons in the user interface. Through these indicators, consistent configuration of CMS is ensured. However, manually following the indicators can still be inefficient at times. A new assistant to the operator has therefore been developed that can automatically perform all the necessary actions in a streamlined order. If additional problems arise, the new assistant tries to automatically recover from these. With the new assistant, a run can be started from any state of the sub-systems with a single click. An ongoing run may be recovered with a single click, once the appropriate recovery action has been selected. We review the automation features of CMS Run Control and discuss the new assistant in detail including first operational experience.

Extracellular Ca²⁺ acts as a mediator of communication from neurons to glia.

PubMed

Torres, Arnulfo; Wang, Fushun; Xu, Qiwu; Fujita, Takumi; Dobrowolski, Radoslaw; Willecke, Klaus; Takano, Takahiro; Nedergaard, Maiken

2012-01-24

Defining the pathways through which neurons and astrocytes communicate may contribute to the elucidation of higher central nervous system functions. We investigated the possibility that decreases in extracellular calcium ion concentration ([Ca(2+)](e)) that occur during synaptic transmission might mediate signaling from neurons to glia. Using noninvasive photolysis of the photolabile Ca(2+) buffer diazo-2 {N-[2-[2-[2-[bis(carboxymethyl)amino]-5-(diazoacetyl)phenoxy]ethoxy]-4-methylphenyl]-N-(carboxymethyl)-, tetrapotassium salt} to reduce [Ca(2+)](e) or caged glutamate to simulate glutamatergic transmission, we found that a local decline in extracellular Ca(2+) triggered astrocytic adenosine triphosphate (ATP) release and astrocytic Ca(2+) signaling. In turn, activation of purinergic P2Y1 receptors on a subset of inhibitory interneurons initiated the generation of action potentials by these interneurons, thereby enhancing synaptic inhibition. Thus, astrocytic ATP release evoked by an activity-associated decrease in [Ca(2+)](e) may provide a negative feedback mechanism that potentiates inhibitory transmission in response to local hyperexcitability.

Extracellular Ca2+ Acts as a Mediator of Communication from Neurons to Glia

PubMed Central

Torres, Arnulfo; Wang, Fushun; Xu, Qiwu; Fujita, Takumi; Dobrowolski, Radoslaw; Willecke, Klaus; Takano, Takahiro; Nedergaard, Maiken

2013-01-01

Defining the pathways through which neurons and astrocytes communicate may contribute to the elucidation of higher central nervous system functions. We investigated the possibility that decreases in extracellular calcium ion concentration ([Ca2+]e) that occur during synaptic transmission might mediate signaling from neurons to glia. Using noninvasive photolysis of the photolabile Ca2+ buffer diazo-2 {N-[2-[2-[2-[bis(carboxymethyl)amino]-5-(diazoacetyl)phenoxy]ethoxy]-4-methylphenyl]-N-(carboxymethyl)-, tetrapotassium salt} to reduce [Ca2+]e or caged glutamate to simulate glutamatergic transmission, we found that a local decline in extracellular Ca2+ triggered astrocytic adenosine triphosphate (ATP) release and astrocytic Ca2+ signaling. In turn, activation of purinergic P2Y1 receptors on a subset of inhibitory interneurons initiated the generation of action potentials by these interneurons, thereby enhancing synaptic inhibition. Thus, astrocytic ATP release evoked by an activity-associated decrease in [Ca2+]e may provide a negative feedback mechanism that potentiates inhibitory transmission in response to local hyperexcitability. PMID:22275221

Global search of triggered non-volcanic tremor

NASA Astrophysics Data System (ADS)

Chao, Tzu-Kai Kevin

Deep non-volcanic tremor is a newly discovered seismic phenomenon with low amplitude, long duration, and no clear P- and S-waves as compared with regular earthquake. Tremor has been observed at many major plate-boundary faults, providing new information about fault slip behaviors below the seismogenic zone. While tremor mostly occurs spontaneously (ambient tremor) or during episodic slow-slip events (SSEs), sometimes tremor can also be triggered during teleseismic waves of distance earthquakes, which is known as "triggered tremor". The primary focus of my Ph.D. work is to understand the physical mechanisms and necessary conditions of triggered tremor by systematic investigations in different tectonic regions. In the first chapter of my dissertation, I conduct a systematic survey of triggered tremor beneath the Central Range (CR) in Taiwan for 45 teleseismic earthquakes from 1998 to 2009 with Mw ≥ 7.5. Triggered tremors are visually identified as bursts of high-frequency (2-8 Hz), non-impulsive, and long-duration seismic energy that are coherent among many seismic stations and modulated by the teleseismic surface waves. A total of 9 teleseismic earthquakes has triggered clear tremor in Taiwan. The peak ground velocity (PGV) of teleseismic surface waves is the most important factor in determining tremor triggering potential, with an apparent threshold of ˜0.1 cm/s, or 7-8 kPa. However, such threshold is partially controlled by the background noise level, preventing triggered tremor with weaker amplitude from being observed. In addition, I find a positive correlation between the PGV and the triggered tremor amplitude, which is consistent with the prediction of the 'clock-advance' model. This suggests that triggered tremor can be considered as a sped-up occurrence of ambient tremor under fast loading from the passing surface waves. Finally, the incident angles of surface waves also play an important rule in controlling the tremor triggering potential. The next chapter focuses on a systematic comparison of triggered tremor around the Calaveras Fault (CF) in northern California (NC), the Parkfield-Cholame section of the San Andreas Fault (SAF) in central California (CC), and the San Jacinto Fault (SJF) in southern California (SC). Out of 42 large (Mw ≥7.5) earthquakes between 2001 and 2010, only the 2002 Mw 7.9 Denali fault earthquake triggered clear tremor in NC and SC. In comparison, abundant triggered and ambient tremor has been observed in CC. Further analysis reveal that the lack of triggered tremor observations in SC and NC is not simply a consequence of their different background noise levels as compared to CC, but rather reflects different background tremor rates in these regions. In the final chapter, I systematically search for triggered tremor following the 2011 Mw9.0 Tohoku-Oki earthquake in the regions where ambient or triggered tremor has been found before. The main purpose is to check whether triggered tremor is observed in regions when certain conditions (e.g., surface wave amplitudes) are met. Triggered tremor is observed in southwest Japan, Taiwan, the Aleutian Arc, south-central Alaska, northern Vancouver Island, the Parkfield-Cholame section of the SAF in CC and the SJF in SC, and the North Island of New Zealand. Such a widespread triggering of tremor is not too surprising because of the large amplitude surface waves (minimum peak value of ˜0.1 cm/s) and the associated dynamic stresses (at least ˜7-8 kPa), which is one of the most important factors in controlling the triggering threshold. The triggered tremor in different region is located close to or nearby the ambient tremor active area. In addition, the amplitudes of triggered tremor have positive correlations with the amplitudes of teleseismic surface waves among many regions. Moreover, both Love and Rayleigh waves participate in triggering tremor in different regions, and their triggering potential is somewhat controlled by the incident angles. In summary, systematically surveys of triggered tremor in different tectonic regions reveal that triggered tremor shares similar physical mechanism (shear failure on the fault interface) as ambient tremor but with different loading conditions. The amplitude of the teleseismic surface wave is one of the most important factors in controlling the tremor triggering threshold. In addition, the frequency contents and incident angles of the triggering waves, and local fault geometry and ambient conditions also play certain roles in determining the triggering potential. On the other hand, the background noise level and seismic network coverage and station quality also could affect the apparent triggering threshold. (Abstract shortened by UMI.).

The use of intraoperative triggered electromyography to detect misplaced pedicle screws: a systematic review and meta-analysis.

PubMed

Mikula, Anthony L; Williams, Seth K; Anderson, Paul A

2016-04-01

Insertion of instruments or implants into the spine carries a risk for injury to neural tissue. Triggered electromyography (tEMG) is an intraoperative neuromonitoring technique that involves electrical stimulation of a tool or screw and subsequent measurement of muscle action potentials from myotomes innervated by nerve roots near the stimulated instrument. The authors of this study sought to determine the ability of tEMG to detect misplaced pedicle screws (PSs). The authors searched the U.S. National Library of Medicine, the Web of Science Core Collection database, and the Cochrane Central Register of Controlled Trials for PS studies. A meta-analysis of these studies was performed on a per-screw basis to determine the ability of tEMG to detect misplaced PSs. Sensitivity, specificity, and receiver operating characteristic (ROC) area under the curve (AUC) were calculated overall and in subgroups. Twenty-six studies were included in the systematic review. The authors analyzed 18 studies in which tEMG was used during PS placement in the meta-analysis, representing data from 2932 patients and 15,065 screws. The overall sensitivity of tEMG for detecting misplaced PSs was 0.78, and the specificity was 0.94. The overall ROC AUC was 0.96. A tEMG current threshold of 10-12 mA (ROC AUC 0.99) and a pulse duration of 300 µsec (ROC AUC 0.97) provided the most accurate testing parameters for detecting misplaced screws. Screws most accurately conducted EMG signals (ROC AUC 0.98). Triggered electromyography has very high specificity but only fair sensitivity for detecting malpositioned PSs.

A Label-Free and Sensitive Fluorescent Qualitative Assay for Bisphenol A Based on Rolling Circle Amplification/Exonuclease III-Combined Cascade Amplification.

PubMed

Li, Xia; Song, Juan; Xue, Qing-Wang; You, Fu-Heng; Lu, Xia; Kong, Yan-Cong; Ma, Shu-Yi; Jiang, Wei; Li, Chen-Zhong

2016-10-21

Bisphenol A (BPA) detection in drinking water and food packaging materials has attracted much attention since the discovery that BPA can interfere with normal physiological processes and cause adverse health effects. Here, we constructed a label-free aptamer fluorescent assay for selective and sensitive detection of BPA based on the rolling circle amplification (RCA)/Exonuclease III (Exo III)-combined cascade amplification strategy. First, the duplex DNA probe (RP) with anti-BPA aptamer and trigger sequence was designed for BPA recognition and signal amplification. Next, under the action of BPA, the trigger probe was liberated from RP to initiate RCA reaction as primary amplification. Subsequently, the RCA products were used to trigger Exo III assisted secondary amplification with the help of hairpin probes, producing plenty of "G-quadruplex" in lantern-like structures. Finally, the continuously enriched "G-quadruplex lanterns" were lightened by zinc(II)-protoporphyrin IX (ZnPPIX) generating enhanced fluorescence signals. By integrating the primary RCA and secondary Exo III mediated cascade amplification strategy, this method displayed an excellent sensitivity with the detection limits of 5.4 × 10 -17 M. In addition, the anti-BPA aptamer exhibits high recognition ability with BPA, guaranteeing the specificity of detection. The reporter signal probe (G-quadruplex with ZnPPIX) provides a label-free fluorescence signals readout without complicated labeling procedures, making the method simple in design and cost-effective in operation. Moreover, environmental samples analysis was also performed, suggesting that our strategy was reliable and had a great potential application in environmental monitoring.

A Label-Free and Sensitive Fluorescent Qualitative Assay for Bisphenol A Based on Rolling Circle Amplification/Exonuclease III-Combined Cascade Amplification

PubMed Central

Li, Xia; Song, Juan; Xue, Qing-Wang; You, Fu-Heng; Lu, Xia; Kong, Yan-Cong; Ma, Shu-Yi; Jiang, Wei; Li, Chen-Zhong

2016-01-01

Bisphenol A (BPA) detection in drinking water and food packaging materials has attracted much attention since the discovery that BPA can interfere with normal physiological processes and cause adverse health effects. Here, we constructed a label-free aptamer fluorescent assay for selective and sensitive detection of BPA based on the rolling circle amplification (RCA)/Exonuclease III (Exo III)-combined cascade amplification strategy. First, the duplex DNA probe (RP) with anti-BPA aptamer and trigger sequence was designed for BPA recognition and signal amplification. Next, under the action of BPA, the trigger probe was liberated from RP to initiate RCA reaction as primary amplification. Subsequently, the RCA products were used to trigger Exo III assisted secondary amplification with the help of hairpin probes, producing plenty of “G-quadruplex” in lantern-like structures. Finally, the continuously enriched “G-quadruplex lanterns” were lightened by zinc(II)-protoporphyrin IX (ZnPPIX) generating enhanced fluorescence signals. By integrating the primary RCA and secondary Exo III mediated cascade amplification strategy, this method displayed an excellent sensitivity with the detection limits of 5.4 × 10−17 M. In addition, the anti-BPA aptamer exhibits high recognition ability with BPA, guaranteeing the specificity of detection. The reporter signal probe (G-quadruplex with ZnPPIX) provides a label-free fluorescence signals readout without complicated labeling procedures, making the method simple in design and cost-effective in operation. Moreover, environmental samples analysis was also performed, suggesting that our strategy was reliable and had a great potential application in environmental monitoring. PMID:28335318

Conflict-Triggered Top-Down Control: Default Mode, Last Resort, or No Such Thing?

ERIC Educational Resources Information Center

Bugg, Julie M.

2014-01-01

The conflict monitoring account posits that globally high levels of conflict trigger engagement of top-down control; however, recent findings point to the mercurial nature of top-down control in high conflict contexts. The current study examined the potential moderating effect of associative learning on conflict-triggered top-down control…

Examining the Parent Trigger as a Strategy for School Reform and Parental Engagement

ERIC Educational Resources Information Center

Rogers, John; Lubienski, Chris; Scott, Janelle; Welner, Kevin G.

2015-01-01

Background: Purpose: This analysis considers the emergence, evidentiary basis, and potential of parent trigger policies. In particular, we focus on the policy, political and social circumstances in which parent trigger legislation emerged in California, the efficacy of the school improvement levers on which it draws, and the underlying assumptions…

Using adaptive processes and adverse outcome pathways to develop meaningful, robust, and actionable environmental monitoring programs.

PubMed

Arciszewski, Tim J; Munkittrick, Kelly R; Scrimgeour, Garry J; Dubé, Monique G; Wrona, Fred J; Hazewinkel, Rod R

2017-09-01

The primary goals of environmental monitoring are to indicate whether unexpected changes related to development are occurring in the physical, chemical, and biological attributes of ecosystems and to inform meaningful management intervention. Although achieving these objectives is conceptually simple, varying scientific and social challenges often result in their breakdown. Conceptualizing, designing, and operating programs that better delineate monitoring, management, and risk assessment processes supported by hypothesis-driven approaches, strong inference, and adverse outcome pathways can overcome many of the challenges. Generally, a robust monitoring program is characterized by hypothesis-driven questions associated with potential adverse outcomes and feedback loops informed by data. Specifically, key and basic features are predictions of future observations (triggers) and mechanisms to respond to success or failure of those predictions (tiers). The adaptive processes accelerate or decelerate the effort to highlight and overcome ignorance while preventing the potentially unnecessary escalation of unguided monitoring and management. The deployment of the mutually reinforcing components can allow for more meaningful and actionable monitoring programs that better associate activities with consequences. Integr Environ Assess Manag 2017;13:877-891. © 2017 The Authors. Integrated Environmental Assessment and Management Published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC). © 2017 The Authors. Integrated Environmental Assessment and Management Published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Neuroprotective properties and mechanisms of resveratrol in in vitro and in vivo experimental cerebral stroke models.

PubMed

Singh, Nilendra; Agrawal, Megha; Doré, Sylvain

2013-08-21

Resveratrol, a natural stilbene present at relatively high concentrations in grape skin and seeds and red wine, is known for its purported antioxidant activity in the vascular and nervous systems. In contrast to its direct antioxidant role within the central nervous system, recent research supports a protective mechanism through increasing endogenous cellular antioxidant defenses, which triggers a cascade of parallel neuroprotective pathways. A growing body of in vitro and in vivo evidence indicates that resveratrol acts through multiple pathways and reduces ischemic damage in vital organs, such as the heart and the brain, in various rodent models. Most of the protective biological actions of resveratrol have been associated with its antioxidative, anti-inflammatory, and antiapoptotic properties and other indirect pathways. Continued public interest and increasing resveratrol supplements on the market warrant a review of the available in vitro and in vivo science reported in the stroke-related literature. Rigorous clinical trials evaluating the effects of resveratrol in stroke are absent, though the general population consumption appears to be relatively safe. Resveratrol has shown potential for treating stroke in laboratory animals and in vitro human cell studies, yet there is still a need for human research in preclinical settings. This review summarizes many of the findings on the neuroprotective potential of resveratrol in cerebral stroke, focusing on both the in vitro and in vivo experimental models and some proposed mechanisms of action.

Towards real-time risk mitigation for NPP in Switzerland: the potential role of EEW and OEF.

NASA Astrophysics Data System (ADS)

Cauzzi, Carlo; Wiemer, Stefan; Behr, Yannik; Clinton, John; Renault, Philippe; Le Guenan, Thomas; Douglas, John; Woessner, Jochen; Biro, Yesim; Caprio, Marta; Cua, Georgia

2014-05-01

Spurred by the research activities being carried out within the EC-funded project REAKT (Strategies and Tools for Real Time Earthquake Risk Reduction, FP7, contract no. 282862, 2011-2014, www.reaktproject.eu), we present herein the key elements to understanding the potential benefits of routinely using Earthquake Early Warning and Operational Earthquake Forecasting methods to mitigate the seismic risk at NPP in Switzerland. The advantages of using the aforementioned real-time risk reduction tools are critically discussed based on the limitations of the current scientific knowledge and technology, as well as on the costs associated to both system maintenance and machine- or human-triggered actions following an alert. Basic inputs to this discussion are, amongst others: a) the performances of the Swiss seismic network (http://www.seismo.ethz.ch/monitor, where SeisComP3 is used as earthquake monitoring software) and the selected EEW algorithm (the Virtual Seismologist, VS, http://www.seiscomp3.org/doc/seattle/2013.200/apps/vs.html), in terms of correct detections, false alerts, and missed events; b) the reliability of time-dependent hazard scenarios for the region of interest; c) a careful assessment of the frequency of occurrence of critical warnings based on the local and regional seismicity; d) the identification of the mitigation actions and their benefits and costs for the stakeholders.

Hardware Trojans - Prevention, Detection, Countermeasures (A Literature Review)

DTIC Science & Technology

2011-07-01

Phase and Location . . . . . . . . . . . . . . . . . . . . . . . . . 4 2.2 Hardware Trojan Actions...12 3.4 Trigger Design Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 4 Prevention 14 4.1 Prevention...The specification is then realised into specific tar- 4 UNCLASSIFIED UNCLASSIFIED DSTO–TN–1012 get technologies with consideration of functional and

76 FR 78524 - Airworthiness Directives; Airbus Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-19

... Airworthiness Directives; Airbus Airplanes AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT). ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for Airbus... an aeroplane from the Airbus production line, a fault message was triggered on FDU1 [fire detection...

Deriving empirical benchmarks from existing monitoring datasets for rangeland adaptive management

USDA-ARS?s Scientific Manuscript database

Under adaptive management, goals and decisions for managing rangeland resources are shaped by requirements like the Bureau of Land Management’s (BLM’s) Land Health Standards, which specify desired conditions. Without formalized, quantitative benchmarks for triggering management actions, adaptive man...

Managing Asthma at School.

ERIC Educational Resources Information Center

Madden, Julie A.

2000-01-01

School personnel must know which students have asthma, typical warning signs, and appropriate actions in an emergency. Administering appropriate medication and reducing environmental triggers are not enough. Policymaking in schools and workplaces and legislation to increase health care access and eliminate substandard housing and air pollution are…

NATIONAL SURVEY ON ENVIRONMENTAL MANAGEMENT OF ASTHMA

EPA Science Inventory

The National Survey on Environmental Management of Asthma is a nation-wide survey on awareness of and existing attitudes toward asthma and its environmental triggers. The survey will generate data which can be used as a benchmark to measure national awareness and action related ...

Hazard potential of volcanic flank collapses raised by new megatsunami evidence

PubMed Central

Ramalho, Ricardo S.; Winckler, Gisela; Madeira, José; Helffrich, George R.; Hipólito, Ana; Quartau, Rui; Adena, Katherine; Schaefer, Joerg M.

2015-01-01

Large-scale gravitational flank collapses of steep volcanic islands are hypothetically capable of triggering megatsunamis with highly catastrophic effects. Yet, evidence for the generation and impact of collapse-triggered megatsunamis and their high run-ups remains scarce or is highly controversial. Therefore, doubts remain on whether island flank failures truly generate enough volume flux to trigger giant tsunamis, leading to diverging opinions concerning the real hazard potential of such collapses. We show that one of the most prominent oceanic volcanoes on Earth—Fogo, in the Cape Verde Islands—catastrophically collapsed and triggered a megatsunami with devastating effects ~73,000 years ago. Our deductions are based on the recent discovery and cosmogenic 3He dating of tsunamigenic deposits found on nearby Santiago Island, which attest to the impact of this giant tsunami and document wave run-up heights exceeding 270 m. The evidence reported here implies that Fogo’s flank failure involved at least one fast and voluminous event that led to a giant tsunami, in contrast to what has been suggested before. Our observations therefore further demonstrate that flank collapses may indeed catastrophically happen and are capable of triggering tsunamis of enormous height and energy, adding to their hazard potential. PMID:26601287

Aiming routines and their electrocortical concomitants among competitive rifle shooters.

PubMed

Konttinen, N; Landers, D M; Lyytinen, H

2000-06-01

The present study focused on an examination of competitive shooters' aiming process during a rifle shooting task. The barrel movements of the rifle, as detected by a laser system during the last 1000-ms time period preceding the triggering, were recorded from six elite and six pre-elite shooters. Electrocortical slow potentials (SPs) from frontal (Fz), centro-lateral (C3, C4), and occipital (Oz) brain areas were recorded to get an additional insight into the underlying covert processing. The results suggested that the elite shooters did not pull the trigger until they reached a sustained rifle position. In the pre-elite shooters the rifle appeared to be in a less stable position, and their strategy was to take advantage of the first appropriate moment of steadiness without a sustained rifle position so they could pull the trigger. The observed pre-trigger readiness potential (RP) shifts at Fz and Oz were more positive among the elite shooters relative to the pre-elite shooters, reflecting their more pronounced covert effort, rather than increasing preparedness for the trigger pull. The present study lends support for the view that a successful aiming strategy is mainly based on sustained rifle balancing. With regards to the brain slow potentials, it can be concluded that the RP shift does not specifically reflect the preparation for the trigger pull.

Physiological properties of anatomically identified axo-axonic cells in the rat hippocampus.

PubMed

Buhl, E H; Han, Z S; Lörinczi, Z; Stezhka, V V; Karnup, S V; Somogyi, P

1994-04-01

1. The properties of a well-defined type of GABAergic local circuit neuron, the axo-axonic cell (n = 17), were investigated in rat hippocampal slice preparations. During intracellular recording we injected axo-axonic cells with biocytin and subsequently identified them with correlated light and electron microscopy. Employing an immunogold-silver intensification technique we showed that one of the physiologically characterized cells was immunoreactive for gamma-aminobutyric acid (GABA). 2. Axo-axonic cells were encountered in the dentate gyrus (n = 5) as well as subfields CA3 (n = 2) and CA1 (n = 10). They generally had smooth, beaded dendrites that extended throughout all hippocampal layers. Their axons ramified densely in the cell body layers and in the subjacent stratum oriens or hilus, respectively. Tested with electron microscopy, labeled terminals (n = 53) established synapses exclusively with the axon initial segment of principal cells in strata oriens and pyramidale and rarely in lower radiatum. Within a 400-microns slice a single CA1 axo-axonic cell was estimated to be in synaptic contact with 686 pyramidal cells. 3. Axo-axonic cells (n = 14) had a mean resting membrane potential of -65.1 mV, an average input resistance of 73.9 M omega, and a mean time constant of 7.7 ms. Action potentials were of short duration (389-microseconds width at half-amplitude) and had a mean amplitude of 64.1 mV. 4. Nine of 10 tested cells showed a varying degree of spike frequency adaptation in response to depolarizing current injection. Current-evoked action potentials were usually curtailed by a deep (10.2 mV) short-latency afterhyperpolarization (AHP) with a mean duration of 28.1 ms. 5. Cells with strong spike frequency accommodation (n = 5) had a characteristic firing pattern with numerous spike doublets. These appeared to be triggered by an underlying depolarizing afterpotential. In the same cells, prolonged bursts of action potentials were followed by a prominent long-duration AHP with a mean time constant of 1.15 s. 6. Axo-axonic cells responded to the stimulation of afferent pathways with short-latency excitatory postsynaptic potentials (EPSPs) or at higher stimulation intensity with up to three action potentials. Axo-axonic cells in the dentate gyrus could be activated by stimulating the CA3 area as well as the perforant path, whereas in the CA1 area responses were elicited after shocks to the perforant path, Schaffer collaterals, and the stratum oriens-alveus border. 7. In the CA1 area the EPSP amplitude increased in response to membrane hyperpolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

Development of a Virtual Reality Coping Skills Game to Prevent Post-Hospitalization Smoking Relapse in Tobacco Dependent Cancer Patients.

PubMed

Krebs, Paul; Burkhalter, Jack; Lewis, Shireen; Hendrickson, Tinesha; Chiu, Ophelia; Fearn, Paul; Perchick, Wendy; Ostroff, Jamie

2009-08-01

Many hospitalized smokers return to smoking after hospital discharge even though continued smoking can compromise treatment effectiveness, reduce survival, increase risk of disease recurrence, and impair quality of life. After leaving a smoke-free hospital, patients encounter smoking cues at home, such as family members who smoke or emotional triggers such as stress, which can elicit powerful urges to smoke and lead to smoking relapse. Enabling smokers to experience such urges in a controlled setting while providing the ability to practice coping skills may be a useful strategy for building quitting self-efficacy. We are developing a virtual reality coping skills (VRCS) game to help hospitalized smokers practice coping strategies to manage these triggers in preparation for returning home after hospitalization. Our multidisciplinary team developed a prototype VRCS game using Second Life, a platform that allowed rapid construction of a virtual reality environment. The prototype contains virtual home spaces (e.g., living room, kitchen) populated with common triggers to smoke and a "toolkit" with scripted actions that enable the avatar to rehearse various coping strategies. Since eliciting and managing urges to smoke is essential to the game's utility as an intervention, we assessed the ability of the prototype virtual environment to engage former smokers in these scenarios. We recruited eight former smokers with a recent history of hospitalization and guided each through a VRCS scenario during which we asked the patient to evaluate the strength of smoking urges and usefulness of coping strategies. Initial data indicate that patients report high urges to smoke (mean = 8.8 on a 10 point scale) when their avatar confronted virtual triggers such as drinking coffee. Patients rated virtual practice of coping strategies, such as drinking water or watching TV, as very helpful (mean = 8.4 on a 10 point scale) in reducing these urges. With further development, this VRCS game may have potential to provide low-cost, effective behavioral rehearsal to prevent relapse to smoking in hospitalized patients.

Detecting Periprocedural Myocardial Infarction in Contemporary Percutaneous Coronary Intervention Trials.

PubMed

Spitzer, Ernest; de Vries, Ton; Cavalcante, Rafael; Tuinman, Marieke; Rademaker-Havinga, Tessa; Alkema, Maaike; Morel, Marie-Angele; Soliman, Osama I; Onuma, Yoshinobu; van Es, Gerrit-Anne; Tijssen, Jan G P; McFadden, Eugene; Serruys, Patrick W

2017-04-10

This study sought to investigate the differences in detecting (e.g., triggering) periprocedural myocardial infarction (PMI) among 3 current definitions. PMI is a frequent component of primary endpoints in coronary device trials. Identification of all potential suspected events is critical for accurate event ascertainment. Automatic triggers based on study databases prevent underreporting of events. We generated automated algorithms to trigger PMI based on each definition and compared results using data from the RESOLUTE all comers trial. The operationalization of current PMI definitions was achieved by defining programmable algorithms used to interrogate the study database. From a total of 636 PMI triggers, we identified 234 for the World Health Organization extended definition, 382 for the Third Universal definition, and 216 for the Society for Cardiovascular Angiography and Interventions definition. Differences among the biomarkers used, different cutoff values, and in the hierarchy among biomarkers within definitions, yielded a different number of triggers, and identified unique triggers for each definition. Only 38 triggers were consistently identified by all definitions. Availability of ECG data, eCRF data on clinical presentation, and the reporting of >2 post-procedural values of the same biomarker influenced considerably the number of PMI triggers identified. PMI definitions are not interchangeable. The number of triggers identified and consequently the potential number of events varies significantly, highlighting the importance of rigorous methodology when PMI is a component of a powered endpoint. Emphasis on collection of biomarkers, ECG data, and clinical status at baseline may improve the correct identification of PMI triggers. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Fusion of Enveloped Viruses in Endosomes

PubMed Central

White, Judith M.; Whittaker, Gary R.

2016-01-01

Ari Helenius launched the field of enveloped virus fusion in endosomes with a seminal paper in the Journal of Cell Biology in 1980. In the intervening years a great deal has been learned about the structures and mechanisms of viral membrane fusion proteins as well as about the endosomes in which different enveloped viruses fuse and the endosomal cues that trigger fusion. We now recognize three classes of viral membrane fusion proteins based on structural criteria and four mechanisms of fusion triggering. After reviewing general features of viral membrane fusion proteins and viral fusion in endosomes, we delve into three characterized mechanisms for viral fusion triggering in endosomes: by low pH, by receptor binding plus low pH, and by receptor binding plus the action of a protease. We end with a discussion of viruses that may employ novel endosomal fusion triggering mechanisms. A key take home message is that enveloped viruses that enter cells by fusing in endosomes traverse the endocytic pathway until they reach an endosome that has all of the environmental conditions (pH, proteases, ions, intracellular receptors, and lipid composition) to (if needed) prime and (in all cases) trigger the fusion protein and to support membrane fusion. PMID:26935856

Mechanisms involved in cardiac sensitization by volatile anesthetics: general applicability to halogenated hydrocarbons?

