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Sample records for action potentials saps

  1. An investigation of potential applications of OP-SAPS: Operational sampled analog processors

    NASA Technical Reports Server (NTRS)

    Parrish, E. A.; Mcvey, E. S.

    1976-01-01

    The impact of charge-coupled device (CCD) processors on future instrumentation was investigated. The CCD devices studied process sampled analog data and are referred to as OP-SAPS - operational sampled analog processors. Preliminary studies into various architectural configurations for systems composed of OP-SAPS show that they have potential in such diverse applications as pattern recognition and automatic control. It appears probable that OP-SAPS may be used to construct computing structures which can serve as special peripherals to large-scale computer complexes used in real time flight simulation. The research was limited to the following benchmark programs: (1) face recognition, (2) voice command and control, (3) terrain classification, and (4) terrain identification. A small amount of effort was spent on examining a method by which OP-SAPS may be used to decrease the limiting ground sampling distance encountered in remote sensing from satellites.

  2. Cardiac action potential imaging

    NASA Astrophysics Data System (ADS)

    Tian, Qinghai; Lipp, Peter; Kaestner, Lars

    2013-06-01

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

  3. Glycosidic activities of Candida albicans after action of vegetable latex saps (natural antifungals) and isoconazole (synthetic antifungal).

    PubMed

    Giordani, R; Moulin-Traffort, J; Régli, P

    1991-01-01

    Glycosidic activities have been examined in Candida albicans grown on medium culture containing latex sap (natural antifungal) or isoconazole (synthetic antifungal). The different types of utilized latex sap were those of Lactuca sativa (latex exuded from articulated laticifers) and Asclepias curassavica (latex flowing from non-articulated laticifers). The same enzyme assays were performed on C. albicans grown without antifungal compounds. Except for alpha-arabinosidase, all glycosidase activities were increased when C. albicans was grown in medium supplemented with L. sativa latex sap. The most stimulated activities were those of beta-fucosidase, alpha-galactosidase, alpha- and beta-glucosidase, alpha- and beta-mannosidase, acetyl-beta-glucosaminidase. The presence of A. curassavica latex sap in culture medium produced similar results: the most stimulated activities were those of alpha-mannosidase, alpha-galactosidase, acetyl-beta-glucosaminidase and beta-fucosidase. Electron microscope observations suggested a correlation between this stimulation of glycosidic activities and the fungal cell wall breakdown. For comparison the presence of isoconazole in culture medium yields no increase in glycosidic activities and no ultrastructural modification of fungal cell wall. The mode of action of latex saps in cell wall breakdown is discussed. PMID:1922192

  4. Development of SAP-DoA techniques for GPR data processing within COST Action TU1208

    NASA Astrophysics Data System (ADS)

    Meschino, Simone; Pajewski, Lara; Marciniak, Marian

    2016-04-01

    This work focuses on the use of Sub-Array Processing (SAP) and Direction of Arrival (DoA) approaches for the processing of Ground-Penetrating Radar data, with the purpose of locating metal scatterers embedded in concrete or buried in the ground. Research activities have been carried out during two Short-Term Scientific Missions (STSMs) funded by the COST (European COoperation in Science and Technology) Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar" in May 2015 and January 2016. In applications involving smart antennas and in the presence of several transmitters operating simultaneously, it is important for a receiving array to be able to estimate the Direction of Arrival (DoA) of the incoming signals, in order to decipher how many emitters are present and predict their positions. A number of methods have been devised for DoA estimation: the MUltiple SIgnal Classification (MUSIC) and Estimation of Signal Parameters via Rotational Invariance Technique (ESPRIT) are amongst the most popular ones [1]. In the scenario considered by us, the electromagnetic sources are the currents induced on metal elements embedded in concrete or buried in the ground. GPR radargrams are processed, to estimate the DoAs of the electric field back-scattered by the sought targets. In order to work in near-field conditions, a sub-array processing (SAP) approach is adopted: the radargram is partitioned in sub-radargrams composed of few A-scans each, the dominant DoA is predicted for each sub-radargram. The estimated angles are triangulated, obtaining a set of crossings with intersections condensed around object locations. This pattern is filtered, in order to remove a noisy background of unwanted crossings, and is processed by applying the statistical procedure described in [2]. We tested our approach on synthetic GPR radargrams, obtained by using the freeware simulator gprMax implementing the Finite-Difference Time-Domain method [3]. In particular, we worked with

  5. Antifungal action of latex saps from Lactuca sativa L. and Asclepias curassavica L.

    PubMed

    Moulin-Traffort, J; Giordani, R; Régli, P

    1990-01-01

    Asclepias curassavica and Lactuca sativa latex saps inhibit the growth of Candida albicans because they degrade a great number of yeasts. This was confirmed by scanning and transmission electron microscopy observations. After a contact of 4 h and 6 h yeasts are deformed and emptied of their cytoplasmic content. Moreover, it appears that these saps, particularly Asclepias, also act on the cell wall: the substances presumed to be responsible for these effects were probably terpens and cardenolids but also enzymes, in particular glucanases. PMID:2090937

  6. 78 FR 43091 - Technical Operations Safety Action Program (T-SAP) and Air Traffic Safety Action Program (ATSAP)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-19

    ... examination in the public docket both before and after the closing date for comments. A report summarizing... will be incorporated in Order JO 7200.20, are eligible to complete a T-SAP report for events that occur... identified in FAA Order JO 7200.20 are eligible to file an ATSAP report for events that occur while acting...

  7. An investigation of potential applications of OP-SAPS: Operational Sampled Analog Processors

    NASA Technical Reports Server (NTRS)

    Parrish, E. A.; Mcvey, E. S.

    1977-01-01

    The application of OP-SAP's (operational sampled analog processors) in pattern recognition system is summarized. Areas investigated include: (1) human face recognition; (2) a high-speed programmable transversal filter system; (3) discrete word (speech) recognition; and (4) a resolution enhancement system.

  8. PROTOPLASMIC POTENTIALS IN HALICYSTIS : IV. VACUOLAR PERFUSION WITH ARTIFICIAL SAP AND SEA WATER.

    PubMed

    Blinks, L R

    1935-01-20

    Perfusion of the vacuole of living cells of Halicystis is described, the method employing two longitudinally fused capillaries as entrance and exit tubes. Natural sap, artificial sap, and sea water have been successfully perfused, with various additions and deficiencies, within the limits of physiological balance. In H. ovalis the P.D. remains positive and scarcely reduced in value when normal sea water, at pH 8.1, is perfused in the vacuole. In H. Osterhoutii the P.D. reverses in sign when the perfused solution has a higher pH than 6.5. In both cases a large P.D. persists when the solutions are the same on both sides of the protoplasm. In the absence of external gradients, there must be some internal gradient or asymmetry of the protoplasm itself to account for the P.D. Since appreciable currents are produced, there must be some metabolic activity as a source of energy. The higher normal P.D. in H. ovalis is not due to the higher KCl content of its sap (as earlier suggested by the author) since it persists nearly unchanged when sea water is substituted for sap. PMID:19872853

  9. Concentrations of metals and potential metal-binding compounds and speciation of Cd, Zn and Cu in phloem and xylem saps from castor bean plants (Ricinus communis) treated with four levels of cadmium.

    PubMed

    Hazama, Kenji; Nagata, Shinji; Fujimori, Tamaki; Yanagisawa, Shuichi; Yoneyama, Tadakatsu

    2015-06-01

    We examined the concentrations of metals (Cd, Zn, Cu, Fe and Mn) and potential metal-binding compounds [nicotianamine (NA), thiol compounds and citrate] in xylem and phloem saps from 4-week-old castor bean plants (Ricinus communis) treated with 0 (control), 0.1, 1.0, and 10 μM Cd for 3 weeks. Treatment with 0.1 and 1 μM Cd produced no visible damage, while 10 μM Cd retarded growth. Cadmium concentrations in both saps were higher than those in the culture solution at 0.1 μM, similar at 1.0 μM and lower at 10 μM. Cd at 10 μM reduced Cu and Fe concentrations in both saps. NA concentrations measured by capillary electrophoresis-mass spectrometry (MS) in xylem sap (20 μM) were higher than the Cu concentrations, and those in phloem sap (150 μM) were higher than those of Zn, Fe and Cu combined. Reduced glutathione concentrations differed in xylem and phloem saps (1-2 and 30-150 μM, respectively), but oxidized glutathione concentrations were similar. Phloem sap phytochelatin 2 concentration increased from 0.8 μM in controls to 8 μM in 10 μM Cd. Free citrate was 2-4 μM in xylem sap and 70-100 μM in phloem sap. Total bound forms of Cd in phloem and xylem saps from 1 μM Cd-treated plants were 54 and 8%, respectively. Treatment of phloem sap with proteinaseK reduced high-molecular compounds while increasing fractions of low-molecular Cd-thiol complexes. Zinc-NA, Fe-NA and Cu-NA were identified in the phloem sap fraction of control plants by electrospray ionization time-of-flight MS, and the xylem sap contained Cu-NA. PMID:25403762

  10. The Secreted Aspartyl Proteinases Sap1 and Sap2 Cause Tissue Damage in an In Vitro Model of Vaginal Candidiasis Based on Reconstituted Human Vaginal Epithelium

    PubMed Central

    Schaller, Martin; Bein, Matthias; Korting, Hans C.; Baur, Stefan; Hamm, Gerald; Monod, Michel; Beinhauer, Sabine; Hube, Bernhard

    2003-01-01

    Secreted aspartyl proteinases (Saps) contribute to the ability of Candida albicans to cause mucosal and disseminated infections. A model of vaginal candidiasis based on reconstituted human vaginal epithelium (RHVE) was used to study the expression and role of these C. albicans proteinases during infection and tissue damage of vaginal epithelium. Colonization of the RHVE by C. albicans SC5314 did not cause any visible epithelial damage 6 h after inoculation, although expression of SAP2, SAP9, and SAP10 was detected by reverse transcriptase PCR. However, significant epithelial damage was observed after 12 h, concomitant with the additional expression of SAP1, SAP4, and SAP5. Additional transcripts of SAP6 and SAP7 were detected at a later stage of the artificial infection (24 h). Similar SAP expression profiles were observed in three samples isolated from human patients with vaginal candidiasis. In experimental infection, secretion of antigens Sap1 to Sap6 by C. albicans was confirmed at the ultrastructural level by using polyclonal antisera raised against Sap1 to Sap6. Addition of the aspartyl proteinase inhibitors pepstatin A and the human immunodeficiency virus proteinase inhibitors ritonavir and amprenavir strongly reduced the tissue damage of the vaginal epithelia by C. albicans cells. Furthermore, SAP null mutants lacking either SAP1 or SAP2 had a drastically reduced potential to cause tissue damage even though SAP3, SAP4, and SAP7 were up-regulated in these mutants. In contrast the vaginopathic potential of mutants lacking SAP3 or SAP4 to SAP6 was not reduced compared to wild-type cells. These data provide further evidence for a crucial role of Sap1 and Sap2 in C. albicans vaginal infections. PMID:12761103

  11. Phosphatidylserine-selective targeting and anticancer effects of SapC-DOPS nanovesicles on brain tumors.

    PubMed

    Blanco, Víctor M; Chu, Zhengtao; Vallabhapurapu, Subrahmanya D; Sulaiman, Mahaboob K; Kendler, Ady; Rixe, Olivier; Warnick, Ronald E; Franco, Robert S; Qi, Xiaoyang

    2014-08-30

    Brain tumors, either primary (e.g., glioblastoma multiforme) or secondary (metastatic), remain among the most intractable and fatal of all cancers. We have shown that nanovesicles consisting of Saposin C (SapC) and dioleylphosphatidylserine (DOPS) are able to effectively target and kill cancer cells both in vitro and in vivo. These actions are a consequence of the affinity of SapC-DOPS for phosphatidylserine, an acidic phospholipid abundantly present in the outer membrane of a variety of tumor cells and tumor-associated vasculature. In this study, we first characterize SapC-DOPS bioavailability and antitumor effects on human glioblastoma xenografts, and confirm SapC-DOPS specificity towards phosphatidylserine by showing that glioblastoma targeting is abrogated after in vivo exposure to lactadherin, which binds phosphatidylserine with high affinity. Second, we demonstrate that SapC-DOPS selectively targets brain metastases-forming cancer cells both in vitro, in co-cultures with human astrocytes, and in vivo, in mouse models of brain metastases derived from human breast or lung cancer cells. Third, we demonstrate that SapC-DOPS have cytotoxic activity against metastatic breast cancer cells in vitro, and prolong the survival of mice harboring brain metastases. Taken together, these results support the potential of SapC-DOPS for the diagnosis and therapy of primary and metastatic brain tumors. PMID:25051370

  12. Phosphatidylserine-selective targeting and anticancer effects of SapC-DOPS nanovesicles on brain tumors

    PubMed Central

    Blanco, Víctor M.; Chu, Zhengtao; Vallabhapurapu, Subrahmanya D.; Sulaiman, Mahaboob K.; Kendler, Ady; Rixe, Olivier; Warnick, Ronald E.; Franco, Robert S.; Qi, Xiaoyang

    2014-01-01

    Brain tumors, either primary (e.g., glioblastoma multiforme) or secondary (metastatic), remain among the most intractable and fatal of all cancers. We have shown that nanovesicles consisting of Saposin C (SapC) and dioleylphosphatidylserine (DOPS) are able to effectively target and kill cancer cells both in vitro and in vivo. These actions are a consequence of the affinity of SapC-DOPS for phosphatidylserine, an acidic phospholipid abundantly present in the outer membrane of a variety of tumor cells and tumor-associated vasculature. In this study, we first characterize SapC-DOPS bioavailability and antitumor effects on human glioblastoma xenografts, and confirm SapC-DOPS specificity towards phosphatidylserine by showing that glioblastoma targeting is abrogated after in vivo exposure to lactadherin, which binds phosphatidylserine with high affinity. Second, we demonstrate that SapC-DOPS selectively targets brain metastases-forming cancer cells both in vitro, in co-cultures with human astrocytes, and in vivo, in mouse models of brain metastases derived from human breast or lung cancer cells. Third, we demonstrate that SapC-DOPS nanovesicles have cytotoxic activity against metastatic breast cancer cells in vitro, and prolong the survival of mice harboring brain metastases. Taken together, these results support the potential of SapC-DOPS for the diagnosis and therapy of primary and metastatic brain tumors. PMID:25051370

  13. Correlation of action potentials in adjacent neurons

    NASA Astrophysics Data System (ADS)

    Shneider, M. N.; Pekker, M.

    2015-12-01

    A possible mechanism for the synchronization of action potential propagation along a bundle of neurons (ephaptic coupling) is considered. It is shown that this mechanism is similar to the salutatory conduction of the action potential between the nodes of Ranvier in myelinated axons. The proposed model allows us to estimate the scale of the correlation, i.e., the distance between neurons in the nervous tissue, wherein their synchronization becomes possible. The possibility for experimental verification of the proposed model of synchronization is discussed.