PubMed

Himmel, Herbert M

2008-01-01

An increased sensitivity of the heart to catecholamines or cardiac sensitization is a recognized risk during acute human exposure to halogenated hydrocarbons used as solvents, foam-blowing or fire-extinguishing agents, refrigerants, and aerosol propellants. Although cardiac sensitization to such "industrial" halocarbons can result in serious arrhythmia and death, research into its mechanistic basis has been limited, whereas the literature on volatile anesthetics (e.g., halothane, chloroform) is comparably extensive. A review of the literature on halocarbons and related volatile anesthetics was conducted. The available experimental evidence suggests that volatile anesthetics at physiologically relevant concentrations interact predominantly with the main repolarizing cardiac potassium channels hERG and I(Ks), as well as with calcium and sodium channels at slightly higher concentrations. On the level of the heart, inhibition of these ion channels is prone to alter both action potential shape (triangulation) and electrical impulse conduction, which may facilitate arrhythmogenesis by volatile anesthetics per se and is potentiated by catecholamines. Action potential triangulation by regionally heterogeneous inhibition of calcium and potassium channels will facilitate catecholamine-induced afterdepolarizations, triggered activity, and enhanced automaticity. Inhibition of cardiac sodium channels will reduce conduction velocity and alter refractory period; this is potentiated by catecholamines and promotes reentry arrhythmias. Other cardiac and/or neuronal mechanisms might also contribute to arrhythmogenesis. The few scattered in vitro data available for halocarbons (e.g., FC-12, halon 1301, trichloroethylene) suggest inhibition of cardiac sodium (conduction), calcium and potassium channels (triangulation), extraneuronal catecholamine reuptake, and various neuronal ion channels. Therefore, it is hypothesized that halocarbons promote cardiac sensitization by similar mechanisms as volatile anesthetics. Experimental approaches for further investigation of these sensitization mechanisms by selected halocarbons are suggested.

DATA COLLECTION ON ENVIRONMENTAL MANAGEMENT OF ASTHMA

EPA Science Inventory

We are working with CDC to determine if we can add a module to one or more of their surveys which would provide information on awareness of and existing attitudes toward asthma and its environmental triggers, actions implemented and barriers to implementation encountered by adult...

Advancements in satellite remote sensing for drought monitoring

USDA-ARS?s Scientific Manuscript database

Drought monitoring is a key component for effective drought preparedness strategies, providing critical information on current conditions that can be used to trigger mitigation actions to lessen the impact of this natural hazard. However, drought can be both complex and challenging to monitor becau...

An Interactive Model of Career Decision Making.

ERIC Educational Resources Information Center

Amundson, Norman E.

1995-01-01

The decision-making model described highlights the interaction between contextual factors, decision triggers, establishing a frame of the problem, reframing, and action planning. The interactive perspective is based on process and change. Career counseling with an interactive decision-making approach requires an acknowledgment of external…

In the grip of the python: conflicts at the university-industry interface.

PubMed

Healy, David

2003-01-01

When the University of Toronto withdrew a contract it held with me in December 2000, it initiated a sequence of events that led to a public letter to the University from senior figures in the world psychopharmacology community protesting against the infringement of academic freedom involved and a first ever legal action, undertake by this author, seeking redress for a violation of academic freedom. The issues of academic freedom surrounding this case have been intertwined with a debate about the possibility that the selective serotonin reuptake inhibitor (SSRI) group of antidepressants have the potential to trigger suicidality in a subgroup of patients. Whether the SSRIs do trigger suicidality or not, exploration of this issue has given rise to a number of worrying sets of observations. First, in my view, there is evidence that pharmaceutical companies have miscoded raw data on suicidal acts and suicidal ideation. Second, this author also maintains that there is a growing body of examples of ghostwriting of articles in the therapeutics domain. Many of the tensions evident in this case, therefore, can be linked to company abilities to keep clinical trial data out of the public domain--this is the point at which the pharmaceutical python gets a grip on academia.

A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone.

PubMed

Song, Ok-Ryul; Kim, Han-Byul; Jouny, Samuel; Ricard, Isabelle; Vandeputte, Alexandre; Deboosere, Nathalie; Marion, Estelle; Queval, Christophe J; Lesport, Pierre; Bourinet, Emmanuel; Henrion, Daniel; Oh, Seog Bae; Lebon, Guillaume; Sandoz, Guillaume; Yeramian, Edouard; Marsollier, Laurent; Brodin, Priscille

2017-07-18

Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans , is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT₂ receptors (angiotensin II type 2 receptors; AT₂R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT₂R, with this action being not affected by known ligands of AT₂R. This result points towards novel AT₂R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics.

Is lipid signaling through cannabinoid 2 receptors part of a protective system?

PubMed Central

Pacher, P.; Mechoulam, R.

2011-01-01

The mammalian body has a highly developed immune system which guards against continuous invading protein attacks and aims at preventing, attenuating or repairing the inflicted damage. It is conceivable that through evolution analogous biological protective systems have been evolved against non-protein attacks. There is emerging evidence that lipid endocannabinoid signaling through cannabinoid 2 (CB2) receptors may represent an example/part of such a protective system/armamentarium. Inflammation/tissue injury triggers rapid elevations in local endocannabinoid levels, which in turn regulate signaling responses in immune and other cells modulating their critical functions. Changes in endocannabinoid levels and/or CB2 receptor expressions have been reported in almost all diseases affecting humans, ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, auto-immune, lung disorders to pain and cancer, and modulating CB2 receptor activity holds tremendous therapeutic potential in these pathologies. While CB2 receptor activation in general mediates immunosuppressive effects, which limit inflammation and associated tissue injury in large number of pathological conditions, in some disease states activation of the CB2 receptor may enhance or even trigger tissue damage, which will also be discussed alongside the protective actions of the CB2 receptor stimulation with endocannabinoids or synthetic agonists, and the possible biological mechanisms involved in these effects. PMID:21295074

Is lipid signaling through cannabinoid 2 receptors part of a protective system?

PubMed

Pacher, P; Mechoulam, R

2011-04-01

The mammalian body has a highly developed immune system which guards against continuous invading protein attacks and aims at preventing, attenuating or repairing the inflicted damage. It is conceivable that through evolution analogous biological protective systems have been evolved against non-protein attacks. There is emerging evidence that lipid endocannabinoid signaling through cannabinoid 2 (CB₂) receptors may represent an example/part of such a protective system/armamentarium. Inflammation/tissue injury triggers rapid elevations in local endocannabinoid levels, which in turn regulate signaling responses in immune and other cells modulating their critical functions. Changes in endocannabinoid levels and/or CB₂ receptor expressions have been reported in almost all diseases affecting humans, ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, autoimmune, lung disorders to pain and cancer, and modulating CB₂ receptor activity holds tremendous therapeutic potential in these pathologies. While CB₂ receptor activation in general mediates immunosuppressive effects, which limit inflammation and associated tissue injury in large number of pathological conditions, in some disease states activation of the CB₂ receptor may enhance or even trigger tissue damage, which will also be discussed alongside the protective actions of the CB₂ receptor stimulation with endocannabinoids or synthetic agonists, and the possible biological mechanisms involved in these effects. Published by Elsevier Ltd.

Drug delivery with topically applied nanoparticles: science fiction or reality.

PubMed

Lademann, J; Richter, H; Meinke, M C; Lange-Asschenfeldt, B; Antoniou, C; Mak, W C; Renneberg, R; Sterry, W; Patzelt, A

2013-01-01

The efficacy of topically applied drugs is determined by their action mechanism and their potential capacity of passing the skin barrier. Nanoparticles are assumed to be efficient carrier systems for drug delivery through the skin barrier. For flexible nanoparticles like liposomes, this effect has been well demonstrated. The penetration properties of solid nanoparticles are currently under intensive investigation. The crucial advantage of nanoparticles over non-particulate substances is their capability to penetrate deeply into the hair follicles where they can be stored for several days. There is no evidence, yet, that solid particles ≥40 nm are capable of passing through the healthy skin barrier. Therefore and in spite of the long-standing research efforts in this field, commercially available solid nanoparticle-based products for drug delivery through the healthy skin are still missing. Nevertheless, the prospects for the clinical use of nanoparticles in drug delivery are tremendous. They can be designed as transport systems delivering drugs efficiently into the hair follicles in the vicinity of specific target structures. Once deposited at these structures, specific signals might trigger the release of the drugs and exert their effects on the target cells. In this article, examples of such triggered drug release are presented. © 2013 S. Karger AG, Basel.

Integrated action of pheromone signals in promoting courtship behavior in male mice

PubMed Central

Haga-Yamanaka, Sachiko; Ma, Limei; He, Jie; Qiu, Qiang; Lavis, Luke D; Looger, Loren L; Yu, C Ron

2014-01-01

The mammalian vomeronasal organ encodes pheromone information about gender, reproductive status, genetic background and individual differences. It remains unknown how pheromone information interacts to trigger innate behaviors. In this study, we identify vomeronasal receptors responsible for detecting female pheromones. A sub-group of V1re clade members recognizes gender-identifying cues in female urine. Multiple members of the V1rj clade are cognate receptors for urinary estrus signals, as well as for sulfated estrogen (SE) compounds. In both cases, the same cue activates multiple homologous receptors, suggesting redundancy in encoding female pheromone cues. Neither gender-specific cues nor SEs alone are sufficient to promote courtship behavior in male mice, whereas robust courtship behavior can be induced when the two cues are applied together. Thus, integrated action of different female cues is required in pheromone-triggered mating behavior. These results suggest a gating mechanism in the vomeronasal circuit in promoting specific innate behavior. DOI: http://dx.doi.org/10.7554/eLife.03025.001 PMID:25073926

Motor Unit Activity during Fatiguing Isometric Muscle Contraction in Hemispheric Stroke Survivors

PubMed Central

McManus, Lara; Hu, Xiaogang; Rymer, William Z.; Suresh, Nina L.; Lowery, Madeleine M.

2017-01-01

Enhanced muscle weakness is commonly experienced following stroke and may be accompanied by increased susceptibility to fatigue. To examine the contributions of central and peripheral factors to isometric muscle fatigue in stroke survivors, this study investigates changes in motor unit (MU) mean firing rate, and action potential duration during, and directly following, a sustained submaximal fatiguing contraction at 30% maximum voluntary contraction (MVC). A series of short contractions of the first dorsal interosseous muscle were performed pre- and post-fatigue at 20% MVC, and again following a 10-min recovery period, by 12 chronic stroke survivors. Individual MU firing times were extracted using surface EMG decomposition and used to obtain the spike-triggered average MU action potential waveforms. During the sustained fatiguing contraction, the mean rate of change in firing rate across all detected MUs was greater on the affected side (-0.02 ± 0.03 Hz/s) than on the less-affected side (-0.004 ± 0.003 Hz/s, p = 0.045). The change in firing rate immediately post-fatigue was also greater on the affected side than less-affected side (-13.5 ± 20 and 0.1 ± 19%, p = 0.04). Mean MU firing rates increased following the recovery period on the less-affected side when compared to the affected side (19.3 ± 17 and 0.5 ± 20%, respectively, p = 0.03). MU action potential duration increased post-fatigue on both sides (10.3 ± 1.2 to 11.2 ± 1.3 ms on the affected side and 9.9 ± 1.7 to 11.2 ± 1.9 ms on the less-affected side, p = 0.001 and p = 0.02, respectively), and changes in action potential duration tended to be smaller in subjects with greater impairment (p = 0.04). This study presents evidence of both central and peripheral fatigue at the MU level during isometric fatiguing contraction for the first time in stroke survivors. Together, these preliminary observations indicate that the response to an isometric fatiguing contraction differs between the affected and less-affected side post-stroke, and may suggest that central mechanisms observed here as changes in firing rate are the dominant processes leading to task failure on the affected side. PMID:29225574

Calsequestrin mutation and catecholaminergic polymorphic ventricular tachycardia: a simulation study of cellular mechanism.

PubMed

Faber, Gregory M; Rudy, Yoram

2007-07-01

Patients with a missense mutation of the calsequestrin 2 gene (CASQ2) are at risk for catecholaminergic polymorphic ventricular tachycardia. This mutation (CASQ2(D307H)) results in decreased ability of CASQ2 to bind Ca2+ in the sarcoplasmic reticulum (SR). In this theoretical study, we investigate a potential mechanism by which CASQ2(D307H) manifests its pro-arrhythmic consequences in patients. Using simulations in a model of the guinea pig ventricular myocyte, we investigate the mutation's effect on SR Ca2+ storage, the Ca2+ transient (CaT), and its indirect effect on ionic currents and membrane potential. We model the effects of isoproterenol (ISO) on Ca(V)1.2 (the L-type Ca2+ current, I(Ca(L))) and other targets of beta-adrenergic stimulation. ISO increases I(Ca(L)), prolonging action potential (AP) duration (Control: 172 ms, +ISO: 207 ms, at cycle length of 1500 ms) and increasing CaT (Control: 0.79 microM, +ISO: 1.61 microM). ISO increases I(Ca(L)) by reducing the fraction of channels which undergo voltage-dependent inactivation and increasing transitions from a non-conducting to conducting mode of channel gating. CASQ2(D307H) reduces SR storage capacity, thereby reducing the magnitude of CaT (Control: 0.79 microM, CASQ2(D307H): 0.52 microM, at cycle length of 1500 ms). The combined effect of CASQ2(D307H) and ISO elevates SR free Ca2+ at a rapid rate, leading to store-overload-induced Ca2+ release and delayed afterdepolarization (DAD). If resting membrane potential is sufficiently elevated, the Na+-Ca2+ exchange-driven DAD can trigger I(Na) and I(Ca(L)) activation, generating a triggered arrhythmogenic AP. The CASQ2(D307H) mutation manifests its pro-arrhythmic consequences due to store-overload-induced Ca2+ release and DAD formation due to excess free SR Ca2+ following rapid pacing and beta-adrenergic stimulation.

On the sensitivity of transtensional versus transpressional tectonic regimes to remote dynamic triggering by Coulomb failure

USGS Publications Warehouse

Hill, David P.

2015-01-01

 Accumulating evidence, although still strongly spatially aliased, indicates that although remote dynamic triggering of small-to-moderate (Mw<5) earthquakes can occur in all tectonic settings, transtensional stress regimes with normal and subsidiary strike-slip faulting seem to be more susceptible to dynamic triggering than transpressional regimes with reverse and subsidiary strike-slip faulting. Analysis of the triggering potential of Love- and Rayleigh-wave dynamic stresses incident on normal, reverse, and strike-slip faults assuming Andersonian faulting theory and simple Coulomb failure supports this apparent difference for rapid-onset triggering susceptibility.

Zoledronic acid at subtoxic dose extends osteoblastic stage span of primary human osteoblasts.

PubMed

Zara, Susi; De Colli, Marianna; di Giacomo, Viviana; Zizzari, Vincenzo Luca; Di Nisio, Chiara; Di Tore, Umberto; Salini, Vincenzo; Gallorini, Marialucia; Tetè, Stefano; Cataldi, Amelia

2015-04-01

This study aimed to check the effect of zoledronic acid (ZA) at subtoxic dose on human osteoblasts (HOs) in terms of cell viability, apoptosis occurrence, and differentiation induction. ZA belongs to the family of bisphosphonates (BPs), largely used in the clinical practice for the treatment of bone diseases, often associated with jaw osteonecrosis onset. Their pharmacological action consists in the direct block of the osteoclast-mediated bone resorption along with indirect action on osteoblasts. HOs were treated choosing the highest limit concentration (10(-5) M) which does not induce toxic effects. Live/dead staining, flow cytometry, mitochondrial membrane potential assay, osteocalcin western blotting, gp38 RT-PCR, collagen type I, PGE2, and IL-6 ELISA assays were performed. Similar viability level between control and ZA-treated samples is found along with no significant increase of apoptotic and necrotic cells in ZA-treated sample. To establish if an early apoptotic pathway was triggered, Bax expression and mitochondrial membrane potential were evaluated finding a higher protein expression in control sample and a good integrity of mitochondrial membrane in both experimental points. Type I collagen secretion and alkaline phosphatase (ALP) activity appear increased in ZA-treated sample, osteocalcin expression level is reduced in ZA-treated cells, whereas no modifications of gp38 mRNA level are evidenced. No statistical differences are identified in PGE2 secretion level whereas IL-6 secretion is lower in ZA-treated HOs with respect to control ones. These results highlight that ZA, delaying the osteoblastic differentiation process versus the osteocytic lineage, strengthens its pharmacological activity enhancing bone density. The knowledge of ZA effects on osteoblasts at subtoxic dose allows to improve therapeutic protocols in order to strengthen drug pharmacological activity through a combined action on both osteoclastic and osteoblastic cells.

Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell–matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis

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

Chen, Yan; Li, Zheng; He, Yan

2014-03-01

Fulvestrant (ICI 182 780, ICI) has been used in treating patients with hormone-sensitive breast cancer, yet initial or acquired resistance to endocrine therapies frequently arises and, in particular, cancer recurs as metastasis. We demonstrate here that both 17-beta-estradiol (E2) and ICI enhance cell adhesion to matrigel in MCF-7 breast cancer cells, with increased autolysis of calpain 1 (large subunit) and proteolysis of focal adhesion kinase (FAK), indicating calpain activation. Additionally, either E2 or ICI induced down-regulation of estrogen receptor α without affecting G protein coupled estrogen receptor 30 (GPR30) expression. Interestingly, GPR30 agonist G1 triggered calpain 1 autolysis but notmore » calpain 2, whereas ER agonist diethylstilbestrol caused no apparent calpain autolysis. Furthermore, the actions of E2 and ICI on calpain and cell adhesion were tremendously suppressed by G15, or knockdown of GPR30. E2 and ICI also induced phosphorylation of extracellular regulated protein kinases 1 and 2 (ERK1/2), and suppression of ERK1/2 phosphorylation by U0126 profoundly impeded calpain activation triggered by estrogenic and antiestrogenic stimulations indicating implication of ERK1/2 in the GPR30-mediated action. Lastly, the E2- or ICI-induced cell adhesion was dramatically impaired by calpain-specific inhibitors, ALLN or calpeptin, suggesting requirement of calpain in the GPR30-associated action. These data show that enhanced cell adhesion by E2 and ICI occurs via a novel GPR30-ERK1/2-calpain pathway. Our results indicate that targeting the GPR30 signaling may be a potential strategy to reduce metastasis and improve the efficacy of antiestrogens in treatment of advanced breast cancer. - Highlights: • Estrogen and ICI augment adhesion to matrigel with calpain activation in MCF-7 cells. • GPR30 mediates cell–matrigel adhesion and calpain activation via ERK1/2. • Calpain is required in the cell–matrigel adhesion induced by E2 and ICI.« less

In vitro Neurons in Mammalian Cortical Layer 4 Exhibit Intrinsic Oscillatory Activity in the 10- to 50-Hz Frequency Range

NASA Astrophysics Data System (ADS)

Llinas, Rodolfo R.; Grace, Anthony A.; Yarom, Yosef

1991-02-01

We report here the presence of fast subthreshold oscillatory potentials recorded in vitro from neurons within layer 4 of the guinea pig frontal cortex. Two types of oscillatory neurons were recorded: (i) One type exhibited subthreshold oscillations whose frequency increased with membrane depolarization and encompassed a range of 10-45 Hz. Action potentials in this type of neuron demonstrated clear after-hyperpolarizations. (ii) The second type of neuron was characterized by narrow-frequency oscillations near 35-50 Hz. These oscillations often outlasted the initiating depolarizing stimulus. No calcium component could be identified in their action potential. In both types of cell the subthreshold oscillations were tetrodotoxin-sensitive, indicating that the depolarizing phase of the oscillation was generated by a voltage-dependent sodium conductance. The initial depolarizing phase was followed by a potassium conductance responsible for the falling phase of the oscillatory wave. In both types of cell, the subthreshold oscillation could trigger spikes at the oscillatory frequency, if the membrane was sufficiently depolarized. Combining intracellular recordings with Lucifer yellow staining showed that the narrow-frequency oscillatory activity was produced by a sparsely spinous interneuron located in layer 4 of the cortex. This neuron has extensive local axonal collaterals that ramify in layers 3 and 4 such that they may contribute to the columnar synchronization of activity in the 40- to 50-Hz range. Cortical activity in this frequency range has been proposed as the basis for the "conjunctive properties" of central nervous system networks.

Astrocyte Transforming Growth Factor Beta 1 Protects Synapses against Aβ Oligomers in Alzheimer's Disease Model.

PubMed

Diniz, Luan Pereira; Tortelli, Vanessa; Matias, Isadora; Morgado, Juliana; Bérgamo Araujo, Ana Paula; Melo, Helen M; Seixas da Silva, Gisele S; Alves-Leon, Soniza V; de Souza, Jorge M; Ferreira, Sergio T; De Felice, Fernanda G; Gomes, Flávia Carvalho Alcantara

2017-07-12

Alzheimer's disease (AD) is characterized by progressive cognitive decline, increasingly attributed to neuronal dysfunction induced by amyloid-β oligomers (AβOs). Although the impact of AβOs on neurons has been extensively studied, only recently have the possible effects of AβOs on astrocytes begun to be investigated. Given the key roles of astrocytes in synapse formation, plasticity, and function, we sought to investigate the impact of AβOs on astrocytes, and to determine whether this impact is related to the deleterious actions of AβOs on synapses. We found that AβOs interact with astrocytes, cause astrocyte activation and trigger abnormal generation of reactive oxygen species, which is accompanied by impairment of astrocyte neuroprotective potential in vitro We further show that both murine and human astrocyte conditioned media (CM) increase synapse density, reduce AβOs binding, and prevent AβO-induced synapse loss in cultured hippocampal neurons. Both a neutralizing anti-transforming growth factor-β1 (TGF-β1) antibody and siRNA-mediated knockdown of TGF-β1, previously identified as an important synaptogenic factor secreted by astrocytes, abrogated the protective action of astrocyte CM against AβO-induced synapse loss. Notably, TGF-β1 prevented hippocampal dendritic spine loss and memory impairment in mice that received an intracerebroventricular infusion of AβOs. Results suggest that astrocyte-derived TGF-β1 is part of an endogenous mechanism that protects synapses against AβOs. By demonstrating that AβOs decrease astrocyte ability to protect synapses, our results unravel a new mechanism underlying the synaptotoxic action of AβOs in AD. SIGNIFICANCE STATEMENT Alzheimer's disease is characterized by progressive cognitive decline, mainly attributed to synaptotoxicity of the amyloid-β oligomers (AβOs). Here, we investigated the impact of AβOs in astrocytes, a less known subject. We show that astrocytes prevent synapse loss induced by AβOs, via production of transforming growth factor-β1 (TGF-β1). We found that AβOs trigger morphological and functional alterations in astrocytes, and impair their neuroprotective potential. Notably, TGF-β1 reduced hippocampal dendritic spine loss and memory impairment in mice that received intracerebroventricular infusions of AβOs. Our results describe a new mechanism underlying the toxicity of AβOs and indicate novel therapeutic targets for Alzheimer's disease, mainly focused on TGF-β1 and astrocytes. Copyright © 2017 the authors 0270-6474/17/376798-13$15.00/0.

Apoptosis- and differentiation-inducing activities of jacaric acid, a conjugated linolenic acid isomer, on human eosinophilic leukemia EoL-1 cells.

PubMed

Liu, Wai-Nam; Leung, Kwok-Nam

2014-11-01

Conjugated linolenic acids (CLNAs) are a group of naturally occurring positional and geometrical isomers of the C18 polyunsaturated essential fatty acid, linolenic acid (LNA), with three conjugated double bonds (C18:3). Although previous research has demonstrated the growth-inhibitory effects of CLNA on a wide variety of cancer cell lines in vitro, their action mechanisms and therapeutic potential on human myeloid leukemia cells remain poorly understood. In the present study, we found that jacaric acid (8Z,10E,12Z-octadecatrienoic acid), a CLNA isomer which is present in jacaranda seed oil, inhibited the in vitro growth of human eosinophilic leukemia EoL-1 cells in a time- and concentration-dependent manner. Mechanistic studies showed that jacaric acid triggered cell cycle arrest of EoL-1 cells at the G0/G1 phase and induced apoptosis of the EoL-1 cells, as measured by the Cell Death Detection ELISAPLUS kit, Annexin V assay and JC-1 dye staining. Notably, the jacaric acid-treated EoL-1 cells also underwent differentiation as revealed by morphological and phenotypic analysis. Collectively, our results demonstrated the capability of jacaric acid to inhibit the growth of EoL-1 cells in vitro through triggering cell cycle arrest and by inducing apoptosis and differentiation of the leukemia cells. Therefore, jacaric acid might be developed as a potential candidate for the treatment of certain forms of myeloid leukemia with minimal toxicity and few side effects.

Very high-energy gamma-ray follow-up program using neutrino triggers from IceCube

NASA Astrophysics Data System (ADS)

IceCube Collaboration; Aartsen, M. G.; Abraham, K.; Ackermann, M.; Adams, J.; Aguilar, J. A.; Ahlers, M.; Ahrens, M.; Altmann, D.; Andeen, K.; Anderson, T.; Ansseau, I.; Anton, G.; Archinger, M.; Argüelles, C.; Auffenberg, J.; Axani, S.; Bai, X.; Barwick, S. W.; Baum, V.; Bay, R.; Beatty, J. J.; Becker Tjus, J.; Becker, K.-H.; BenZvi, S.; Berley, D.; Bernardini, E.; Bernhard, A.; Besson, D. Z.; Binder, G.; Bindig, D.; Bissok, M.; Blaufuss, E.; Blot, S.; Bohm, C.; Börner, M.; Bos, F.; Bose, D.; Böser, S.; Botner, O.; Braun, J.; Brayeur, L.; Bretz, H.-P.; Bron, S.; Burgman, A.; Carver, T.; Casier, M.; Cheung, E.; Chirkin, D.; Christov, A.; Clark, K.; Classen, L.; Coenders, S.; Collin, G. H.; Conrad, J. M.; Cowen, D. F.; Cross, R.; Day, M.; de André, J. P. A. M.; De Clercq, C.; del Pino Rosendo, E.; Dembinski, H.; De Ridder, S.; Desiati, P.; de Vries, K. D.; de Wasseige, G.; de With, M.; DeYoung, T.; Díaz-Vélez, J. C.; di Lorenzo, V.; Dujmovic, H.; Dumm, J. P.; Dunkman, M.; Eberhardt, B.; Ehrhardt, T.; Eichmann, B.; Eller, P.; Euler, S.; Evenson, P. A.; Fahey, S.; Fazely, A. R.; Feintzeig, J.; Felde, J.; Filimonov, K.; Finley, C.; Flis, S.; Fösig, C.-C.; Franckowiak, A.; Franke, R.; Friedman, E.; Fuchs, T.; Gaisser, T. K.; Gallagher, J.; Gerhardt, L.; Ghorbani, K.; Giang, W.; Gladstone, L.; Glauch, T.; Glüsenkamp, T.; Goldschmidt, A.; Golup, G.; Gonzalez, J. G.; Grant, D.; Griffith, Z.; Haack, C.; Haj Ismail, A.; Hallgren, A.; Halzen, F.; Hansen, E.; Hansmann, T.; Hanson, K.; Hebecker, D.; Heereman, D.; Helbing, K.; Hellauer, R.; Hickford, S.; Hignight, J.; Hill, G. C.; Hoffman, K. D.; Hoffmann, R.; Holzapfel, K.; Hoshina, K.; Huang, F.; Huber, M.; Hultqvist, K.; In, S.; Ishihara, A.; Jacobi, E.; Japaridze, G. S.; Jeong, M.; Jero, K.; Jones, B. J. P.; Jurkovic, M.; Kappes, A.; Karg, T.; Karle, A.; Katz, U.; Kauer, M.; Keivani, A.; Kelley, J. L.; Kheirandish, A.; Kim, M.; Kintscher, T.; Kiryluk, J.; Kittler, T.; Klein, S. R.; Kohnen, G.; Koirala, R.; Kolanoski, H.; Konietz, R.; Köpke, L.; Kopper, C.; Kopper, S.; Koskinen, D. J.; Kowalski, M.; Krings, K.; Kroll, M.; Krückl, G.; Krüger, C.; Kunnen, J.; Kunwar, S.; Kurahashi, N.; Kuwabara, T.; Labare, M.; Lanfranchi, J. L.; Larson, M. J.; Lauber, F.; Lennarz, D.; Lesiak-Bzdak, M.; Leuermann, M.; Lu, L.; Lünemann, J.; Madsen, J.; Maggi, G.; Mahn, K. B. M.; Mancina, S.; Mandelartz, M.; Maruyama, R.; Mase, K.; Maunu, R.; McNally, F.; Meagher, K.; Medici, M.; Meier, M.; Meli, A.; Menne, T.; Merino, G.; Meures, T.; Miarecki, S.; Mohrmann, L.; Montaruli, T.; Moulai, M.; Nahnhauer, R.; Naumann, U.; Neer, G.; Niederhausen, H.; Nowicki, S. C.; Nygren, D. R.; Obertacke Pollmann, A.; Olivas, A.; O'Murchadha, A.; Palczewski, T.; Pandya, H.; Pankova, D. V.; Peiffer, P.; Penek, Ö.; Pepper, J. A.; Pérez de los Heros, C.; Pieloth, D.; Pinat, E.; Price, P. B.; Przybylski, G. T.; Quinnan, M.; Raab, C.; Rädel, L.; Rameez, M.; Rawlins, K.; Reimann, R.; Relethford, B.; Relich, M.; Resconi, E.; Rhode, W.; Richman, M.; Riedel, B.; Robertson, S.; Rongen, M.; Rott, C.; Ruhe, T.; Ryckbosch, D.; Rysewyk, D.; Sabbatini, L.; Sanchez Herrera, S. E.; Sandrock, A.; Sandroos, J.; Sarkar, S.; Satalecka, K.; Schlunder, P.; Schmidt, T.; Schoenen, S.; Schöneberg, S.; Schumacher, L.; Seckel, D.; Seunarine, S.; Soldin, D.; Song, M.; Spiczak, G. M.; Spiering, C.; Stanev, T.; Stasik, A.; Stettner, J.; Steuer, A.; Stezelberger, T.; Stokstad, R. G.; Stößl, A.; Ström, R.; Strotjohann, N. L.; Sullivan, G. W.; Sutherland, M.; Taavola, H.; Taboada, I.; Tatar, J.; Tenholt, F.; Ter-Antonyan, S.; Terliuk, A.; Tešić, G.; Tilav, S.; Toale, P. A.; Tobin, M. N.; Toscano, S.; Tosi, D.; Tselengidou, M.; Turcati, A.; Unger, E.; Usner, M.; Vandenbroucke, J.; van Eijndhoven, N.; Vanheule, S.; van Rossem, M.; van Santen, J.; Veenkamp, J.; Vehring, M.; Voge, M.; Vogel, E.; Vraeghe, M.; Walck, C.; Wallace, A.; Wallraff, M.; Wandkowsky, N.; Weaver, Ch.; Weiss, M. J.; Wendt, C.; Westerhoff, S.; Whelan, B. J.; Wickmann, S.; Wiebe, K.; Wiebusch, C. H.; Wille, L.; Williams, D. R.; Wills, L.; Wolf, M.; Wood, T. R.; Woolsey, E.; Woschnagg, K.; Xu, D. L.; Xu, X. W.; Xu, Y.; Yanez, J. P.; Yodh, G.; Yoshida, S.; Zoll, M.; MAGIC Collaboration; Ahnen, M. L.; Ansoldi, S.; Antonelli, L. A.; Antoranz, P.; Babic, A.; Banerjee, B.; Bangale, P.; Barres de Almeida, U.; Barrio, J. A.; Becerra González, J.; Bednarek, W.; Bernardini, E.; Berti, A.; Biasuzzi, B.; Biland, A.; Blanch, O.; Bonnefoy, S.; Bonnoli, G.; Borracci, F.; Bretz, T.; Buson, S.; Carosi, A.; Chatterjee, A.; Clavero, R.; Colin, P.; Colombo, E.; Contreras, J. L.; Cortina, J.; Covino, S.; Da Vela, P.; Dazzi, F.; De Angelis, A.; De Lotto, B.; de Oña Wilhelmi, E.; Di Pierro, F.; Doert, M.; Domínguez, A.; Dominis Prester, D.; Dorner, D.; Doro, M.; Einecke, S.; Eisenacher Glawion, D.; Elsaesser, D.; Engelkemeier, M.; Fallah Ramazani, V.; Fernández-Barral, A.; Fidalgo, D.; Fonseca, M. V.; Font, L.; Frantzen, K.; Fruck, C.; Galindo, D.; García López, R. J.; Garczarczyk, M.; Garrido Terrats, D.; Gaug, M.; Giammaria, P.; Godinović, N.; González Muñoz, A.; Góra, D.; Guberman, D.; Hadasch, D.; Hahn, A.; Hanabata, Y.; Hayashida, M.; Herrera, J.; Hose, J.; Hrupec, D.; Hughes, G.; Idec, W.; Kodani, K.; Konno, Y.; Kubo, H.; Kushida, J.; La Barbera, A.; Lelas, D.; Lindfors, E.; Lombardi, S.; Longo, F.; López, M.; López-Coto, R.; Majumdar, P.; Makariev, M.; Mallot, K.; Maneva, G.; Manganaro, M.; Mannheim, K.; Maraschi, L.; Marcote, B.; Mariotti, M.; Martínez, M.; Mazin, D.; Menzel, U.; Miranda, J. M.; Mirzoyan, R.; Moralejo, A.; Moretti, E.; Nakajima, D.; Neustroev, V.; Niedzwiecki, A.; Nievas Rosillo, M.; Nilsson, K.; Nishijima, K.; Noda, K.; Nogués, L.; Overkemping, A.; Paiano, S.; Palacio, J.; Palatiello, M.; Paneque, D.; Paoletti, R.; Paredes, J. M.; Paredes-Fortuny, X.; Pedaletti, G.; Peresano, M.; Perri, L.; Persic, M.; Poutanen, J.; Prada Moroni, P. G.; Prandini, E.; Puljak, I.; Reichardt, I.; Rhode, W.; Ribó, M.; Rico, J.; Rodriguez Garcia, J.; Saito, T.; Satalecka, K.; Schroeder, S.; Schultz, C.; Schweizer, T.; Sillanpää, A.; Sitarek, J.; Snidaric, I.; Sobczynska, D.; Stamerra, A.; Steinbring, T.; Strzys, M.; Surić, T.; Takalo, L.; Tavecchio, F.; Temnikov, P.; Terzić, T.; Tescaro, D.; Teshima, M.; Thaele, J.; Torres, D. F.; Toyama, T.; Treves, A.; Vanzo, G.; Verguilov, V.; Vovk, I.; Ward, J. E.; Will, M.; Wu, M. H.; Zanin, .; VERITAS Collaboration; Abeysekara, A. U.; Archambault, S.; Archer, A.; Benbow, W.; Bird, R.; Bourbeau, E.; Buchovecky, M.; Bugaev, V.; Byrum, K.; Cardenzana, J. V.; Cerruti, M.; Ciupik, L.; Connolly, M. P.; Cui, W.; Dickinson, H. J.; Dumm, J.; Eisch, J. D.; Errando, M.; Falcone, A.; Feng, Q.; Finley, J. P.; Fleischhack, H.; Flinders, A.; Fortson, L.; Furniss, A.; Gillanders, G. H.; Griffin, S.; Hütten, J. Grube M.; Håkansson, N.; Hervet, O.; Holder, J.; Humensky, T. B.; Johnson, C. A.; Kaaret, P.; Kar, P.; Kelley-Hoskins, N.; Kertzman, M.; Kieda, D.; Krause, M.; Krennrich, F.; Kumar, S.; Lang, M. J.; Maier, G.; McArthur, S.; McCann, A.; Moriarty, P.; Mukherjee, R.; Nguyen, T.; Nieto, D.; O'Brien, S.; Ong, R. A.; Otte, A. N.; Park, N.; Pohl, M.; Popkow, A.; Pueschel, E.; Quinn, J.; Ragan, K.; Reynolds, P. T.; Richards, G. T.; Roache, E.; Rulten, C.; Sadeh, I.; Santander, M.; Sembroski, G. H.; Shahinyan, K.; Staszak, D.; Telezhinsky, I.; Tucci, J. V.; Tyler, J.; Wakely, S. P.; Weinstein, A.; Wilcox, P.; Wilhelm, A.; Williams, D. A.; Zitzer, B.