  14. Screening Action Potentials: The Power of Light

    PubMed Central

    Kaestner, Lars; Lipp, Peter

    2011-01-01

    Action potentials reflect the concerted activity of all electrogenic constituents in the plasma membrane during the excitation of a cell. Therefore, the action potential is an integrated read out and a promising parameter to detect electrophysiological failures or modifications thereof in diagnosis as well as in drug screens. Cellular action potentials can be recorded by optical approaches. To fulfill the pre-requirements to scale up for, e.g., pharmacological screens the following preparatory work has to be provided: (i) model cells under investigation need to represent target cells in the best possible manner; (ii) optical sensors that can be either small molecule dyes or genetically encoded potential probes need to provide a reliable read out with minimal interaction with the naive behavior of the cells and (iii) devices need to be capable to stimulate the cells, read out the signals with the appropriate speed as well as provide the capacity for a sufficient throughput. Here we discuss several scenarios for all three categories in the field of cardiac physiology and pharmacology and provide a perspective to use the power of light in screening cardiac action potentials. PMID:21847381

  15. Introducing the Action Potential to Psychology Students

    ERIC Educational Resources Information Center

    Simon-Dack, Stephanie L.

    2014-01-01

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

  16. Transferrin: structure, function and potential therapeutic actions.

    PubMed

    Gomme, Peter T; McCann, Karl B; Bertolini, Joseph

    2005-02-15

    There are many proteins that can multi-task. Transferrin, widely known as an iron-binding protein, is one such example of a multi-tasking protein. In this review, the multiple biological actions of transferrin, including its growth and cytoprotective activities, are discussed with the view of highlighting the potential therapeutic applications of this protein. PMID:15708745

  17. Mechanical surface waves accompany action potential propagation.

    PubMed

    El Hady, Ahmed; Machta, Benjamin B

    2015-01-01

    Many diverse studies have shown that a mechanical displacement of the axonal membrane accompanies the electrical pulse defining the action potential (AP). We present a model for these mechanical displacements as arising from the driving of surface wave modes in which potential energy is stored in elastic properties of the neuronal membrane and cytoskeleton while kinetic energy is carried by the axoplasmic fluid. In our model, these surface waves are driven by the travelling wave of electrical depolarization characterizing the AP, altering compressive electrostatic forces across the membrane. This driving leads to co-propagating mechanical displacements, which we term Action Waves (AWs). Our model allows us to estimate the shape of the AW that accompanies any travelling wave of voltage, making predictions that are in agreement with results from several experimental systems. Our model can serve as a framework for understanding the physical origins and possible functional roles of these AWs. PMID:25819404

  18. Mechanical surface waves accompany action potential propagation

    NASA Astrophysics Data System (ADS)

    El Hady, Ahmed; Machta, Benjamin B.

    2015-03-01

    Many diverse studies have shown that a mechanical displacement of the axonal membrane accompanies the electrical pulse defining the action potential (AP). We present a model for these mechanical displacements as arising from the driving of surface wave modes in which potential energy is stored in elastic properties of the neuronal membrane and cytoskeleton while kinetic energy is carried by the axoplasmic fluid. In our model, these surface waves are driven by the travelling wave of electrical depolarization characterizing the AP, altering compressive electrostatic forces across the membrane. This driving leads to co-propagating mechanical displacements, which we term Action Waves (AWs). Our model allows us to estimate the shape of the AW that accompanies any travelling wave of voltage, making predictions that are in agreement with results from several experimental systems. Our model can serve as a framework for understanding the physical origins and possible functional roles of these AWs.

  19. Interactions between a Sap Beetle, Sabal Palm, Scale Insect, Filamentous Fungi and Yeast, with Discovery of Potential Antifungal Compounds

    PubMed Central

    Cline, Andrew R.; Skelley, Paul E.; Kinnee, Scott A.; Rooney-Latham, Suzanne; Winterton, Shaun L.; Borkent, Christopher J.; Audisio, Paolo

    2014-01-01

    The multi-trophic relationship between insects, yeast, and filamentous fungi is reported on sabal palm (Sabal palmetto (Walter) Lodd. ex Schult. & Schult. f.). Gut content analyses and observations of adult and larval feeding of the sap beetle Brachypeplus glaber LeConte indicate that niche partitioning of fungal food substrata occurs between adults and larvae. This is the first report of specific mycophagous niche partitioning among beetle life stages based on gut content analyses. Fungi isolated from the beetle gut of adults, larvae, and pupae include species of Fusarium Link, Cladosporium Link, and Penicillium Link, which were differentially ingested by larvae and adults; Fusarium solani and Penicillium species in larvae, whereas F. oxysoproum, F. verticillioides, and Cladosporium in adults. These data indicate the first species-level host data for Brachypeplus Erichson species. Fusarium proliferatum (Matsush.) Nirenberg was the most commonly occurring fungal gut component, being isolated from the palm as well as gut of larvae, pupae, and adults; representing a commonly shared food resource. One species of yeast, Meyerozyma caribbica (Vaughan-Mart. et al.) Kurtzman & Suzuki (basionym = Pichia caribbica), was isolated from all life stages and is likely responsible for anti-fungal properties observed in the pupae and represents a promising source of antifungal compounds; rearing and diagnostic protocols are provided to aid biomedical researchers. Feeding and cleaning behaviors are documented using time-lapse video-micrography, and discussed in a behavioral and functional morphological context. Adults spent long periods feeding, often >1/3 of the two-hour observation period. A generic adult body posture was observed during feeding, and included substrate antennation before and after ingestion. Adult grooming behaviors were manifested in distinct antennal and tarsal cleaning mechanisms. Larval behaviors were different from adults, and larvae feeding on Fusarium

  20. Ca channel gating during cardiac action potentials.

    PubMed

    Mazzanti, M; DeFelice, L J

    1990-10-01

    How do Ca channels conduct Ca ions during the cardiac action potential? We attempt to answer this question by applying a two-microelectrode technique, previously used for Na and K currents, in which we record the patch current and the action potential at the same time (Mazzanti, M., and L. J. DeFelice. 1987. Biophys. J. 12:95-100, and 1988. Biophys. J. 54:1139-1148; Wellis, D., L. J. DeFelice, and M. Mazzanti. 1990. Biophys. J. 57:41-48). In this paper, we also compare the action currents obtained by the technique with the step-protocol currents obtained during standard voltage-clamp experiments. Individual Ca channels were measured in 10 mM Ca/1 Ba and 10 mM Ba. To describe part of our results, we use the nomenclature introduced by Hess, P., J. B. Lansman, and R. W. Tsien (1984. Nature (Lond.). 311:538-544). With Ba as the charge carrier, Ca channel kinetics convert rapidly from long to short open times as the patch voltage changes from 20 to -20 mV. This voltage-dependent conversion occurs during action potentials and in step-protocol experiments. With Ca as the charge carrier, the currents are brief at all voltages, and it is difficult to define either the number of channels in the patch or the conductance of the individual channels. Occasionally, however, Ca-conducting channels spontaneously convert to long-open-time kinetics (in Hess et al., 1984, notation, mode 2). When this happens, which is about once in every 100beats, there usually appears to be only one channel in the patch. In this rare configuration, the channel is open long enough to measure its conductance in 10 Ca/ 1 Ba. The value is 8-10 pS, which is about half the conductance in Ba. Because the long openings occur so infrequently with Ca as the charge carrier, they contribute negligibly to the average Ca current at any particular time during an action potential. However, the total number of Ca ions entering during these long openings may be significant when compared to the number entering by the

  1. Structure and genotypic plasticity of the Campylobacter fetus sap locus.

    PubMed

    Tu, Zheng-Chao; Wassenaar, Trudy M; Thompson, Stuart A; Blaser, Martin J

    2003-05-01

    The Campylobacter fetus surface layer proteins (SLPs), encoded by five to nine sapA homologues, are major virulence factors. To characterize the sapA homologues further, a 65.9 kb C. fetus genomic region encompassing the sap locus from wild-type strain 23D was completely sequenced and analysed; 44 predicted open reading frames (ORFs) were recognized. The 53.8 kb sap locus contained eight complete and one partial sapA homologues, varying from 2769 to 3879 bp, sharing conserved 553-2622 bp 5' regions, with partial sharing of 5' and 3' non-coding regions. All eight sapA homologues were expressed in Escherichia coli as antigenic proteins and reattached to the surface of SLP- strain 23B, indicating their conserved function. Analysis of the sap homologues indicated three phylogenetic groups. Promoter-specific polymerase chain reactions (PCRs) and sapA homologue-specific reverse transcription (RT)-PCRs showed that the unique sapA promoter can potentially express all eight sapA homologues. Reciprocal DNA recombination based on the 5' conserved regions can involve each of the eight sapA homologues, with frequencies from 10(-1) to 10(-3). Intragenic recombination between sapA7 and sapAp8, mediated by their conserved regions with a 10(-1)-10(-2) frequency, allows the formation of new sap homologues. As divergent SLP C-termini possess multiple antigenic sites, their reciprocal recombination behind the unique sap promoter leads to continuing antigenic variation. PMID:12694614

  2. Mechanical Surface Waves Accompany Action Potential Propagation

    NASA Astrophysics Data System (ADS)

    Machta, Benjamin; El Hady, Ahmed

    2015-03-01

    The action potential (AP) is the basic mechanism by which information is transmitted along neuronal axons. Although the excitable nature of axons is understood to be primarily electrical, many experimental studies have shown that a mechanical displacement of the axonal membrane co-propagates with the electrical signal. While the experimental evidence for co-propagating mechanical waves is diverse and compelling, there is no consensus for their physical underpinnings. We present a model in which these mechanical displacements arise from the driving of mechanical surface waves, in which potential energy is stored in elastic deformations of the neuronal membrane and cytoskeleton while kinetic energy is stored in the movement of the axoplasmic fluid. In our model these surface waves are driven by the traveling wave of electrical depolarization that characterizes the AP, altering the electrostatic forces across the membrane as it passes. Our model allows us to predict the shape of the displacement that should accompany any traveling wave of voltage, including the well-characterized AP. We expect our model to serve as a framework for understanding the physical origins and possible functional roles of these AWs in neurobiology. See Arxiv/1407.7600

  3. Tree hydraulics: how sap rises

    NASA Astrophysics Data System (ADS)

    Denny, Mark

    2012-01-01

    Trees transport water from roots to crown—a height that can exceed 100 m. The physics of tree hydraulics can be conveyed with simple fluid dynamics based upon the Hagen-Poiseuille equation and Murray's law. Here the conduit structure is modelled as conical pipes and as branching pipes. The force required to lift sap is generated mostly by transpiration or capillary action; we investigate the effectiveness of both these forces for the two conduit architectures considered. The level of analysis is appropriate for undergraduates. The subject is of broad interest because it provides a naturally-occurring example of an unusual metastable state of matter: liquid under tension.

  4. Action potential broadening in a presynaptic channelopathy.

    PubMed

    Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E; Kullmann, Dimitri M

    2016-01-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca(2+) influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction. PMID:27381274

  5. Action potential broadening in a presynaptic channelopathy

    PubMed Central

    Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E.; Kullmann, Dimitri M.

    2016-01-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction. PMID:27381274

  6. Action potential broadening in a presynaptic channelopathy

    NASA Astrophysics Data System (ADS)

    Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E.; Kullmann, Dimitri M.

    2016-07-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction.

  7. Teachers in Action Research: Assumptions and Potentials

    ERIC Educational Resources Information Center

    Li, Yuen-Ling

    2008-01-01

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

  8. Microcomputer program for automated action potential waveform analysis.

    PubMed

    Soto, E; Salceda, E; Cruz, R; Ortega, A; Vega, R

    2000-06-01

    A program for action potential waveform analysis based on a PC compatible computer is described. Single or averaged action potentials are analyzed by obtaining its first derivative and using criteria which allow automatic measurement of several action potential components, including: depolarization rate, repolarization rate, amplitude, duration, resting membrane potential and afterhyperpolarization amplitude and slope. Data can be imported from pClamp (Axon Instruments) and exported to other software such as Excel, Sigmaplot and MatLab for example. PMID:10764940

  9. 7 CFR 1437.107 - Maple sap.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Yield Coverage Using Actual Production History § 1437.107 Maple sap. (a) NAP assistance for maple sap is... maple sap. (g) The actual production history for maple sap shall be recorded on the basis of gallons...

  10. 7 CFR 1437.107 - Maple sap.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... limited to maple sap produced on private property for sale as sap or syrup. Eligible maple sap must be... sap must be established for the value of the sap before processing into syrup. If price data is available only for maple syrup, this data must be converted to a maple sap basis. The wholesale price for...

  11. 7 CFR 1437.107 - Maple sap.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... limited to maple sap produced on private property for sale as sap or syrup. Eligible maple sap must be... sap must be established for the value of the sap before processing into syrup. If price data is available only for maple syrup, this data must be converted to a maple sap basis. The wholesale price for...

  12. 7 CFR 1437.107 - Maple sap.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... limited to maple sap produced on private property for sale as sap or syrup. Eligible maple sap must be... sap must be established for the value of the sap before processing into syrup. If price data is available only for maple syrup, this data must be converted to a maple sap basis. The wholesale price for...

  13. 7 CFR 1437.107 - Maple sap.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... limited to maple sap produced on private property for sale as sap or syrup. Eligible maple sap must be... sap must be established for the value of the sap before processing into syrup. If price data is available only for maple syrup, this data must be converted to a maple sap basis. The wholesale price for...

  14. From Sap to Syrup

    ERIC Educational Resources Information Center

    Bjork, Janna

    2005-01-01

    Warm days, cold nights, melting snow-signs winter is waning and spring is nearing. Though winter may just be getting started in some areas, it's always fun to appreciate the good things about winter, including the special time at the end of winter in New England known as "sugaring time." The sap starts flowing in the sugar maples, and the process…

  15. (BOREAS) BOREAS TE-7 Sap Flow Data

    NASA Technical Reports Server (NTRS)

    Hall, Forrest G. (Editor); Papagno, Andrea (Editor); Hogg, E. H.; Hurdle, P. A.

    2000-01-01

    The BOREAS TE-7 team collected data sets in support of its efforts to characterize and interpret information on the sap flow of boreal vegetation. The heat pulse method was used to monitor sap flow and to estimate rates of transpiration from aspen, black spruce, and mixed wood forests at the SSAOA, MIX, SSA-OBS. and Batoche sites in Saskatchewan, Canada. Measurements were made at the various sites from May to October 1994, May to October 1995, and April to October 1996. A scaling procedure was used to estimate canopy transpiration rates from the sap flow measurements. The data were stored in tabular ASCII files. Analyses to date show a tendency for sap flow in aspen to remain remarkably constant over a wide range of environmental conditions VPD from 1.0 to 4.8 kPa and solar radiation less than 400 W/sq m). For forests with high aerodynamic conductance, the results would indicate an inverse relationship between stomatal conductance and VPD, for VPD greater than 1 kPa. A possible interpretation is that stomata are operating to maintain leaf water potentials above a critical minimum value, which in turn places a maximum value on the rate of sap flow that can be sustained by the tree. The data files are available on a CD-ROM (see document number 20010000884), or from the Oak Ridge National Laboratory (ORNL) Distrobuted Activity Archive Center (DAAC).

  16. Simulating nectarine tree transpiration and dynamic water storage from responses of leaf conductance to light and sap flow to stem water potential and vapor pressure deficit.

    PubMed

    Paudel, Indira; Naor, Amos; Gal, Yoni; Cohen, Shabtai

    2015-04-01

    For isohydric trees mid-day water uptake is stable and depends on soil water status, reflected in pre-dawn leaf water potential (Ψpd) and mid-day stem water potential (Ψmd), tree hydraulic conductance and a more-or-less constant leaf water potential (Ψl) for much of the day, maintained by the stomata. Stabilization of Ψl can be represented by a linear relationship between canopy resistance (Rc) and vapor pressure deficit (D), and the slope (BD) is proportional to the steady-state water uptake. By analyzing sap flow (SF), meteorological and Ψmd measurements during a series of wetting and drying (D/W) cycles in a nectarine orchard, we found that for the range of Ψmd relevant for irrigated orchards the slope of the relationship of Rc to D, BD is a linear function of Ψmd. Rc was simulated using the above relationships, and its changes in the morning and evening were simulated using a rectangular hyperbolic relationship between leaf conductance and photosynthetic irradiance, fitted to leaf-level measurements. The latter was integrated with one-leaf, two-leaf and integrative radiation models, and the latter gave the best results. Simulated Rc was used in the Penman-Monteith equation to simulate tree transpiration, which was validated by comparing with SF from a separate data set. The model gave accurate estimates of diurnal and daily total tree transpiration for the range of Ψmds used in regular and deficit irrigation. Diurnal changes in tree water content were determined from the difference between simulated transpiration and measured SF. Changes in water content caused a time lag of 90-105 min between transpiration and SF for Ψmd between -0.8 and -1.55 MPa, and water depletion reached 3 l h(-1) before noon. Estimated mean diurnal changes in water content were 5.5 l day(-1) tree(-1) at Ψmd of -0.9 MPa and increased to 12.5 l day(-1) tree(-1) at -1.45 MPa, equivalent to 6.5 and 16.5% of daily tree water use, respectively. Sixteen percent

  17. [Individualised medicine - potentials and need for action].

    PubMed

    Hüsing, Bärbel

    2010-01-01

    Individualised medicine aims to classify seemingly homogenous patient groups into smaller clinically relevant subgroups (stratification) in order to be able to treat them differently, thus contributing to the improvement of health care services, to the prevention of inappropriate treatments and to the reduction of adverse effects. This article summarises a report to the Office of Technology Assessment at the German Bundestag and points out the need for action for transferring individualised medicine from research to clinical application: significant incentives are required in order to prove the clinical validity of newly identified biomarkers of complex diseases. Sustainable business models for the joint development of new applications by research institutions, biotechnology companies, pharmaceuticals and medical devices companies are required. Instruments for transferring knowledge from bench to bedside (translational research) and the existing regulatory framework should be further developed in order to strike an appropriate balance between incentives for accelerating the transfer of innovative technology to the health care sector while, at the same time, ensuring patient safety, high quality and clinical utility. PMID:21147435

  18. Selective effects of an octopus toxin on action potentials

    PubMed Central

    Dulhunty, Angela; Gage, Peter W.

    1971-01-01

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

  19. The effects of temperature on human compound action potentials.

    PubMed Central

    Bolton, C F; Sawa, G M; Carter, K

    1981-01-01

    The upper limbs of 10 healthy subjects were cooled and then warmed over physiological temperature ranges. The compound action potentials of median digital nerves, median sensory nerve at the wrist, radial sensory nerve at the wrist, and median thenar muscle, all showed progressive reduction in latency, amplitude, duration and area during rising temperature. Our studies suggest that the sensory compound action potential changes occur predominantly because of the summated effects of reduction in the duration of the action potentials of single myelinated fibres, although disproportionate increase in the conduction velocity of larger myelinated fibres also plays a role. Images PMID:7264687

  20. Synchronization of action potentials during low-magnesium-induced bursting

    PubMed Central

    Johnson, Sarah E.; Hudson, John L.

    2015-01-01

    The relationship between mono- and polysynaptic strength and action potential synchronization was explored using a reduced external Mg2+ model. Single and dual whole cell patch-clamp recordings were performed in hippocampal cultures in three concentrations of external Mg2+. In decreased Mg2+ medium, the individual cells transitioned to spontaneous bursting behavior. In lowered Mg2+ media the larger excitatory synaptic events were observed more frequently and fewer transmission failures occurred, suggesting strengthened synaptic transmission. The event synchronization was calculated for the neural action potentials of the cell pairs, and it increased in media where Mg2+ concentration was lowered. Analysis of surrogate data where bursting was present, but no direct or indirect connections existed between the neurons, showed minimal action potential synchronization. This suggests the synchronization of action potentials is a product of the strengthening synaptic connections within neuronal networks. PMID:25609103

  1. Intracellular recording of action potentials by nanopillar electroporation

    NASA Astrophysics Data System (ADS)

    Xie, Chong; Lin, Ziliang; Hanson, Lindsey; Cui, Yi; Cui, Bianxiao

    2012-03-01

    Action potentials have a central role in the nervous system and in many cellular processes, notably those involving ion channels. The accurate measurement of action potentials requires efficient coupling between the cell membrane and the measuring electrodes. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios. However, the invasive nature of intracellular methods usually limits the recording time to a few hours, and their complexity makes it difficult to simultaneously record more than a few cells. Extracellular recording methods, such as multielectrode arrays and multitransistor arrays, are non-invasive and allow long-term and multiplexed measurements. However, extracellular recording sacrifices the one-to-one correspondence between the cells and electrodes, and also suffers from significantly reduced signal strength and quality. Extracellular techniques are not, therefore, able to record action potentials with the accuracy needed to explore the properties of ion channels. As a result, the pharmacological screening of ion-channel drugs is usually performed by low-throughput intracellular recording methods. The use of nanowire transistors, nanotube-coupled transistors and micro gold-spine and related electrodes can significantly improve the signal strength of recorded action potentials. Here, we show that vertical nanopillar electrodes can record both the extracellular and intracellular action potentials of cultured cardiomyocytes over a long period of time with excellent signal strength and quality. Moreover, it is possible to repeatedly switch between extracellular and intracellular recording by nanoscale electroporation and resealing processes. Furthermore, vertical nanopillar electrodes can detect subtle changes in action

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

    PubMed

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

    2015-01-01

    The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon's action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1-40 in incremental steps of 1) and the node drive potential (0-2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxon's programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems. PMID:26539072

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

    PubMed Central

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

    2015-01-01

    The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon's action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1–40 in incremental steps of 1) and the node drive potential (0–2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxon's programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems. PMID:26539072

  4. Opposing actions of the synapse-associated protein of 97-kDa molecular weight (SAP97) and Disrupted in Schizophrenia 1 (DISC1) on Wnt/β-catenin signaling.

    PubMed

    Boccitto, M; Doshi, S; Newton, I P; Nathke, I; Neve, R; Dong, F; Mao, Y; Zhai, J; Zhang, L; Kalb, R

    2016-06-21

    It has been suggested that synapse-associated protein of 97-kDa molecular weight (SAP97) is a susceptibility factor for childhood and adult neuropsychiatric disorders. SAP97 is a scaffolding protein that shares direct and indirect binding partners with the Disrupted in Schizophrenia 1 (DISC1) gene product, a gene with strong association with neuropsychiatric disorders. Here we investigated the possibility that these two proteins converge upon a common molecular pathway. Since DISC1 modifies Wnt/β-catenin signaling via changes in glycogen synthase kinase 3 beta (GSK3β) phosphorylation, we asked if SAP97 impacts Wnt/β-catenin signaling and GSK3β phosphorylation. We find that SAP97 acts as inhibitor of Wnt signaling activity and can suppress the stimulatory effects of DISC1 on β-catenin transcriptional activity. Reductions in SAP97 abundance also decrease GSK3β phosphorylation. In addition, we find that over expression of DISC1 leads to an increase in the abundance of SAP97, by inhibiting its proteasomal degradation. Our findings suggest that SAP97 and DISC1 contribute to maintaining Wnt/β-catenin signaling activity within a homeostatic range by regulating GSK3β phosphorylation. PMID:27026592

  5. Measuring sap flow in plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sap flow measurements provide a powerful tool for quantifying plant water use and monitoring qualitative physiological responses of plants to environmental conditions. As such, sap flow methods are widely employed to invesitgate the agronomic, ecological and hydrological outcomes of plant growth. T...

  6. Membrane, action, and oscillatory potentials in simulated protocells.

    PubMed

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

    1982-12-01

    Electrical membrane potentials, oscillations, and action potentials are observed in proteinoid microspheres impaled with (3 M KC1) microelectrodes. Although effects are of greater magnitude when the vesicles contain glycerol and natural or synthetic lecithin, the results in the purely synthetic thermal protein structures are substantial, attaining 20 mV amplitude in some cases. The results add the property of electrical potential to the other known properties of proteinoid microspheres, in their role as models for protocells. PMID:7162535

  7. Membrane, action, and oscillatory potentials in simulated protocells

    NASA Astrophysics Data System (ADS)

    Przybylski, Aleksander T.; Stratten, Wilford P.; Syren, Robert M.; Fox, Sidney W.

    1982-12-01

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

  8. Membrane, action, and oscillatory potentials in simulated protocells

    NASA Technical Reports Server (NTRS)

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

    1982-01-01

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

  9. Far-field potentials recorded from action potentials and from a tripole in a hemicylindrical volume.

    PubMed

    Jewett, D L; Deupree, D L

    1989-05-01

    There is growing evidence in support of the hypothesis that far-field potentials are recorded when action potentials encounter discontinuities in the surrounding volume. The present study found further support for this hypothesis using two methods of experimentation. The first method recorded potentials when the action potential from an isolated bullfrog sciatic nerve in a hemicylindrical volume (i) encountered a change in the shape of the surrounding volume, (ii) crossed a boundary between 2 volumes of differing resistivities, (iii) reached a bend in the nerve, or (iv) reached the functional end of the nerve. In the second method, potentials were recorded when an electrical tripole, constructed in a way to produce the electrical equivalent of an action potential, encountered the same discontinuities as well as when it was configured to simulate a curved nerve. These results are consistent with the hypothesis that dipole components of an action potential predominant in far-field recordings. PMID:2469568

  10. Action prediction based on anticipatory brain potentials during simulated driving

    NASA Astrophysics Data System (ADS)

    Khaliliardali, Zahra; Chavarriaga, Ricardo; Gheorghe, Lucian Andrei; Millán, José del R.

    2015-12-01

    Objective. The ability of an automobile to infer the driver’s upcoming actions directly from neural signals could enrich the interaction of the car with its driver. Intelligent vehicles fitted with an on-board brain-computer interface able to decode the driver’s intentions can use this information to improve the driving experience. In this study we investigate the neural signatures of anticipation of specific actions, namely braking and accelerating. Approach. We investigated anticipatory slow cortical potentials in electroencephalogram recorded from 18 healthy participants in a driving simulator using a variant of the contingent negative variation (CNV) paradigm with Go and No-go conditions: count-down numbers followed by ‘Start’/‘Stop’ cue. We report decoding performance before the action onset using a quadratic discriminant analysis classifier based on temporal features. Main results. (i) Despite the visual and driving related cognitive distractions, we show the presence of anticipatory event related potentials locked to the stimuli onset similar to the widely reported CNV signal (with an average peak value of -8 μV at electrode Cz). (ii) We demonstrate the discrimination between cases requiring to perform an action upon imperative subsequent stimulus (Go condition, e.g. a ‘Red’ traffic light) versus events that do not require such action (No-go condition; e.g. a ‘Yellow’ light); with an average single trial classification performance of 0.83 ± 0.13 for braking and 0.79 ± 0.12 for accelerating (area under the curve). (iii) We show that the centro-medial anticipatory potentials are observed as early as 320 ± 200 ms before the action with a detection rate of 0.77 ± 0.12 in offline analysis. Significance. We show for the first time the feasibility of predicting the driver’s intention through decoding anticipatory related potentials during simulated car driving with high recognition rates.

  11. Propagation of Action Potentials: An Active Participation Exercise.

    ERIC Educational Resources Information Center

    Felsten, Gary

    1998-01-01

    Describes an active participation exercise that demonstrates the propagation of action potentials (the ability to transmit information through the neural network, dependent upon chemical interactions in the brain). Students assume the structure and function of the network by lining up around the room and communicating through hand signals and…

  12. Passive Responses Resembling Action Potentials: A Device for the Classroom

    ERIC Educational Resources Information Center

    Newman, Ian A.; Pickard, Barbara G.

    1975-01-01

    Describes the construction and operation of a network of entirely passive electrical components that gives a response to an electrical shock similar to an action potential. The network of resistors, capacitors, and diodes was developed to produce responses that would mimic those observed, for example, when a dark-grown pea epicotyl is shocked…

  13. Sodium and potassium conductance changes during a membrane action potential.

    PubMed

    Bezanilla, F; Rojas, E; Taylor, R E

    1970-12-01

    1. A method for turning a membrane potential control system on and off in less than 10 musec is described. This method was used to record membrane currents in perfused giant axons from Dosidicus gigas and Loligo forbesi after turning on the voltage clamp system at various times during the course of a membrane action potential.2. The membrane current measured just after the capacity charging transient was found to have an almost linear relation to the controlled membrane potential.3. The total membrane conductance taken from these current-voltage curves was found to have a time course during the action potential similar to that found by Cole & Curtis (1939).4. The instantaneous current voltage curves were linear enough to make it possible to obtain a good estimate of the individual sodium and potassium channel conductances, either algebraically or by clamping to the sodium, or potassium, reversal potentials. Good general agreement was obtained with the predictions of the Hodgkin-Huxley equations.5. We consider these results to constitute the first direct experimental demonstration of the conductance changes to sodium and potassium during the course of an action potential. PMID:5505231

  14. [Ion channels and action potentials in olfactory receptor cells].