2016-11-01

We describe and report the status of a neutrino-triggered program in IceCube that generates real-time alerts for gamma-ray follow-up observations by atmospheric-Cherenkov telescopes (MAGIC and VERITAS). While IceCube is capable of monitoring the whole sky continuously, high-energy gamma-ray telescopes have restricted fields of view and in general are unlikely to be observing a potential neutrino-flaring source at the time such neutrinos are recorded. The use of neutrino-triggered alerts thus aims at increasing the availability of simultaneous multi-messenger data during potential neutrino flaring activity, which can increase the discovery potential and constrain the phenomenological interpretation of the high-energy emission of selected source classes (e.g. blazars). The requirements of a fast and stable online analysis of potential neutrino signals and its operation are presented, along with first results of the program operating between 14 March 2012 and 31 December 2015.

The role of Rho-kinase and calcium ions in constriction triggered by ET-1.

PubMed

Wiciński, Michał; Szadujkis-Szadurska, Katarzyna; Węclewicz, Mateusz M; Malinowski, Bartosz; Matusiak, Grzegorz; Walczak, Maciej; Wódkiewicz, Eryk; Grześk, Grzegorz; Pawlak-Osińska, Katarzyna

2018-05-05

Endothelin-1 (ET-1) is one of the key factors regulating tension of smooth muscles in blood vessels. It is believed that ET-1 plays an important role in pathogenesis of hypertension, and cardiovascular diseases; therefore, research in order to limit ET-1-mediated action is still in progress. The main objective of this paper was to evaluate the role of Rho-kinase in the ET-1-induced constriction of arteries. The analysis also included significance of intra- and extracellular pool of calcium ions in constriction triggered by ET-1. The studies were performed on perfused Wistar rat tail arteries. Concentration response curve (CRC) was determined for ET-1 in the presence of increased concentrations of Rho-kinase inhibitor (Y-27632) and IP3-receptor antagonist (2APB), both in reference to constriction triggered by solely ET-1. Afterwards, the influence of calcium ions present in the perfusion fluid was evaluated in terms of the effect triggered by 2APB and occurring in arteries constricted by ET-1. ET-1, in concentration dependent manner, leads to increase in perfusion pressure. Y-27632 and 2APB lead to shift of the concentration response curve for ET-1 to the right with simultaneously lowered maximum effect. There was no difference in reaction of the artery constricted by ET-1 and treated with 2APB in solution containing calcium and in calcium-free solution. Vasoconstrictive action of endothelin is not significantly dependent on the inflow of extracellular calcium, but it is proportional to inflow of Ca 2+ related to activation of IP3 receptors and to Rho-kinase activity. Copyright © 2018. Published by Elsevier Inc.

Wired and Wireless Camera Triggering with Arduino

NASA Astrophysics Data System (ADS)

Kauhanen, H.; Rönnholm, P.

2017-10-01

Synchronous triggering is an important task that allows simultaneous data capture from multiple cameras. Accurate synchronization enables 3D measurements of moving objects or from a moving platform. In this paper, we describe one wired and four wireless variations of Arduino-based low-cost remote trigger systems designed to provide a synchronous trigger signal for industrial cameras. Our wireless systems utilize 315 MHz or 434 MHz frequencies with noise filtering capacitors. In order to validate the synchronization accuracy, we developed a prototype of a rotating trigger detection system (named RoTriDeS). This system is suitable to detect the triggering accuracy of global shutter cameras. As a result, the wired system indicated an 8.91 μs mean triggering time difference between two cameras. Corresponding mean values for the four wireless triggering systems varied between 7.92 and 9.42 μs. Presented values include both camera-based and trigger-based desynchronization. Arduino-based triggering systems appeared to be feasible, and they have the potential to be extended to more complicated triggering systems.

Dynamic stresses, coulomb failure, and remote triggering: corrected

USGS Publications Warehouse

Hill, David P.

2012-01-01

Dynamic stresses associated with crustal surface waves with 15–30 s periods and peak amplitudes <1  MPa are capable of triggering seismicity at sites remote from the generating mainshock under appropriate conditions. Coulomb failure models based on a frictional strength threshold offer one explanation for instances of rapid‐onset triggered seismicity that develop during the surface‐wave peak dynamic stressing. Evaluation of the triggering potential of surface‐wave dynamic stresses acting on critically stressed faults using a Mohr’s circle representation together with the Coulomb failure criteria indicates that Love waves should have a higher triggering potential than Rayleigh waves for most fault orientations and wave incidence angles. That (1) the onset of triggered seismicity often appears to begin during the Rayleigh wave rather than the earlier arriving Love wave, and (2) Love‐wave amplitudes typically exceed those for Rayleigh waves suggests that the explanation for rapid‐onset dynamic triggering may not reside solely with a simple static‐threshold friction mode. The results also indicate that normal faults should be more susceptible to dynamic triggering by 20‐s Rayleigh‐wave stresses than thrust faults in the shallow seismogenic crust (<10  km) while the advantage tips in favor of reverse faults greater depths. This transition depth scales with wavelength and coincides roughly with the transition from retrograde‐to‐prograde particle motion. Locally elevated pore pressures may have a role in the observed prevalence of dynamic triggering in extensional regimes and geothermal/volcanic systems. The result is consistent with the apparent elevated susceptibility of extensional or transtensional tectonic regimes to remote triggering by Rayleigh‐wave dynamic stresses than compressional or transpressional regimes.

78 FR 33114 - Sunshine Act Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-03

... LEGAL SERVICES CORPORATION Sunshine Act Meetings ACTION: Notice. Date And Time: The Legal Services... meeting, please refrain from placing the call on hold if doing so will trigger recorded music or other sound. From time to time, the Chair may solicit comments from the public. Status Of Meeting: Open...

Conflicts as Aversive Signals

ERIC Educational Resources Information Center

Dreisbach, Gesine; Fischer, Rico

2012-01-01

Theories of human action control deal with the question of how cognitive control is dynamically adjusted to task demands. The conflict monitoring theory of anterior cingulate (ACC) function suggests that the ACC monitors for response conflicts in the ongoing processing stream thereby triggering the mobilization of cognitive control. Alternatively,…

Health Care Reform and Young Adults' Access to Sexual Health Care: An Exploration of Potential Confidentiality Implications of the Affordable Care Act

PubMed Central

Garcia, Carolyn M.; Long, Sharon K.; Lechner, Kate E.; Lust, Katherine; Eisenberg, Marla E.

2012-01-01

One provision of the 2010 Affordable Care Act is extension of dependent coverage for young adults aged up to 26 years on their parent’s private insurance plan. This change, meant to increase insurance coverage for young adults, might yield unintended consequences. Confidentiality concerns may be triggered by coverage through parental insurance, particularly regarding sexual health. The existing literature and our original research suggest that actual or perceived limits to confidentiality could influence the decisions of young adults about whether, and where, to seek care for sexual health issues. Further research is needed on the scope and outcomes of these concerns. Possible remedial actions include enhanced policies to protect confidentiality in billing and mechanisms to communicate confidentiality protections to young adults. PMID:22897544

Apoptosis triggered by pyropheophorbide-α methyl ester-mediated photodynamic therapy in a giant cell tumor in bone

NASA Astrophysics Data System (ADS)

Li, K.-T.; Zhang, J.; Duan, Q.-Q.; Bi, Y.; Bai, D.-Q.; Ou, Y.-S.

2014-06-01

A giant cell tumor in bone is the common primary bone tumor with aggressive features, occurring mainly in young adults. Photodynamic therapy is a new therapeutic technique for tumors. In this study, we investigated the effects of Pyropheophorbide-α methyl ester (MPPa)-mediated photodynamic therapy on the proliferation of giant cell tumor cells and its mechanism of action. Cell proliferation was evaluated using an MTT assay. Cellular apoptosis was detected by Hoechst nuclear staining, and flow cytometric assay. Mitochondrial membrane potential changes and cytochrome c, caspase-9, caspase-3, and Bcl-2 expression was assessed. Finally, we found that MPPa-mediated photodynamic therapy could effectively suppress the proliferation of human giant cell tumor cells and induce apoptosis. The mitochondrial pathway was involved in the MPPa-photodynamic therapy-induced apoptosis.

Erythropoietin: new approaches to improved molecular designs and therapeutic alternatives.

PubMed

Debeljak, N; Sytkowski, A J

2008-01-01

Erythropoietin (Epo) is a glycoprotein hormone that is the prime regulator of erythropoiesis. Recombinant Epo is a highly effective pharmaceutical used to correct anemias associated with renal insufficiency, cancer and other diseases. Efforts to increase its efficacy in vivo by manipulating the protein's structure have met with some success, and novel Epo-like agents are in development. Additionally, efforts to create Epo mimetic agents are underway, as is the design of agents to increase endogenous production. Because Epo has tissue protective actions outside of erythropoiesis, other designs have focused on producing erythropoietically inactive molecules that still retain extra-hematopoietic activity. The demonstration that Epo can trigger signaling in some cancer cells with, potentially, adverse effects on patient health has raised warning signs in the medical community and has gained the attention of regulatory authorities.

The Neuroscience of Growth Mindset and Intrinsic Motivation.

PubMed

Ng, Betsy

2018-01-26

Our actions can be triggered by intentions, incentives or intrinsic values. Recent neuroscientific research has yielded some results about the growth mindset and intrinsic motivation. With the advances in neuroscience and motivational studies, there is a global need to utilize this information to inform educational practice and research. Yet, little is known about the neuroscientific interplay between growth mindset and intrinsic motivation. This paper attempts to draw on the theories of growth mindset and intrinsic motivation, together with contemporary ideas in neuroscience, outline the potential for neuroscientific research in education. It aims to shed light on the relationship between growth mindset and intrinsic motivation in terms of supporting a growth mindset to facilitate intrinsic motivation through neural responses. Recent empirical research from the educational neuroscience perspective that provides insights into the interplay between growth mindset and intrinsic motivation will also be discussed.

Impulsive action: emotional impulses and their control

PubMed Central

Frijda, Nico H.; Ridderinkhof, K. Richard; Rietveld, Erik

2014-01-01

This paper presents a novel theoretical view on impulsive action, integrating thus far separate perspectives on non-reflective action, motivation, emotion regulation, and impulse control. We frame impulsive action in terms of directedness of the individual organism toward, away, or against other givens – toward future states and away from one’s present state. First, appraisal of a perceived or thought-of event or object on occasion, rapidly and without premonition or conscious deliberation, triggers a motive to modify one’s relation to that event or object. Situational specifics of the event as perceived and appraised motivate and guide selection of readiness for a particular kind of purposive action. Second, perception of complex situations can give rise to multiple appraisals, multiple motives, and multiple simultaneous changes in action readiness. Multiple states of action readiness may interact in generating action, by reinforcing or attenuating each other, thereby yielding impulse control. We show how emotion control can itself result from a motive state or state of action readiness. Our view links impulsive action mechanistically to states of action readiness, which is the central feature of what distinguishes one kind of emotion from another. It thus provides a novel theoretical perspective to the somewhat fragmented literature on impulsive action. PMID:24917835

Neuro-cognitive mechanisms of decision making in joint action: a human-robot interaction study.

PubMed

Bicho, Estela; Erlhagen, Wolfram; Louro, Luis; e Silva, Eliana Costa

2011-10-01

In this paper we present a model for action preparation and decision making in cooperative tasks that is inspired by recent experimental findings about the neuro-cognitive mechanisms supporting joint action in humans. It implements the coordination of actions and goals among the partners as a dynamic process that integrates contextual cues, shared task knowledge and predicted outcome of others' motor behavior. The control architecture is formalized by a system of coupled dynamic neural fields representing a distributed network of local but connected neural populations. Different pools of neurons encode task-relevant information about action means, task goals and context in the form of self-sustained activation patterns. These patterns are triggered by input from connected populations and evolve continuously in time under the influence of recurrent interactions. The dynamic model of joint action is evaluated in a task in which a robot and a human jointly construct a toy object. We show that the highly context sensitive mapping from action observation onto appropriate complementary actions allows coping with dynamically changing joint action situations. Copyright © 2010 Elsevier B.V. All rights reserved.

Influences of unconscious priming on voluntary actions: Role of the rostral cingulate zone.

PubMed

Teuchies, Martyn; Demanet, Jelle; Sidarus, Nura; Haggard, Patrick; Stevens, Michaël A; Brass, Marcel

2016-07-15

The ability to make voluntary, free choices is fundamental to what it means to be human. A key brain region that is involved in free choices is the rostral cingulate zone (RCZ), which is part of the medial frontal cortex. Previous research has shown that activity in this brain region can be modulated by bottom-up information while making free choices. The current study extends those findings, and shows, for the first time, that activation in the RCZ can also be modulated by subliminal information. We used a subliminal response priming paradigm to bias free and cued choices. We observed more activation in the RCZ when participants made a choice that went against the prime's suggestion, compared to when they chose according to the prime. This shows that the RCZ plays an important role in overcoming externally-triggered conflict between different response options, even when the stimuli triggering this conflict are not consciously perceived. Our results suggest that an important mechanism of endogenous action in the RCZ may therefore involve exerting an internally-generated action choice against conflicting influences, such as external sensory evidence. We further found that subliminal information also modulated activity in the anterior insula and the supramarginal gyrus. Copyright © 2016 Elsevier Inc. All rights reserved.

The Advanced Gamma-ray Imaging System (AGIS): A Nanosecond Time Scale Stereoscopic Array Trigger System.

NASA Astrophysics Data System (ADS)

Krennrich, Frank; Buckley, J.; Byrum, K.; Dawson, J.; Drake, G.; Horan, D.; Krawzcynski, H.; Schroedter, M.

2008-04-01

Imaging atmospheric Cherenkov telescope arrays (VERITAS, HESS) have shown unprecedented background suppression capabilities for reducing cosmic-ray induced air showers, muons and night sky background fluctuations. Next-generation arrays with on the order of 100 telescopes offer larger collection areas, provide the possibility to see the air shower from more view points on the ground, have the potential to improve the sensitivity and give additional background suppression. Here we discuss the design of a fast array trigger system that has the potential to perform a real time image analysis allowing substantially improved background rate suppression at the trigger level.

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.

Trigger chemistries for better industrial formulations.

PubMed

Wang, Hsuan-Chin; Zhang, Yanfeng; Possanza, Catherine M; Zimmerman, Steven C; Cheng, Jianjun; Moore, Jeffrey S; Harris, Keith; Katz, Joshua S

2015-04-01

In recent years, innovations and consumer demands have led to increasingly complex liquid formulations. These growing complexities have provided industrial players and their customers access to new markets through product differentiation, improved performance, and compatibility/stability with other products. One strategy for enabling more complex formulations is the use of active encapsulation. When encapsulation is employed, strategies are required to effect the release of the active at the desired location and time of action. One particular route that has received significant academic research effort is the employment of triggers to induce active release upon a specific stimulus, though little has translated for industrial use to date. To address emerging industrial formulation needs, in this review, we discuss areas of trigger release chemistries and their applications specifically as relevant to industrial use. We focus the discussion on the use of heat, light, shear, and pH triggers as applied in several model polymeric systems for inducing active release. The goal is that through this review trends will emerge for how technologies can be better developed to maximize their value through industrial adaptation.

Pancreatic cancer-specific cell death induced in vivo by cytoplasmic-delivered polyinosine-polycytidylic acid

PubMed Central

Bhoopathi, Praveen; Quinn, Bridget A.; Gui, Qin; Shen, Xue-Ning; Grossman, Steven R.; Das, Swadesh K.; Sarkar, Devanand; Fisher, Paul B.; Emdad, Luni

2014-01-01

Polyinosine-polycytidylic acid (pIC) is a synthetic dsRNA that acts as an immune agonist of TLR3 and RLR to activate dendritic and NK cells that can kill tumor cells. pIC can also trigger apoptosis in pancreatic ductal adenocarcinoma cells but its mechanism of action is obscure. In this study, we investigated the potential therapeutic activity of a formulation of pIC with polyethylenimine ([pIC]PEI) in PDAC and investigated its mechanism of action. [pIC]PEI stimulated apoptosis in PDAC cells without affecting normal pancreatic epithelial cells. Mechanistically, [pIC]PEI repressed XIAP and survivin expression and activated an immune response by inducing MDA-5, RIG-I and NOXA. Phosphorylation of AKT was inhibited by [pIC]PEI in PDAC and this event was critical for stimulating apoptosis through XIAP and survivin degradation. In vivo administration of [pIC]PEI inhibited tumor growth via AKT-mediated XIAP degradation in both subcutaneous and quasi-orthotopic-models of PDAC. Taken together, these results offer a preclinical proof-of-concept for the evaluation of [pIC]PEI as an immunochemotherapy to treat pancreatic cancer. PMID:25205107

NRG1-Fc improves metabolic health via dual hepatic and central action.

PubMed

Zhang, Peng; Kuang, Henry; He, Yanlin; Idiga, Sharon O; Li, Siming; Chen, Zhimin; Yang, Zhao; Cai, Xing; Zhang, Kezhong; Potthoff, Matthew J; Xu, Yong; Lin, Jiandie D

2018-03-08

Neuregulins (NRGs) are emerging as an important family of signaling ligands that regulate glucose and lipid homeostasis. NRG1 lowers blood glucose levels in obese mice, whereas the brown fat-enriched secreted factor NRG4 protects mice from high-fat diet-induced insulin resistance and hepatic steatosis. However, the therapeutic potential of NRGs remains elusive, given the poor plasma half-life of the native ligands. Here, we engineered a fusion protein using human NRG1 and the Fc domain of human IgG1 (NRG1-Fc) that exhibited extended half-life in circulation and improved potency in receptor signaling. We evaluated its efficacy in improving metabolic parameters and dissected the mechanisms of action. NRG1-Fc treatment triggered potent AKT activation in the liver, lowered blood glucose, improved insulin sensitivity, and suppressed food intake in obese mice. NRG1-Fc acted as a potent secretagogue for the metabolic hormone FGF21; however, the latter was largely dispensable for its metabolic effects. NRG1-Fc directly targeted the hypothalamic POMC neurons to promote membrane depolarization and increase firing rate. Together, NRG1-Fc exhibits improved pharmacokinetic properties and exerts metabolic benefits through dual inhibition of hepatic gluconeogenesis and caloric intake.

NRG1-Fc improves metabolic health via dual hepatic and central action

PubMed Central

Kuang, Henry; Idiga, Sharon O.; Li, Siming; Chen, Zhimin; Cai, Xing; Zhang, Kezhong; Potthoff, Matthew J.; Xu, Yong; Lin, Jiandie D.

2018-01-01

Neuregulins (NRGs) are emerging as an important family of signaling ligands that regulate glucose and lipid homeostasis. NRG1 lowers blood glucose levels in obese mice, whereas the brown fat–enriched secreted factor NRG4 protects mice from high-fat diet–induced insulin resistance and hepatic steatosis. However, the therapeutic potential of NRGs remains elusive, given the poor plasma half-life of the native ligands. Here, we engineered a fusion protein using human NRG1 and the Fc domain of human IgG1 (NRG1-Fc) that exhibited extended half-life in circulation and improved potency in receptor signaling. We evaluated its efficacy in improving metabolic parameters and dissected the mechanisms of action. NRG1-Fc treatment triggered potent AKT activation in the liver, lowered blood glucose, improved insulin sensitivity, and suppressed food intake in obese mice. NRG1-Fc acted as a potent secretagogue for the metabolic hormone FGF21; however, the latter was largely dispensable for its metabolic effects. NRG1-Fc directly targeted the hypothalamic POMC neurons to promote membrane depolarization and increase firing rate. Together, NRG1-Fc exhibits improved pharmacokinetic properties and exerts metabolic benefits through dual inhibition of hepatic gluconeogenesis and caloric intake. PMID:29515030

Mapping perception to action in piano practice: a longitudinal DC-EEG study

PubMed Central

Bangert, Marc; Altenmüller, Eckart O

2003-01-01

Background Performing music requires fast auditory and motor processing. Regarding professional musicians, recent brain imaging studies have demonstrated that auditory stimulation produces a co-activation of motor areas, whereas silent tapping of musical phrases evokes a co-activation in auditory regions. Whether this is obtained via a specific cerebral relay station is unclear. Furthermore, the time course of plasticity has not yet been addressed. Results Changes in cortical activation patterns (DC-EEG potentials) induced by short (20 minute) and long term (5 week) piano learning were investigated during auditory and motoric tasks. Two beginner groups were trained. The 'map' group was allowed to learn the standard piano key-to-pitch map. For the 'no-map' group, random assignment of keys to tones prevented such a map. Auditory-sensorimotor EEG co-activity occurred within only 20 minutes. The effect was enhanced after 5-week training, contributing elements of both perception and action to the mental representation of the instrument. The 'map' group demonstrated significant additional activity of right anterior regions. Conclusion We conclude that musical training triggers instant plasticity in the cortex, and that right-hemispheric anterior areas provide an audio-motor interface for the mental representation of the keyboard. PMID:14575529

Sensory-based expert monitoring and control

NASA Astrophysics Data System (ADS)

Yen, Gary G.

1999-03-01

Field operators use their eyes, ears, and nose to detect process behavior and to trigger corrective control actions. For instance: in daily practice, the experienced operator in sulfuric acid treatment of phosphate rock may observe froth color or bubble character to control process material in-flow. Or, similarly, (s)he may use acoustic sound of cavitation or boiling/flashing to increase or decrease material flow rates in tank levels. By contrast, process control computers continue to be limited to taking action on P, T, F, and A signals. Yet, there is sufficient evidence from the fields that visual and acoustic information can be used for control and identification. Smart in-situ sensors have facilitated potential mechanism for factory automation with promising industry applicability. In respond to these critical needs, a generic, structured health monitoring approach is proposed. The system assumes a given sensor suite will act as an on-line health usage monitor and at best provide the real-time control autonomy. The sensor suite can incorporate various types of sensory devices, from vibration accelerometers, directional microphones, machine vision CCDs, pressure gauges to temperature indicators. The decision can be shown in a visual on-board display or fed to the control block to invoke controller reconfigurration.

Testosterone and dihydrotestosterone reduce platelet activation and reactivity in older men and women.

PubMed

Karolczak, Kamil; Konieczna, Lucyna; Kostka, Tomasz; Witas, Piotr J; Soltysik, Bartlomiej; Baczek, Tomasz; Watala, Cezary

2018-05-02

The cardiovascular effects of testosterone and dihydrotestosterone are generally attributed to their modulatory action on lipid and glucose metabolism. However, no ex vivo studies suggest that circulating androgen levels influence the activation and reactivity of blood platelets - one of the main components of the haemostasis system directly involved in atherosclerosis. The levels of testosterone, dihydrotestosterone and oestradiol in plasma from men and women aged from 60 to 65 years were measured by LC-MS; the aim was to identify any potential relationships between sex steroid levels and the markers of platelet activation (surface membrane expression of GPII/IIIa complex and P-selectin) and platelet reactivity in response to arachidonate, collagen or ADP, monitored with whole blood aggregometry and flow cytometry. The results of the ex vivo part of the study indicate that the concentrations of testosterone and its reduced form, dihydrotestosterone are significantly negatively associated with platelet activation and reactivity. These observations were confirmed in an in vitro model: testosterone and dihydrotestosterone significantly inhibited platelet aggregation triggered by arachidonate or collagen. Our findings indicate that testosterone and dihydrotestosterone are significant haemostatic steroids with inhibitory action on blood platelets in older people.

Dual-afferent sensory input training for voluntary movement after stroke: A pilot randomized controlled study.

PubMed

Bae, Seahyun; Kim, Kyung-Yoon

2017-01-01

Stimulation through afferent sensory input is necessary to improve voluntary functional movement in stroke patients. Dual-afferent sensory input, which combines electromyography-triggered functional electric stimulation (ETFES) and action observation, was investigated to determine its effects on voluntary movements in stroke patients. This study was conducted on 18 patients with left hemiplegia diagnosed between 6 and 24 months prior. The 9 subjects in the dual-afferent sensory input (DASI) group underwent ETFES with action observation training for 4 weeks (20 min/d, 5 d/wk), while the 9 control group subjects underwent functional electric stimulation (FES) for the same duration. The outcome measures were the movement-related cortical potential (MRCP), H-reflex, electromyography (EMG), and balance. The control and DASI groups showed significant increases in MRCP, muscle activity, and balance, while H-reflex was significantly decreased. MRCP and balance showed significant differences between DASI and control groups. DASI stimulates voluntary movement in patients, causes rapid activation of the cerebral cortex, and reduces excessive excitation of spinal motor neurons. Therefore, DASI, which stimulates voluntary movement, has a greater effect on brain activation in stroke patients.

Events at blood collection area due to nonconforming blood bags and plateletpheresis kits: need for timely corrective and preventive actions.