    PubMed

    Kawai, Fusao; Miyachi, Ei-ichi

    2007-11-01

    The first step in olfactory sensation involves the binding of odorant molecules to specific receptor proteins on the ciliary surface of olfactory receptor cells (ORCs). Odorant receptors coupled to G-proteins activate adenylyl cyclase leading to the generation of cAMP, which directly gates a cyclic nucleotide-gated cationic channel in the ciliary membrane. This initial excitation causes a slow and graded depolarizing voltage change, which is encoded into a train of action potentials. Action potentials of ORCs are generated by voltage-gated Na- currents and T-type Ca2- currents in the somatic membrane. Isolated ORCs that have lost their cilia during the dissociation procedure are known to exhibit spike frequency accommodation by injecting the steady current. This raises the possibility that somatic ionic channels in ORCs may serve for odor adaptation at the level of spike encoding, although odor adaptation is mainly accomplished by the ciliary transduction machinery. This review discusses current knowledge concerning the mechanisms of spike generation in ORCs. It also reviews how neurotransmitters and hormones modulate ionic currents and action potentials in ORCs. PMID:18154041

  15. Warm Body Temperature Facilitates Energy Efficient Cortical Action Potentials

    PubMed Central

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

    2012-01-01

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

  16. SapC-DOPS Nanovesicles as Targeted Therapy for Lung Cancer

    PubMed Central

    Zhao, Shuli; Chu, Zhengtao; Blanco, Victor M.; Nie, Yunzhong; Hou, Yayi; Qi, Xiaoyang

    2014-01-01

    Lung cancer is the deadliest type of cancer for both men and women. In this study, we evaluate the in vitro and in vivo efficacy of a biotherapeutic agent composed of a lysosomal protein (Saposin C, SapC) and a phospholipid (dioleoylphosphatidylserine, DOPS) which can be assembled into nanovesicles (SapC-DOPS) with selective antitumor activity. SapC-DOPS targets phosphatidylserine, an anionic phospholipid preferentially exposed in the surface of cancer cells and tumor-associated vasculature. Since binding of SapC to phosphatidylserine is favored at acidic pHs, and the latter characterizes the milieu of many solid tumors, we tested the effect of pH on the binding capacity of SapC-DOPS to lung tumor cells. Results showed that SapC-DOPS binding to cancer cells was more pronounced at low pH. Viability assays on a panel of human lung tumor cells showed that SapC-DOPS cytotoxicity was positively correlated with cell surface phosphatidylserine levels, whereas mitochondrial membrane potential measurements were consistent with apoptosis-related cell death. Using a fluorescence tracking method in live mice, we show that SapC-DOPS specifically targets human lung cancer xenografts, and that systemic therapy with SapC-DOPS induces tumor apoptosis and significantly inhibits tumor growth. These results suggest that SapC-DOPS nanovesicles are a promising treatment option for lung cancer. PMID:25670331

  17. SapC-DOPS nanovesicles as targeted therapy for lung cancer.

    PubMed

    Zhao, Shuli; Chu, Zhengtao; Blanco, Victor M; Nie, Yunzhong; Hou, Yayi; Qi, Xiaoyang

    2015-02-01

    Lung cancer is the deadliest type of cancer for both men and women. In this study, we evaluate the in vitro and in vivo efficacy of a biotherapeutic agent composed of a lysosomal protein (Saposin C, SapC) and a phospholipid (dioleoylphosphatidylserine, DOPS), which can be assembled into nanovesicles (SapC-DOPS) with selective antitumor activity. SapC-DOPS targets phosphatidylserine, an anionic phospholipid preferentially exposed in the surface of cancer cells and tumor-associated vasculature. Because binding of SapC to phosphatidylserine is favored at acidic pHs, and the latter characterizes the milieu of many solid tumors, we tested the effect of pH on the binding capacity of SapC-DOPS to lung tumor cells. Results showed that SapC-DOPS binding to cancer cells was more pronounced at low pH. Viability assays on a panel of human lung tumor cells showed that SapC-DOPS cytotoxicity was positively correlated with cell surface phosphatidylserine levels, whereas mitochondrial membrane potential measurements were consistent with apoptosis-related cell death. Using a fluorescence tracking method in live mice, we show that SapC-DOPS specifically targets human lung cancer xenografts, and that systemic therapy with SapC-DOPS induces tumor apoptosis and significantly inhibits tumor growth. These results suggest that SapC-DOPS nanovesicles are a promising treatment option for lung cancer. PMID:25670331

  18. Variability of sap flow on forest hillslopes: patterns and controls

    NASA Astrophysics Data System (ADS)

    Hassler, Sibylle; Blume, Theresa

    2013-04-01

    Sap flow in trees is an essential variable in integrated studies of hydrologic fluxes. It gives indication of transpiration rates for single trees and, with a suitable method of upscaling, for whole stands. This information is relevant for hydrologic and climate models, especially for the prediction of change in water fluxes in the soil-plant-atmosphere continuum under climate change. To this end, we do not only need knowledge concerning the response of sapflow to atmospheric forcing but also an understanding of the main controls on its spatial variability. Our study site consists of several subcatchments of the Attert basin in Luxembourg underlain by schists of the Ardennes massif. Within these subcatchments we measure sap flow in more than 20 trees on a range of forested hillslopes covered by a variety of temperate deciduous tree species such as beech, oak, hornbeam and maple as well as conifers such as firs. Our sap flow sensors are based on the heat pulse velocity method and consist of three needles, one needle acting as the heating device and the other two holding three thermistors each, enabling us to simultaneously measure sap flow velocity at three different depths within the tree. In close proximity to the trees we collect additional data on soil moisture, matric potential and groundwater levels. First results show that the sensor design seems promising for an upscaling of the measured sap flow velocities to sap flow at the tree level. The maximum depth of actively used sapwood as well as the decrease in sap flow velocity with increasing depth in the tree can be determined by way of the three thermistors. Marked differences in sap flow velocity profiles are visible between the different species, resulting in differences in sap flow for trees of similar diameter. We examine the range of tree sap flow values and variation due to species, size class, slope position and exposition and finally relate them to the dynamics of soil moisture conditions with the

  19. A portable NMR sensor to measure dynamic changes in the amount of water in living stems or fruit and its potential to measure sap flow.

    PubMed

    Windt, Carel W; Blümler, Peter

    2015-04-01

    Nuclear magnetic resonance (NMR) and NMR imaging (magnetic resonance imaging) offer the possibility to quantitatively and non-invasively measure the presence and movement of water. Unfortunately, traditional NMR hardware is expensive, poorly suited for plants, and because of its bulk and complexity, not suitable for use in the field. But does it need to be? We here explore how novel, small-scale portable NMR devices can be used as a flow sensor to directly measure xylem sap flow in a poplar tree (Populus nigra L.), or in a dendrometer-like fashion to measure dynamic changes in the absolute water content of fruit or stems. For the latter purpose we monitored the diurnal pattern of growth, expansion and shrinkage in a model fruit (bean pod, Phaseolus vulgaris L.) and in the stem of an oak tree (Quercus robur L.). We compared changes in absolute stem water content, as measured by the NMR sensor, against stem diameter variations as measured by a set of conventional point dendrometers, to test how well the sensitivities of the two methods compare and to investigate how well diurnal changes in trunk absolute water content correlate with the concomitant diurnal variations in stem diameter. Our results confirm the existence of a strong correlation between the two parameters, but also suggest that dynamic changes in oak stem water content could be larger than is apparent on the basis of the stem diameter variation alone. PMID:25595754

  20. Action potentials of curved nerves in finite limbs.

    PubMed

    Xiao, S; McGill, K C; Hentz, V R

    1995-06-01

    Previous simulations of volume-conducted nerve-fiber action-potentials have modeled the limb as semi-infinite or circularly cylindrical, and the fibers as straight lines parallel to the limb surface. The geometry of actual nerves and limbs, however, can be considerably more complicated. This paper presents a general method for computing the potentials of fibers with arbitrary paths in arbitrary finite limbs. It involves computing the propagating point-source response (PPSR), which is the potential arising from a single point source (dipole or tripole) travelling along the fiber. The PPSR can be applied to fibers of different conduction velocities by simple dilation or compression. The method is illustrated for oblique and spiralling nerve fibers. Potentials from oblique fibers are shown to be different for orthodromic and antidromic propagation. Such results show that the straight-line models are not always adequate for nerves with anatomical amounts of curvature. PMID:7790016

  1. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties

    PubMed Central

    Casale, Amanda E.; Foust, Amanda J.; Bal, Thierry

    2015-01-01

    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca2+-activated K+ channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. SIGNIFICANCE STATEMENT Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons

  2. Comparative analysis of the ternary complex factors Elk-1, SAP-1a and SAP-2 (ERP/NET).

    PubMed

    Price, M A; Rogers, A E; Treisman, R

    1995-06-01

    A transcription factor ternary complex composed of Serum Response Factor (SRF) and Ternary Complex Factor (TCF) mediates the response of the c-fos Serum Response Element (SRE) to growth factors and mitogens. Three Ets domain proteins, Elk-1, SAP-1 and ERP/NET, have been reported to have the properties of TCF. Here we compare Elk-1 and SAP-1a with the human ERP/NET homologue SAP-2. All three TCF RNAs are ubiquitously expressed at similar relative levels. All three proteins contain conserved regions that interact with SRF and the c-fos SRE with comparable efficiency, but in vitro complex formation by SAP-2 is strongly inhibited by its C-terminal sequences. Similarly, only Elk-1 and SAP-1a efficiently bind the c-fos SRE in vivo; ternary complex formation by SAP-2 is weak and is substantially unaffected by serum stimulation or v-ras co-expression. All three TCFs contain C-terminal transcriptional activation domains that are phosphorylated following growth factor stimulation. Activation requires conserved S/T-P motifs found in all the TCF family members. Each TCF activation domain can be phosphorylated in vitro by partially purified ERK2, and ERK activation in vivo is sufficient to potentiate transcriptional activation. PMID:7540136

  3. 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. PMID:23422156

  4. Uncertainty Propagation in Nerve Impulses Through the Action Potential Mechanism.

    PubMed

    Torres Valderrama, Aldemar; Witteveen, Jeroen; Navarro, Maria; Blom, Joke

    2015-12-01

    We investigate the propagation of probabilistic uncertainty through the action potential mechanism in nerve cells. Using the Hodgkin-Huxley (H-H) model and Stochastic Collocation on Sparse Grids, we obtain an accurate probabilistic interpretation of the deterministic dynamics of the transmembrane potential and gating variables. Using Sobol indices, out of the 11 uncertain parameters in the H-H model, we unravel two main uncertainty sources, which account for more than 90 % of the fluctuations in neuronal responses, and have a direct biophysical interpretation. We discuss how this interesting feature of the H-H model allows one to reduce greatly the probabilistic degrees of freedom in uncertainty quantification analyses, saving CPU time in numerical simulations and opening possibilities for probabilistic generalisation of other deterministic models of great importance in physiology and mathematical neuroscience. PMID:26458902

  5. The bioelectrical source in computing single muscle fiber action potentials.

    PubMed Central

    van Veen, B K; Wolters, H; Wallinga, W; Rutten, W L; Boom, H B

    1993-01-01

    Generally, single muscle fiber action potentials (SFAPs) are modeled as a convolution of the bioelectrical source (being the transmembrane current) with a weighting or transfer function, representing the electrical volume conduction. In practice, the intracellular action potential (IAP) rather than the transmembrane current is often used as the source, because the IAP is relatively easy to obtain under experimental conditions. Using a core conductor assumption, the transmembrane current equals the second derivative of the IAP. In previous articles, discrepancies were found between experimental and simulated SFAPs. Adaptations in the volume conductor slightly altered the simulation results. Another origin of discrepancy might be an erroneous description of the source. Therefore, in the present article, different sources were studied. First, an analytical description of the IAP was used. Furthermore, an experimental IAP, a special experimental SFAP, and a measured transmembrane current scaled to our experimental situation were applied. The results for the experimental IAP were comparable to those with the analytical IAP. The best agreement between experimental and simulated data was found for a measured transmembrane current as source, but differences are still apparent. PMID:8324186

  6. A web portal for in-silico action potential predictions

    PubMed Central

    Williams, Geoff; Mirams, Gary R.

    2015-01-01

    Introduction Multiple cardiac ion channels are prone to block by pharmaceutical compounds, and this can have large implications for cardiac safety. The effect of a compound on individual ion currents can now be measured in automated patch clamp screening assays. In-silico action potential models are proposed as one way of predicting the integrated compound effects on whole-cell electrophysiology, to provide an improved indication of pro-arrhythmic risk. Methods We have developed open source software to run cardiac electrophysiology simulations to predict the overall effect of compounds that block IKr, ICaL, INa, IKs, IK1 and Ito to varying degrees, using a choice of mathematical electrophysiology models. To enable safety pharmacology teams to run and evaluate these simulations easily, we have also developed an open source web portal interface to this simulator. Results The web portal can be found at https://chaste.cs.ox.ac.uk/ActionPotential. Users can enter details of compound affinities for ion channels in the form of IC50 or pIC50 values, run simulations, store the results for later retrieval, view summary graphs of the results, and export data to a spreadsheet format. Discussion This web portal provides a simple interface to reference versions of mathematical models, and well-tested state-of-the-art equation solvers. It provides safety teams easy access to the emerging technology of cardiac electrophysiology simulations for use in the drug-discovery process. PMID:25963830

  7. Flexible graphene transistors for recording cell action potentials

    NASA Astrophysics Data System (ADS)

    Blaschke, Benno M.; Lottner, Martin; Drieschner, Simon; Bonaccini Calia, Andrea; Stoiber, Karolina; Rousseau, Lionel; Lissourges, Gaëlle; Garrido, Jose A.

    2016-06-01

    Graphene solution-gated field-effect transistors (SGFETs) are a promising platform for the recording of cell action potentials due to the intrinsic high signal amplification of graphene transistors. In addition, graphene technology fulfills important key requirements for in-vivo applications, such as biocompability, mechanical flexibility, as well as ease of high density integration. In this paper we demonstrate the fabrication of flexible arrays of graphene SGFETs on polyimide, a biocompatible polymeric substrate. We investigate the transistor’s transconductance and intrinsic electronic noise which are key parameters for the device sensitivity, confirming that the obtained values are comparable to those of rigid graphene SGFETs. Furthermore, we show that the devices do not degrade during repeated bending and the transconductance, governed by the electronic properties of graphene, is unaffected by bending. After cell culture, we demonstrate the recording of cell action potentials from cardiomyocyte-like cells with a high signal-to-noise ratio that is higher or comparable to competing state of the art technologies. Our results highlight the great capabilities of flexible graphene SGFETs in bioelectronics, providing a solid foundation for in-vivo experiments and, eventually, for graphene-based neuroprosthetics.

  8. Click- and chirp-evoked human compound action potentials.

    PubMed

    Chertoff, Mark; Lichtenhan, Jeffery; Willis, Marie

    2010-05-01

    In the experiments reported here, the amplitude and the latency of human compound action potentials (CAPs) evoked from a chirp stimulus are compared to those evoked from a traditional click stimulus. The chirp stimulus was created with a frequency sweep to compensate for basilar membrane traveling wave delay using the O-Chirp equations from Fobel and Dau [(2004). J. Acoust. Soc. Am. 116, 2213-2222] derived from otoacoustic emission data. Human cochlear traveling wave delay estimates were obtained from derived compound band action potentials provided by Eggermont [(1979). J. Acoust. Soc. Am. 65, 463-470]. CAPs were recorded from an electrode placed on the tympanic membrane (TM), and the acoustic signals were monitored with a probe tube microphone attached to the TM electrode. Results showed that the amplitude and latency of chirp-evoked N1 of the CAP differed from click-evoked CAPs in several regards. For the chirp-evoked CAP, the N1 amplitude was significantly larger than the click-evoked N1s. The latency-intensity function was significantly shallower for chirp-evoked CAPs as compared to click-evoked CAPs. This suggests that auditory nerve fibers respond with more unison to a chirp stimulus than to a click stimulus. PMID:21117748

  9. Metabolic syndrome potentiates the cardiac action potential-prolonging action of drugs: a possible 'anti-proarrhythmic' role for amlodipine.

    PubMed

    Caillier, Bertrand; Pilote, Sylvie; Patoine, Dany; Levac, Xavier; Couture, Christian; Daleau, Pascal; Simard, Chantale; Drolet, Benoit

    2012-03-01

    Type II diabetes was shown to prolong the QT interval on the ECG and to promote cardiac arrhythmias. This is not so clear for metabolic syndrome, a precursor state of type II diabetes. The objectives of the present study were to generate a guinea pig model of metabolic syndrome by long-term exposure to diabetogenic diets, and to evaluate the monophasic action potential duration (MAPD)-modulating effects of drugs in these animals. Male Hartley guinea pigs were fed with either the control, the High Fat High Sucrose (HFHS) or the High Fat High Fructose (HFHF) diet for 150 days. Evolution of weight, blood cholesterol, triglycerides, urea and glucose tolerance were regularly monitored. Histopathological evolution was also evaluated in target organs such as pancreas, heart, liver and kidneys. Ex vivo experiments using the Langendorff retroperfusion technique, isolated hearts from guinea pigs either fed with the control, the HFHS or the HFHF diet were exposed to dofetilide 20 nM (D), chromanol 293B 10 μM (C) and amlodipine 100 nM (A) in different drug combinations and monophasic action potential duration was measured at 90% repolarization (MAPD₉₀). Our data show that it is possible to generate a guinea pig model of metabolic syndrome by chronic exposure to diabetogenic diets. Minor histopathological abnormalities were observed, mainly in the pancreas and the liver. Metabolic syndrome potentiates the MAPD-prolonging actions of I(Kr)-blocking (dofetilide) and I(Ks)-blocking (chromanol 293B) drugs, an effect that is reversible upon administration of the calcium channel blocker amlodipine. PMID:22154802

  10. Dynamic control of osmolality and ionic composition of the xylem sap in two mangrove species.

    PubMed

    López-Portillo, Jorge; Ewers, Frank W; Méndez-Alonzo, Rodrigo; Paredes López, Claudia L; Angeles, Guillermo; Alarcón Jiménez, Ana Luisa; Lara-Domínguez, Ana Laura; Torres Barrera, María Del Carmen

    2014-06-01

    • Premise of the study: Xylem sap osmolality and salinity is a critical unresolved issue in plant function with impacts on transport efficiency, pressure gradients, and living cell turgor pressure, especially for halophytes such as mangrove trees.• Methods: We collected successive xylem vessel sap samples from stems and shoots of Avicennia germinans and Laguncularia racemosa using vacuum and pressure extraction and measured their osmolality. Following a series of extractions with the pressure chamber, we depressurized the shoot and pressurized again after various equilibration periods (minutes to hours) to test for dynamic control of osmolality. Transpiration and final sap osmolality were measured in shoots perfused with deionized water or different seawater dilutions.• Key results: For both species, the sap osmolality values of consecutive samples collected by vacuum extraction were stable and matched those of the initial samples extracted with the pressure chamber. Further extraction of samples with the pressure chamber decreased sap osmolality, suggesting reverse osmosis occurred. However, sap osmolalities increased when longer equilibration periods after sap extraction were allowed. Analysis of expressed sap with HPLC indicated a 1:1 relation between measured osmolality and the osmolality of the inorganic ions in the sap (mainly Na(+), K(+), and Cl(-)), suggesting no contamination by organic compounds. In stems perfused with deionized water, the sap osmolality increased to mimic the native sap osmolality.• Conclusions: Xylem sap osmolality and ionic contents are dynamically adjusted by mangroves and may help modulate turgor pressure, hydraulic conductivity, and water potential, thus being important for mangrove physiology, survival, and distribution. PMID:24907254

  11. Tree Hydraulics: How Sap Rises

    ERIC Educational Resources Information Center

    Denny, Mark

    2012-01-01

    Trees transport water from roots to crown--a height that can exceed 100 m. The physics of tree hydraulics can be conveyed with simple fluid dynamics based upon the Hagen-Poiseuille equation and Murray's law. Here the conduit structure is modelled as conical pipes and as branching pipes. The force required to lift sap is generated mostly by…

  12. The Potential of Deweyan-Inspired Action Research

    ERIC Educational Resources Information Center

    Stark, Jody L.

    2014-01-01

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

  13. Cardiac dynamics: a simplified model for action potential propagation

    PubMed Central

    2012-01-01

    This paper analyzes a new semiphysiological ionic model, used recently to study reexitations and reentry in cardiac tissue [I.R. Cantalapiedra et al, PRE 82 011907 (2010)]. The aim of the model is to reproduce action potencial morphologies and restitution curves obtained, either from experimental data, or from more complex electrophysiological models. The model divides all ion currents into four groups according to their function, thus resulting into fast-slow and inward-outward currents. We show that this simplified model is flexible enough as to accurately capture the electrical properties of cardiac myocytes, having the advantage of being less computational demanding than detailed electrophysiological models. Under some conditions, it has been shown to be amenable to mathematical analysis. The model reproduces the action potential (AP) change with stimulation rate observed both experimentally and in realistic models of healthy human and guinea pig myocytes (TNNP and LRd models, respectively). When simulated in a cable it also gives the right dependence of the conduction velocity (CV) with stimulation rate. Besides reproducing correctly these restitution properties, it also gives a good fit for the morphology of the AP, including the notch typical of phase 1. Finally, we perform simulations in a realistic geometric model of the rabbit’s ventricles, finding a good qualitative agreement in AP propagation and the ECG. Thus, this simplified model represents an alternative to more complex models when studying instabilities in wave propagation. PMID:23194429

  14. OpenGGCM-RCM modeling of SAPS events

    NASA Astrophysics Data System (ADS)

    Raeder, J.; Cramer, W. D.; Jensen, J. B.; Toffoletto, F. R.; Sazykin, S. Y.; Vo, H. B.

    2015-12-01

    Sub-Auroral Polarization Streams (SAPS), also known as Sub-Auroral Ion Drifts (SAIDs), are fast westward flows in the ionosphere that occur at latitudes lower than auroral precipitation, and well separated from the high-latitude convection pattern. Although SAPS were first observed in the ionosphere, they can also be seen in the magnetosphere and are believed to be driven by a combination of region-2 currents and low ionospheric conductance. SAPS are thus governed both by magnetosphere and ionosphere processes and require self-consistently coupled models of the outer magnetosphere, the inner magnetosphere and the ring current, and the ionosphere-thermosphere system. Here, we present first results from the OpenGGCM-RCM coupled model, which includes all of the required physical processes and feedbacks. In particular, the ionospheric conductance is computed self-consistently from both magnetosphere electron precipitation, solar ionization, and ionospheric chemistry within the fully dynamical CTIM sub model of OpenGGCM. Furthermore, CTIM includes the recombination feedback of streaming ions. We focus on the GEM-CEDAR storm events of 2013-03-17, 2011-04-27, 2012-05-07, and 2012-09-02. We show that the coupled model produces SAPS that compare well with data in terms of location, extent, and magnitude. By modifying the conductances in the code we evaluate the potential positive feedback process of the ionospheric conductance on SAPS.

  15. Dipole characterization of single neurons from their extracellular action potentials

    PubMed Central

    Victor, Jonathan D.

    2011-01-01

    The spatial variation of the extracellular action potentials (EAP) of a single neuron contains information about the size and location of the dominant current source of its action potential generator, which is typically in the vicinity of the soma. Using this dependence in reverse in a three-component realistic probe + brain + source model, we solved the inverse problem of characterizing the equivalent current source of an isolated neuron from the EAP data sampled by an extracellular probe at multiple independent recording locations. We used a dipole for the model source because there is extensive evidence it accurately captures the spatial roll-off of the EAP amplitude, and because, as we show, dipole localization, beyond a minimum cell-probe distance, is a more accurate alternative to approaches based on monopole source models. Dipole characterization is separable into a linear dipole moment optimization where the dipole location is fixed, and a second, nonlinear, global optimization of the source location. We solved the linear optimization on a discrete grid via the lead fields of the probe, which can be calculated for any realistic probe + brain model by the finite element method. The global source location was optimized by means of Tikhonov regularization that jointly minimizes model error and dipole size. The particular strategy chosen reflects the fact that the dipole model is used in the near field, in contrast to the typical prior applications of dipole models to EKG and EEG source analysis. We applied dipole localization to data collected with stepped tetrodes whose detailed geometry was measured via scanning electron microscopy. The optimal dipole could account for 96% of the power in the spatial variation of the EAP amplitude. Among various model error contributions to the residual, we address especially the error in probe geometry, and the extent to which it biases estimates of dipole parameters. This dipole characterization method can be applied to

  16. Short latency compound action potentials from mammalian gravity receptor organs

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  17. Modelling Action Potential Generation and Propagation in Fibroblastic Cells

    NASA Astrophysics Data System (ADS)

    Torres, J. J.; Cornelisse, L. N.; Harks, E. G. A.; Theuvenet, A. P. R.; Ypey, D. L.

    2003-04-01

    Using a standard Hodgkin-Huxley (HH) formalism, we present a mathematical model for action potential (AP) generation and intercellular AP propagation in quiescent (serum-deprived) normal rat kidney (NRK) fibroblasts [1], based on the recent experimental identification of the ion channels involved [2]. The principal ion channels described are those of an inwardly rectifying K+ conductance (GKIR), an L-type calcium conductance (GCaL), an intracellular calcium activated Cl- conductance (GCl(Ca)), a residual leak conductance Gleak, and gap junctional channels between the cells (Ggj). The role of each one of these components in the particular shape of the AP wave-form has been analyzed and compared with experimental observations. In addition, we have studied the role of subcellular processes like intracellular calcium dynamics and calcium buffering in AP generation. AP propagation between cells was reconstructed in a hexagonal model of cells coupled by Ggj with physiological conductance values. The model revealed an excitability mechanism of quiescent NRK cells with a particular role of intracellular calcium dynamics. It allows further explorations of the mechanism of signal generation and transmission in NRK cell cultures and its dependence on growth conditions.

  18. Aldehydes: occurrence, carcinogenic potential, mechanism of action and risk assessment.

    PubMed

    Feron, V J; Til, H P; de Vrijer, F; Woutersen, R A; Cassee, F R; van Bladeren, P J

    1991-01-01

    Aldehydes constitute a group of relatively reactive organic compounds. They occur as natural (flavoring) constituents in a wide variety of foods and food components, often in relatively small, but occasionally in very large concentrations, and are also widely used as food additives. Evidence of carcinogenic potential in experimental animals is convincing for formaldehyde and acetaldehyde, limited for crotonaldehyde, furfural and glycidaldehyde, doubtful for malondialdehyde, very weak for acrolein and absent for vanillin. Formaldehyde carcinogenesis is a high-dose phenomenon in which the cytotoxicity plays a crucial role. Cytotoxicity may also be of major importance in acetaldehyde carcinogenesis but further studies are needed to prove or disprove this assumption. For a large number of aldehydes (relevant) data on neither carcinogenicity nor genotoxicity are available. From epidemiological studies there is no convincing evidence of aldehyde exposure being related to cancer in humans. Overall assessment of the cancer risk of aldehydes in the diet leads to the conclusion that formaldehyde, acrolein, citral and vanillin are no dietary risk factors, and that the opposite may be true for acetaldehyde, crotonaldehyde and furfural. Malondialdehyde, glycidaldehyde, benzaldehyde, cinnamaldehyde and anisaldehyde cannot be evaluated on the basis of the available data. A series of aldehydes should be subjected to at least mutagenicity, cytogenicity and cytotoxicity tests. Priority setting for testing should be based on expected mechanism of action and degree of human exposure. PMID:2017217

  19. Pharmacological actions of statins: potential utility in COPD.

    PubMed

    Young, R P; Hopkins, R; Eaton, T E

    2009-12-01

    Chronic obstructive pulmonary disease (COPD) is characterised by minimally reversible airflow limitation and features of systemic inflammation. Current therapies for COPD have been shown to reduce symptoms and infective exacerbations and to improve quality of life. However, these drugs have little effect on the natural history of the disease (progressive decline in lung function and exercise tolerance) and do not improve mortality. The anti-inflammatory effects of statins on both pulmonary and systemic inflammation through inhibition of guanosine triphosphatase and nuclear factor-κB mediated activation of inflammatory and matrix remodelling pathways could have substantial benefits in patients with COPD due to the following. 1) Inhibition of cytokine production (tumour necrosis factor-α, interleukin (IL)-6 and IL-8) and neutrophil infiltration into the lung; 2) inhibition of the fibrotic activity in the lung leading to small airways fibrosis and irreversible airflow limitation; 3) antioxidant and anti-inflammatory (IL-6 mediated) effects on skeletal muscle; 4) reduced inflammatory response to pulmonary infection; and 5) inhibition of the development (or reversal) of epithelial-mesenchymal transition, a precursor event to lung cancer. This review examines the pleiotropic pharmacological action of statins which inhibit key inflammatory and remodelling pathways in COPD and concludes that statins have considerable potential as adjunct therapy in COPD. PMID:20956147

  20. Autophagy regulation revealed by SapM-induced block of autophagosome-lysosome fusion via binding RAB7

    SciTech Connect

    Hu, Dong; Wu, Jing; Wang, Wan; Mu, Min; Zhao, Runpeng; Xu, Xuewei; Chen, Zhaoquan; Xiao, Jian; Hu, Fengyu; Yang, Yabo; Zhang, Rongbo

    2015-05-29

    The mechanism underlying autophagy alteration by mycobacterium tuberculosis remains unclear. Our previous study shows LpqH, a lipoprotein of mycobacterium tuberculosis, can cause autophagosomes accumulation in murine macrophages. It is well known that SapM, another virulence factor, plays an important role in blocking phagosome-endosome fusion. However, the mechanism that SapM interferes with autophagy remains poorly defined. In this study, we report that SapM suppresses the autophagy flux by blocking autophagosome fusion with lysosome. Exposure to SapM results in accumulations of autophagosomes and decreased co-localization of autophagosome with lysosome. Molecularly, Rab7, a small GTPase, is blocked by SapM through its CT domain and is prevented from involvement of autophagosome-lysosome fusion. In conclusion, our study reveals that SapM takes Rab7 as a previously unknown target to govern a distinct molecular mechanism underlying autophagosome-lysosome fusion, which may bring light to a new thought about developing potential drugs or vaccines against tuberculosis. - Highlights: • A mechanism for disrupting autophagosome-lysosome fusion induced by SapM. • Rab7 is involved in SapM-inhibited autophagy. • SapM interacts with Rab7 by CT-domain. • CT-domain is indispensable to SapM-inhibited autophagy.

  1. The impact of synaptic conductance on action potential waveform: evoking realistic action potentials with a simulated synaptic conductance.

    PubMed

    Johnston, Jamie; Postlethwaite, Michael; Forsythe, Ian D

    2009-10-15

    Most current clamp studies trigger action potentials (APs) by step current injection through the recording electrode and assume that the resulting APs are essentially identical to those triggered by orthodromic synaptic inputs. However this assumption is not always valid, particularly when the synaptic conductance is of large magnitude and of close proximity to the axon initial segment. We addressed this question of similarity using the Calyx of Held/MNTB synapse; we compared APs evoked by long duration step current injections, short step current injections and orthodromic synaptic stimuli. Neither injected current protocol evoked APs that matched the evoked orthodromic AP waveform, showing differences in AP height, half-width and after-hyperpolarization. We postulated that this 'error' could arise from changes in the instantaneous conductance during the combined synaptic and AP waveforms, since the driving forces for the respective ionic currents are integrating and continually evolving over this time-course. We demonstrate that a simple Ohm's law manipulation of the EPSC waveform, which accounts for the evolving driving force on the synaptic conductance during the AP, produces waveforms that closely mimic those generated by physiological synaptic stimulation. This stimulation paradigm allows supra-threshold physiological stimulation (single stimuli or trains) without the variability caused by quantal fluctuation in transmitter release, and can be implemented without a specialised dynamic clamp system. Combined with pharmacological tools this method provides a reliable means to assess the physiological roles of postsynaptic ion channels without confounding affects from the presynaptic input. PMID:19560491

  2. Response of Sap-Flow Measurements on Environmental Forcings

    NASA Astrophysics Data System (ADS)

    Howe, J. A.; Dragoni, D.; Schmid, H.