PubMed

Verma, Anupam; Sachan, Deepti; Elhence, Priti; Pandey, Hem; Dubey, Anju

2012-07-01

Good blood banking practice requires that every effort should be made to detect any deviation or defect in blood bank products and to identify any potential risk to blood donor or recipient(s). We report the findings of an exercise that provide an insight into why feedback from the user side is crucial. Various events involving blood bags and plateletpheresis kits and the corresponding appropriate actions instituted for remedial measures were recorded. These scattered events were recorded for 6 months following the use of a new batch of improved blood bags with add-on features. Several events related to plateletpheresis kits from three different manufacturers were also recorded for 1 year. The affected blood bags were utilized with no untoward incident. The complaint was closed following satisfactory response from the blood bag manufacturing company that acted in a timely manner in addressing the root causes of the problems. However, corrective and preventive actions (CAPA) could not be implemented for plateletpheresis kits. The rate of undesirable events was higher with plateletpheresis kits as compared with whole blood bags (1.75% vs. 0.06%). As defects or deviations that trigger the need for CAPA can stem from numerous sources, it is important to clearly identify and document the problems and level of risk so that appropriate investigations can be instituted and remedial actions can be taken in a timely manner. This study demonstrates the usefulness of a quality initiative to collate and analyze blood product faults in conjunction with blood product manufacturers. © 2012 American Association of Blood Banks.

From "Conflict" to "Constitutional Question": Transformations in Early American Public Discourse.

ERIC Educational Resources Information Center

Zarefsky, David; Gallagher, Victoria J.

1990-01-01

Suggests that the United States Constitution contains nearly universal concepts but also ambiguities which trigger conflicts. Describes the evolution of the document through its framing and through controversy surrounding the Alien and Sedition Acts, state nullification of federal action, and secession. Concludes that the Constitution provides a…

Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity

EPA Science Inventory

To support a paradigm shift in regulatory toxicology testing and risk assessment, the Adverse Outcome Pathway (AOP) concept has recently been proposed. This concept is similar to that for Mode of Action (MOA), describing a sequence of measurable key events triggered by a molecula...

Acting without being in control: Exploring volition in Parkinson's disease with impulsive compulsive behaviours.

PubMed

Ricciardi, Lucia; Haggard, Patrick; de Boer, Lieke; Sorbera, Chiara; Stenner, Max-Philipp; Morgante, Francesca; Edwards, Mark J

2017-07-01

Several aspects of volitional control of action may be relevant in the pathophysiology of impulsive-compulsive behaviours (ICB) in Parkinson's disease (PD). We aimed to explore multiple aspects of action control, assessing reward-related behaviour, inhibition (externally and internally triggered) and sense of agency in PD patients, with and without ICB compared to healthy subjects. Nineteen PD patients with ICB (PD-ICB), 19 PD without ICB (PD-no-ICB) and 19 healthy controls (HC) underwent a battery of tests including: Intentional Binding task which measures sense of agency; Stop Signal Reaction Time (SSRT) measuring capacity for reactive inhibition; the Marble task, assessing intentional inhibition; Balloon Analog Risk Task for reward sensitivity. One-way ANOVA showed significant main effect of group for action binding (p = 0.004, F = 6.27). Post hoc analysis revealed that PD-ICB had significantly stronger action binding than HC (p = 0.004), and PD-no-ICB (p = 0.04). There was no difference between PD-no-ICB and HC. SSRT did not differ between PD groups, whereas a significant difference between PD-no-ICB and HC was detected (p = 0.01). No other differences were found among groups in the other tasks. PD patients with ICB have abnormal performance on a psychophysical task assessing sense of agency, which might be related to a deficit in action representation at cognitive/experiential level. Yet, they have no deficit on tasks evaluating externally and internally triggered inhibitory control, or in reward-based decision-making. We conclude that impaired sense of agency may be a factor contributing to ICB in PD patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Carvedilol analogue inhibits triggered activities evoked by both early and delayed afterdepolarizations.

PubMed

Maruyama, Mitsunori; Xiao, Jianmin; Zhou, Qiang; Vembaiyan, Kannan; Chua, Su-Kiat; Rubart-von der Lohe, Michael; Lin, Shien-Fong; Back, Thomas G; Chen, S R Wayne; Chen, Peng-Sheng

2013-01-01

Carvedilol and its analogues suppress delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardias by direct action on the cardiac ryanodine receptor type 2 (RyR2). To test a hypothesis that carvedilol analogue may also prevent triggered activities (TAs) through the suppression of early afterdepolarizations (EADs). Intracellular Ca(2+) and membrane voltage were simultaneously recorded by using optical mapping technique in Langendorff-perfused mouse and rabbit hearts to study the effect of carvedilol analogue VK-II-36, which does not have significant beta-blocking effects. Spontaneous intracellular Ca(2+) elevations (SCaEs) during diastole were induced by rapid ventricular pacing and isoproterenol infusion in intact rabbit ventricles. Systolic and diastolic SCaEs were simultaneously noted in Langendorff-perfused RyR2 R4496(+/-) mouse hearts after creating atrioventricular block. VK-II-36 effectively suppressed SCaEs and eliminated TAs observed in both mouse and rabbit ventricles. We tested the effect of VK-II-36 on EADs by using a rabbit model of acquired long QT syndrome, in which phase 2 and phase 3 EADs were observed in association with systolic SCaEs. VK-II-36 abolished the systolic SCaEs and phase 2 EADs, and greatly decreased the dispersion of repolarization and the amplitude of phase 3 EADs. VK-II-36 completely prevented EAD-mediated TAs in all ventricles studied. A carvedilol analogue, VK-II-36, inhibits ventricular tachyarrhythmias in intact mouse and rabbit ventricles by the suppression of SCaEs, independent of beta-blocking activity. The RyR2 may be a potential target for treating focal ventricular arrhythmias triggered by either EADs or DADs. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Multi-Inhibitory Effects of A2A Adenosine Receptor Signaling on Neutrophil Adhesion Under Flow.

PubMed

Yago, Tadayuki; Tsukamoto, Hiroki; Liu, Zhenghui; Wang, Ying; Thompson, Linda F; McEver, Rodger P

2015-10-15

A2A adenosine receptor (A2AAR) signaling negatively regulates inflammatory responses in many disease models, but the detailed mechanisms remain unclear. We used the selective A2AAR agonist, ATL313, to examine how A2AAR signaling affects human and murine neutrophil adhesion under flow. Treating neutrophils with ATL313 inhibited selectin-induced, β2 integrin-dependent slow rolling and chemokine-induced, β2 integrin-dependent arrest on ICAM-1. ATL313 inhibited selectin-induced β2 integrin extension, which supports slow rolling, and chemokine-induced hybrid domain "swing-out," which supports arrest. Furthermore, ATL313 inhibited integrin outside-in signaling as revealed by reduced neutrophil superoxide production and spreading on immobilized anti-β2 integrin Ab. ATL313 suppressed selectin-triggered activation of Src family kinases (SFKs) and p38 MAPK, chemokine-triggered activation of Ras-related protein 1, and β2 integrin-triggered activation of SFKs and Vav cytoskeletal regulatory proteins. ATL313 activated protein kinase A and its substrate C-terminal Src kinase, an inhibitor of SFKs. Treating neutrophils with a protein kinase A inhibitor blocked the actions of ATL313. In vivo, ATL313-treated neutrophils rolled faster and arrested much less frequently in postcapillary venules of the murine cremaster muscle after TNF-α challenge. Furthermore, ATL313 markedly suppressed neutrophil migration into the peritoneum challenged with thioglycollate. ATL313 did not affect A2AAR-deficient neutrophils, confirming its specificity. Our findings provide new insights into the anti-inflammatory mechanisms of A2AAR signaling and the potential utility of A2AAR agonists in inflammatory diseases. Copyright © 2015 by The American Association of Immunologists, Inc.

Multi-inhibitory effects of A2A adenosine receptor signaling on neutrophil adhesion under flow**

PubMed Central

Yago, Tadayuki; Tsukamoto, Hiroki; Liu, Zhenghui; Wang, Ying; Thompson, Linda F.; McEver, Rodger P.

2015-01-01

A2A adenosine receptor (A2AAR) signaling negatively regulates inflammatory responses in many disease models, but the detailed mechanisms remain unclear. We used the selective A2AAR agonist, ATL313, to examine how A2AAR signaling affects human and murine neutrophil adhesion under flow. Treating neutrophils with ATL313 inhibited selectin-induced, β2 integrin-dependent slow rolling and chemokine-induced, β2 integrin-dependent arrest on ICAM-1. ATL313 inhibited selectin-induced β2 integrin extension, which supports slow rolling, and chemokine-induced hybrid domain “swing-out”, which supports arrest. Furthermore, ATL313 inhibited integrin outside-in signaling as revealed by reduced neutrophil superoxide production and spreading on immobilized anti-β2 integrin antibody. ATL313 suppressed selectin-triggered activation of Src family kinases (SFKs) and p38 MAPK, chemokine-triggered activation of Ras-related protein 1 (Rap1), and β2 integrin-triggered activation of SFKs and Vav cytoskeletal regulatory proteins. ATL313 activated protein kinase A (PKA) and its substrate C-terminal Src kinase (Csk), an inhibitor of SFKs. Treating neutrophils with a PKA inhibitor blocked the actions of ATL313. In vivo, ATL313-treated neutrophils rolled faster and arrested much less frequently in postcapillary venules of the murine cremaster muscle after TNF-α challenge. Furthermore, ATL313 markedly suppressed neutrophil migration into the peritoneum challenged with thioglycollate. ATL313 did not affect A2AAR-deficient neutrophils, confirming its specificity. Our findings provide new insights into the anti-inflammatory mechanisms of A2AAR signaling and the potential utility of A2AAR agonists in inflammatory diseases. PMID:26355151

Conscious control over the content of unconscious cognition.

PubMed

Kunde, Wilfried; Kiesel, Andrea; Hoffmann, Joachim

2003-06-01

Visual stimuli (primes) presented too briefly to be consciously identified can nevertheless affect responses to subsequent stimuli - an instance of unconscious cognition. There is a lively debate as to whether such priming effects originate from unconscious semantic processing of the primes or from reactivation of learned motor responses that conscious stimuli afford during preceding practice. In four experiments we demonstrate that unconscious stimuli owe their impact neither to automatic semantic categorization nor to memory traces of preceding stimulus-response episodes, but to their match with pre-specified cognitive action-trigger conditions. The intentional creation of such triggers allows actors to control the way unconscious stimuli bias their behaviour.

The politics of obesity: seven steps to government action.

PubMed

Kersh, Rogan; Morone, James

2002-01-01

Concern is rapidly growing about obesity rates in the United States. This paper analyzes the political consequences. Despite myths about individualism and self-reliance, the U.S. government has a long tradition of regulating ostensibly private behavior. We draw on the historical experience in four other private realms (alcohol, illegal drugs, tobacco, and sexuality) to identify seven "triggers" that prompt government to intervene in citizens' private habits. We suggest which of those triggers have been tripped--or are in play--in the case of obesity and food consumption. Finally, we review what government now does in this field and what it might do in the future.

Threats to social identity can trigger social deviance.

PubMed

Belmi, Peter; Barragan, Rodolfo Cortes; Neale, Margaret A; Cohen, Geoffrey L

2015-04-01

We hypothesized that threats to people's social (i.e., group) identity can trigger deviant attitudes and behaviors. A correlational study and five experiments showed that experiencing or recalling situations associated with the devaluation of a social identity caused participants to endorse or engage in deviant actions, including stealing, cheating, and lying. The effect was driven by the tendency to construe social identity threats not as isolated incidents but as symbolic of the continuing devaluation and disrespectful treatment of one's group. Supplementing sociological approaches to deviance and delinquency, the results suggest the relevance and utility of a social-psychological account. © 2015 by the Society for Personality and Social Psychology, Inc.

The influence of action-outcome delay and arousal on sense of agency and the intentional binding effect.

PubMed

Wen, Wen; Yamashita, Atsushi; Asama, Hajime

2015-11-01

The sense of agency refers to the feeling of being able to initiate and control events through one's actions. The "intentional binding" effect (Haggard, Clark, & Kalogeras, 2002), refers to a subjective compression of the temporal interval between actions and their effects. The present study examined the influence of action-outcome delays and arousal on both the subjective judgment of agency and the intentional binding effect. In the experiment, participants pressed a key to trigger a central square to jump after various delays. A red central square was used in the high-arousal condition. Results showed that a longer interval between actions and their effects was associated with a lower sense of agency but a stronger intentional binding effect. Furthermore, although arousal enhanced the intentional binding effect, it did not influence the judgment of agency. Copyright © 2015 Elsevier Inc. All rights reserved.

Overlearned responses hinder S-R binding.

PubMed

Moeller, Birte; Frings, Christian

2017-01-01

Two mechanisms that are important for human action control are the integration of individual action plans (see Hommel, Müsseler, Aschersleben, & Prinz, 2001) and the automatization of overlearned actions to familiar stimuli (see Logan, 1988). In the present study, we analyzed the influence of automatization on action plan integration. Integration with pronunciation responses were compared for response incompatible word and nonword stimuli. Stimulus-response binding effects were observed for nonwords. In contrast, words that automatically triggered an overlearned pronunciation response were not integrated with pronunciation of a different word. That is, automatized response retrieval hindered binding effects regarding the retrieving stimulus and a new response. The results are a first indication of the way that binding and learning processes interact, and might also be a first step to understanding the more complex interdependency of the processes responsible for stimulus-response binding in action control and stimulus-response associations in learning research. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Nonlinear dynamo action in a precessing cylindrical container.

PubMed

Nore, C; Léorat, J; Guermond, J-L; Luddens, F

2011-07-01

It is numerically demonstrated by means of a magnetohydrodynamics code that precession can trigger the dynamo effect in a cylindrical container. When the Reynolds number, based on the radius of the cylinder and its angular velocity, increases, the flow, which is initially centrosymmetric, loses its stability and bifurcates to a quasiperiodic motion. This unsteady and asymmetric flow is shown to be capable of sustaining dynamo action in the linear and nonlinear regimes. The magnetic field thus generated is unsteady and quadrupolar. These numerical evidences of dynamo action in a precessing cylindrical container may be useful for an experiment now planned at the Dresden sodium facility for dynamo and thermohydraulic studies in Germany.

Aedes ægypti control in urban areas: A systemic approach to a complex dynamic.

PubMed

Carvalho, Marilia Sá; Honorio, Nildimar Alves; Garcia, Leandro Martin Totaro; Carvalho, Luiz Carlos de Sá

2017-07-01

The available strategy for controlling the diseases transmitted by Aedes ægypti (dengue fever, Zika, and chikungunya) relies on continued community participation. Despite slogans emphasizing how easy it should be, no country has achieved it since the seventies. To better investigate potentially sustainable interventions, we developed a systemic model based on a multidisciplinary approach, integrating as deeply as possible specialized knowledge and field experience. The resulting model is composed of 4 external and 8 internal subsystems and 31 relationships, consistent with the literature and checked over multiple iterations with specialists of the many areas. We analyzed the model and the main feedback loops responsible for the system's stability, searching for possible interventions that could shift the existing balance. We suggest the introduction of 1 more player, the local primary health care structure, with the potential to change the undesired equilibrium. The health agents in the areas are the first to detect disease cases, and they could stimulate individuals to inform about potential mosquitoes' breeding sites and bring timely information to the vector-control program. Triggering such an action could introduce changes in people's attitude through a positive feedback loop in the desired direction.

Molecular cloning and structural characterization of Ecdysis Triggering Hormone from Choristoneura fumiferana.

PubMed

P, Bhagath Kumar; K, Kasi Viswanath; S, Tuleshwori Devi; R, Sampath Kumar; Doucet, Daniel; Retnakaran, Arthur; Krell, Peter J; Feng, Qili; Ampasala, Dinakara Rao

2016-07-01

At the end of each stadium, insects undergo a precisely orchestrated process known as ecdysis which results in the replacement of the old cuticle with a new one. This physiological event is necessary to accommodate growth in arthropods since they have a rigid chitinous exoskeleton. Ecdysis is initiated by the direct action of Ecdysis Triggering Hormones on the central nervous system. Choristoneura fumiferana is a major defoliator of coniferous forests in Eastern North America. It is assumed that, studies on the ecdysis behavior of this pest might lead to the development of novel pest management strategies. Hence in this study, the cDNA of CfETH was cloned. The open reading frame of the cDNA sequence was found to encode three putative peptides viz., Pre-Ecdysis Triggering Hormone (PETH), Ecdysis Triggering Hormone (ETH), and Ecdysis Triggering Hormone Associated Peptide (ETH-AP). The CfETH transcript was detected in the epidermal tissue of larval and pupal stages, but not in eggs and adults. In order to explore the structural conformation of ETH, ab initio modelling and Molecular Dynamics (MD) Simulations were performed. Further, a library of insecticides was generated and virtual screening was performed to identify the compounds displaying high binding capacity to ETH. Copyright © 2016 Elsevier B.V. All rights reserved.

Timing paradox of stepping and falls in ageing: not so quick and quick(er) on the trigger

PubMed Central

Mille, Marie‐Laure

2016-01-01

Abstract Physiological and degenerative changes affecting human standing balance are major contributors to falls with ageing. During imbalance, stepping is a powerful protective action for preserving balance that may be voluntarily initiated in recognition of a balance threat, or be induced by an externally imposed mechanical or sensory perturbation. Paradoxically, with ageing and falls, initiation slowing of voluntary stepping is observed together with perturbation‐induced steps that are triggered as fast as or faster than for younger adults. While age‐associated changes in sensorimotor conduction, central neuronal processing and cognitive functions are linked to delayed voluntary stepping, alterations in the coupling of posture and locomotion may also prolong step triggering. It is less clear, however, how these factors may explain the accelerated triggering of induced stepping. We present a conceptual model that addresses this issue. For voluntary stepping, a disruption in the normal coupling between posture and locomotion may underlie step‐triggering delays through suppression of the locomotion network based on an estimation of the evolving mechanical state conditions for stability. During induced stepping, accelerated step initiation may represent an event‐triggering process whereby stepping is released according to the occurrence of a perturbation rather than to the specific sensorimotor information reflecting the evolving instability. In this case, errors in the parametric control of induced stepping and its effectiveness in stabilizing balance would be likely to occur. We further suggest that there is a residual adaptive capacity with ageing that could be exploited to improve paradoxical triggering and other changes in protective stepping to impact fall risk. PMID:26915664

The neurobiology of collective action

PubMed Central

Zak, Paul J.; Barraza, Jorge A.

2013-01-01

This essay introduces a neurologically-informed mathematical model of collective action (CA) that reveals the role for empathy and distress in motivating costly helping behaviors. We report three direct tests of model with a key focus on the neuropeptide oxytocin as well as a variety of indirect tests. These studies, from our lab and other researchers, show support for the model. Our findings indicate that empathic concern, via the brain's release of oxytocin, is a trigger for CA. We discuss the implications from this model for our understanding why human beings engage in costly CA. PMID:24311995

Advanced integrated safeguards using front-end-triggering devices

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

Howell, J.A.; Whitty, W.J.

This report addresses potential uses of front-end-triggering devices for enhanced safeguards. Such systems incorporate video surveillance as well as radiation and other sensors. Also covered in the report are integration issues and analysis techniques.

Upgrade project and plans for the ATLAS detector and trigger

NASA Astrophysics Data System (ADS)

Pastore, Francesca; Atlas Collaboration

2013-08-01

The LHC is expected to under go upgrades over the coming years in order to extend its scientific potential. Through two different phases (namely Phase-I and Phase-II), the average luminosity will be increased by a factor 5-10 above the design luminosity, 1034 cm-2 s-1. Consequently, the LHC experiments will need upgraded detectors and new infrastructure of the trigger and DAQ systems, to take into account the increase of radiation level and of particle rates foreseen at such high luminosity. In this paper we describe the planned changes and the investigations for the ATLAS experiment, focusing on the requirements for the trigger system to handle the increase rate of collisions per beam crossing, while maintaining widely inclusive selections. In different steps, the trigger detectors will improve their selectivity by benefiting from increased granularity. To improve the flexibility of the system, the use of the tracking information in the lower levels of the trigger selection is also discussed. Lastly different scenarios are compared, based on the expected physics potential of ATLAS in this high luminosity regime.

Myofascial trigger points: spontaneous electrical activity and its consequences for pain induction and propagation

PubMed Central

2011-01-01

Active myofascial trigger points are one of the major peripheral pain generators for regional and generalized musculoskeletal pain conditions. Myofascial trigger points are also the targets for acupuncture and/or dry needling therapies. Recent evidence in the understanding of the pathophysiology of myofascial trigger points supports The Integrated Hypothesis for the trigger point formation; however unanswered questions remain. Current evidence shows that spontaneous electrical activity at myofascial trigger point originates from the extrafusal motor endplate. The spontaneous electrical activity represents focal muscle fiber contraction and/or muscle cramp potentials depending on trigger point sensitivity. Local pain and tenderness at myofascial trigger points are largely due to nociceptor sensitization with a lesser contribution from non-nociceptor sensitization. Nociceptor and non-nociceptor sensitization at myofascial trigger points may be part of the process of muscle ischemia associated with sustained focal muscle contraction and/or muscle cramps. Referred pain is dependent on the sensitivity of myofascial trigger points. Active myofascial trigger points may play an important role in the transition from localized pain to generalized pain conditions via the enhanced central sensitization, decreased descending inhibition and dysfunctional motor control strategy. PMID:21439050

Cholecystokinin from the entorhinal cortex enables neural plasticity in the auditory cortex

PubMed Central

Li, Xiao; Yu, Kai; Zhang, Zicong; Sun, Wenjian; Yang, Zhou; Feng, Jingyu; Chen, Xi; Liu, Chun-Hua; Wang, Haitao; Guo, Yi Ping; He, Jufang

2014-01-01

Patients with damage to the medial temporal lobe show deficits in forming new declarative memories but can still recall older memories, suggesting that the medial temporal lobe is necessary for encoding memories in the neocortex. Here, we found that cortical projection neurons in the perirhinal and entorhinal cortices were mostly immunopositive for cholecystokinin (CCK). Local infusion of CCK in the auditory cortex of anesthetized rats induced plastic changes that enabled cortical neurons to potentiate their responses or to start responding to an auditory stimulus that was paired with a tone that robustly triggered action potentials. CCK infusion also enabled auditory neurons to start responding to a light stimulus that was paired with a noise burst. In vivo intracellular recordings in the auditory cortex showed that synaptic strength was potentiated after two pairings of presynaptic and postsynaptic activity in the presence of CCK. Infusion of a CCKB antagonist in the auditory cortex prevented the formation of a visuo-auditory association in awake rats. Finally, activation of the entorhinal cortex potentiated neuronal responses in the auditory cortex, which was suppressed by infusion of a CCKB antagonist. Together, these findings suggest that the medial temporal lobe influences neocortical plasticity via CCK-positive cortical projection neurons in the entorhinal cortex. PMID:24343575

Accumulation of K+ in the synaptic cleft modulates activity by influencing both vestibular hair cell and calyx afferent in the turtle

PubMed Central

Contini, Donatella; Price, Steven D.

2016-01-01

Key points In the synaptic cleft between type I hair cells and calyceal afferents, K+ ions accumulate as a function of activity, dynamically altering the driving force and permeation through ion channels facing the synaptic cleft.High‐fidelity synaptic transmission is possible due to large conductances that minimize hair cell and afferent time constants in the presence of significant membrane capacitance.Elevated potassium maintains hair cells near a potential where transduction currents are sufficient to depolarize them to voltages necessary for calcium influx and synaptic vesicle fusion.Elevated potassium depolarizes the postsynaptic afferent by altering ion permeation through hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels, and contributes to depolarizing the afferent to potentials where a single EPSP (quantum) can generate an action potential.With increased stimulation, hair cell depolarization increases the frequency of quanta released, elevates [K+]cleft and depolarizes the afferent to potentials at which smaller and smaller EPSPs would be sufficient to trigger APs. Abstract Fast neurotransmitters act in conjunction with slower modulatory effectors that accumulate in restricted synaptic spaces found at giant synapses such as the calyceal endings in the auditory and vestibular systems. Here, we used dual patch‐clamp recordings from turtle vestibular hair cells and their afferent neurons to show that potassium ions accumulating in the synaptic cleft modulated membrane potentials and extended the range of information transfer. High‐fidelity synaptic transmission was possible due to large conductances that minimized hair cell and afferent time constants in the presence of significant membrane capacitance. Increased potassium concentration in the cleft maintained the hair cell near potentials that promoted the influx of calcium necessary for synaptic vesicle fusion. The elevated potassium concentration also depolarized the postsynaptic neuron by altering ion permeation through hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels. This depolarization enabled the afferent to reliably generate action potentials evoked by single AMPA‐dependent EPSPs. Depolarization of the postsynaptic afferent could also elevate potassium in the synaptic cleft, and would depolarize other hair cells enveloped by the same neuritic process increasing the fidelity of neurotransmission at those synapses as well. Collectively, these data demonstrate that neuronal activity gives rise to potassium accumulation, and suggest that potassium ion action on HCN channels can modulate neurotransmission, preserving the fidelity of high‐speed synaptic transmission by dynamically shifting the resting potentials of both presynaptic and postsynaptic cells. PMID:27633787

Action and perception in social contexts: intentional binding for social action effects

PubMed Central

Pfister, Roland; Obhi, Sukhvinder S.; Rieger, Martina; Wenke, Dorit

2014-01-01

The subjective experience of controlling events in the environment alters the perception of these events. For instance, the interval between one's own actions and their consequences is subjectively compressed—a phenomenon known as intentional binding. In two experiments, we studied intentional binding in a social setting in which actions of one agent prompted a second agent to perform another action. Participants worked in pairs and were assigned to a “leader” and a “follower” role, respectively. The leader's key presses triggered (after a variable interval) a tone and this tone served as go signal for the follower to perform a keypress as well. Leaders and followers estimated the interval between the leader's keypress and the following tone, or the interval between the tone and the follower's keypress. The leader showed reliable intentional binding for both intervals relative to the follower's estimates. These results indicate that human agents experience a pre-reflective sense of agency for genuinely social consequences of their actions. PMID:25228869

Closing a Venus Flytrap with electrical and mid-IR photon stimulations

NASA Astrophysics Data System (ADS)

Eisen, David; Janssen, Douglas; Chen, Xing; Choa, Fow-Sen; Kostov, Dan; Fan, Jenyu

2013-03-01

Plants have mechanisms to perceive and transmit information between its organs and tissues. These signals had long been considered as hormonal or hydraulic in nature, but recent studies have shown that electrical signals are also produced causing physiological responses. In this work we show that Venus Flytrap, Dionaea muscipula, can respond to both electrical and optical signals beside mechanical stimulations. While the Venus Flytrap does not have any neurons, it does contain transport cells with very similar characteristics to neurotransmitters and uses ionic mechanisms, as human neurons do, to generate action potentials. In our electrical stimulation study, electrodes made out of soft cloth were soaked in salt water before being placed to the midrib (+) and lobe (-). The flytrap's surface resistance was determined by subtracting out the average electrode resistance from the measured electrode to plant surface resistance, yielding an average contact resistance of around 0.98MΩ. A logarithmic amplifier was used to monitor mechanically generated electrical signals. Two electrical pulses were generated by mechanically touching the trigger hairs in the lobe twice within 20 seconds. By discharging around 600μC charge stored in a capacitor we demonstrated electrically closing of the flytrap. For optical excitation we found in our FTIR study it's tissue contains very similar protein absorption peaks to that of insects. A 7.35μm laser with 50mw power was then used for the stimulation study. Electrical action potential was generated twice by mid-infrared photons before closure of the flytrap.

hERG K+ channel-associated cardiac effects of the antidepressant drug desipramine.

PubMed

Staudacher, Ingo; Wang, Lu; Wan, Xiaoping; Obers, Sabrina; Wenzel, Wolfgang; Tristram, Frank; Koschny, Ronald; Staudacher, Kathrin; Kisselbach, Jana; Koelsch, Patrick; Schweizer, Patrick A; Katus, Hugo A; Ficker, Eckhard; Thomas, Dierk

2011-02-01

Cardiac side effects of antidepressant drugs are well recognized. Adverse effects precipitated by the tricyclic drug desipramine include prolonged QT intervals, torsade de pointes tachycardia, heart failure, and sudden cardiac death. QT prolongation has been primarily attributed to acute blockade of hERG/I(Kr) currents. This study was designed to provide a more complete picture of cellular effects associated with desipramine. hERG channels were expressed in Xenopus laevis oocytes and human embryonic kidney (HEK 293) cells, and potassium currents were recorded using patch clamp and two-electrode voltage clamp electrophysiology. Ventricular action potentials were recorded from guinea pig cardiomyocytes. Protein trafficking and cell viability were evaluated in HEK 293 cells and in HL-1 mouse cardiomyocytes by immunocytochemistry, Western blot analysis, or colorimetric MTT assay, respectively. We found that desipramine reduced hERG currents by binding to a receptor site inside the channel pore. hERG protein surface expression was reduced after short-term treatment, revealing a previously unrecognized mechanism. When long-term effects were studied, forward trafficking was impaired and hERG currents were decreased. Action potential duration was prolonged upon acute and chronic desipramine exposure. Finally, desipramine triggered apoptosis in cells expressing hERG channels. Desipramine exerts at least four different cellular effects: (1) direct hERG channel block, (2) acute reduction of hERG surface expression, (3) chronic disruption of hERG trafficking, and (4) induction of apoptosis. These data highlight the complexity of hERG-associated drug effects.

Neuroprotective Properties and Mechanisms of Resveratrol in in Vitro and in Vivo Experimental Cerebral Stroke Models

PubMed Central

2013-01-01

Resveratrol, a natural stilbene present at relatively high concentrations in grape skin and seeds and red wine, is known for its purported antioxidant activity in the vascular and nervous systems. In contrast to its direct antioxidant role within the central nervous system, recent research supports a protective mechanism through increasing endogenous cellular antioxidant defenses, which triggers a cascade of parallel neuroprotective pathways. A growing body of in vitro and in vivo evidence indicates that resveratrol acts through multiple pathways and reduces ischemic damage in vital organs, such as the heart and the brain, in various rodent models. Most of the protective biological actions of resveratrol have been associated with its antioxidative, anti-inflammatory, and antiapoptotic properties and other indirect pathways. Continued public interest and increasing resveratrol supplements on the market warrant a review of the available in vitro and in vivo science reported in the stroke-related literature. Rigorous clinical trials evaluating the effects of resveratrol in stroke are absent, though the general population consumption appears to be relatively safe. Resveratrol has shown potential for treating stroke in laboratory animals and in vitro human cell studies, yet there is still a need for human research in preclinical settings. This review summarizes many of the findings on the neuroprotective potential of resveratrol in cerebral stroke, focusing on both the in vitro and in vivo experimental models and some proposed mechanisms of action. PMID:23758534

Post-Inhibitory Rebound Spikes in Rat Medial Entorhinal Layer II/III Principal Cells: In Vivo, In Vitro, and Computational Modeling Characterization

PubMed Central

Ferrante, Michele; Shay, Christopher F.; Tsuno, Yusuke; William Chapman, G.; Hasselmo, Michael E.

2017-01-01

Abstract Medial entorhinal cortex Layer-II stellate cells (mEC-LII-SCs) primarily interact via inhibitory interneurons. This suggests the presence of alternative mechanisms other than excitatory synaptic inputs for triggering action potentials (APs) in stellate cells during spatial navigation. Our intracellular recordings show that the hyperpolarization-activated cation current (Ih) allows post-inhibitory-rebound spikes (PIRS) in mEC-LII-SCs. In vivo, strong inhibitory-post-synaptic potentials immediately preceded most APs shortening their delay and enhancing excitability. In vitro experiments showed that inhibition initiated spikes more effectively than excitation and that more dorsal mEC-LII-SCs produced faster and more synchronous spikes. In contrast, PIRS in Layer-II/III pyramidal cells were harder to evoke, voltage-independent, and slower in dorsal mEC. In computational simulations, mEC-LII-SCs morphology and Ih homeostatically regulated the dorso-ventral differences in PIRS timing and most dendrites generated PIRS with a narrow range of stimulus amplitudes. These results suggest inhibitory inputs could mediate the emergence of grid cell firing in a neuronal network. PMID:26965902

Inhibitors of connexin and pannexin channels as potential therapeutics

PubMed Central

Willebrords, Joost; Maes, Michaël; Crespo Yanguas, Sara; Vinken, Mathieu

2018-01-01

While gap junctions support the exchange of a number of molecules between neighboring cells, connexin hemichannels provide communication between the cytosol and the extracellular environment of an individual cell. The latter equally holds true for channels composed of pannexin proteins, which display an architecture reminiscent of connexin hemichannels. In physiological conditions, gap junctions are usually open, while connexin hemichannels and, to a lesser extent, pannexin channels are typically closed, yet they can be activated by a number of pathological triggers. Several agents are available to inhibit channels built up by connexin and pannexin proteins, including alcoholic substances, glycyrrhetinic acid, anesthetics and fatty acids. These compounds not always strictly distinguish between gap junctions, connexin hemichannels and pannexin channels, and may have effects on other targets as well. An exception lies with mimetic peptides, which reproduce specific amino acid sequences in connexin or pannexin primary protein structure. In this paper, a state-of-the-art overview is provided on inhibitors of cellular channels consisting of connexins and pannexins with specific focus on their mode-of-action and therapeutic potential. PMID:28720428

Common key-signals in learning and neurodegeneration: focus on excito-amino acids, beta-amyloid peptides and alpha-synuclein.

PubMed

Agnati, L F; Leo, G; Genedani, S; Piron, L; Rivera, A; Guidolin, D; Fuxe, K

2009-08-01

In this paper a hypothesis that some special signals ("key-signals" excito-amino acids, beta-amyloid peptides and alpha-synuclein) are not only involved in information handling by the neuronal circuits, but also trigger out substantial structural and/or functional changes in the Central Nervous System (CNS) is introduced. This forces the neuronal circuits to move from one stable state towards a new state, but in doing so these signals became potentially dangerous. Several mechanisms are put in action to protect neurons and glial cells from these potentially harmful signals. However, in agreement with the Red Queen Theory of Ageing (Agnati et al. in Acta Physiol Scand 145:301-309, 1992), it is proposed that during ageing these neuroprotective processes become less effective while, in the meantime, a shortage of brain plasticity occurs together with an increased need of plasticity for repairing the wear and tear of the CNS. The paper presents findings supporting the concept that such key-signals in instances such as ageing may favour neurodegenerative processes in an attempt of maximizing neuronal plasticity.

Wyatt v Stickney: 10 Years in Review--Past, Present and Future.

ERIC Educational Resources Information Center

Marchetti, Allen

The paper recounts the background of Wyatt v Stickney, which resulted in a landmark decision establishing a constitutional right to treatment for mentally retarded persons. Events which triggered the Wyatt litigation include an employee action brought about by staff in an effort to obtain re-employment. The involvement of the American Association…

Problem Drift: Teaching Curriculum With(in) a World of Emerging Significance

ERIC Educational Resources Information Center

Banting, Nat; Simmt, Elaine

2017-01-01

In this paper we frame our observations in enactivism, specifically problem posing, to propose the notion of problem drift as a method to analyze the curriculum generating actions of small group learning systems in relation to teacher interventions intended to trigger specific content goals. Teacher attentiveness to problem drift is suggested to…

Strategic Aggression: Conditions that Could Trigger Aggressive Military Action by the People’s Republic of China

DTIC Science & Technology

2013-05-23

growth, its plans for defense spending and force posture are not so lucid . The government publishes defense white papers, which outline vague...is Unhappy: The Great Era, the Grand Goal, and Our Internal Anxieties and External Challenges (2009) and China Dream : Great Power Thinking and

77 FR 7603 - Notice of a Change in Status of an Extended Benefit (EB) Period for Alaska

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... Extended Benefit (EB) Period for Alaska AGENCY: Employment and Training Administration, Labor. ACTION... Extended Benefits program began January 22, 2012. The trigger notice covering state eligibility for the EB... governed by the Federal- State Extended Unemployment Compensation Act of 1970, as amended, and the...

The Politics of Parental Involvement: How Opportunity Hoarding and Prying Shape Educational Opportunity

ERIC Educational Resources Information Center

Lyken-Segosebe, Dawn; Hinz, Serena E.

2015-01-01

As more state legislatures join the debate on school-choice and parent-trigger legislation, their discussions draw attention to an evolving landscape outside school walls where parental action shapes educational opportunity. Parents wield their political, social, economic, and cultural capital to secure the best educational outcomes for their…

Bacillus thuringiensis toxins trigger receptor shedding from gypsy moth midgut cells

Treesearch

Algimantas P. Valaitis

2007-01-01

The mechanism of action of the Cry1 insecticidal proteins produced by Bacillus thuringiensis (Bt) begins with the processing of these proteins in the larval gut. After proteolytic activation, the Bt toxins bind to specific midgut receptors and insert into the membrane of the gut epithelial cells, causing insect death.

78 FR 59374 - Announcement Regarding a Change in Eligibility for Unemployment Insurance (UI) Claimants in...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-26

... Eligibility for Unemployment Insurance (UI) Claimants in Alaska, Mississippi, and Wisconsin in the Emergency Unemployment Compensation 2008 (EUC08) Program AGENCY: Employment and Training Administration, Labor. ACTION... week insured unemployment rate in Alaska was 3.9 percent, falling below the 4.0 percent trigger rate...

78 FR 68865 - Announcement Regarding a Change in Eligibility for Unemployment Insurance (UI) Claimants in...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-15

... Eligibility for Unemployment Insurance (UI) Claimants in Alaska, Mississippi, and Wisconsin in the Emergency Unemployment Compensation 2008 (EUC08) Program AGENCY: Employment and Training Administration, Labor. ACTION... week insured unemployment rate in Alaska was 3.9 percent, falling below the 4.0 percent trigger rate...

The Other Shoe Drops: Courts Make College Admission a Risky Business.

ERIC Educational Resources Information Center

Van Tyle, Peter

1996-01-01

The University of Texas law school's race-based admissions process triggered the boldest judicial statement addressing affirmative action since 1978. Colleges and universities throughout the country must now look at student diversity on a student-by-student basis and without reference to racial classifications. Admissions offices failing to comply…

75 FR 32845 - Consultative Examination-Annual Onsite Review of Medical Providers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-10

.... ACTION: Final rules. SUMMARY: We are revising the threshold billing amount that triggers annual on-site... titles II and XVI of the Social Security Act (Act). The revision will raise the threshold amount to reflect the increase in billing amounts since we first established the threshold amount in 1991. We expect...

β-glucans and eicosapolyenoic acids as MAMPs in plant–oomycete interactions: past and present

PubMed Central

Robinson, Sara M.; Bostock, Richard M.

2015-01-01

Branched β-1,3-glucans and the eicosapolyenoic acids (EP) are among the best characterized oomycete elicitors that trigger innate immune responses in plants. These elicitors were identified over three decades ago, and they were useful in the study of the sequence of physiological, biochemical and molecular events that induce resistance in plants. However, in spite of the cross-kingdom parallels where these molecules are well-characterized as immune system modulators in animals, their perception and modes of action in plants remains obscure. Oomycetes are among the most important plant pathogens, responsible for diseases that devastate crops, ornamentals, and tree species worldwide. With the recent interest and advances in our understanding of innate immunity in plants, and the redefining of many of the classical elicitors as microbe-associated molecular patterns (MAMPs), it seems timely and important to reexamine β-glucans and EP using contemporary approaches. In this review, we highlight early studies of β-glucans and EP, discuss their roles as evolutionarily conserved signals, and consider their action in relation to current models of MAMP-triggered immunity. PMID:25628639

Hyperhomocysteinemia impairs regional blood flow: involvements of endothelial and neuronal nitric oxide.

PubMed

Toda, Noboru; Okamura, Tomio

2016-09-01

Increasing evidence support the idea that hyperhomocysteinemia (HHcy) is responsible for pathogenesis underlying cerebral, coronary, renal, and other vascular circulatory disorders and for hypertension. Impaired synthesis of nitric oxide (NO) in the endothelium or increased production of asymmetric dimethylarginine and activated oxygen species are involved in the impairment of vasodilator effects of NO. Impaired circulation in the brain derived from reduced synthesis and actions of NO would be an important triggering factor to dementia and Alzheimer's disease. Reduced actions of NO and brain hypoperfusion trigger increased production of amyloid-β that inhibits endothelial function, thus establishing a vicious cycle for impairing brain circulation. HHcy is involved in the genesis of anginal attack and coronary myocardial infarction. HHcy is also involved in renal circulatory diseases. The homocysteine (Hcy)-induced circulatory failure is promoted by methionine and is prevented by increased folic acid and vitamin B6/B12. Eliminating poor life styles, such as smoking and being sedentary; keeping favorable dietary habits; and early treatment maintaining constitutive NOS functions healthy, reducing oxidative stresses would be beneficial in protecting HHcy-induced circulatory failures.

Spike Timing and Reliability in Cortical Pyramidal Neurons: Effects of EPSC Kinetics, Input Synchronization and Background Noise on Spike Timing

PubMed Central

Rodriguez-Molina, Victor M.; Aertsen, Ad; Heck, Detlef H.

2007-01-01

In vivo studies have shown that neurons in the neocortex can generate action potentials at high temporal precision. The mechanisms controlling timing and reliability of action potential generation in neocortical neurons, however, are still poorly understood. Here we investigated the temporal precision and reliability of spike firing in cortical layer V pyramidal cells at near-threshold membrane potentials. Timing and reliability of spike responses were a function of EPSC kinetics, temporal jitter of population excitatory inputs, and of background synaptic noise. We used somatic current injection to mimic population synaptic input events and measured spike probability and spike time precision (STP), the latter defined as the time window (Δt) holding 80% of response spikes. EPSC rise and decay times were varied over the known physiological spectrum. At spike threshold level, EPSC decay time had a stronger influence on STP than rise time. Generally, STP was highest (≤2.45 ms) in response to synchronous compounds of EPSCs with fast rise and decay kinetics. Compounds with slow EPSC kinetics (decay time constants>6 ms) triggered spikes at lower temporal precision (≥6.58 ms). We found an overall linear relationship between STP and spike delay. The difference in STP between fast and slow compound EPSCs could be reduced by incrementing the amplitude of slow compound EPSCs. The introduction of a temporal jitter to compound EPSCs had a comparatively small effect on STP, with a tenfold increase in jitter resulting in only a five fold decrease in STP. In the presence of simulated synaptic background activity, precisely timed spikes could still be induced by fast EPSCs, but not by slow EPSCs. PMID:17389910

Mechanism of As2O3-Induced Action Potential Prolongation and Using hiPS-CMs to Evaluate the Rescue Efficacy of Drugs With Different Rescue Mechanism.

PubMed

Yan, Meng; Feng, Lifang; Shi, Yanhui; Wang, Junnan; Liu, Yan; Li, Fengmei; Li, Baoxin

2017-08-01

Arsenic trioxide (As2O3) has been verified as a breakthrough in the management of acute promyelocytic leukemia in recent decades. However, cardiotoxicity, especially long QT syndrome (LQTS) has become the most important issue during As2O3 treatment. The characterized mechanisms behind this adverse effect are inhibition of cardiac hERG channel trafficking and increase of cardiac calcium currents. In our study, we found a new pathway underlying As2O3-induced cardiotoxicity that As2O3 accelerates lysosomal degradation of hERG on plasma membrane after using brefeldin A (BFA) to block protein trafficking. Then we explored pharmacological rescue strategies on As2O3-induced LQTS, and found that 4 therapeutic agents exert rescue efficacy via 3 different pathways: fexofenadine and astemizole facilitate hERG trafficking via promotion of channel-chaperone formation after As2O3 incubation; ranolazine slows hERG degradation in the presence of As2O3; and resveratrol shows significant attenuation on calcium current increase triggered by As2O3. Moreover, we used human-induced pluripotent stem cell derived cardiomyocytes (hiPS-CMs) to evaluate the rescue effects of the above agents on As2O3-induced prolongation of action potential duration (APD) and demonstrated that fexofenadine and resveratrol significantly ameliorate the prolonged APD. These observations suggested that pharmacological chaperone like fexofenadine and resveratrol might have the potential to protect against the cardiotoxicity of As2O3. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Identifying and Evaluating Possible Trigger Mechanisms for Glacial Lake Outburst Floods in the Hindu Kush Himalayas Using Remote Sensing Satellite Data

NASA Astrophysics Data System (ADS)

Hess, T. G.; Haritashya, U. K.

2014-12-01

Glacierized basins in high-altitude and mountainous areas, such as the Himalayas, have seen an increase in the number of glacial lakes over the years as a result of a changing climate. As the meltwater becomes more prevalent, the runoff can accumulate in a depression left behind by the receding glacier and can be bound by the walls of frontal and lateral moraines. These moraines, however, often are comprised of loose, unconsolidated sediment and can prove to be unstable dam structures for proglacial lakes. The factor of instability associated with the moraines poses a serious threat for failure and severe flooding. If the moraines were to be breached by the lake water, a phenomenon known as a glacial lake outburst flood (GLOF) can occur, potentially putting lives and infrastructure in harm's way. Consequently, this study examines the likelihood of a GLOF occurrence by analyzing potential trigger mechanisms associated with three proglacial lakes in the Hindu Kush Himalayan region. Using ASTER satellite imagery, one lake from Nepal, India, and Bhutan have each been assessed for possible trigger mechanisms. Our results suggest that steep-sided moraines, rugged topography, unstable masses on the upper reaches of steep slopes, and smaller lakes perched high above can all be classified as possible trigger mechanisms for the areas of study. It is imperative to be able to successfully identify potential trigger mechanisms using satellite data so that further ground observations can be made and mitigation efforts can be incorporated where needed. As lakes continue to grow, so does the cause for concern for possible GLOFs. Glacial lake outburst floods are being studied more extensively now due to the greater number of glacial lakes in high-mountainous areas. It is vitally important to understand the dynamics of a GLOF, especially the potential trigger mechanisms associated with it.

Internet cigarette sales and Native American sovereignty: political and public health contexts.

PubMed

Samuel, Kari A; Ribisl, Kurt M; Williams, Rebecca S

2012-05-01

Internet cigarette vendors (ICVs) advertise low prices for tobacco products, subverting public health policy efforts to curtail smoking by raising prices. Many online retailers in the United States claim affiliation with Native American tribes and share in tribal tax-free status. Sales of discounted cigarettes from both online vendors and brick-and-mortar stores have angered non-Native retailers and triggered enforcement actions by state and federal governments in the United States concerned over lost cigarette excise tax revenue. Examination of the history and politics of cigarette sales on reservations and attempts to regulate Internet cigarette sales highlights the potential role for greater use of negotiated intergovernmental agreements to address reservation-based tobacco sales. Our review notes global parallels and explicates history and politics of such regulation in the United States, and offers background for collaborative efforts to regulate tobacco sales and decrease tobacco use.

Isolation and antitumor efficacy evaluation of a polysaccharide from Nostoc commune Vauch.

PubMed

Guo, Min; Ding, Guo-Bin; Guo, Songjia; Li, Zhuoyu; Zhao, Liangqi; Li, Ke; Guo, Xiangrong

2015-09-01

Nostoc commune Vauch. has been traditionally used as a healthy food and medicine for centuries especially in China. It has been demonstrated that the polysaccharides isolated from Nostoc commune Vauch. exhibit strong antimicrobial and antioxidant activities. However, little is known about their anticancer activities and the underlying mechanisms of action. Herein, we report the isolation of a polysaccharide from Nostoc commune Vauch. (NVPS), and its physicochemical properties were analyzed. In an attempt to demonstrate the potential application of NVPS in tumor chemotherapy, the in vitro antitumor activity was determined. NVPS significantly suppressed the growth and proliferation of MCF-7 and DLD1 cells. The molecular mechanism underlying this in vitro antitumor efficacy was elucidated, and the results indicated that NVPS simultaneously triggered intrinsic, extrinsic and endoplasmic reticulum stress (ERS)-mediated apoptotic signaling pathways. Collectively, these findings demonstrate that NVPS could be used as a novel promising source of natural antitumor agents.

Are corticothalamic 'up' states fragments of wakefulness?

PubMed

Destexhe, Alain; Hughes, Stuart W; Rudolph, Michelle; Crunelli, Vincenzo

2007-07-01

The slow (<1 Hz) oscillation, with its alternating 'up' and 'down' states in individual neurons, is a defining feature of the electroencephalogram (EEG) during slow-wave sleep (SWS). Although this oscillation is well preserved across mammalian species, its physiological role is unclear. Electrophysiological and computational evidence from the cortex and thalamus now indicates that slow-oscillation 'up' states and the 'activated' state of wakefulness are remarkably similar dynamic entities. This is consistent with behavioural experiments suggesting that slow-oscillation 'up' states provide a context for the replay, and possible consolidation, of previous experience. In this scenario, the T-type Ca(2+) channel-dependent bursts of action potentials that initiate each 'up' state in thalamocortical (TC) neurons might function as triggers for synaptic and cellular plasticity in corticothalamic networks. This review is part of the INMED/TINS special issue Physiogenic and pathogenic oscillations: the beauty and the beast, based on presentations at the annual INMED/TINS symposium (http://inmednet.com).

Spike-timing dependent plasticity in primate corticospinal connections induced during free behavior

PubMed Central

Nishimura, Yukio; Perlmutter, Steve I.; Eaton, Ryan W.; Fetz, Eberhard E.

2014-01-01

Motor learning and functional recovery from brain damage involve changes in the strength of synaptic connections between neurons. Relevant in vivo evidence on the underlying cellular mechanisms remains limited and indirect. We found that the strength of neural connections between motor cortex and spinal cord in monkeys can be modified with an autonomous recurrent neural interface that delivers electrical stimuli in the spinal cord triggered by action potentials of corticospinal cells during free behavior. The activity-dependent stimulation modified the strength of the terminal connections of single corticomotoneuronal cells, consistent with a bidirectional spike-timing dependent plasticity rule previously derived from in vitro experiments. For some cells the changes lasted for days after the end of conditioning, but most effects eventually reverted to preconditioning levels. These results provide the first direct evidence of corticospinal synaptic plasticity in vivo at the level of single neurons induced by normal firing patterns during free behavior. PMID:24210907

Berberine exposure triggers developmental effects on planarian regeneration

PubMed Central

Balestrini, Linda; Isolani, Maria Emilia; Pietra, Daniele; Borghini, Alice; Bianucci, Anna Maria; Deri, Paolo; Batistoni, Renata

2014-01-01

The mechanisms of action underlying the pharmacological properties of the natural alkaloid berberine still need investigation. Planarian regeneration is instrumental in deciphering developmental responses following drug exposure. Here we report the effects of berberine on regeneration in the planarian Dugesia japonica. Our findings demonstrate that this compound perturbs the regenerative pattern. By real-time PCR screening for the effects of berberine exposure on gene expression, we identified alterations in the transcriptional profile of genes representative of different tissues, as well as of genes involved in extracellular matrix (ECM) remodeling. Although berberine does not influence cell proliferation/apoptosis, our experiments prove that this compound causes abnormal regeneration of the planarian visual system. Potential berberine-induced cytotoxic effects were noticed in the intestine. Although we were unable to detect abnormalities in other structures, our findings, sustained by RNAi-based investigations, support the possibility that berberine effects are critically linked to anomalous ECM remodeling in treated planarians. PMID:24810466

'They don't just come for Machu Picchu': locals' views of tourist-local sexual relationships in Cuzco, Peru.

PubMed

Bauer, Irmgard

2008-08-01

Sexual and romantic relationships between local people and tourists have long taken place. Such encounters are not a modern phenomenon, but the potential of sexually transmitted infections (STIs), including HIV/AIDS, warrants greater research into the issue. This paper analyses local people's views of local-tourist relationships in Cuzco/Peru. Data were obtained through in-depth interviews, participant and non-participant observation and informal discussions. Attraction based on physical difference was reportedly the main trigger for such relationships. Emerging themes discussed include issues of self-esteem, strategies of approach, tourists' motives, emotional involvement and expectations from such encounters. Levels of unprotected sexual behaviour and lack of STI awareness are of sufficient concern to recommend urgent action. Suggestions for sexual health education are made with particular emphasis on targeting local people involved in the tourism and hospitality industries.

The Neuroscience of Growth Mindset and Intrinsic Motivation

PubMed Central

Ng, Betsy

2018-01-01

Our actions can be triggered by intentions, incentives or intrinsic values. Recent neuroscientific research has yielded some results about the growth mindset and intrinsic motivation. With the advances in neuroscience and motivational studies, there is a global need to utilize this information to inform educational practice and research. Yet, little is known about the neuroscientific interplay between growth mindset and intrinsic motivation. This paper attempts to draw on the theories of growth mindset and intrinsic motivation, together with contemporary ideas in neuroscience, outline the potential for neuroscientific research in education. It aims to shed light on the relationship between growth mindset and intrinsic motivation in terms of supporting a growth mindset to facilitate intrinsic motivation through neural responses. Recent empirical research from the educational neuroscience perspective that provides insights into the interplay between growth mindset and intrinsic motivation will also be discussed. PMID:29373496

The impact of mast cells on cardiovascular diseases.

PubMed

Kritikou, Eva; Kuiper, Johan; Kovanen, Petri T; Bot, Ilze

2016-05-05

Mast cells comprise an innate immune cell population, which accumulates in tissues proximal to the outside environment and, upon activation, augments the progression of immunological reactions through the release and diffusion of either pre-formed or newly generated mediators. The released products of mast cells include histamine, proteases, as well as a variety of cytokines, chemokines and growth factors, which act on the surrounding microenvironment thereby shaping the immune responses triggered in various diseased states. Mast cells have also been detected in the arterial wall and are implicated in the onset and progression of numerous cardiovascular diseases. Notably, modulation of distinct mast cell actions using genetic and pharmacological approaches highlights the crucial role of this cell type in cardiovascular syndromes. The acquired evidence renders mast cells and their mediators as potential prognostic markers and therapeutic targets in a broad spectrum of pathophysiological conditions related to cardiovascular diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Non-Gaussian, non-dynamical stochastic resonance

NASA Astrophysics Data System (ADS)

Szczepaniec, Krzysztof; Dybiec, Bartłomiej

2013-11-01

The classical model revealing stochastic resonance is a motion of an overdamped particle in a double-well fourth order potential when combined action of noise and external periodic driving results in amplifying of weak signals. Resonance behavior can also be observed in non-dynamical systems. The simplest example is a threshold triggered device. It consists of a periodic modulated input and noise. Every time an output crosses the threshold the signal is recorded. Such a digitally filtered signal is sensitive to the noise intensity. There exists the optimal value of the noise intensity resulting in the "most" periodic output. Here, we explore properties of the non-dynamical stochastic resonance in non-equilibrium situations, i.e. when the Gaussian noise is replaced by an α-stable noise. We demonstrate that non-equilibrium α-stable noises, depending on noise parameters, can either weaken or enhance the non-dynamical stochastic resonance.

Motivational Modulation of Self-Initiated and Externally Triggered Movement Speed Induced by Threat of Shock: Experimental Evidence for Paradoxical Kinesis in Parkinson’s Disease

PubMed Central

McDonald, Louise M.; Griffin, Harry J.; Angeli, Aikaterini; Torkamani, Mariam; Georgiev, Dejan; Jahanshahi, Marjan

2015-01-01

Background Paradoxical kinesis has been observed in bradykinetic people with Parkinson’s disease. Paradoxical kinesis occurs in situations where an individual is strongly motivated or influenced by relevant external cues. Our aim was to induce paradoxical kinesis in the laboratory. We tested whether the motivation of avoiding a mild electric shock was sufficient to induce paradoxical kinesis in externally-triggered and self-initiated conditions in people with Parkinson’s disease tested on medication and in age-matched controls. Methods Participants completed a shock avoidance behavioural paradigm in which half of the trials could result in a mild electric shock if the participant did not move fast enough. Half of the trials of each type were self-initiated and half were externally-triggered. The criterion for avoiding shock was a maximum movement time, adjusted according to each participant’s performance on previous trials using a staircase tracking procedure. Results On trials with threat of shock, both patients with Parkinson’s disease and controls had faster movement times compared to no potential shock trials, in both self-initiated and externally-triggered conditions. The magnitude of improvement of movement time from no potential shock to potential shock trials was positively correlated with anxiety ratings. Conclusions When motivated to avoid mild electric shock, patients with Parkinson’s disease, similar to healthy controls, showed significant speeding of movement execution. This was observed in both self-initiated and externally-triggered versions of the task. Nevertheless, in the ET condition the improvement of reaction times induced by motivation to avoid shocks was greater for the PD patients than controls, highlighting the value of external cues for movement initiation in PD patients. The magnitude of improvement from the no potential shock to the potential shock trials was associated with the threat-induced anxiety. This demonstration of paradoxical kinesis in the laboratory under both self-initiated and externally-triggered conditions has implications for motivational and attentional enhancement of movement speed in Parkinson’s disease. PMID:26284366

Emodin induces human T cell apoptosis in vitro by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction

PubMed Central

Qu, Kai; Shen, Nai-ying; Xu, Xin-sen; Su, Hai-bo; Wei, Ji-chao; Tai, Ming-hui; Meng, Fan-di; Zhou, Lei; Zhang, Yue-lang; Liu, Chang

2013-01-01

Aim: To elucidate the molecular mechanisms underlying the immunosuppressive effects of emodin isolated from Rheum palmatum L. Methods: Human T cells were isolated from the peripheral venous blood of 10 healthy adult donors. Cell viability was analyzed with MTT assay. AO/EB and Annexin V/PI staining and DNA damage assay were used to detect cell apoptosis. Fluorescence staining was used to detect the levels of ROS, the mitochondrial membrane potential and intracellular Ca2+. Colorimetry was used to detect the levels of MDA and total SOD and GSH/GSSG ratio. The expression and activity of caspase-3, -4, and -9 were detected with Western blotting and a fluorometric assay. Western blotting was also used to detect the expression of Bcl-2, Bax, cytochrome C, and endoplasmic reticulum (ER) markers. Results: Emodin (1, 10, and 100 μmol/L) inhibited the growth of human T cells and induced apoptosis in dose- and time dependent manners. Emodin triggered ER stress and significantly elevated intracellular free Ca2+ in human T cells. It also disrupted mitochondrial membrane potential, and increased cytosolic level of cytochrome C, and the levels of activated cleavage fragments of caspase-3, -4, and -9 in human T cells. Furthermore, emodin significantly increased the levels of ROS and MDA, inhibited both SOD level and GSH/GSSG ratio in human T cells, whereas co-incubation with the ROS scavenger N-acetylcysteine (NAC, 20 μmol/L) almost completely blocked emodin-induced ER stress and mitochondrial dysfunction in human T cells, and decreased the caspase cascade-mediated apoptosis. Conclusion: Emodin exerts immunosuppressive actions at least partly by inducing apoptosis of human T cells, which is triggered by ROS-mediated ER stress and mitochondrial dysfunction. PMID:23811723

Hypodermal delivery of cosmetic actives for improved facial skin morphology and functionality.

PubMed

Bojanowski, K

2013-12-01

Skin compartments traditionally targeted by cosmetic actives - epidermis and dermis - are anchored and nourished by the underlying hypodermis, which therefore should be a key target for skin-rejuvenating formulations. However, given the difficulty to reach even the superficial layers of the skin, and to its 'unglamorous' fatty composition, the regenerative potential of hypodermis remains largely untapped. Therefore, this study was to investigate the capacity of a cosmetic material to trigger a regenerative response in dermis and epidermis through a selective action on hypodermis. Furthermore, it aimed to establish the effect of such cosmetic material in transbuccal hypodermal delivery form, on the hypodermal precursor cells - the preadipocytes. A combination of grape seed extract and soy phospholipids was formulated and standardized for elastase activity and free radical inhibition. This formulation was then used to contact the hypodermal layer of human skin biopsies and - under a transbuccal delivery vehicle form - the 3T3-L1 preadipocytes, and its effects were quantified using PCR arrays and histochemistry. Application of the standardized grape/soy material to the hypodermal layer of skin triggered modulation of gene expression in the upper layers of the skin and resulted in the clear morphological improvement at the dermal and epidermal levels. Furthermore, when this material was formulated in a mucoadhesive, intraoral film and applied on 3T3-L1 preadipocytes, the resulting modulation of gene expression in these cells was consistent with differentiation and detoxification effects. These results suggest that transbuccal formulations of nutraceutical grade cosmetics have potential to induce signal transduction pathways in facial hypodermis, resulting in anti-aging effects throughout all skin compartments, including dermal and epidermal layers. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury

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

Chen, Jiao; Shetty, Sreerama; Zhang, Ping

The presence of endotoxin in blood can lead to acute kidney injury (AKI) and septic shock. Resolvins, the endogenous lipid mediators derived from docosahexaenoic acid, have been reported to exhibit potent anti-inflammatory action. Using a mouse model of lipopolysaccharide (LPS)-induced AKI, we investigated the effects of aspirin-triggered resolvin D1 (AT-RvD1) on inflammatory kidney injury. Administration of AT-RvD1 1 h after LPS challenge protected the mice from kidney injury as indicated by the measurements of blood urea nitrogen, serum creatinine, and morphological alterations associated with tubular damage. The protective effects were evidenced by decreased neutrophil infiltration in the kidney indicating reductionmore » in inflammation. AT-RvD1 treatment restored kidney cell junction protein claudin-4 expression, which was otherwise reduced after LPS challenge. AT-RvD1 treatment inhibited endotoxin-induced NF-κB activation and suppressed LPS-induced ICAM-1 and VCAM-1 expression in the kidney. Moreover, AT-RvD1 treatment markedly decreased LPS-induced IL-6 level in the kidney and blocked IL-6-mediated signaling including STAT3 and ERK phosphorylation. Our findings demonstrate that AT-RvD1 is a potent anti-inflammatory mediator in LPS-induced kidney injury, and AT-RvD1 has therapeutic potential against AKI during endotoxemia.« less

Stimuli-responsive polymeric nanocarriers for the controlled transport of active compounds: concepts and applications.