    2005-05-01

    The exchange of water between the atmosphere and biosphere is an important determinant of climate and the productivity of vegetation. Both evaporation and transpiration involve substantial amounts of energy exchange at the interface of the biosphere and atmosphere. Knowing how transpiration changes throughout the seasonal and diurnal cycles can help increase the understanding of how a forest reacts to changes in the biosphere and atmosphere. A common way to estimate transpiration is by measuring the sap flowing through the living tissues of trees. A study was conducted at Morgan-Monroe State Forest, a mixed deciduous forest in south central Indiana (USA), to investigate how sap flow in trees responds to changes in meteorological and environmental conditions. The heat -dissipation technique was used to estimate sap velocities from two Big Tooth Aspen (Populus grandidentata) and two Tulip Poplars (Liriodendron tulipifera). Sap velocity patterns (normalized by a reference potential evapo-transpiration) were directly compared with meteorological and ecological measurements, such as vapor pressure deficits, photosynthetic active radiation (PAR), rain fall, and soil moisture content. In this study, we also investigated the uncertainties and problems that arise in using the heat dissipation technique to extrapolate the single-tree measurements to the forest scale.

  3. Empirical Model of Subauroral Polarization Streams (SAPS) During Geomagnetic Storms

    NASA Astrophysics Data System (ADS)

    Landry, R. G.

    2015-12-01

    Subauroral Polarization Streams (SAPS) are important electromagnetic phenomena associated with geomagnetic storms that affect the inner magnetosphere and ionosphere. They are characterized by strong sunward plasma flows caused by poleward-directed electric fields in the region of the ionosphere equatorword of the auroral zone. To examine the effects subauroral electric fields have on ITM coupling and magnetospheric-ionospheric convection we are developing an empirical model of SAPS using data acquired by the Defense Meteorological Satellite Program (DMSP) spacecraft which have made decades of in-situ measurements of ionospheric ion drifts, composition, and precipitating auroral particles. These measurements are used to characterize the subauroral electric fields relative to the location of the auroral boundary at varying magnetic local times and magnetic activity levels. As a critical component of this model, we have developed a model of the nightside zero energy electron precipitation boundary equatorward of the auroral oval parameterized by AE and MLT, using boundary identifications derived from DMSP data. We will use this model to create a global subauroral potential model and perform a superposed epoch study of SAPS fields in relationship to the auroral boundary during selected geomagnetic storms as a function of storm phase. A global empirical model of SAPS electric fields of this kind is required to realistically model thermosphere-ionosphere coupling and inner-magnetospheric convection.

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

    ERIC Educational Resources Information Center

    Rodriguez-Falces, Javier

    2015-01-01

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

  5. Ontogeny of vestibular compound action potentials in the domestic chicken

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  6. N-SAP and G-SAP neutron and gamma ray albedo model scatter shield analysis program

    NASA Technical Reports Server (NTRS)

    Sapovchak, B. J.; Stephenson, L. D.

    1967-01-01

    Computer program calculates neutron or gamma ray first order scattering from a plane or cylindrical surface to a detector point. The SAP Codes, G-SAP and N-SAP, constitute a multiple scatter albedo model shield analysis.

  7. Flood pulse alterations and productivity of the Tonle Sap ecosystem: a model for impact assessment.

    PubMed

    Lamberts, Dirk; Koponen, Jorma

    2008-05-01

    Tonle Sap Lake is a large and complex data-deficient ecosystem in the Mekong River Basin. Highly valuable in biodiversity and natural livelihoods capital, it is susceptible to degradation when the flood pulse that drives its productivity is altered as a result of hydropower and irrigation development on the Mekong River. To date, there are no tools to assess the consequences of such flood pulse alterations, leaving the Tonle Sap underrated in water-resources use and planning. A combined ecological-hydrodynamic model is presented for the production potential of the Tonle Sap ecosystem and its likely response to hydrological changes. PMID:18595272

  8. Gifted Potential and Poverty: A Call for Extraordinary Action

    ERIC Educational Resources Information Center

    Kitano, Margie K.

    2003-01-01

    Dr. Robinson's proposed action plan will serve the needs of highly achieving gifted students. However, defining giftedness as high academic performance based on traditional assessment procedures could reverse the field's fledgling success in supporting culturally diverse gifted children and youth. Changing the focus of equity in gifted education…

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

    PubMed

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

    2014-10-15

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

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

    PubMed

    Rodriguez-Falces, Javier

    2015-03-01

    A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However, this model is unsuitably complex for teaching purposes. In addition, the Hodgkin and Huxley approach describes the shape of the action potential only in terms of ionic currents, i.e., it is unable to explain the electrical significance of the action potential or describe the electrical field arising from this source using basic concepts of electromagnetic theory. The goal of the present report was to propose a new model to describe the electrical behaviour of the action potential in terms of elementary electrical sources (in particular, dipoles). The efficacy of this model was tested through a closed-book written exam. The proposed model increased the ability of students to appreciate the distributed character of the action potential and also to recognize that this source spreads out along the fiber as function of space. In addition, the new approach allowed students to realize that the amplitude and sign of the extracellular electrical potential arising from the action potential are determined by the spatial derivative of this intracellular source. The proposed model, which incorporates intuitive graphical representations, has improved students' understanding of the electrical potentials generated by bioelectrical sources and has heightened their interest in bioelectricity. PMID:25727465

  11. Mekong Floods Fill Tonle Sap

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The monsoon season in Southeast Asia brings recurring, often devastating floods to countries in the region, but these floods also play a necessary role in the region's water cycle. These MODIS images centered on Cambodia reveal extensive flooding of the Mekong River, which comes in from Laos in the north, to the right of center in the images, and flows south through Cambodia and southeast through Vietnam to empty into the South China Sea. The true-color image shows the brownish, sediment-laden floodwaters filling the Mekong Delta in southern Cambodia and Vietnam on September 15, 2001. The false color image above has been enhanced to bring out the contrast between the floodwaters and the lands, with sediment-carrying floodwaters in purple. Sediment can be seen flowing into the South China Sea as well. This year's floods have affected over a million people, and 100 people have been killed in Vietnam alone. The monsoon floods bring not only devastation, but renewal. The large body of water just left of center in Cambodia is the Tonle Sap. This shallow lake plays a changing role in the regional water cycle. During the dry season, the stream-fed Tonle Sap drains via the Tonle Sab River into the Mekong River. During the wet season (June-November), flooding of the Mekong reverses the course of the Tonle Sab, roughly tripling the lake's size from about 3000 km2 to about 10,000. When the dry season returns, the lake once again begins to drain into the Mekong Delta, where it provides a flow of fresh water that balances the intrusion of salty seawater into the delta's agricultural lands. Image courtesy Jacques Descloitres, MODIS Land Rapid Response Team at NASA GSFC

  12. SapC-DOPS-induced lysosomal cell death synergizes with TMZ in glioblastoma.

    PubMed

    Wojton, Jeffrey; Meisen, Walter Hans; Jacob, Naduparambil K; Thorne, Amy Haseley; Hardcastle, Jayson; Denton, Nicholas; Chu, Zhengtao; Dmitrieva, Nina; Marsh, Rachel; Van Meir, Erwin G; Kwon, Chang-Hyuk; Chakravarti, Arnab; Qi, Xiaoyang; Kaur, Balveen

    2014-10-30

    SapC-DOPS is a novel nanotherapeutic that has been shown to target and induce cell death in a variety of cancers, including glioblastoma (GBM). GBM is a primary brain tumor known to frequently demonstrate resistance to apoptosis-inducing therapeutics. Here we explore the mode of action for SapC-DOPS in GBM, a treatment being developed by Bexion Pharmaceuticals for clinical testing in patients. SapC-DOPS treatment was observed to induce lysosomal dysfunction of GBM cells characterized by decreased glycosylation of LAMP1 and altered proteolytic processing of cathepsin D independent of apoptosis and autophagic cell death. We observed that SapC-DOPS induced lysosomal membrane permeability (LMP) as shown by LysoTracker Red and Acridine Orange staining along with an increase of sphingosine, a known inducer of LMP. Additionally, SapC-DOPS displayed strong synergistic interactions with the apoptosis-inducing agent TMZ. Collectively our data suggest that SapC-DOPS induces lysosomal cell death in GBM cells, providing a new approach for treating tumors resistant to traditional apoptosis-inducing agents. PMID:25210852

  13. Freezing of Xylem Sap Without Cavitation

    PubMed Central

    Hammel, H. T.

    1967-01-01

    Freezing of stem sections and entire twigs of hemlock (Tsuga canadensis) has been demonstrated to occur without increasing the resistance to the movement of water through the frozen part after rewarming. This was interpreted to mean that freezing did not produce cavitation in the xylem sap even though A) the sap was unquestionably frozen; B) it contained dissolved gases; and C) it was under tension before freezing and after. Freezing stem sections of some other evergreen gymnosperms during the summer again produced no evidence for cavitation of the xylem sap. On the other hand, freezing stem sections of some angiosperms invariably increased the resistance to sap flow leading to wilting and death in a few hours when the sap tension was at normal daytime values at the time of freezing. These results were interpreted to mean that the bordered pits on the tracheids of gymnosperms function to isolate the freezing sap in each tracheid so that the expansion of water upon freezing not only eliminates any existing tension but also develops positive pressure in the sap. Dissolved gases frozen out of solution may then be redissolved under this positive pressure as melting occurs. As the bubbles are reduced in size by this ice pressure developed in an isolated tracheid, further pressure is applied by the surface tension of the water against air. If the bubbles are redissolved or are reduced to sufficient small size by the time the tension returns to the sap as the last ice crystals melt, then the internal pressure from surface tension in any existing small bubbles may exceed the hydrostatic tension of the melted sap and the bubbles cannot expand and will continue to dissolve. PMID:16656485

  14. Epidermal laser stimulation of action potentials in the frog sciatic nerve

    NASA Astrophysics Data System (ADS)

    Jindra, Nichole M.; Goddard, Douglas; Imholte, Michelle; Thomas, Robert J.

    2010-01-01

    Measurements of laser-stimulated action potentials in the sciatic nerve of leopard frogs (Rana pipiens) are made using two infrared lasers. The dorsal sides of the frog's hind limbs are exposed to short-pulsed 1540- and 1064-nm wavelengths at three separate spot sizes: 2, 3, and 4 mm. Energy density thresholds are determined for eliciting an action potential at each experimental condition. Results from these exposures show similar evoked potential thresholds for both wavelengths. The 2-mm-diam spot sizes yield action potentials at radiant exposure levels almost double that seen with larger beam sizes.

  15. Rice OsiSAP7 negatively regulates ABA stress signalling and imparts sensitivity to water-deficit stress in Arabidopsis.

    PubMed

    Sharma, Gunjan; Giri, Jitender; Tyagi, Akhilesh K

    2015-08-01

    Stress associated protein (SAP) genes in plants regulate abiotic stress responses. SAP gene family consists of 18 members in rice. Although their abiotic stress responsiveness is well established, the mechanism of their action is poorly understood. OsiSAP7 was chosen to investigate the mechanism of its action based on the dual nature of its sub-cellular localization preferentially in the nucleus or sub-nuclear speckles upon transient expression in onion epidermal cells. Its expression was down-regulated in rice seedlings under abiotic stresses. OsiSAP7 was localized evenly in the nucleus under unstressed conditions and in sub-nuclear speckles on MG132 treatment. OsiSAP7 exhibits E3 ubiquitin ligase activity in vitro. Abiotic stress responses of OsiSAP7 were assessed by its overexpression in Arabidopsis under the control of a stress inducible promoter rd29A. Stress response assessment was done at seed germination and advanced stages of development. Transgenics were ABA insensitive at seed germination stage and sensitive to water-deficit stress at advanced stage as compared to wild type (WT). They were also impaired in ABA and stress-responsive gene expression. Our study suggests that OsiSAP7 acts as a negative regulator of ABA and water-deficit stress signalling by acting as an E3 ubiquitin ligase. PMID:26089154

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

    NASA Astrophysics Data System (ADS)

    Crago, Patrick E.; Makowski, Nathaniel S.

    2014-10-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2004-05-01

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

  18. The FORTRAN static source code analyzer program (SAP) system description

    NASA Technical Reports Server (NTRS)

    Decker, W.; Taylor, W.; Merwarth, P.; Oneill, M.; Goorevich, C.; Waligora, S.

    1982-01-01

    A source code analyzer program (SAP) designed to assist personnel in conducting studies of FORTRAN programs is described. The SAP scans FORTRAN source code and produces reports that present statistics and measures of statements and structures that make up a module. The processing performed by SAP and of the routines, COMMON blocks, and files used by SAP are described. The system generation procedure for SAP is also presented.

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

    NASA Astrophysics Data System (ADS)

    Eickenscheidt, Max; Zeck, Günther

    2014-06-01

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

  20. Noncontact subnanometer measurement of transient surface displacement during action potential propagation

    NASA Astrophysics Data System (ADS)

    Akkin, Taner; Dave, Digant P.; Rylander, H. Grady, III; Milner, Thomas E.

    2005-04-01

    We have demonstrated non-contact, sub-nanometer optical measurement of neural surface displacement associated with action potential propagation without applying exogenous chemicals or reflection coatings. Signals recorded from crayfish leg nerve using a phase-sensitive optical low coherence reflectometer show that transient neural surface displacement due to action potential propagation is approximately 1 nm in amplitude and 1 ms in duration. Measured optical signals are coincident with electrical action potential arrival to the optical measurement site. Recent experiments indicate signals with similar amplitude and duration are observed in response to repetitive fast stimulation (200 stimuli/s).

  1. Developmental changes in the inward current of the action potential of Rohon-Beard neurones

    PubMed Central

    Baccaglini, Paola I.; Spitzer, Nicholas C.

    1977-01-01

    1. Rohon-Beard cells in the spinal cord of Xenopus tadpoles have been studied in animals from early neural tube to free-swimming larval stages. The onset and further development of electrical excitability of these neurones has been investigated in different ionic environments, to determine the ionic species carrying the inward current of the action potential. 2. The cells appear inexcitable at early stages (Nieuwkoop & Faber stages 18-20) and do not give action potentials to depolarizing current pulses. 3. The action potential is first recorded at stage 20. (A) The inward current is carried by Ca2+ at stages 20-25, since it is blocked by mm quantitites of La3+, Co2+ or Mn2+ and is unaffected by removal of Na+ or the addition of tetrodotoxin (TTX). (B) The action potential is an elevated plateau of long duration (mean 190 msec at stages 20-22). The duration decreases exponentially with repetitive stimulation. (C) The specific Ca2+ conductance (gCa) at the onset of the plateau of the action potential is 2·6 × 10-4 mho/cm2. Calculations show that a single action potential raises [Ca2+]1 by more than 100-fold. 4. At later times (stages 25-40), the inward current of the action potential is carried by both Na+ and Ca2+: the action potential has two components, an initial spike which is blocked by removal of Na+ or addition of TTX, followed by a plateau which is blocked by La3+, Co2+ or Mn2+. 5. Finally (stages 40-51), the inward current is primarily carried by Na+, since the action potential is blocked only by removal of Na+ or addition of TTX, and the overshoot agrees with the prediction of the Nernst equation for a Na-selective membrane. When the outward current channel is blocked and cells exposed to Na-free solutions, 67% of cells at the latest stages studied were incapable of producing action potentials in which the inward current is carried by divalent cations. 6. The duration of the action potential decreases from a maximum of about 1000 msec to about 1 msec

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

    PubMed Central

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

    2014-01-01

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

  3. Consequences of converting graded to action potentials upon neural information coding and energy efficiency.

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2012-01-01

    Functional MRI (fMRI) measures neural activity indirectly by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In this study, we used MR to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation, and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background-subtracted FID exhibited a systematic change, with a peak phase difference of (-1.2 ± 0.3) × 10(-5) radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase caused by a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using MR. PMID:21728204

  6. Action potential detection by non-linear microscopy

    NASA Astrophysics Data System (ADS)

    Sacconi, Leonardo; Lotti, Jacopo; O'Connor, Rodney P.; Mapelli, Jonathan; Gandolfi, Daniela; D'Angelo, Egidio; Pavone, Francesco S.