PubMed

Fleige, Emanuel; Quadir, Mohiuddin A; Haag, Rainer

2012-06-15

The use of polymeric nanocarriers to transport active compounds like small-molecular drugs, peptides, or genes found an increased attention throughout the different fields of natural sciences. Not only that these nanocarriers enhance the properties of already existing drugs in terms of solubility, bioavailability, and prolonged circulation times, furthermore they can be tailor-made in such a manner that they selectively release their cargo at the desired site of action. For the triggered release, these so-called smart drug delivery systems are designed to react on certain stimuli like pH, temperature, redox potential, enzymes, light, and ultrasound. Some of these stimuli are naturally occurring in vivo, for example the difference in pH in different cellular compartments while others are caused by the disease, which is to be treated, like differences in pH and temperature in some tumor tissues. Other external applied stimuli, like light and ultrasound, allow the temporal and spatial control of the release, since they are not triggered by any biological event. This review gives a brief overview about some types of stimuli-responsive nanocarriers with the main focus on organic polymer-based systems. Furthermore, the different stimuli and the design of corresponding responsive nanocarriers will be discussed with the help of selected examples from the literature. Copyright © 2012 Elsevier B.V. All rights reserved.

A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone

PubMed Central

Song, Ok-Ryul; Kim, Han-Byul; Jouny, Samuel; Ricard, Isabelle; Vandeputte, Alexandre; Deboosere, Nathalie; Marion, Estelle; Queval, Christophe J.; Lesport, Pierre; Henrion, Daniel; Oh, Seog Bae; Lebon, Guillaume; Sandoz, Guillaume; Yeramian, Edouard; Marsollier, Laurent; Brodin, Priscille

2017-01-01

Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans, is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT2 receptors (angiotensin II type 2 receptors; AT2R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT2R, with this action being not affected by known ligands of AT2R. This result points towards novel AT2R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics. PMID:28718822

Biological Activities of Uric Acid in Infection Due to Enteropathogenic and Shiga-Toxigenic Escherichia coli

PubMed Central

Broome, Jacqueline E.; Lis, Agnieszka

2016-01-01

In previous work, we identified xanthine oxidase (XO) as an important enzyme in the interaction between the host and enteropathogenic Escherichia coli (EPEC) and Shiga-toxigenic E. coli (STEC). Many of the biological effects of XO were due to the hydrogen peroxide produced by the enzyme. We wondered, however, if uric acid generated by XO also had biological effects in the gastrointestinal tract. Uric acid triggered inflammatory responses in the gut, including increased submucosal edema and release of extracellular DNA from host cells. While uric acid alone was unable to trigger a chloride secretory response in intestinal monolayers, it did potentiate the secretory response to cyclic AMP agonists. Uric acid crystals were formed in vivo in the lumen of the gut in response to EPEC and STEC infections. While trying to visualize uric acid crystals formed during EPEC and STEC infections, we noticed that uric acid crystals became enmeshed in the neutrophilic extracellular traps (NETs) produced from host cells in response to bacteria in cultured cell systems and in the intestine in vivo. Uric acid levels in the gut lumen increased in response to exogenous DNA, and these increases were enhanced by the actions of DNase I. Interestingly, addition of DNase I reduced the numbers of EPEC bacteria recovered after a 20-h infection and protected against EPEC-induced histologic damage. PMID:26787720

[Psychological stress and sudden death].

PubMed

Pignalberi, Carlo; Ricci, Renato; Santini, Massimo

2002-10-01

Recent studies provide relevant evidence that psychological stress significantly influences the pathogenesis of sudden cardiac death. Psychological stress expresses a situation of imbalance, derived from a real or perceived disparity between environmental demands and the individual's ability to cope with these demands. A situation of psychological stress may include different components: personality factors and character traits, anxiety and depression, social isolation and acute or chronic adverse life events. In particular, it has been documented that a sudden extremely hard event, such as an earthquake or a war strike, can significantly increase the incidence of sudden death. Nevertheless, each one of these factors, if not present, can balance a partially unfavorable situation; this overview suggests a multifactorial situation where almost all elements are present and in which the relative influence of each one varies according to the individual examined. Sudden death occurs when a transient disruption (such as acute myocardial ischemia, platelet activation or neuroendocrine variations), occurring in a patient with a diseased myocardium (such as one with a post-necrotic scar or hypertrophy), triggers a malignant arrhythmia. Psychological stress acts at both levels: by means of a "chronic" action it contributes to create the myocardial background, while by means of an acute action it can create the transient trigger precipitating sudden death. In the chronic action two possible mechanisms can be detected: the first is a direct interaction, which contributes to cause a hypertension status or to exacerbate coronary atherosclerosis consequent to endothelial dysfunction; the second one acts through adverse health behaviors, such as a poor diet, alcohol consumption or smoking. In case of acute psychological stress, the mechanisms involved are mainly the ability to trigger myocardial ischemia, to promote arrhythmogenesis, to stimulate platelet function, and to increase blood viscosity. Finally, some individuals have a sympathetic nervous system hyper-responsitivity, manifesting as exaggerated heart rate and blood pressure responses which result in accelerated atherosclerosis.

Guilty Feelings, Targeted Actions

PubMed Central

Cryder, Cynthia E.; Springer, Stephen; Morewedge, Carey K.

2014-01-01

Early investigations of guilt cast it as an emotion that prompts broad reparative behaviors that help guilty individuals feel better about themselves or about their transgressions. The current investigation found support for a more recent representation of guilt as an emotion designed to identify and correct specific social offenses. Across five experiments, guilt influenced behavior in a targeted and strategic way. Guilt prompted participants to share resources more generously with others, but only did so when those others were persons whom the participant had wronged and only when those wronged individuals could notice the gesture. Rather than trigger broad reparative behaviors that remediate one’s general reputation or self-perception, guilt triggers targeted behaviors intended to remediate specific social transgressions. PMID:22337764

Guilty feelings, targeted actions.

PubMed

Cryder, Cynthia E; Springer, Stephen; Morewedge, Carey K

2012-05-01

Early investigations of guilt cast it as an emotion that prompts broad reparative behaviors that help guilty individuals feel better about themselves or about their transgressions. The current investigation found support for a more recent representation of guilt as an emotion designed to identify and correct specific social offenses. Across five experiments, guilt influenced behavior in a targeted and strategic way. Guilt prompted participants to share resources more generously with others, but only did so when those others were persons whom the participant had wronged and only when those wronged individuals could notice the gesture. Rather than trigger broad reparative behaviors that remediate one's general reputation or self-perception, guilt triggers targeted behaviors intended to remediate specific social transgressions.

Rainfall-triggered landslides, anthropogenic hazards, and mitigation strategies

USGS Publications Warehouse

Larsen, M.C.

2008-01-01

Rainfall-triggered landslides are part of a natural process of hillslope erosion that can result in catastrophic loss of life and extensive property damage in mountainous, densely populated areas. As global population expansion on or near steep hillslopes continues, the human and economic costs associated with landslides will increase. Landslide hazard mitigation strategies generally involve hazard assessment mapping, warning systems, control structures, and regional landslide planning and policy development. To be sustainable, hazard mitigation requires that management of natural resources is closely connected to local economic and social interests. A successful strategy is dependent on a combination of multi-disciplinary scientific and engineering approaches, and the political will to take action at the local community to national scale.

An insight into the hepatocellular death induced by amphetamines, individually and in combination: the involvement of necrosis and apoptosis.

PubMed

Dias da Silva, Diana; Carmo, Helena; Lynch, Adam; Silva, Elisabete

2013-12-01

The liver is a vulnerable target for amphetamine toxicity, but the mechanisms involved in the drug's hepatotoxicity remain poorly understood. The purpose of the current research was to characterize the mode of death elicited by four amphetamines and to evaluate whether their combination triggered similar mechanisms in immortalized human HepG2 cells. The obtained data revealed a time- and temperature-dependent mortality of HepG2 cells exposed to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy; 1.3 mM), methamphetamine (3 mM), 4-methylthioamphetamine (0.5 mM) and D-amphetamine (1.7 mM), alone or combined (1.6 mM mixture). At physiological temperature (37 °C), 24-h exposures caused HepG2 death preferentially by apoptosis, while a rise to 40.5 °C favoured necrosis. ATP levels remained unaltered when the drugs where tested at normothermia, but incubation at 40.5 °C provoked marked ATP depletion for all treatments. Further investigations on the apoptotic mechanisms triggered by the drugs (alone or combined) showed a decline in BCL-2 and BCL- XL mRNA levels, with concurrent upregulation of BAX, BIM, PUMA and BID genes. Elevation of Bax, cleaved Bid, Puma, Bak and Bim protein levels was also seen. To the best of our knowledge, Puma, Bim and Bak have never been linked with the toxicity induced by amphetamines. Time-dependent caspase-3/-7 activation, but not mitochondrial membrane potential (∆ψm) disruption, also mediated amphetamine-induced apoptosis. The cell dismantling was confirmed by poly(ADP-ribose)polymerase proteolysis. Overall, for all evaluated parameters, no relevant differences were detected between individual amphetamines and the mixture (all tested at equieffective cytotoxic concentrations), suggesting that the mode of action of the amphetamines in combination does not deviate from the mode of action of the drugs individually, when eliciting HepG2 cell death.

Timing paradox of stepping and falls in ageing: not so quick and quick(er) on the trigger.

PubMed

Rogers, Mark W; Mille, Marie-Laure

2016-08-15

Physiological and degenerative changes affecting human standing balance are major contributors to falls with ageing. During imbalance, stepping is a powerful protective action for preserving balance that may be voluntarily initiated in recognition of a balance threat, or be induced by an externally imposed mechanical or sensory perturbation. Paradoxically, with ageing and falls, initiation slowing of voluntary stepping is observed together with perturbation-induced steps that are triggered as fast as or faster than for younger adults. While age-associated changes in sensorimotor conduction, central neuronal processing and cognitive functions are linked to delayed voluntary stepping, alterations in the coupling of posture and locomotion may also prolong step triggering. It is less clear, however, how these factors may explain the accelerated triggering of induced stepping. We present a conceptual model that addresses this issue. For voluntary stepping, a disruption in the normal coupling between posture and locomotion may underlie step-triggering delays through suppression of the locomotion network based on an estimation of the evolving mechanical state conditions for stability. During induced stepping, accelerated step initiation may represent an event-triggering process whereby stepping is released according to the occurrence of a perturbation rather than to the specific sensorimotor information reflecting the evolving instability. In this case, errors in the parametric control of induced stepping and its effectiveness in stabilizing balance would be likely to occur. We further suggest that there is a residual adaptive capacity with ageing that could be exploited to improve paradoxical triggering and other changes in protective stepping to impact fall risk. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

What started your labor? Responses from mothers in the third pregnancy, infection, and nutrition study.

PubMed

Bovbjerg, Marit L; Evenson, Kelly R; Bradley, Chyrise; Thorp, John M

2014-01-01

Many behaviors and substances have been purported to induce labor. Using data from the Third Pregnancy, Infection, and Nutrition cohort, we focus on 663 women who experienced spontaneous labor. Of the women who reported a specific labor trigger, 32% reported physical activity (usually walking), 24% a clinician-mediated trigger, 19% a natural phenomenon, 14% some other physical trigger (including sexual activity), 12% reported ingesting something, 12% an emotional trigger, and 7% maternal illness. With the exceptions of walking and sexual intercourse, few women reported any one specific trigger, although various foods/substances were listed in the "ingesting something" category. Discussion of potential risks associated with "old wives' tale" ways to induce labor may be warranted as women approach term.

A Xanthomonas oryzae pv. oryzae effector, XopR, associates with receptor-like cytoplasmic kinases and suppresses PAMP-triggered stomatal closure.

PubMed

Wang, Shuangfeng; Sun, Jianhang; Fan, Fenggui; Tan, Zhaoyun; Zou, Yanmin; Lu, Dongping

2016-09-01

Receptor-like kinases (RLKs) play important roles in plant immunity signaling; thus, many are hijacked by pathogen effectors to promote successful pathogenesis. Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of rice leaf blight disease. The strain PXO99A has 18 non-TAL (transcription activation-like) effectors; however, their mechanisms of action and host target proteins remain largely unknown. Although the effector XopR from the Xoo strain MAFF311018 was shown to suppress PAMP-triggered immune responses in Arabidopsis, its target has not yet been identified. Here, we show that PXO99A XopR interacts with BIK1 at the plasma membrane. BIK1 is a receptor-like cytoplasmic kinase (RLCK) belonging to the RLK family of proteins and mediates PAMP-triggered stomatal immunity. In turn, BIK1 phosphorylates XopR. Furthermore, XopR suppresses PAMP-triggered stomatal closure in transgenic Arabidopsis expressing XopR. In addition, XopR is able to associate with RLCKs other than BIK1. These results suggest that XopR likely suppresses plant immunity by targeting BIK1 and other RLCKs.

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

The diet factor in pediatric and adolescent migraine.

PubMed

Millichap, J Gordon; Yee, Michelle M

2003-01-01

Diet can play an important role in the precipitation of headaches in children and adolescents with migraine. The diet factor in pediatric migraine is frequently neglected in favor of preventive drug therapy. The list of foods, beverages, and additives that trigger migraine includes cheese, chocolate, citrus fruits, hot dogs, monosodium glutamate, aspartame, fatty foods, ice cream, caffeine withdrawal, and alcoholic drinks, especially red wine and beer. Underage drinking is a significant potential cause of recurrent headache in today's adolescent patients. Tyramine, phenylethylamine, histamine, nitrites, and sulfites are involved in the mechanism of food intolerance headache. Immunoglobulin E-mediated food allergy is an infrequent cause. Dietary triggers affect phases of the migraine process by influencing release of serotonin and norepinephrine, causing vasoconstriction or vasodilatation, or by direct stimulation of trigeminal ganglia, brainstem, and cortical neuronal pathways. Treatment begins with a headache and diet diary and the selective avoidance of foods presumed to trigger attacks. A universal migraine diet with simultaneous elimination of all potential food triggers is generally not advised in practice. A well-balanced diet is encouraged, with avoidance of fasting or skipped meals. Long-term prophylactic drug therapy is appropriate only after exclusion of headache-precipitating trigger factors, including dietary factors.

A framework for responding to coral disease outbreaks that facilitates adaptive management.

PubMed

Beeden, Roger; Maynard, Jeffrey A; Marshall, Paul A; Heron, Scott F; Willis, Bette L

2012-01-01

Predicted increases in coral disease outbreaks associated with climate change have implications for coral reef ecosystems and the people and industries that depend on them. It is critical that coral reef managers understand these implications and have the ability to assess and reduce risk, detect and contain outbreaks, and monitor and minimise impacts. Here, we present a coral disease response framework that has four core components: (1) an early warning system, (2) a tiered impact assessment program, (3) scaled management actions and (4) a communication plan. The early warning system combines predictive tools that monitor the risk of outbreaks of temperature-dependent coral diseases with in situ observations provided by a network of observers who regularly report on coral health and reef state. Verified reports of an increase in disease prevalence trigger a tiered response of more detailed impact assessment, targeted research and/or management actions. The response is scaled to the risk posed by the outbreak, which is a function of the severity and spatial extent of the impacts. We review potential management actions to mitigate coral disease impacts and facilitate recovery, considering emerging strategies unique to coral disease and more established strategies to support reef resilience. We also describe approaches to communicating about coral disease outbreaks that will address common misperceptions and raise awareness of the coral disease threat. By adopting this framework, managers and researchers can establish a community of practice and can develop response plans for the management of coral disease outbreaks based on local needs. The collaborations between managers and researchers we suggest will enable adaptive management of disease impacts following evaluating the cost-effectiveness of emerging response actions and incrementally improving our understanding of outbreak causation.

Dynamic Interplay of Value and Sensory Information in High-Speed Decision Making.

PubMed

Afacan-Seref, Kivilcim; Steinemann, Natalie A; Blangero, Annabelle; Kelly, Simon P

2018-03-05

In dynamic environments, split-second sensorimotor decisions must be prioritized according to potential payoffs to maximize overall rewards. The impact of relative value on deliberative perceptual judgments has been examined extensively [1-6], but relatively little is known about value-biasing mechanisms in the common situation where physical evidence is strong but the time to act is severely limited. In prominent decision models, a noisy but statistically stationary representation of sensory evidence is integrated over time to an action-triggering bound, and value-biases are affected by starting the integrator closer to the more valuable bound. Here, we show significant departures from this account for humans making rapid sensory-instructed action choices. Behavior was best explained by a simple model in which the evidence representation-and hence, rate of accumulation-is itself biased by value and is non-stationary, increasing over the short decision time frame. Because the value bias initially dominates, the model uniquely predicts a dynamic "turn-around" effect on low-value cues, where the accumulator first launches toward the incorrect action but is then re-routed to the correct one. This was clearly exhibited in electrophysiological signals reflecting motor preparation and evidence accumulation. Finally, we construct an extended model that implements this dynamic effect through plausible sensory neural response modulations and demonstrate the correspondence between decision signal dynamics simulated from a behavioral fit of that model and the empirical decision signals. Our findings suggest that value and sensory information can exert simultaneous and dynamically countervailing influences on the trajectory of the accumulation-to-bound process, driving rapid, sensory-guided actions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Botulinum toxin for pain.

PubMed

Casale, Roberto; Tugnoli, Valeria

2008-01-01

Botulinum toxin (BTX) injection is being increasingly used 'off label' in the management of chronic pain. Data support the hypothesis of a direct analgesic effect of BTX, different to that exerted on muscle. Although the pain-reducing effect of BTX is mainly due to its ability to block acetylcholine release at the synapse, other effects on the nervous system are also thought to be involved. BTX affects cholinergic transmission in both the somatic and the autonomic nervous systems. Proposed mechanisms of action of BTX for pain relief of trigger points, muscular spasms, fibromyalgia and myofascial pain include direct action on muscle and indirect effects via action at the neuromuscular junction. Invitro and invivo data have shown that BTX has specific antinociceptive activity relating to its effects on inflammation, axonal transport, ganglion inhibition, and spinal and suprasegmental level inhibition. Our review of the mechanisms of action, efficacy, administration techniques and therapeutic dosage of BTX for the management of chronic pain in a variety of conditions shows that although muscular tone and movement disorders remain the most important therapeutic applications for BTX, research suggests that BTX can also provide benefits related to effects on cholinergic control of the vascular system, autonomic function, and cholinergic control of nociceptive and antinociceptive systems. Furthermore, it appears that BTX may influence the peripheral and central nervous systems. The therapeutic potential of BTX depends mainly on the ability to deliver the toxin to the target structures, cholinergic or otherwise. Evidence suggests that BTX can be administered at standard dosages in pain disorders, where the objective is alteration of muscle tone. For conditions requiring an analgesic effect, the optimal therapeutic dosage of BTX remains to be defined.

A Framework for Responding to Coral Disease Outbreaks that Facilitates Adaptive Management

NASA Astrophysics Data System (ADS)

Beeden, Roger; Maynard, Jeffrey A.; Marshall, Paul A.; Heron, Scott F.; Willis, Bette L.

2012-01-01

Predicted increases in coral disease outbreaks associated with climate change have implications for coral reef ecosystems and the people and industries that depend on them. It is critical that coral reef managers understand these implications and have the ability to assess and reduce risk, detect and contain outbreaks, and monitor and minimise impacts. Here, we present a coral disease response framework that has four core components: (1) an early warning system, (2) a tiered impact assessment program, (3) scaled management actions and (4) a communication plan. The early warning system combines predictive tools that monitor the risk of outbreaks of temperature-dependent coral diseases with in situ observations provided by a network of observers who regularly report on coral health and reef state. Verified reports of an increase in disease prevalence trigger a tiered response of more detailed impact assessment, targeted research and/or management actions. The response is scaled to the risk posed by the outbreak, which is a function of the severity and spatial extent of the impacts. We review potential management actions to mitigate coral disease impacts and facilitate recovery, considering emerging strategies unique to coral disease and more established strategies to support reef resilience. We also describe approaches to communicating about coral disease outbreaks that will address common misperceptions and raise awareness of the coral disease threat. By adopting this framework, managers and researchers can establish a community of practice and can develop response plans for the management of coral disease outbreaks based on local needs. The collaborations between managers and researchers we suggest will enable adaptive management of disease impacts following evaluating the cost-effectiveness of emerging response actions and incrementally improving our understanding of outbreak causation.

Hazard Potential of Volcanic Flank Collapses Raised by New Megatsunami Evidence

NASA Astrophysics Data System (ADS)

Ramalho, R. S.; Winckler, G.; Madeira, J.; Helffrich, G. R.; Hipólito, A.; Quartau, R.; Adena, K.; Schaefer, J. M.

2015-12-01

Large-scale gravitational flank collapses of steep volcanic islands are hypothetically capable of triggering megatsunamis with highly catastrophic effects. Yet evidence for the existence and impact of collapsed-triggered megatsunamis and their run-up heights remains scarce and/or is highly contentious. Therefore a considerable debate still exists over the potential magnitude of collapse-triggered tsunamis and their inherent hazard. In particular, doubts still remain whether or not large-scale flank failures typically generate enough volume flux to result in megatsunamis, or alternatively operate by slow-moving or multiple smaller episodic failures with much lower tsunamigenic potential. Here we show that one of the tallest and most active oceanic volcanoes on Earth - Fogo, in the Cape Verde Islands - collapsed catastrophically and triggered a megatsunami with devastating near-field effects ~73,000 years ago. Our deductions are based on the recent discovery and cosmogenic 3He dating of tsunamigenic deposits - comprising fields of stranded megaclasts, chaotic conglomerates, and sand sheets - found on the adjacent Santiago Island, which attest to the impact of this megatsunami and document wave run-up heights exceeding 270 m. The evidence reported here implies that Fogo's flank failure involved at least one sudden and voluminous event that resulted in a megatsunami, in contrast to what has been suggested before. Our work thus provides another line of evidence that large-scale flank failures at steep volcanic islands may indeed happen catastrophically and are capable of triggering tsunamis of enormous height and energy. This new line of evidence therefore reinforces the hazard potential of volcanic island collapses and stands as a warning that such hazard should not be underestimated, particularly in areas where volcanic island edifices are close to other islands or to highly populated continental margins.

System monitoring feedback in cinemas and harvesting energy of the air conditioning condenser

NASA Astrophysics Data System (ADS)

Pop, P. P.; Pop-Vadean, A.; Barz, C.; Latinovic, T.; Chiver, O.

2017-05-01

Our article monitors the degree of emotional involvement of the audience in the action film in theaters by measuring the concentration of CO2. The software performs data processing obtained dispersion sensors and displays data during the film. The software will also trigger the start of the air conditioning condenser where we can get harvesting energy by installing a piezoelectric device. Useful energy can be recovered from various waste produced in cinema. The time lag between actions and changes in environmental systems determines that decisions made now will affect subsequent generations and the future of our environment.

Automatic motor activation in the executive control of action

PubMed Central

McBride, Jennifer; Boy, Frédéric; Husain, Masud; Sumner, Petroc

2012-01-01

Although executive control and automatic behavior have often been considered separate and distinct processes, there is strong emerging and convergent evidence that they may in fact be intricately interlinked. In this review, we draw together evidence showing that visual stimuli cause automatic and unconscious motor activation, and how this in turn has implications for executive control. We discuss object affordances, alien limb syndrome, the visual grasp reflex, subliminal priming, and subliminal triggering of attentional orienting. Consideration of these findings suggests automatic motor activation might form an intrinsic part of all behavior, rather than being categorically different from voluntary actions. PMID:22536177

Proposal of a trigger tool to assess adverse events in dental care.

PubMed

Corrêa, Claudia Dolores Trierweiler Sampaio de Oliveira; Mendes, Walter

2017-11-21

The aim of this study was to propose a trigger tool for research of adverse events in outpatient dentistry in Brazil. The tool was elaborated in two stages: (i) to build a preliminary set of triggers, a literature review was conducted to identify the composition of trigger tools used in other areas of health and the principal adverse events found in dentistry; (ii) to validate the preliminarily constructed triggers a panel of experts was organized using the modified Delphi method. Fourteen triggers were elaborated in a tool with explicit criteria to identify potential adverse events in dental care, essential for retrospective patient chart reviews. Studies on patient safety in dental care are still incipient when compared to other areas of health care. This study intended to contribute to the research in this field. The contribution by the literature and guidance from the expert panel allowed elaborating a set of triggers to detect adverse events in dental care, but additional studies are needed to test the instrument's validity.

Tidal Triggering of Microearthquakes Over an Eruption Cycle at 9°50'N East Pacific Rise

NASA Astrophysics Data System (ADS)

Tan, Yen Joe; Tolstoy, Maya; Waldhauser, Felix; Bohnenstiehl, DelWayne R.

2018-02-01

Studies have found that earthquake timing often correlates with tides at mid-ocean ridges and some terrestrial settings. Studies have also suggested that tidal triggering may preferentially happen when a region is critically stressed, making it a potential tool to forecast earthquakes and volcanic eruptions. We examine tidal triggering of ˜100,000 microearthquakes near 9°50'N East Pacific Rise recorded between October 2003 and January 2007, which encompasses an eruption in January 2006. This allows us to look at how tidal triggering signal varies over an eruption cycle to examine its utility as a forecasting tool. We find that tidal triggering signal is strong but does not vary systematically in the 2+ years leading up to the eruption. However, tidal triggering signal disappears immediately posteruption. Our findings suggest that tidal triggering variation may not be useful for forecasting mid-ocean ridge eruptions over a 2+ year timescale but might be useful over a longer timescale.

Identifying Potential Ventilator Auto-Triggering Among Organ Procurement Organization Referrals.

PubMed

Henry, Nicholas R; Russian, Christopher J; Nespral, Joseph

2016-06-01

Ventilator auto-trigger is the delivery of an assisted mechanical ventilated breath over the set ventilator frequency in the absence of a spontaneous inspiratory effort and can be caused by inappropriate ventilator trigger sensitivity. Ventilator auto-trigger can be misinterpreted as a spontaneous breath and has the potential to delay or prevent brain death testing and confuse health-care professionals and/or patient families. To determine the frequency of organ donor referrals from 1 Organ Procurement Organization (OPO) that could benefit from an algorithm designed to assist organ recovery coordinators to identify and correct ventilator auto-triggering. This retrospective analysis evaluated documentation of organ donor referrals from 1 OPO in central Texas during the 2013 calendar year that resulted in the withdrawal of care by the patient's family and the recovery of organs. The frequency of referrals that presented with absent brain stem reflexes except for additional respirations over the set ventilator rate was determined to assess for the need of the proposed algorithm. Documentation of 672 organ procurement organization referrals was evaluated. Documentation from 42 referrals that resulted in the withdrawal of care and 21 referrals that resulted in the recovery of organs were identified with absent brain stem reflexes except for spontaneous respirations on the mechanical ventilator. As a result, an algorithm designed to identify and correct ventilator auto-trigger could have been used 63 times during the 2013 calendar year. © 2016, NATCO.

Emotional triggers in myocardial infarction: do they matter?

PubMed

Edmondson, Donald; Newman, Jonathan D; Whang, William; Davidson, Karina W

2013-01-01

Considerable excitement and interest have arisen recently concerning the role that acute emotional triggers may play in precipitating a myocardial infarction (MI). Observational studies have found repeatedly that patients report excessive anger, anxiety, sadness, grief, or acute stress immediately prior to onset of MI, and recent meta-analyses summarizing these findings reported strong associations between MI occurrence and many of these acute emotions. However, it is unclear whether and through what mechanisms acute emotional triggers might influence MI, and whether there is any clinical utility in knowing if or how emotions trigger MI. We debate whether emotional triggers matter by reviewing the recent evidence for the association between acute emotional triggers and MI and by describing the potential pathophysiological characteristics and mechanisms underlying this association and the preventive strategies that could be used to mitigate the risk of acute MI. We also examine whether the study of emotional triggers could influence clinical risk management or changes in clinical practice/management. We offer suggestions for research that might shed light on whether emotional triggers could initiate a paradigm shift in preventive cardiology, or whether acute emotional triggers are either intractable catalysts for, or merely an epiphenomenon of, some MIs.

Emotional triggers in myocardial infarction: do they matter?

PubMed Central

Edmondson, Donald; Newman, Jonathan D.; Whang, William; Davidson, Karina W.

2013-01-01

Considerable excitement and interest have arisen recently concerning the role that acute emotional triggers may play in precipitating a myocardial infarction (MI). Observational studies have found repeatedly that patients report excessive anger, anxiety, sadness, grief, or acute stress immediately prior to onset of MI, and recent meta-analyses summarizing these findings reported strong associations between MI occurrence and many of these acute emotions. However, it is unclear whether and through what mechanisms acute emotional triggers might influence MI, and whether there is any clinical utility in knowing if or how emotions trigger MI. We debate whether emotional triggers matter by reviewing the recent evidence for the association between acute emotional triggers and MI and by describing the potential pathophysiological characteristics and mechanisms underlying this association and the preventive strategies that could be used to mitigate the risk of acute MI. We also examine whether the study of emotional triggers could influence clinical risk management or changes in clinical practice/management. We offer suggestions for research that might shed light on whether emotional triggers could initiate a paradigm shift in preventive cardiology, or whether acute emotional triggers are either intractable catalysts for, or merely an epiphenomenon of, some MIs. PMID:23178642

Regular and Random Components in Aiming-Point Trajectory During Rifle Aiming and Shooting

PubMed Central

Goodman, Simon; Haufler, Amy; Shim, Jae Kun; Hatfield, Bradley

2009-01-01

The authors examined the kinematic qualities of the aiming trajectory as related to expertise. In all, 2 phases of the trajectory were discriminated. The first phase was regular approximation to the target accompanied by substantial fluctuations obeying the Weber–Fechner law. During the first phase, shooters did not initiate the triggering despite any random closeness of the aiming point (AP) to the target. In the second phase, beginning at 0.6–0.8 s before the trigger pull, shooters applied a different control strategy: They waited until the following random fluctuation brought the AP closer to the target and then initiated triggering. This strategy is tenable when sensitivity of perception is greater than precision of the motor action, and could be considered a case of stochastic resonance. The strategies that novices and experts used distinguished only in the values of parameters. The authors present an analytical model explaining the main properties of shooting. PMID:19508963

Auditory Imagery Shapes Movement Timing and Kinematics: Evidence from a Musical Task

ERIC Educational Resources Information Center

Keller, Peter E.; Dalla Bella, Simone; Koch, Iring

2010-01-01

The role of anticipatory auditory imagery in music-like sequential action was investigated by examining timing accuracy and kinematics using a motion capture system. Musicians responded to metronomic pacing signals by producing three unpaced taps on three vertically aligned keys at the given tempo. Taps triggered tones in two out of three blocked…

Pastoral community organization, livelihoods and biodiversity conservation in Mongolia's Southern Gobi Region

Treesearch

Sabine M. Schmidt

2006-01-01

In this paper I describe processes and impacts of collective action by mobile pastoralist communities, and of external support strategies to strengthen local institutions and cooperation in Mongolia’s southern Gobi. The need for pastoral mobility triggered the processes leading to community organization, and the emergence, or re-emergence, of local informal...

How to Represent Adaptation in e-Learning with IMS Learning Design

ERIC Educational Resources Information Center

Burgos, Daniel; Tattersall, Colin; Koper, Rob

2007-01-01

Adaptation in e-learning has been an important research topic for the last few decades in computer-based education. In adaptivity the behaviour of the user triggers some actions in the system that guides the learning process. In adaptability, the user makes changes and takes decisions. Progressing from computer-based training and adaptive…

50 CFR 648.90 - NE multispecies assessment, framework procedures and specifications, and flexible area action...

Code of Federal Regulations, 2014 CFR

2014-10-01

..., and DAS baselines, adjustments for steaming time, etc.; modifications to capacity measures, such as... time of the overage that triggered the AM. (iv) ACL monitoring—(A) Landings. For the purposes of... which the overage occurred only if there is sufficient time to do so in a manner consistent with the...

Language for action: Motor resonance during the processing of human and robotic voices.

PubMed

Di Cesare, G; Errante, A; Marchi, M; Cuccio, V

2017-11-01

In this fMRI study we evaluated whether the auditory processing of action verbs pronounced by a human or a robotic voice in the imperative mood differently modulates the activation of the mirror neuron system (MNs). The study produced three results. First, the activation pattern found during listening to action verbs was very similar in both the robot and human conditions. Second, the processing of action verbs compared to abstract verbs determined the activation of the fronto-parietal circuit classically involved during the action goal understanding. Third, and most importantly, listening to action verbs compared to abstract verbs produced activation of the anterior part of the supramarginal gyrus (aSMG) regardless of the condition (human and robot) and in the absence of any object name. The supramarginal gyrus is a region considered to underpin hand-object interaction and associated to the processing of affordances. These results suggest that listening to action verbs may trigger the recruitment of motor representations characterizing affordances and action execution, coherently with the predictive nature of motor simulation that not only allows us to re-enact motor knowledge to understand others' actions but also prepares us for the actions we might need to carry out. Copyright © 2017 Elsevier Inc. All rights reserved.

Vasoconstriction triggered by hydrogen sulfide: Evidence for Na+,K+,2Cl-cotransport and L-type Ca2+ channel-mediated pathway.

PubMed

Orlov, Sergei N; Gusakova, Svetlana V; Smaglii, Liudmila V; Koltsova, Svetlana V; Sidorenko, Svetalana V

2017-12-01

This study examined the dose-dependent actions of hydrogen sulfide donor sodium hydrosulphide (NaHS) on isometric contractions and ion transport in rat aorta smooth muscle cells (SMC). Isometric contraction was measured in ring aortas segments from male Wistar rats. Activity of Na + /K + -pump and Na + ,K + ,2Cl - cotransport was measured in cultured endothelial and smooth muscle cells from the rat aorta as ouabain-sensitive and ouabain-resistant, bumetanide-sensitive components of the 86 Rb influx, respectively. NaHS exhibited the bimodal action on contractions triggered by modest depolarization ([K + ] o =30 mM). At 10 -4 M, NaHS augmented contractions of intact and endothelium-denuded strips by ~ 15% and 25%, respectively, whereas at concentration of 10 -3  M it decreased contractile responses by more than two-fold. Contractions evoked by 10 -4  M NaHS were completely abolished by bumetanide, a potent inhibitor of Na + ,K + ,2Cl - cotransport, whereas the inhibition seen at 10 -3  M NaHS was suppressed in the presence of K + channel blocker TEA. In cultured SMC, 5×10 -5  M NaHS increased Na + ,K + ,2Cl - - cotransport without any effect on the activity of this carrier in endothelial cells. In depolarized SMC, 45 Ca influx was enhanced in the presence of 10 -4  M NaHS and suppressed under elevation of [NaHS] up to 10 -3  M. 45 Ca influx triggered by 10 -4  M NaHS was abolished by bumetanide and L-type Ca 2+ channel blocker nicardipine. Our results strongly suggest that contractions of rat aortic rings triggered by low doses of NaHS are mediated by activation of Na + ,K + ,2Cl - cotransport and Ca 2+ influx via L-type channels.

Erratum to Dynamic stresses, Coulomb failure, and remote triggering and to Surface wave potential for triggering tectonic (nonvolcanic) tremor

USGS Publications Warehouse

Hill, David P.

2012-01-01

Hill (2008) and Hill (2010) contain two technical errors: (1) a missing factor of 2 for computed Love‐wave amplitudes, and (2) a sign error in the off‐diagonal elements in the Euler rotation matrix.

From Forecasters to the General Public: A Communication Tool to Understand Decision-making Challenges in Weather-related Early Warning Systems

NASA Astrophysics Data System (ADS)

Terti, G.; Ruin, I.; Kalas, M.; Lorini, V.; Sabbatini, T.; i Alonso, A. C.

2017-12-01

New technologies are currently adopted worldwide to improve weather forecasts and communication of the corresponding warnings to the end-users. "EnhANcing emergency management and response to extreme WeatHER and climate Events" (ANYWHERE) project is an innovating action that aims at developing and implementing a European decision-support platform for weather-related risks integrating cutting-edge forecasting technology. The initiative is built in a collaborative manner where researchers, developers, potential users and other stakeholders meet frequently to define needs, capabilities and challenges. In this study, we propose a role-playing game to test the added value of the ANYWHERE platform on i) the decision-making process and the choice of warning levels under uncertainty, ii) the management of the official emergency response and iii) the crisis communication and triggering of protective actions at different levels of the warning system (from hazard detection to citizen response). The designed game serves as an interactive communication tool. Here, flood and flash flood focused simulations seek to enhance participant's understanding of the complexities and challenges embedded in various levels of the decision-making process under the threat of weather disasters (e.g., forecasting/warnings, official emergency actions, self-protection). Also, we facilitate collaboration and coordination between the participants who belong to different national or local agencies/authorities across Europe. The game is first applied and tested in ANYWHERE's workshop in Helsinki (September, 2017) where about 30-50 people, including researchers, forecasters, civil protection and representatives of related companies, are anticipated to play the simulation. The main idea is to provide to the players a virtual case study that well represents realistic uncertainties and dilemmas embedded in the real-time forecasting-warning processes. At the final debriefing step the participants are encouraged to exchange knowledge, thoughts and insights on their capability or difficulty to decide and communicate their action based on the available information and given constrains. Such feedback will be analyzed and presented and future potentialities for the application of the game will be discussed.

Upper crustal fault reactivation and the potential of triggered earthquakes on the Atacama Fault System, N-Chile

NASA Astrophysics Data System (ADS)

Victor, Pia; Ewiak, Oktawian; Thomas, Ziegenhagen; Monika, Sobiesiak; Bernd, Schurr; Gabriel, Gonzalez; Onno, Oncken

2016-04-01

The Atacama Fault System (AFS) is an active trench-parallel fault system, located in the forearc of N-Chile directly above the subduction zone interface. Due to its well-exposed position in the hyper arid forearc of N-Chile it is the perfect target to investigate the interaction between the deformation cycle in the overriding forearc and the subduction zone seismic cycle of the underlying megathrust. Although the AFS and large parts of the upper crust are devoid of any noteworthy seismicity, at least three M=7 earthquakes in the past 10 ky have been documented in the paleoseismological record, demonstrating the potential of large events in the future. We apply a two-fold approach to explore fault activation and reactivation patterns through time and to investigate the triggering potential of upper crustal faults. 1) A new methodology using high-resolution topographic data allows us to investigate the number of past earthquakes for any given segment of the fault system as well as the amount of vertical displacement of the last increment. This provides us with a detailed dataset of past earthquake rupture of upper plate faults which is potentially linked to large subduction zone earthquakes. 2) The IPOC Creepmeter array (http://www.ipoc-network.org/index.php/observatory/creepmeter.html) provides us with high-resolution time series of fault displacement accumulation for 11 stations along the 4 most active branches of the AFS. This array monitors the displacement across the fault with 2 samples/min with a resolution of 1μm. Collocated seismometers record the seismicity at two of the creepmeters, whereas the regional seismicity is provided by the IPOC Seismological Networks. Continuous time series of the creepmeter stations since 2009 show that the shallow segments of the fault do not creep permanently. Instead the accumulation of permanent deformation occurs by triggered slip caused by local or remote earthquakes. The 2014 Mw=8.2 Pisagua Earthquake, located close to the creepmeter array, triggered large displacement events on all stations. Another event recorded on all stations was the 2010 Mw=8.8 Maule earthquake located 1500km south of the array. Exploring observations from both datasets, we can clearly state that triggering of upper crustal faults is observed for small-scale displacements. These findings allow us to speculate that the observed larger events in the past are likely being triggered events that require a critically prestressed condition of the target fault that is unclamped by stress changes triggered by large or potentially even small subduction zone earthquakes.

Remotely triggered nonvolcanic tremor in Sumbawa, Indonesia

NASA Astrophysics Data System (ADS)

Fuchs, Florian; Lupi, Matteo; Miller, Stephen

2015-04-01

Nonvolcanic (or tectonic) tremor is a seismic phenomenom which can provide important information about dynamics of plate boundaries but the underlying mechanisms are not well understood. Tectonic tremor is often associated with slow-slip (termed episodic tremor and slip) and understanding the mechanisms driving tremor presents an important challenge because it is likely a dominant aspect of the evolutionary processes leading to tsunamigenic, megathrust subduction zone earthquakes. Tectonic tremor is observed worldwide, mainly along major subduction zones and plate boundaries such as in Alaska/Aleutians, Cascadia, the San Andreas Fault, Japan or Taiwan. We present, for the first time, evidence for triggered tremor beneath the island of Sumbawa, Indonesia. The island of Sumbawa, Indonesia, is part of the Lesser Sunda Group about 250 km north of the Australian/Eurasian plate collision at the Java Trench with a convergence rate of approximately 70 mm/yr. We show surface wave triggered tremor beneath Sumbawa in response to three teleseismic earthquakes: the Mw9.0 2011 Tohoku earthquake and two oceanic strike-slip earthquakes (Mw 8.6 and Mw8.2) offshore of Sumatra in 2012. Tremor amplitudes scale with ground motion and peak at 180 nm/s ground velocity on the horizontal components. A comparison of ground motion of the three triggering events and a similar (nontriggering) Mw7.6 2012 Philippines event constrains an apparent triggering threshold of approximately 1 mm/s ground velocity or 8 kPa dynamic stress. Surface wave periods of 45-65 s appear optimal for triggering tremor at Sumbawa which predominantly correlates with Rayleigh waves, even though the 2012 oceanic events have stronger Love wave amplitudes and triggering potential. Rayleigh wave triggering, low-triggering amplitudes, and the tectonic setting all favor a model of tremor generated by localized fluid transport. We could not locate the tremor because of minimal station coverage, but data indicate several potential source volumes including the Flores Thrust, the Java subduction zone, or Tambora volcano.

[Pharmacological possibilities for the prevention of complications following myocardial infarction].

PubMed

Szekeres, L

1986-01-01

Sudden cardiac death (SCD) due to acute myocardial infarction (AMI) is mostly the result of ventricular fibrillation (VP) which is an electrical accident appearing on the basis of electrical instability of the myocardium. In addition to the chronic electrical instability predisposing to ventricular arrhythmias the trigger effect of a precipitating factor also seems necessary which may disrupt the normal sequence of cardiac contractions. In view of this hypothesis the following strategy of therapeutic interventions aimed at preventing SCD from AMI seems to be logical: Prophylactic measures to prevent pathological processes underlying chronic electrical instability of the heart i.e. elimination of identified risk factors of ischemic heart disease. Protection from SCD due to AMI: by using drugs which could, prevent further electrical destabilization as shifts in myocardial and plasma ionic balance, in pH, in pCO2, accumulation of potentially arrhythmogenic metabolites: Inhibit the trigger effect of sudden changes: in hemodynamics, in the autonomic nervous outflow and balance. The general supportive measures include therapeutic interventions which are not directly connected with appearance of lethal arrhythmias but may indirectly contribute to their development as pain, arterial Hb desaturation, deep vein thrombosis. Some of the measures listed above are capable of limiting the size of the developing infarct, a major determinant of the future conditions of life and prognosis of the patient. In the prehospital phase of AMI when two thirds of all coronary deaths occur general supportive measures and drug treatment of life threatening arrhythmias should be applied simultaneously. Sedatives and anxiolytics, furthermore analgetics are widely used. They are however often associated with bradycardia and sometimes with hypotension. This latter is dominant in patients with inferior infarction, showing a parasympathetic hyperactivity, when atropine treatment is needed. Sympathetic hyperactivity responds to analgesia and sedation but beta blockers may be required to reduce increased MVO2. These agents belong to the group of anti-ischemic drugs. The beneficial anti-ischemic action of beta-blockers is mostly due to their negative chronotropic and inotropic effect. A direct metabolic action was shown by use as well as the presence of a positive steal phenomenon in the experimental angina model in dogs. Anti-ischemic action of coronary vasodilators. The most reliable drug for preventing or abolishing anginal attack is still the classic nitroglycerin. On the other hand persantine a potent coronary dilator failed to protect against anginal attack in man.

Widespread Triggering of Earthquakes in the Central US by the 2011 M9.0 Tohoku-Oki Earthquake

NASA Astrophysics Data System (ADS)

Rubinstein, J. L.; Savage, H. M.

2011-12-01

The strong shaking of the 2011 M9.0 off-Tohoku earthquake triggered tectonic tremor and earthquakes in many locations around the world. We analyze broadband records from the USARRAY to identify triggered seismicity in more than 10 different locations in the Central United States. We identify triggered events in many states including: Kansas, Nebraska, Arkansas, Minnesota, and Iowa. The locally triggered earthquakes are obscured in broadband records by the Tohoku-Oki mainshock but can be revealed with high-pass filtering. With the exception of one location (central Arkansas), the triggered seismicity occurred in regions that are seismically quiet. The coincidence of this seismicity with the Tohoku-Oki event suggests that these earthquakes were triggered. The triggered seismicity in Arkansas occurred in a region where there has been an active swarm of seismicity since August 2010. There are two lines of evidence to indicate that the seismicity in Arkansas is triggered instead of part of the swarm: (1) we observe two earthquakes that initiate coincident with the arrival of shear wave and Love wave; (2) the seismicity rate increased dramatically following the Tohoku-Oki mainshock. Our observations of widespread earthquake triggering in regions thought to be seismically quiet remind us that earthquakes can occur in most any location. Studying additional teleseismic events has the potential to reveal regions with a propensity for earthquake triggering.

[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.

Detecting wrong notes in advance: neuronal correlates of error monitoring in pianists.

PubMed

Ruiz, María Herrojo; Jabusch, Hans-Christian; Altenmüller, Eckart

2009-11-01

Music performance is an extremely rapid process with low incidence of errors even at the fast rates of production required. This is possible only due to the fast functioning of the self-monitoring system. Surprisingly, no specific data about error monitoring have been published in the music domain. Consequently, the present study investigated the electrophysiological correlates of executive control mechanisms, in particular error detection, during piano performance. Our target was to extend the previous research efforts on understanding of the human action-monitoring system by selecting a highly skilled multimodal task. Pianists had to retrieve memorized music pieces at a fast tempo in the presence or absence of auditory feedback. Our main interest was to study the interplay between auditory and sensorimotor information in the processes triggered by an erroneous action, considering only wrong pitches as errors. We found that around 70 ms prior to errors a negative component is elicited in the event-related potentials and is generated by the anterior cingulate cortex. Interestingly, this component was independent of the auditory feedback. However, the auditory information did modulate the processing of the errors after their execution, as reflected in a larger error positivity (Pe). Our data are interpreted within the context of feedforward models and the auditory-motor coupling.

Topical Erythropoietin Treatment Accelerates the Healing of Cutaneous Burn Wounds in Diabetic Pigs Through an Aquaporin-3-Dependent Mechanism.

PubMed

Hamed, Saher; Ullmann, Yehuda; Egozi, Dana; Keren, Aviad; Daod, Essam; Anis, Omer; Kabha, Hoda; Belokopytov, Mark; Ashkar, Manal; Shofti, Rona; Zaretsky, Asaph; Schlesinger, Michal; Teot, Luc; Liu, Paul Y

2017-08-01

We have previously reported that the topical application of erythropoietin (EPO) to cutaneous wounds in rats and mice with experimentally induced diabetes accelerates their healing by stimulating angiogenesis, reepithelialization, and collagen deposition, and by suppressing the inflammatory response and apoptosis. Aquaporins (AQPs) are integral membrane proteins whose function is to regulate intracellular fluid hemostasis by enabling the transport of water and glycerol. AQP3 is the AQP that is expressed in the skin where it facilitates cell migration and proliferation and re-epithelialization during wound healing. In this report, we provide the results of an investigation that examined the contribution of AQP3 to the mechanism of EPO action on the healing of burn wounds in the skin of pigs with experimentally induced type 1 diabetes. We found that topical EPO treatment of the burns accelerated their healing through an AQP3-dependent mechanism that activates angiogenesis, triggers collagen and hyaluronic acid synthesis and the formation of the extracellular matrix (ECM), and stimulates reepithelialization by keratinocytes. We also found that incorporating fibronectin, a crucial constituent of the ECM, into the topical EPO-containing gel, can potentiate the accelerating action of EPO on the healing of the burn injury. © 2017 by the American Diabetes Association.

A Precision Medicine Approach to the Rescue of Function on Malignant Calmodulinopathic Long-QT Syndrome.

PubMed

Limpitikul, Worawan B; Dick, Ivy E; Tester, David J; Boczek, Nicole J; Limphong, Pattraranee; Yang, Wanjun; Choi, Myoung Hyun; Babich, Jennifer; DiSilvestre, Deborah; Kanter, Ronald J; Tomaselli, Gordon F; Ackerman, Michael J; Yue, David T

2017-01-06

Calmodulinopathies comprise a new category of potentially life-threatening genetic arrhythmia syndromes capable of producing severe long-QT syndrome (LQTS) with mutations involving CALM1, CALM2, or CALM3. The underlying basis of this form of LQTS is a disruption of Ca 2+ /calmodulin (CaM)-dependent inactivation of L-type Ca 2+ channels. To gain insight into the mechanistic underpinnings of calmodulinopathies and devise new therapeutic strategies for the treatment of this form of LQTS. We generated and characterized the functional properties of induced pluripotent stem cell-derived cardiomyocytes from a patient with D130G-CALM2-mediated LQTS, thus creating a platform with which to devise and test novel therapeutic strategies. The patient-derived induced pluripotent stem cell-derived cardiomyocytes display (1) significantly prolonged action potentials, (2) disrupted Ca 2+ cycling properties, and (3) diminished Ca 2+ /CaM-dependent inactivation of L-type Ca 2+ channels. Next, taking advantage of the fact that calmodulinopathy patients harbor a mutation in only 1 of 6 redundant CaM-encoding alleles, we devised a strategy using CRISPR interference to selectively suppress the mutant gene while sparing the wild-type counterparts. Indeed, suppression of CALM2 expression produced a functional rescue in induced pluripotent stem cell-derived cardiomyocytes with D130G-CALM2, as shown by the normalization of action potential duration and Ca 2+ /CaM-dependent inactivation after treatment. Moreover, CRISPR interference can be designed to achieve selective knockdown of any of the 3 CALM genes, making it a generalizable therapeutic strategy for any calmodulinopathy. Overall, this therapeutic strategy holds great promise for calmodulinopathy patients as it represents a generalizable intervention capable of specifically altering CaM expression and potentially attenuating LQTS-triggered cardiac events, thus initiating a path toward precision medicine. © 2016 American Heart Association, Inc.

Locomotor adaptations of some gelatinous zooplankton.

PubMed

Bone, Q

1985-01-01

Swimming behaviour and locomotor adaptations are described in chaetognaths, larvacean tunicates, some cnidaria, and thaliacean tunicates. The first two groups swim by oscillating a flattened tail, the others by jet propulsion. In chaetognaths, the locomotor muscle fibres are extensively coupled and relatively sparsely innervated, they exhibit compound spike-like potentials. The motoneurons controlling the rhythmic activity of the locomotor muscle lie in a ventral ganglion whose organization is briefly described. Rhythmic swimming bursts in larvaceans are similarly driven by a caudal ganglion near the base of the tail, but each caudal muscle cell is separately innervated by two sets of motor nerves, as well as being coupled to its neighbours. The external epithelium is excitable, and linked to the caudal ganglion by the axons of central cells. Mechanical stimulation of the epithelium evokes receptor potentials followed by action potentials and by bursts of rapid swimming. The trachyline medusa Aglantha and the small siphonophore Chelophyes also show rapid escape responses; in Aglantha these are driven by a specialized giant axon system lacking in other hydromedusae, and in Chelophyes. Slow swimming in Aglantha apparently involves a second nerve supply to the same muscle sheets used in rapid swimming, whereas in Chelophyes slow swimming results from the activity of the smaller posterior nectophore. Slow swimming in siphonophores is more economical than the rapid responses. In the hydrozoan medusa Polyorchis (as in Chelophyes) action potentials in the locomotor muscle sheet change in shape during swimming bursts, and their duration is related to the size of the medusa; they are not simply triggers of muscular contraction. The two groups of thaliacean tunicates are specialized differently. Doliolum is adapted for single rapid jet pulses (during which it achieves instantaneous velocities of 50 body lengths s-l), whilst salps are adapted for slow continuous swimming. The cost of locomotion is greater in Doliolum. Few gelatinous zooplankton show special adaptations both for rapid escape movements, and for slow sustained swimming, those that do deserve further study.

More About The Video Event Trigger

NASA Technical Reports Server (NTRS)

Williams, Glenn L.

1996-01-01

Report presents additional information about system described in "Video Event Trigger" (LEW-15076). Digital electronic system processes video-image data to generate trigger signal when image shows significant change, such as motion, or appearance, disappearance, change in color, brightness, or dilation of object. Potential uses include monitoring of hallways, parking lots, and other areas during hours when supposed unoccupied, looking for fires, tracking airplanes or other moving objects, identification of missing or defective parts on production lines, and video recording of automobile crash tests.

Popular sweetner sucralose as a migraine trigger.

PubMed

Patel, Rajendrakumar M; Sarma, Rakesh; Grimsley, Edwin

2006-09-01

Sucralose (trichlorogalactosucrose, or better known as Splenda) is an artificial sweetener from native sucrose that was approved by the FDA on April 1, 1998 (April Fool's Day). This observation of a potential causal relationship between sucralose and migraines may be important for physicians to remember this can be a possible trigger during dietary history taking. Identifying further triggers for migraine headaches, in this case sucralose, may help alleviate some of the cost burden (through expensive medical therapy or missed work opportunity) as well as provide relief to migraineurs.

Does Entrepreneurial Education Trigger More or Less Neoliberalism in Education?

ERIC Educational Resources Information Center

Lackéus, Martin

2017-01-01

Purpose: An emerging scholarly critique has claimed that entrepreneurial education triggers more neoliberalism in education, leading to increased inequality, neglect of civic values and an unjust blame of poor citizens for their misfortunes. The purpose of this paper is to develop a deeper understanding of this potentially problematic relationship…

[Establishment of visceral left-right asymmetry in mammals: the role of ciliary action and leftward fluid flow in the region of Hensen's node].

PubMed

Ermakov, A S

2013-01-01

During individual development of vertebrates, the anteroposterior, dorsoventral, and left-right axes of the body are established. Although the vertebrates are bilaterally symmetric outside, their internal structure is asymmetric. Of special interest is the insight into establishment of visceral left-right asymmetry in mammals, since it has not only basic but also an applied medical significance. As early as 1976, it was hypothesized that the ciliary action could be associated with the establishment of left-right asymmetry in mammals. Currently, the majority of researchers agree that the ciliary action in the region of Hensen's node and the resulting leftward laminar fluid flow play a key role in the loss of bilateral symmetry and triggering of expression of the genes constituting the Nodal-Ptx2 signaling cascade, specific of the left side of the embryo. The particular mechanism underlying this phenomenon is still insufficiently clear. There are three competing standpoints on how leftward fluid flow induces expression of several genes in the left side of the embryo. The morphogen gradient hypothesis postulates that the leftward flow creates a high concentration of a signaling biomolecule in the left side of Hensen's node, which, in turn, stimulates triggering of.gene expression of the Nodal-Ptx2 cascade. The biomechanical hypothesis (or two-cilia model) states that the immotile cilia located in the periphery of Hensen's node act as mechanosensors, activate mechanosensory ion channels, and trigger calcium signaling in the left side of the embryo. Finally, the "shuttle-bus model" holds that leftward fluid flow carries the lipid vesicles, which are crashed when colliding immotile cilia in the periphery of Hensen's node to release the contained signaling biomolecules. It is also noteworthy that the association between the ciliary action and establishment of asymmetry has been recently discovered in representatives of the lower invertebrates. In this paper, the author considers evolution of concepts on the mechanisms underlying establishment of visceral left-right asymmetry since 1976 until the present and critically reexamines the current concepts in this field of science. According to the author, serious arguments favoring the biomechanical hypothesis for determination of left-right asymmetry in mammals have been obtained.

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.

Role of Automatic Wireless Remote Monitoring Immediately Following ICD Implant: The Lumos-T Reduces Routine Office Device Follow-Up Study (TRUST) Trial.

PubMed

Varma, Niraj; Epstein, Andrew E; Schweikert, Robert; Michalski, Justin; Love, Charles J

2016-03-01

The incidence of unscheduled encounters and problem occurrence between ICD implant and first in-person evaluation (IPE) recommended at 12 weeks is unknown. Automatic remote home monitoring (HM) may be useful in this potentially unstable period. ICD patients were randomized 2:1 to HM enabled post-implant (n = 908) or to conventional monitoring (CM; n = 431). Groups were compared between implant and prior to first scheduled IPE for IPE incidence, causes, and actionability (reprogramming, system revision, medication changes) and event detection time. HM and CM patients were similar (mean age 63 years, 72% male, LVEF 29%, primary prevention 73%, DDD 57%). In the post-implant interval assessed (HM 100 ± 21.3 days vs. CM 101 ± 20.8 days, P = 0.54), 85.4% (776/908) HM patients and 87.7% CM (378/431) patients had no cause for IPE (P = 0.31). When IPE occurred, actionability in HM (64/177 [36.2%]) was greater versus CM (15/62 [24.2%], P = 0.12). Actionable items were discovered sooner with HM (P = 0.025). Device reprogramming or lead revision was triggered following 53/177 (29.9%) IPEs in HM versus 9/62 (14.5%) in CM (P = 0.018). Arrhythmia detection was enhanced by HM: 276 atrial and ventricular episodes were detected in 135 follow-ups in contrast to CM (65 episodes at 17 IPEs). More silent arrhythmic episodes were discovered by HM (7.2% vs. 1.5% [P = 0.15]). Since 27/42 (64.3%) IPEs driven by HM alerts were actionable, event notification was a valuable method for problem detection. Importantly, HM did not increase incidence of non-actionable IPEs (P = 0.72). Activation of automatic remote monitoring should be encouraged soon post-ICD implant. © 2015 Wiley Periodicals, Inc.

Seeing fearful body language rapidly freezes the observer's motor cortex.

PubMed

Borgomaneri, Sara; Vitale, Francesca; Gazzola, Valeria; Avenanti, Alessio

2015-04-01

Fearful body language is a salient signal alerting the observer to the presence of a potential threat in the surrounding environment. Although detecting potential threats may trigger an immediate reduction of motor output in animals (i.e., freezing behavior), it is unclear at what point in time similar reductions occur in the human motor cortex and whether they originate from excitatory or inhibitory processes. Using single-pulse and paired-pulse transcranial magnetic stimulation (TMS), here we tested the hypothesis that the observer's motor cortex implements extremely fast suppression of motor readiness when seeing emotional bodies - and fearful body expressions in particular. Participants observed pictures of body postures and categorized them as happy, fearful or neutral while receiving TMS over the right or left motor cortex at 100-125 msec after picture onset. In three different sessions, we assessed corticospinal excitability, short intracortical inhibition (SICI) and intracortical facilitation (ICF). Independently of the stimulated hemisphere and the time of the stimulation, watching fearful bodies suppressed ICF relative to happy and neutral body expressions. Moreover, happy expressions reduced ICF relative to neutral actions. No changes in corticospinal excitability or SICI were found during the task. These findings show extremely rapid bilateral modulation of the motor cortices when seeing emotional bodies, with stronger suppression of motor readiness when seeing fearful bodies. Our results provide neurophysiological support for the evolutionary notions that emotion perception is inherently linked to action systems and that fear-related cues induce an urgent mobilization of motor reactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Role of the motor system in language knowledge.