    2009-02-01

    In this work, we combined the advantages of second-harmonic generation (SHG) with a random access (RA) excitation scheme to realize a new microscope (RA-SHG) capable of optically recording fast membrane potential events occurring in a wide-field configuration. The RA-SHG microscope in combination with a bulk staining method with FM4-64 was used to simultaneously record electrical activity from clusters of Purkinje cells (PCs) in acute cerebellar slices. Spontaneous electrical activity was also monitored simultaneously in pairs of neurons, where APs were recorded in a single trial without averaging. These results show the strength of this technique to describe the temporal dynamics of neuronal assemblies.

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

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 13 2011-01-01 2009-01-01 true Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid...

  8. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 13 2012-01-01 2012-01-01 false Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid...

  9. Fast Susceptibility-Weighted Imaging (SWI) with 3D Short-Axis Propeller (SAP)-EPI

    PubMed Central

    Holdsworth, Samantha J.; Yeom, Kristen W.; Moseley, Michael E.; Skare, S.

    2014-01-01

    Purpose Susceptibility-Weighted Imaging (SWI) in neuroimaging can be challenging due to long scan times of 3D Gradient Recalled Echo (GRE), while faster techniques such as 3D interleaved EPI (iEPI) are prone to motion artifacts. Here we outline and implement a 3D Short-Axis Propeller Echo-Planar Imaging (SAP-EPI) trajectory as a faster, motion-correctable approach for SWI. Methods Experiments were conducted on a 3T MRI system. 3D SAP-EPI, 3D iEPI, and 3D GRE SWI scans were acquired on two volunteers. Controlled motion experiments were conducted to test the motion-correction capability of 3D SAP-EPI. 3D SAP-EPI SWI data were acquired on two pediatric patients as a potential alternative to 2D GRE used clinically. Results 3D GRE images had a better target resolution (0.47 × 0.94 × 2mm, scan time = 5min), iEPI and SAP-EPI images (resolution = 0.94 × 0.94 × 2mm) were acquired in a faster scan time (1:52min) with twice the brain coverage. SAP-EPI showed motion-correction capability and some immunity to undersampling from rejected data. Conclusion While 3D SAP-EPI suffers from some geometric distortion, its short scan time and motion-correction capability suggest that SAP-EPI may be a useful alternative to GRE and iEPI for use in SWI, particularly in uncooperative patients. PMID:24956237

  10. A novel stress-associated protein 'AtSAP10' from Arabidopsis thaliana confers tolerance to nickel, manganese, zinc, and high temperature stress.

    PubMed

    Dixit, Anirudha R; Dhankher, Om Parkash

    2011-01-01

    We describe here the functional characterization of a novel AtSAP10, a member of the Stress Associated Protein (SAP) gene family, from Arabidopsis thaliana ecotype Columbia. AtSAP10 contains an A20 and AN1 zinc-finger domain at the N- and C-terminal, respectively. Arabidopsis SAP10 showed differential regulation by various abiotic stresses such as heavy metals and metalloids (Ni, Cd, Mn, Zn, and As), high and low temperatures, cold, and ABA. Overexpression of AtSAP10 in Arabidopsis conferred strong tolerance to heavy metals such as Ni, Mn, and Zn and to high temperature stress. AtSAP10 transgenic plants under these stress conditions grew green and healthy, attained several-fold more biomass, and had longer roots as compared to wild type plants. Further, while these transgenic plants accumulated significantly greater amounts of Ni and Mn in both shoots and root tissues, there was no significant difference in the accumulation of Zn. AtSAP10 promoter-GUS fusion studies revealed a root and floral organ-specific expression of AtSAP10. Overexpression of AtSAP10-GFP fusion protein showed the localization in both nucleus and cytoplasm. Taken together, these results showed that AtSAP10 is a potentially useful candidate gene for engineering tolerance to heavy metals and to abiotic stress in cultivated plants. PMID:21695274

  11. A Novel Stress-Associated Protein ‘AtSAP10’ from Arabidopsis thaliana Confers Tolerance to Nickel, Manganese, Zinc, and High Temperature Stress

    PubMed Central

    Dixit, Anirudha R.; Dhankher, Om Parkash

    2011-01-01

    We describe here the functional characterization of a novel AtSAP10, a member of the Stress Associated Protein (SAP) gene family, from Arabidopsis thaliana ecotype Columbia. AtSAP10 contains an A20 and AN1 zinc-finger domain at the N- and C-terminal, respectively. Arabidopsis SAP10 showed differential regulation by various abiotic stresses such as heavy metals and metalloids (Ni, Cd, Mn, Zn, and As), high and low temperatures, cold, and ABA. Overexpression of AtSAP10 in Arabidopsis conferred strong tolerance to heavy metals such as Ni, Mn, and Zn and to high temperature stress. AtSAP10 transgenic plants under these stress conditions grew green and healthy, attained several-fold more biomass, and had longer roots as compared to wild type plants. Further, while these transgenic plants accumulated significantly greater amounts of Ni and Mn in both shoots and root tissues, there was no significant difference in the accumulation of Zn. AtSAP10 promoter-GUS fusion studies revealed a root and floral organ-specific expression of AtSAP10. Overexpression of AtSAP10-GFP fusion protein showed the localization in both nucleus and cytoplasm. Taken together, these results showed that AtSAP10 is a potentially useful candidate gene for engineering tolerance to heavy metals and to abiotic stress in cultivated plants. PMID:21695274

  12. Uniform Action Potential Repolarization within the Sarcolemma of In Situ Ventricular Cardiomyocytes

    PubMed Central

    Bu, Guixue; Adams, Heather; Berbari, Edward J.; Rubart, Michael

    2009-01-01

    Previous studies have speculated, based on indirect evidence, that the action potential at the transverse (t)-tubules is longer than at the surface membrane in mammalian ventricular cardiomyocytes. To date, no technique has enabled recording of electrical activity selectively at the t-tubules to directly examine this hypothesis. We used confocal line-scan imaging in conjunction with the fast response voltage-sensitive dyes ANNINE-6 and ANNINE-6plus to resolve action potential-related changes in fractional dye fluorescence (ΔF/F) at the t-tubule and surface membranes of in situ mouse ventricular cardiomyocytes. Peak ΔF/F during action potential phase 0 depolarization averaged −21% for both dyes. The shape and time course of optical action potentials measured with the water-soluble ANNINE-6plus were indistinguishable from those of action potentials recorded with intracellular microelectrodes in the absence of the dye. In contrast, optical action potentials measured with the water-insoluble ANNINE-6 were significantly prolonged compared to the electrical recordings obtained from dye-free hearts, suggesting electrophysiological effects of ANNINE-6 and/or its solvents. With either dye, the kinetics of action potential-dependent changes in ΔF/F during repolarization were found to be similar at the t-tubular and surface membranes. This study provides what to our knowledge are the first direct measurements of t-tubule electrical activity in ventricular cardiomyocytes, which support the concept that action potential duration is uniform throughout the sarcolemma of individual cells. PMID:19289075

  13. Pharmacological actions and potential uses of Momordica charantia: a review.

    PubMed

    Grover, J K; Yadav, S P

    2004-07-01

    Since ancient times, plants and herbal preparations have been used as medicine. Research carried out in last few decades has certified several such claims of use of several plants of traditional medicine. Popularity of Momordica charantia (MC) in various systems of traditional medicine for several ailments (antidiabetic, abortifacient, anthelmintic, contraceptive, dysmenorrhea, eczema, emmenagogue, antimalarial, galactagogue, gout, jaundice, abdominal pain, kidney (stone), laxative, leprosy, leucorrhea, piles, pneumonia, psoriasis, purgative, rheumatism, fever and scabies) focused the investigator's attention on this plant. Over 100 studies using modern techniques have authenticated its use in diabetes and its complications (nephropathy, cataract, insulin resistance), as antibacterial as well as antiviral agent (including HIV infection), as anthelmintic and abortifacient. Traditionally it has also been used in treating peptic ulcers, interestingly in a recent experimental studies have exhibited its potential against Helicobacter pylori. Most importantly, the studies have shown its efficacy in various cancers (lymphoid leukemia, lymphoma, choriocarcinoma, melanoma, breast cancer, skin tumor, prostatic cancer, squamous carcinoma of tongue and larynx, human bladder carcinomas and Hodgkin's disease). There are few reports available on clinical use of MC in diabetes and cancer patients that have shown promising results. PMID:15182917

  14. Plant fluid proteomics: Delving into the xylem sap, phloem sap and apoplastic fluid proteomes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The phloem sap, xylem sap and apoplastic fluid play key roles in long and short distance transport of signals and nutrients, and act as a barrier against local and systemic pathogen infection. Among other components, these plant fluids contain proteins, which are likely to be important players in th...

  15. Action potentials of embryonic dorsal root ganglion neurones in Xenopus tadpoles.

    PubMed Central

    Baccaglini, P I

    1978-01-01

    1. Several classes of action potentials can be distinguished in dorsal root ganglion cells, studied by intracellular recording techniques in Xenopus laevis tadpoles 4.5--51 days old. The ionic basis of the action potential was investigated by changing the ionic environment of the cells and applying various blocking agents. 2. The Ca2+-dependent action potential is a plateau of relatively long duration (mean 8.7 msec). It is unaffected by removal of Na+ but blocked by mM quantities of Co2+. It is present only in small cells. 3. Ca2+/Na+-dependent action potentials. Type I is a spike followed by a plateau or hump of different durations (mean 8.1 msec). The spike is selectively blocked by removal of Na+, leaving the plateau which is in turn blocked by Co2+. It is present in cells of small and intermediate size. Type II is a spike of short duration (mean 2.0 msec) with only an inflection on the falling phase. The spike is blocked by removal of Na+ and no other components can be elicited. The inflection is blocked by Co2+. It is present in cells of all sizes. Type III is similar to type I but is seen only in solutions in which the outward current is blocked. It was observed only very infrequently. 4. Na+-dependent action potentials. Type I a is a short duration spike (mean 1.1 msec). It is abolished by removal of Na+ or addition of tetrodotoxin (TTX), but largely unaffected by Co2+ or La3+. It is present in cells of all sizes. When the outward current channels are blocked and cells exposed to Na+-free solutions, all cells are capable of producing an action potential in which the inward current is carried by divalent cations. Type I b is a spike with a smooth, more slowly falling phase. It has the same pharmacological properties as type I a action potential and is present in cells of small size. 5. Na+-dependent action potentials. Type II is a spike with an inflection on the falling phase (mean duration 3.4 msec). It is prolonged by Co2+ and La3+. Removal of Na

  16. Implementation of SAP Waste Management System

    SciTech Connect

    Frost, M.L.; LaBorde, C.M.; Nichols, C.D.

    2008-07-01

    The Y-12 National Security Complex (Y-12) assumed responsibility for newly generated waste on October 1, 2005. To ensure effective management and accountability of newly generated waste, Y-12 has opted to utilize SAP, Y-12's Enterprise Resource Planning (ERP) tool, to track low-level radioactive waste (LLW), mixed waste (MW), hazardous waste, and non-regulated waste from generation through acceptance and disposal. SAP Waste will include the functionality of the current waste tracking system and integrate with the applicable modules of SAP already in use. The functionality of two legacy systems, the Generator Entry System (GES) and the Waste Information Tracking System (WITS), and peripheral spreadsheets, databases, and e-mail/fax communications will be replaced by SAP Waste. Fundamentally, SAP Waste will promote waste acceptance for certification and disposal, not storage. SAP Waste will provide a one-time data entry location where waste generators can enter waste container information, track the status of their waste, and maintain documentation. A benefit of the new system is that it will provide a single data repository where Y-12's Waste Management organization can establish waste profiles, verify and validate data, maintain inventory control utilizing hand-held data transfer devices, schedule and ship waste, manage project accounting, and report on waste handling activities. This single data repository will facilitate the production of detailed waste generation reports for use in forecasting and budgeting, provide the data for required regulatory reports, and generate metrics to evaluate the performance of the Waste Management organization and its subcontractors. SAP Waste will replace the outdated and expensive legacy system, establish tools the site needs to manage newly generated waste, and optimize the use of the site's ERP tool for integration with related business processes while promoting disposition of waste. (authors)

  17. Pulsed magnetic stimulation modifies amplitude of action potentials in vitro via ionic channels-dependent mechanism.

    PubMed

    Ahmed, Zaghloul; Wieraszko, Andrzej

    2015-07-01

    This paper investigates the influence of pulsed magnetic fields (PMFs) on amplitude of evoked, compound action potential (CAP) recorded from the segments of sciatic nerve in vitro. PMFs were applied for 30 min at frequency of 0.16 Hz and intensity of 15 mT. In confirmation of our previous reports, PMF exposure enhanced amplitude of CAPs. The effect persisted beyond PMF activation period. As expected, CAP amplitude was attenuated by antagonists of sodium channel, lidocaine, and tetrodotoxin. Depression of the potential by sodium channels antagonists was reversed by subsequent exposure to PMFs. The effect of elevated potassium concentration and veratridine on the action potential was modified by exposure to PMFs as well. Neither inhibitors of protein kinase C and protein kinase A, nor known free radicals scavengers had any effects on PMF action. Possible mechanisms of PMF action are discussed. PMID:25884360

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

    PubMed Central

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

    2010-01-01

    Somatic spiking is known to regulate dendritic signaling and associative synaptic plasticity in many types of large neurons, but it is unclear whether somatic action potentials play similar roles in small neurons. Here we ask whether somatic action potentials can also influence dendritic signaling in an electrically compact neuron, the cerebellar stellate cell (SC). Experiments were conducted in rat brain slices using a combination of imaging and electrophysiology. We find that somatic action potentials elevate dendritic calcium levels in SCs. There was little attenuation of calcium signals with distance from the soma in SCs from P17-19 rats, which had dendrites that averaged 60 µm in length and in short SC dendrites from P30-33 rats. Somatic action potentials evoke dendritic calcium increases that are not affected by blocking dendritic sodium channels. This indicates that dendritic signals in SCs do not rely on dendritic sodium channels, which differs from many types of large neurons where dendritic sodium channels and backpropagating action potentials allow somatic spikes to control dendritic calcium signaling. Despite the lack of active backpropagating action potentials, we find that trains of somatic action potentials elevate dendritic calcium sufficiently to release endocannabinoids and retrogradely suppress parallel fiber to SC synapses in P17-19 rats. Prolonged SC firing at physiologically realistic frequencies produces retrograde suppression when combined with low-level group I metabotropic glutamate receptor activation. Somatic spiking also interacts with synaptic stimulation to promote associative plasticity. These findings indicate that in small neurons the passive spread of potential within dendrites can allow somatic spiking to regulate dendritic calcium signaling and synaptic plasticity. PMID:19535592