PubMed

Berent, Iris; Brem, Anna-Katharine; Zhao, Xu; Seligson, Erica; Pan, Hong; Epstein, Jane; Stern, Emily; Galaburda, Albert M; Pascual-Leone, Alvaro

2015-02-17

All spoken languages express words by sound patterns, and certain patterns (e.g., blog) are systematically preferred to others (e.g., lbog). What principles account for such preferences: does the language system encode abstract rules banning syllables like lbog, or does their dislike reflect the increased motor demands associated with speech production? More generally, we ask whether linguistic knowledge is fully embodied or whether some linguistic principles could potentially be abstract. To address this question, here we gauge the sensitivity of English speakers to the putative universal syllable hierarchy (e.g., blif ≻ bnif ≻ bdif ≻ lbif) while undergoing transcranial magnetic stimulation (TMS) over the cortical motor representation of the left orbicularis oris muscle. If syllable preferences reflect motor simulation, then worse-formed syllables (e.g., lbif) should (i) elicit more errors; (ii) engage more strongly motor brain areas; and (iii) elicit stronger effects of TMS on these motor regions. In line with the motor account, we found that repetitive TMS pulses impaired participants' global sensitivity to the number of syllables, and functional MRI confirmed that the cortical stimulation site was sensitive to the syllable hierarchy. Contrary to the motor account, however, ill-formed syllables were least likely to engage the lip sensorimotor area and they were least impaired by TMS. Results suggest that speech perception automatically triggers motor action, but this effect is not causally linked to the computation of linguistic structure. We conclude that the language and motor systems are intimately linked, yet distinct. Language is designed to optimize motor action, but its knowledge includes principles that are disembodied and potentially abstract.

A role for heme oxygenase-1 in the antioxidant and antiapoptotic effects of erythropoietin: the start of a good news/bad news story?

PubMed

Calò, Lorenzo A; Davis, Paul A; Piccoli, Antonio; Pessina, Achille C

2006-01-01

Erythropoietin (EPO) is the major regulator of erythropoiesis. EPO's actions have been shown to be antiapoptotic and dependent on JAK2 signaling and Akt phosphorylation. These effects serve as link between EPO and heme oxygenase-1 (HO-1). HO-1 is an inducible enzyme with potent antioxidant and antiapoptotic activities which are regulated by Akt signaling. EPO's ability to alter cellular systems that involve apoptosis and oxidants suggests that EPO treatments are likely to have multiple and different effects which may start a good news/bad news story. Recombinant human EPO is the recognized treatment of choice to address anemia and to stimulate erythropoiesis in chronic renal failure patients, through its antiapoptotic action which likely involves HO-1. On the other hand, EPO treatment to address anemia in cancer patients, while providing significant improvements in cancer patients' quality of life, its effects on survival are equivocal, likely due to its linkage with HO-1. Two clinical trials of EPO in patients with solid tumors have, in fact, shown specific negative effects on survival. However, EPO's effect on tumor growth and survival is not uniformily pro growth and pro survival, as EPO may act synergistically with chemotherapy to induce apoptosis. Finally, compounds have been synthesized that do not trigger EPO receptor and thus may allow experimental distinction and, therefore, at least potentially affect at the clinical level the tissue-protective effects of EPO (e.g., antiapoptosis) without provoking its other potentially detrimental effects. Copyright 2006 S. Karger AG, Basel

Shade-Induced Action Potentials in Helianthus annuus L. Originate Primarily from the Epicotyl

PubMed Central

Stephens, Nicholas R; Cleland, Robert E; Van Volkenburgh, Elizabeth

2006-01-01

Repeated observations that shading (a drastic reduction in illumination rate) increased the generation of spikes (rapidly reversed depolarizations) in leaves and stems of many cucumber and sunflower plants suggests a phenomenon widespread among plant organs and species. Although shaded leaves occasionally generate spikes and have been suggested to trigger systemic action potentials (APs) in sunflower stems, we never found leaf-generated spikes to propagate out of the leaf and into the stem. On the contrary, our data consistently implicate the epicotyl as the location where most spikes and APs (propagating spikes) originate. Microelectrode studies of light and shading responses in mesophyll cells of leaf strips and in epidermis/cortex cells of epicotyl segments confirm this conclusion and show that spike induction is not confined to intact plants. 90% of the epicotyl-generated APs undergo basipetal propagation to the lower epicotyl, hypocotyl and root. They propagate with an average rate of 2 ± 0.3 mm s−1 and always undergo a large decrement from the hypocotyl to the root. The few epicotyl-derived APs that can be tracked to leaf blades (< 10%) undergo either a large decrement or fail to be transmitted at all. Occasionally (5% of the observations) spikes were be generated in hypocotyl and lower epicotyl that moved towards the upper epicotyl unaltered, decremented, or amplified. This study confirms that plant APs arise to natural, nontraumatic changes. In simultaneous recordings with epicotyl growth, AP generation was found to parallel the acceleration of stem growth under shade. The possible relatedness of both processes must be further investigated. PMID:19521471

Induction of apoptosis by pinostrobin in human cervical cancer cells: Possible mechanism of action.

PubMed

Jaudan, Alka; Sharma, Sapna; Malek, Sri Nurestri Abd; Dixit, Aparna

2018-01-01

Pinostrobin (PN) is a naturally occurring dietary bioflavonoid, found in various medicinal herbs/plants. Though anti-cancer potential of many such similar constituents has been demonstrated, critical biochemical targets and exact mechanism for their apoptosis-inducing actions have not been fully elucidated. The present study was aimed to investigate if PN induced apoptosis in cervical cancer cells (HeLa) of human origin. It is demonstrated that PN at increasing dose effectivity reduced the cell viability as well as GSH and NO2- levels. Condensed nuclei with fragmented chromatin and changes in mitochondrial matrix morphology clearly indicated the role of mitochondria in PN induced apoptosis. A marked reduction in mitochondrial membrane potential and increased ROS production after PN treatment showed involvement of free radicals, which in turn further augment ROS levels. PN treatment resulted in DNA damage, which could have been triggered by an increase in ROS levels. Decrease in apoptotic cells in the presence of caspase 3 inhibitor in PN-treated cells suggested that PN induced apoptosis via caspase dependent pathways. Additionally, a significant increase in the expression of proteins of extrinsic (TRAIL R1/DR4, TRAIL R2/DR5, TNF RI/TNFRSF1A, FADD, Fas/TNFRSF6) and intrinsic pathway (Bad, Bax, HTRA2/Omi, SMAC/Diablo, cytochrome C, Pro-Caspase-3, Cleaved Caspase-3) was observed in the cells exposed to PN. Taken together, these observations suggest that PN efficiently induces apoptosis through ROS mediated extrinsic and intrinsic dependent signaling pathways, as well as ROS mediated mitochondrial damage in HeLa cells.

Role of the motor system in language knowledge

PubMed Central

Berent, Iris; Brem, Anna-Katharine; Zhao, Xu; Seligson, Erica; Pan, Hong; Epstein, Jane; Stern, Emily; Galaburda, Albert M.; Pascual-Leone, Alvaro

2015-01-01

All spoken languages express words by sound patterns, and certain patterns (e.g., blog) are systematically preferred to others (e.g., lbog). What principles account for such preferences: does the language system encode abstract rules banning syllables like lbog, or does their dislike reflect the increased motor demands associated with speech production? More generally, we ask whether linguistic knowledge is fully embodied or whether some linguistic principles could potentially be abstract. To address this question, here we gauge the sensitivity of English speakers to the putative universal syllable hierarchy (e.g., blif≻bnif≻bdif≻lbif) while undergoing transcranial magnetic stimulation (TMS) over the cortical motor representation of the left orbicularis oris muscle. If syllable preferences reflect motor simulation, then worse-formed syllables (e.g., lbif) should (i) elicit more errors; (ii) engage more strongly motor brain areas; and (iii) elicit stronger effects of TMS on these motor regions. In line with the motor account, we found that repetitive TMS pulses impaired participants’ global sensitivity to the number of syllables, and functional MRI confirmed that the cortical stimulation site was sensitive to the syllable hierarchy. Contrary to the motor account, however, ill-formed syllables were least likely to engage the lip sensorimotor area and they were least impaired by TMS. Results suggest that speech perception automatically triggers motor action, but this effect is not causally linked to the computation of linguistic structure. We conclude that the language and motor systems are intimately linked, yet distinct. Language is designed to optimize motor action, but its knowledge includes principles that are disembodied and potentially abstract. PMID:25646465

Brugada Syndrome. Clinical, Genetic, Molecular, Cellular and Ionic Aspects

PubMed Central

Antzelevitch, Charles; Patocskai, Bence

2015-01-01

The Brugada syndrome (BrS) is an inherited cardiac arrhythmia syndrome first described as a new clinical entity in 1992. Electrocardiographically characterized by distinct coved type ST segment elevation in the right precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young adults, and less frequently in infants and children. The ECG manifestations of the BrS are often concealed and may be unmasked or aggravated by sodium channel blockers, a febrile state, vagotonic agents, as well as by tricyclic and tetracyclic antidepressants. An implantable cardioverter defibrillator (ICD) is the most widely accepted approach to therapy. Pharmacological therapy is designed to produce an inward shift in the balance of currents active during the early phases of the right ventricular action potential and can be used to abort electrical storms or as an adjunct or alternative to device therapy when use of an ICD is not possible. Isoproterenol, cilostazol and milrinone boost calcium channel current and drugs like quinidine, bepridil and the Chinese herb extract Wenxin Keli inhibit the transient outward current, acting to diminish the action potential (AP) notch and thus to suppress the substrate and trigger for VT/VF. Radiofrequency ablation of the right ventricular outflow tract epicardium of BrS patients has recently been shown to reduce arrhythmia-vulnerability and the ECG-manifestation of the disease, presumably by destroying the cells with more prominent AP notch. This review provides an overview of the clinical, genetic, molecular and cellular aspects of the BrS as well as the approach to therapy. PMID:26671757

Tyrosine Phosphorylation Determines Afterdischarge Initiation by Regulating an Ionotropic Cholinergic Receptor.

PubMed

White, Sean H; Sturgeon, Raymond M; Gu, Yueling; Nensi, Alysha; Magoski, Neil S

2018-02-21

Changes to neuronal activity often involve a rapid and precise transition from low to high excitability. In the marine snail, Aplysia, the bag cell neurons control reproduction by undergoing an afterdischarge, which begins with synaptic input releasing acetylcholine to open an ionotropic cholinergic receptor. Gating of this receptor causes depolarization and a shift from silence to continuous action potential firing, leading to the neuroendocrine secretion of egg-laying hormone and ovulation. At the onset of the afterdischarge, there is a rise in intracellular Ca 2+ , followed by both protein kinase C (PKC) activation and tyrosine dephosphorylation. To determine whether these signals influence the acetylcholine ionotropic receptor, we examined the bag cell neuron cholinergic response both in culture and isolated clusters using whole-cell and/or sharp-electrode electrophysiology. The acetylcholine-induced current was not altered by increasing intracellular Ca 2+ via voltage-gated Ca 2+ channels, clamping intracellular Ca 2+ with exogenous Ca 2+ buffers, or activating PKC with phorbol esters. However, lowering phosphotyrosine levels by inhibiting tyrosine kinases both reduced the cholinergic current and prevented acetylcholine from triggering action potentials or afterdischarge-like bursts. In other systems, acetylcholine receptors are often modulated by multiple signals, but bag cell neurons appear to be more restrictive in this regard. Prior work finds that, as the afterdischarge proceeds, tyrosine dephosphorylation leads to biophysical alterations that promote persistent firing. Because this firing is subsequent to the cholinergic input, inhibiting the acetylcholine receptor may represent a means of properly orchestrating synaptically induced changes in excitability. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Endocannabinoid-Dependent Long-Term Potentiation of Synaptic Transmission at Rat Barrel Cortex.

PubMed

Maglio, Laura Eva; Noriega-Prieto, José Antonio; Maraver, Maria Jesús; Fernández de Sevilla, David

2018-05-01

Brain-derived neurotrophic factor (BDNF) plays a critical role in modulating plasticity in sensory cortices. Indeed, a BDNF-dependent long-term potentiation (LTP) at distal basal excitatory synapses of Layer 5 pyramidal neurons (L5PNs) has been demonstrated in disinhibited rat barrel cortex slices. Although it is well established that this LTP requires the pairing of excitatory postsynaptic potentials (PSPs) with Ca2+ spikes, its induction when synaptic inhibition is working remains unexplored. Here we show that low-frequency stimulation at basal dendrites of L5PNs is able to trigger a PSP followed by an action potential (AP) and a slow depolarization (termed PSP-Ca2+ response) in thalamocortical slices without blocking synaptic inhibition. We demonstrate that AP barrage-mediated release of endocannabinoids (eCBs) from the recorded L5PNs induces PSP-Ca2+ response facilitation and BDNF-dependent LTP. Indeed, this LTP requires the type 1 cannabinoid receptors activation, is prevented by postsynaptic intracellular 1,2-bis(2-aminophenoxy) ethane-N,N,N,N'-tetraacetic acid (BAPTA) or the anandamide membrane transporter inhibitor AM404, and only occurs in L5PNs neurons showing depolarization-induced suppression of inhibition. Additionally, electrical stimulation at the posteromedial thalamic nucleus induced similar response and LTP. These results reveal a novel form of eCB-dependent LTP at L5PNs that could be relevant in the processing of sensory information in the barrel cortex.

Pharmaco-mechanical coupling in the response to acetylcholine and substance P in the smooth muscle of the rat iris sphincter.

PubMed Central

Banno, H.; Imaizumi, Y.; Watanabe, M.

1985-01-01

In the rat iris sphincter muscle contractile responses to transmural stimulation consisted of two components, a fast cholinergic followed by a slow non-adrenergic, non-cholinergic (NANC) one. The magnitude of the latter varied widely and was on average 5% of that of the cholinergic component. Exogenous substance P (1 nM-1 microM) produced a concentration-dependent contraction, the maximum amplitude of which was as large as that produced by acetylcholine (ACh). Capsaicin (10 microM) induced a transient contraction only once in each preparation. After the treatment with capsaicin the NANC component disappeared. Neither nerve nor direct electrical stimulation with short pulses elicited any active change in the membrane potential under physiological conditions, but an action potential was triggered by direct stimulation when the extracellular Ca ion was totally replaced by Ba ion. Under the latter conditions spontaneous spike potentials occurred repetitively. ACh and substance P produced a large contraction without modifying the membrane potential. This was also the case in the presence of 5 mM Ba. These results suggest that substance P-ergic innervation may have a far lesser physiological significance than that which has been described in rabbits and that pure pharmaco-mechanical coupling is characteristic of the responses to acetylcholine, substance P, and nerve stimulation in the rat iris sphincter muscle. PMID:2412624

Major Life Events as Potential Triggers of Sudden Cardiac Arrest

PubMed Central

Wicks, April F; Lumley, Thomas; Lemaitre, Rozenn N; Sotoodehnia, Nona; Rea, Thomas D; McKnight, Barbara; Strogatz, David S; Bovbjerg, Viktor E; Siscovick, David S

2012-01-01

Background We investigated recent loss of or separation from afamily member or friend and risk of sudden cardiac arrest. Methods Our case-crossover study included 490 apparently-healthy married residents of King County, Washington, who suffered sudden cardiac arrest between 1988 and 2005. We compared exposure to spouse-reported family/friend events occurring ≤ 1 month before sudden cardiac arrest with events occurring n the previous 5 months. We evaluated potential effect modification by habitual vigorous physical activity. Results Recent family/friend events were associated with a higher risk of sudden cardiac arrest (odds ratio (OR) = 1.6 [95% confidence interval (CI) = 1.1-2.4]). ORs for cases with and without habitual vigorous physical activity were 1.1 (0.6-2.2) and 2.0 (1.2-3.1), respectively, (interaction P = 0.02). Conclusions These results suggest family/friend events may trigger sudden cardiac arrest and raise the hypothesis that habitual vigorous physical activity may lower susceptibility to these potential triggers. PMID:22415111

Major life events as potential triggers of sudden cardiac arrest.

PubMed

Wicks, April F; Lumley, Thomas; Lemaitre, Rozenn N; Sotoodehnia, Nona; Rea, Thomas D; McKnight, Barbara; Strogatz, David S; Bovbjerg, Viktor E; Siscovick, David S

2012-05-01

We investigated the risk of sudden cardiac arrest in association with the recent loss of, or separation from, a family member or friend. Our case-crossover study included 490 apparently healthy married residents of King County, Washington, who suffered sudden cardiac arrest between 1988 and 2005. We compared exposure to spouse-reported family/friend events occurring ≤ 1 month before sudden cardiac arrest with events occurring in the previous 5 months. We evaluated potential effect modification by habitual vigorous physical activity. Recent family/friend events were associated with a higher risk of sudden cardiac arrest (odds ratio [OR] = 1.6; 95% confidence interval [CI] = 1.1-2.4). ORs for cases with and without habitual vigorous physical activity were 1.1 (0.6-2.2) and 2.0 (1.2-3.1), respectively (interaction P = 0.02). These results suggest family/friend events may trigger sudden cardiac arrest and raise the hypothesis that habitual vigorous physical activity may lower susceptibility to these potential triggers.

Emotional stressors trigger cardiovascular events.

PubMed

Schwartz, B G; French, W J; Mayeda, G S; Burstein, S; Economides, C; Bhandari, A K; Cannom, D S; Kloner, R A

2012-07-01

To describe the relation between emotional stress and cardiovascular events, and review the literature on the cardiovascular effects of emotional stress, in order to describe the relation, the underlying pathophysiology, and potential therapeutic implications. Targeted PUBMED searches were conducted to supplement the authors' existing database on this topic. Cardiovascular events are a major cause of morbidity and mortality in the developed world. Cardiovascular events can be triggered by acute mental stress caused by events such as an earthquake, a televised high-drama soccer game, job strain or the death of a loved one. Acute mental stress increases sympathetic output, impairs endothelial function and creates a hypercoagulable state. These changes have the potential to rupture vulnerable plaque and precipitate intraluminal thrombosis, resulting in myocardial infarction or sudden death. Therapies targeting this pathway can potentially prevent acute mental stressors from initiating plaque rupture. Limited evidence suggests that appropriately timed administration of beta-blockers, statins and aspirin might reduce the incidence of triggered myocardial infarctions. Stress management and transcendental meditation warrant further study. © 2012 Blackwell Publishing Ltd.

Thermosensitive liposomes for localized delivery and triggered release of chemotherapy

PubMed Central

Ta, Terence; Porter, Tyrone M.

2016-01-01

Liposomes are a promising class of nanomedicine with the potential to provide site-specific chemotherapy, thus improving the quality of cancer patient care. First-generation liposomes have emerged as one of the first nanomedicines used clinically for localized delivery of chemotherapy. Second-generation liposomes, i.e. stimuli-responsive liposomes, have the potential to not only provide site-specific chemotherapy, but also triggered drug release and thus greater spatial and temporal control of therapy. Temperature-sensitive liposomes are an especially attractive option, as tumors can be heated in a controlled and predictable manner with external energy sources. Traditional thermosensitive liposomes are composed of lipids that undergo a gel-to-liquid phase transition at several degrees above physiological temperature. More recently, temperature-sensitization of liposomes has been demonstrated with the use of lysolipids and synthetic temperature-sensitive polymers. The design, drug release behavior, and clinical potential of various temperature-sensitive liposomes, as well as the various heating modalities used to trigger release, are discussed in this review. PMID:23583706

Characteristics of action potentials and their underlying outward currents in rat taste receptor cells.

PubMed

Chen, Y; Sun, X D; Herness, S

1996-02-01

1. Taste receptor cells produce action potentials as a result of transduction mechanisms that occur when these cells are stimulated with tastants. These action potentials are thought to be key signaling events in relaying information to the central nervous system. We explored the ionic basis of action potentials from dissociated posterior rat taste cells using the patch-clamp recording technique in both voltage-clamp and current-clamp modes. 2. Action potentials were evoked by intracellular injection of depolarizing current pulses from a holding potential of -80 mV. The threshold potential for firing of action potentials was approximately -35 mV; the input resistance of these cells averaged 6.9 G omega. With long depolarizing pulses, two or three action potentials could be elicited with successive attenuation of the spike height. Afterhyperpolarizations were observed often. 3. Both sodium and calcium currents contribute to depolarizing phases of the action potential. Action potentials were blocked completely in the presence of the sodium channel blocker tetrodotoxin. Calcium contributions could be visualized as prolonged calcium plateaus when repolarizing potassium currents were blocked and barium was used as a charge carrier. 4. Outward currents were composed of sustained delayed rectifier current, transient potassium current, and calcium-activated potassium current. Transient and sustained potassium currents activated close to -30 mV and increased monotonically with further depolarization. Up to half the outward current inactivated with decay constants on the order of seconds. Sustained and transient currents displayed steep voltage dependence in conductance and inactivation curves. Half inactivation occurred at -20 +/- 3.1 mV (mean +/- SE) with a decrease of 11.2 +/- 0.5 mV per e-fold. Half maximal conductance occurred at 3.6 +/- 1.8 mV and increased 12.2 +/- 0.6 mV per e-fold. Calcium-activated potassium current was evidenced by application of apamin and the use of calcium-free bathing solution. It was most obvious at more depolarized holding potentials that inactivated much of the transient and sustained outward currents. 5. Potassium currents contribute to both the repolarization and afterhyperpolarization phases of the action potential. These currents were blocked by bath application of tetraethylammonium, which also substantially broadened the action potential. Application of 4-aminopyridine was able to selectively block transient potassium currents without affecting sustained currents. This also broadened the action potential as well as eliminated the afterhyperpolarization. 6. A second type of action potential was observed that differed in duration. These slow action potentials had t1/2 durations of 9.6 ms compared with 1.4 ms for fast action potentials. Input resistances of the two groups were indistinguishable. Approximately one-fourth of the cells eliciting action potentials were of the slow type. 7. Cells eliciting fast action potentials had large outward currents capable of producing a quick repolarization, whereas cells with slow action potentials had small outward currents by comparison. The average values of fast cells were 2,563 pA and 1.4 ms compared with 373 pA and 9.6 ms for slow cells. Current and duration values were related exponentially. No significant difference was noted for inward currents. 8. These results suggest that many taste receptor cells conduct action potentials, which may be classified broadly into two groups on the basis of action potential duration and potassium current magnitude. These groups may be related to cell turnover. The physiological role of action potentials remains to be elucidated but may be important for communication within the taste bud as well as to the afferent nerve.

Context-aware system for pre-triggering irreversible vehicle safety actuators.

PubMed

Böhmländer, Dennis; Dirndorfer, Tobias; Al-Bayatti, Ali H; Brandmeier, Thomas

2017-06-01

New vehicle safety systems have led to a steady improvement of road safety and a reduction in the risk of suffering a major injury in vehicle accidents. A huge leap forward in the development of new vehicle safety systems are actuators that have to be activated irreversibly shortly before a collision in order to mitigate accident consequences. The triggering decision has to be based on measurements of exteroceptive sensors currently used in driver assistance systems. This paper focuses on developing a novel context-aware system designed to detect potential collisions and to trigger safety actuators even before an accident occurs. In this context, the analysis examines the information that can be collected from exteroceptive sensors (pre-crash data) to predict a certain collision and its severity to decide whether a triggering is entitled or not. A five-layer context-aware architecture is presented, that is able to collect contextual information about the vehicle environment and the actual driving state using different sensors, to perform reasoning about potential collisions, and to trigger safety functions upon that information. Accident analysis is used in a data model to represent uncertain knowledge and to perform reasoning. A simulation concept based on real accident data is introduced to evaluate the presented system concept. Copyright © 2017 Elsevier Ltd. All rights reserved.

Where do we stand after twenty years of dynamic triggering studies? (Invited)

NASA Astrophysics Data System (ADS)

Prejean, S. G.; Hill, D. P.

2013-12-01

In the past two decades, remote dynamic triggering of earthquakes by other earthquakes has been explored in a variety of physical environments with a wide array of observation and modeling techniques. These studies have significantly refined our understanding of the state of the crust and the physical conditions controlling earthquake nucleation. Despite an ever growing database of dynamic triggering observations, significant uncertainties remain and vigorous debate in almost all aspects of the science continues. For example, although dynamic earthquake triggering can occur with peak dynamic stresses as small as 1 kPa, triggering thresholds and their dependence on local stress state, hydrological environment, and frictional properties of faults are not well understood. Some studies find a simple threshold based on the peak amplitude of shaking while others find dependencies on frequency, recharge time, and other parameters. Considerable debate remains over the range of physical processes responsible for dynamic triggering, and the wide variation in dynamic triggering responses and time scales suggests triggering by multiple physical processes. Although Coulomb shear failure with various friction laws can often explain dynamic triggering, particularly instantaneous triggering, delayed dynamic triggering may be dependent on fluid transport and other slowly evolving aseismic processes. Although our understanding of the global distribution of dynamic triggering has improved, it is far from complete due to spatially uneven monitoring. A major challenge involves establishing statistical significance of potentially triggered earthquakes, particularly if they are isolated events or time-delayed with respect to triggering stresses. Here we highlight these challenges and opportunities with existing data. We focus on environmental dependence of dynamic triggering by large remote earthquakes particularly in volcanic and geothermal systems, as these systems often have high rates of background seismicity. In many volcanic and geothermal systems, such as the Geysers in Northern California, dynamic triggering of micro-earthquakes is frequent and predictable. In contrast, most active and even erupting volcanoes in Alaska (with the exception of the Katmai Volcanic Cluster) do not experience dynamic triggering. We explore why.

Women: Tapping a New Resource for Energy.

ERIC Educational Resources Information Center

Consumer Action Now, New York, NY.

In 1973 the Arab oil embargo triggered what has come to be known as the "energy crisis." In 1974, Consumer Action Now (CAN) decided to devote its full efforts to the grave issues of energy and to look for options that would preserve our choices as a new energy era is entered. Any transition to a more energy-efficient society depends on a…

The Power, and Dilemma, of Honesty: Action Learning for Social Entrepreneurs

ERIC Educational Resources Information Center

Weinstein, Krystyna

2005-01-01

This is an account of one particular set meeting during a year long programme for social entrepreneurs. It triggered a number of questions and insights for me about the amazing value of honesty, and its power. It released a great deal of energy, ownership and "control". I realized how important it was to highlight, discuss and reflect on…

Light-triggered thermoelectric conversion based on a carbon nanotube-polymer hybrid gel.

PubMed

Miyako, Eijiro; Nagata, Hideya; Funahashi, Ryoji; Hirano, Ken; Hirotsu, Takahiro

2009-01-01

Lights? Nanotubes? Action! A hydrogel comprising lysozymes, poly(ethylene glycol), phospholipids, and functionalized single-walled carbon nanotubes is employed for light-driven thermoelectric conversion. A photoinduced thermoelectric conversion module based on the hydrogel functions as a novel electric power generator (see image). This concept may find application in various industries, such as robotics and aerospace engineering.

Poverty Impact Trigger Act of 2013

THOMAS, 113th Congress

Rep. Lee, Barbara [D-CA-13

2013-01-04

House - 01/04/2013 Referred to the Committee on Rules, and in addition to the Committee on the Budget, for a period to be subsequently determined by the Speaker, in each case for consideration of such provisions as fall within the jurisdiction of the committee concerned. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

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.

Plum pox virus capsid protein suppresses plant pathogen-associated molecular pattern (PAMP)-triggered immunity.

PubMed

Nicaise, Valerie; Candresse, Thierry

2017-08-01

The perception of pathogen-associated molecular patterns (PAMPs) by immune receptors launches defence mechanisms referred to as PAMP-triggered immunity (PTI). Successful pathogens must suppress PTI pathways via the action of effectors to efficiently colonize their hosts. So far, plant PTI has been reported to be active against most classes of pathogens, except viruses, although this defence layer has been hypothesized recently as an active part of antiviral immunity which needs to be suppressed by viruses for infection success. Here, we report that Arabidopsis PTI genes are regulated upon infection by viruses and contribute to plant resistance to Plum pox virus (PPV). Our experiments further show that PPV suppresses two early PTI responses, the oxidative burst and marker gene expression, during Arabidopsis infection. In planta expression of PPV capsid protein (CP) was found to strongly impair these responses in Nicotiana benthamiana and Arabidopsis, revealing its PTI suppressor activity. In summary, we provide the first clear evidence that plant viruses acquired the ability to suppress PTI mechanisms via the action of effectors, highlighting a novel strategy employed by viruses to escape plant defences. © 2016 BSPP AND JOHN WILEY & SONS LTD.

Miro phosphorylation sites regulate Parkin recruitment and mitochondrial motility.

PubMed

Shlevkov, Evgeny; Kramer, Tal; Schapansky, Jason; LaVoie, Matthew J; Schwarz, Thomas L

2016-10-11

The PTEN-induced putative kinase 1 (PINK1)/Parkin pathway can tag damaged mitochondria and trigger their degradation by mitophagy. Before the onset of mitophagy, the pathway blocks mitochondrial motility by causing Miro degradation. PINK1 activates Parkin by phosphorylating both Parkin and ubiquitin. PINK1, however, has other mitochondrial substrates, including Miro (also called RhoT1 and -2), although the significance of those substrates is less clear. We show that mimicking PINK1 phosphorylation of Miro on S156 promoted the interaction of Parkin with Miro, stimulated Miro ubiquitination and degradation, recruited Parkin to the mitochondria, and via Parkin arrested axonal transport of mitochondria. Although Miro S156E promoted Parkin recruitment it was insufficient to trigger mitophagy in the absence of broader PINK1 action. In contrast, mimicking phosphorylation of Miro on T298/T299 inhibited PINK1-induced Miro ubiquitination, Parkin recruitment, and Parkin-dependent mitochondrial arrest. The effects of the T298E/T299E phosphomimetic were dominant over S156E substitution. We propose that the status of Miro phosphorylation influences the decision to undergo Parkin-dependent mitochondrial arrest, which, in the context of PINK1 action on other substrates, can restrict mitochondrial dynamics before mitophagy.