  19. Seasonal and diel variation in xylem CO2 concentration and sap pH in sub-Mediterranean oak stems.

    PubMed

    Salomón, Roberto; Valbuena-Carabaña, María; Teskey, Robert; McGuire, Mary Anne; Aubrey, Doug; González-Doncel, Inés; Gil, Luis; Rodríguez-Calcerrada, Jesús

    2016-04-01

    Since a substantial portion of respired CO2 remains within the stem, diel and seasonal trends in stem CO2 concentration ([CO2]) are of major interest in plant respiration and carbon budget research. However, continuous long-term stem [CO2] studies are scarce, and generally absent in Mediterranean climates. In this study, stem [CO2] was monitored every 15min together with stem and air temperature, sap flow, and soil water storage during a growing season in 16 stems of Quercus pyrenaica to elucidate the main drivers of stem [CO2] at different temporal scales. Fluctuations in sap pH were also assessed during two growing seasons to evaluate potential errors in estimates of the concentration of CO2 dissolved in xylem sap ([CO2*]) calculated using Henry's law. Stem temperature was the best predictor of stem [CO2] and explained more than 90% and 50% of the variability in stem [CO2] at diel and seasonal scales, respectively. Under dry conditions, soil water storage was the main driver of stem [CO2]. Likewise, the first rains after summer drought caused intense stem [CO2] pulses, suggesting enhanced stem and root respiration and increased resistance to radial CO2 diffusion. Sap flow played a secondary role in controlling stem [CO2] variations. We observed night-time sap pH acidification and progressive seasonal alkalinization. Thus, if the annual mean value of sap pH (measured at midday) was assumed to be constant, night-time sap [CO2*] was substantially overestimated (40%), and spring and autumn sap [CO2*] were misestimated by 25%. This work highlights that diel and seasonal variations in temperature, tree water availability, and sap pH substantially affect xylem [CO2] and sap [CO2*]. PMID:27012285

  20. Increased Event-Related Potentials and Alpha-, Beta-, and Gamma-Activity Associated with Intentional Actions

    PubMed Central

    Karch, Susanne; Loy, Fabian; Krause, Daniela; Schwarz, Sandra; Kiesewetter, Jan; Segmiller, Felix; Chrobok, Agnieszka I.; Keeser, Daniel; Pogarell, Oliver

    2016-01-01

    Objective: Internally guided actions are defined as being purposeful, self-generated and offering choices between alternatives. Intentional actions are essential to reach individual goals. In previous empirical studies, internally guided actions were predominantly related to functional responses in frontal and parietal areas. The aim of the present study was to distinguish event-related potentials and oscillatory responses of intentional actions and externally guided actions. In addition, we compared neurobiological findings of the decision which action to perform with those referring to the decision whether or not to perform an action. Methods: Twenty-eight subjects participated in adapted go/nogo paradigms, including a voluntary selection condition allowing participants to (1) freely decide whether to press the response button or (2) to decide whether they wanted to press the response button with the right index finger or the left index finger. Results: The reaction times were increased when participants freely decided whether and how they wanted to respond compared to the go condition. Intentional processes were associated with a fronto-centrally located N2 and P3 potential. N2 and P3 amplitudes were increased during intentional actions compared to instructed responses (go). In addition, increased activity in the alpha-, beta- and gamma-frequency range was shown during voluntary behavior rather than during externally guided responses. Conclusion: These results may indicate that an additional cognitive process is needed for intentional actions compared to instructed behavior. However, the neural responses were comparatively independent of the kind of decision that was made (1) decision which action to perform; (2) decision whether or not to perform an action). Significance: The study demonstrates the importance of fronto-central alpha-, beta-, and gamma oscillations for voluntary behavior. PMID:26834680

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

    PubMed Central

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

    2012-01-01

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

  2. 76 FR 21938 - Potential Environmental Impacts of the Proposed Runway 13 Extension and Associated Actions for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-19

    ... Federal Aviation Administration Potential Environmental Impacts of the Proposed Runway 13 Extension and... Administration (FAA), Department of Transportation (DOT). ACTION: Notice of availability of a final EA and FONSI/ROD for the evaluation of the potential environmental impacts associated with the proposed Runway...

  3. The cytosolic calcium transient modulates the action potential of rat ventricular myocytes.

    PubMed Central

    duBell, W H; Boyett, M R; Spurgeon, H A; Talo, A; Stern, M D; Lakatta, E G

    1991-01-01

    1. The modulation of the action potential by the cytosolic Ca2+ (Cai2+) transient was studied in single isolated rat ventricular myocytes loaded with the acetoxymethyl ester form of the Ca(2+)-sensitive fluorescent dye Indo-1. Stimulation following rest and exposure to ryanodine were used to change the amount of Ca2+ released from the sarcoplasmic reticulum and thus the size of the Cai2+ transient. The Cai2+ transient was measured as the change, upon stimulation, in the ratio of Indo-1 fluorescence at 410 nm to that at 490 nm (410/490) and action potentials or membrane currents were recorded using patch-type microelectrodes. 2. When stimulation was initiated following rest, the magnitude of the Cai2+ transient decreased in a beat-dependent manner until a steady state was reached. The negative staircase in the Cai2+ transient was accompanied by a similar beat-dependent decrease in the duration of the action potential, manifested primarily as a gradual loss of the action potential plateau (approximately -45 mV). A slow terminal phase of repolarization of a few millivolts in amplitude was found to parallel the terminal decay of the Cai2+ transient. 3. The terminal portion of phase-plane loops of membrane potential (Vm) vs. Indo-1 ratio from all of the beats of a stimulus train followed a common linear trajectory even though the individual beats differed markedly in the duration and amplitude of the action potential and Cai2+ transient. 4. When the stimulation dependence of the Cai2+ transient was titrated away with submaximal exposure to ryanodine, the stimulation-dependent changes in the action potential plateau and terminal phase of repolarization were also eliminated. The same effect was noted in cells which, fortuitously, did not show a staircase in the Cai2+ transient following a period of rest. 5. When action potentials were triggered immediately following spontaneous release of Ca2+ from the sarcoplasmic reticulum, which results in a small depolarization at the

  4. A device for emulating cuff recordings of action potentials propagating along peripheral nerves.

    PubMed

    Rieger, Robert; Schuettler, Martin; Chuang, Sheng-Chih

    2014-09-01

    This paper describes a device that emulates propagation of action potentials along a peripheral nerve, suitable for reproducible testing of bio-potential recording systems using nerve cuff electrodes. The system is a microcontroller-based stand-alone instrument which uses established nerve and electrode models to represent neural activity of real nerves recorded with a nerve cuff interface, taking into consideration electrode impedance, voltages picked up by the electrodes, and action potential propagation characteristics. The system emulates different scenarios including compound action potentials with selectable propagation velocities and naturally occurring nerve traffic from different velocity fiber populations. Measured results from a prototype implementation are reported and compared with in vitro recordings from Xenopus Laevis frog sciatic nerve, demonstrating that the electrophysiological setting is represented to a satisfactory degree, useful for the development, optimization and characterization of future recording systems. PMID:24760928

  5. Prolonged action potential duration in cardiac ablation of PDK1 mice.

    PubMed

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

    2015-01-01

    The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis. PMID:26131127

  6. Effect of nanomaterials on the compound action potential of the shore crab, Carcinus maenas.

    PubMed

    Windeatt, Kirsten M; Handy, Richard D

    2013-06-01

    Little is known about the effects of manufactured nanomaterials on the function of nerves. The experiment aimed to test the effects of three different nanomaterials (1 mg l⁻¹ of TiO₂ NPs, Ag NPs or SWCNT) on the compound action potential of the shore crab (Carcinus maenas) compared with an appropriate bulk powder or metal salt control (bulk TiO₂ powder, AgNO₃ and carbon black respectively). In single action potential recordings, there were no effects of any of the nanomaterials on the peak amplitude, duration, rate of rise (depolarisation), or rate of decrease (repolarisation) of the compound action potential in crab saline, despite settling of each nanomaterial directly onto the nerve preparation. The ability of the crab nerve to be stimulated to tetanus was also unaffected by exposure to the nanomaterials compared with the appropriate bulk powder or metal salt control. Solvent controls with sodium dodecyl sulfate (SDS) also had no effect on action potentials. Overall, the study concludes that there were no effects of the materials at the concentrations tested on the compound action potential of the shore crab in physiological saline. PMID:22394242

  7. The role of inward Na(+)-Ca2+ exchange current in the ferret ventricular action potential.

    PubMed Central

    Janvier, N C; Harrison, S M; Boyett, M R

    1997-01-01

    1. Inward Na(+)-Ca2+ exchange current (iNaCa) was either blocked in ferret ventricular cells by replacing extracellular Na+ with Li+ or substantially reduced by the almost complete elimination of the Ca2+ transient by buffering intracellular Ca2+ with the acetoxymethyl ester form of BAPTA (BAPTA AM). 2. During square wave voltage clamp pulses to 0 mV, replacing extracellular Na+ with Li+ or buffering intracellular Ca2+ with BAPTA AM resulted in the loss of a transient inward current. This current was increased by the application of isoprenaline (expected to increase the underlying Ca2+ transient) and displayed the voltage-dependent characteristics of inward iNaCa. 3. Replacing extracellular Na+ with Li+ or buffering intracellular Ca2+ caused a significant shortening of the action potential (at -65 mV, 44 +/- 2% with Li+ and 20 +/- 2% with BAPTA AM). The shortening can be explained by changes in iNaCa. 4. The action potential clamp technique was used to measure the BAPTA-sensitive current (putative iNaCa) and the Ca2+ current (ica; measured using nifedipine) during the action potential. Under control conditions, the inward BAPTA-sensitive current makes approximately the same contribution as iCa during much of the action potential plateau. These results suggest an important role for inward iNaCa in the ferret ventricular action potential. PMID:9051574

  8. BOREAS TE-11 Sap Flow Data

    NASA Technical Reports Server (NTRS)

    Hall, Forrest G. (Editor); Papagno, Andrea (Editor); Saugier, Bernard

    2000-01-01

    The BOREAS TE-11 team collected several data sets in support of its efforts to characterize and interpret information on the sap flow, gas exchange, and lichen photosynthesis of boreal vegetation and meteorological data of the area studied. This data set contains measurements of sap flow conducted at the SSA-OJP site in the growing seasons of 1993 and 1994. The data are stored in ASCII files. The data files are available on a CD-ROM (see document number 20010000884), or from the Oak Ridge National Laboratory (ORNL) Distributed Active Center (DAAC).

  9. 21 CFR 133.186 - Sap sago cheese.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Sap sago cheese. 133.186 Section 133.186 Food and... Products § 133.186 Sap sago cheese. (a) Description. (1) Sap sago cheese is the food prepared by the... method described in § 133.5. Sap sago cheese is not less than 5 months old. (2) One or more of the...

  10. 21 CFR 133.186 - Sap sago cheese.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Sap sago cheese. 133.186 Section 133.186 Food and... Products § 133.186 Sap sago cheese. (a) Description. (1) Sap sago cheese is the food prepared by the... method described in § 133.5. Sap sago cheese is not less than 5 months old. (2) One or more of the...

  11. 21 CFR 133.186 - Sap sago cheese.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Sap sago cheese. 133.186 Section 133.186 Food and... Products § 133.186 Sap sago cheese. (a) Description. (1) Sap sago cheese is the food prepared by the... method described in § 133.5. Sap sago cheese is not less than 5 months old. (2) One or more of the...

  12. 21 CFR 133.186 - Sap sago cheese.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Sap sago cheese. 133.186 Section 133.186 Food and... Products § 133.186 Sap sago cheese. (a) Description. (1) Sap sago cheese is the food prepared by the... method described in § 133.5. Sap sago cheese is not less than 5 months old. (2) One or more of the...

  13. 21 CFR 133.186 - Sap sago cheese.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Sap sago cheese. 133.186 Section 133.186 Food and... Products § 133.186 Sap sago cheese. (a) Description. (1) Sap sago cheese is the food prepared by the... method described in § 133.5. Sap sago cheese is not less than 5 months old. (2) One or more of the...

  14. Optical coherence tomography for detection of compound action potential in Xenopus Laevis sciatic nerve

    NASA Astrophysics Data System (ADS)

    Troiani, Francesca; Nikolic, Konstantin; Constandinou, Timothy G.

    2016-03-01

    Due to optical coherence tomography (OCT) high spatial and temporal resolution, this technique could be used to observe the quick changes in the refractive index that accompany action potential. In this study we explore the use of time domain Optical Coherence Tomography (TD-OCT) for real time action potential detection in ex vivo Xenopus Laevis sciatic nerve. TD-OCT is the easiest and less expensive OCT technique and, if successful in detecting real time action potential, it could be used for low cost monitoring devices. A theoretical investigation into the order of magnitude of the signals detected by a TD-OCT setup is provided by this work. A linear dependence between the refractive index and the intensity changes is observed and the minimum SNR for which the setup could work is found to be SNR = 2 x 104.

  15. Initiation and blocking of the action potential in an axon in weak ultrasonic or microwave fields

    NASA Astrophysics Data System (ADS)

    Shneider, M. N.; Pekker, M.

    2014-05-01

    In this paper, we analyze the effect of the redistribution of the transmembrane ion channels in an axon caused by longitudinal acoustic vibrations of the membrane. These oscillations can be excited by an external source of ultrasound and weak microwave radiation interacting with the charges sitting on the surface of the lipid membrane. It is shown, using the Hodgkin-Huxley model of the axon, that the density redistribution of transmembrane sodium channels may reduce the threshold of the action potential, up to its spontaneous initiation. At the significant redistribution of sodium channels in the membrane, the rarefaction zones of the transmembrane channel density are formed, blocking the propagation of the action potential. Blocking the action potential propagation along the axon is shown to cause anesthesia in the example case of a squid axon. Various approaches to experimental observation of the effects considered in this paper are discussed.

  16. DBI potential, DBI inflation action and general Lagrangian relative to phantom, K-essence and quintessence

    SciTech Connect

    Zhang, Qing; Huang, Yong-Chang

    2011-11-01

    We derive a Dirac-Born-Infeld (DBI) potential and DBI inflation action by rescaling the metric. The determinant of the induced metric naturally includes the kinetic energy and the potential energy. In particular, the potential energy and kinetic energy can convert into each other in any order, which is in agreement with the limit of classical physics. This is quite different from the usual DBI action. We show that the Taylor expansion of the DBI action can be reduced into the form in the non-linear classical physics. These investigations are the support for the statement that the results of string theory are consistent with quantum mechanics and classical physics. We deduce the Phantom, K-essence, Quintessence and Generalized Klein-Gordon Equation from the DBI model.

  17. Optical magnetic detection of single-neuron action potentials using NV-diamond

    NASA Astrophysics Data System (ADS)

    Turner, Matthew; Barry, John; Schloss, Jennifer; Glenn, David; Walsworth, Ron

    2016-05-01

    A key challenge for neuroscience is noninvasive, label-free sensing of action potential dynamics in whole organisms with single-neuron resolution. Here, we report a new approach to this problem: using nitrogen-vacancy (NV) color centers in diamond to measure the time-dependent magnetic fields produced by single-neuron action potentials. We demonstrate our method using excised single neurons from two invertebrate species, marine worm and squid; and then by single-neuron action potential magnetic sensing exterior to whole, live, opaque marine worms for extended periods with no adverse effect. The results lay the groundwork for real-time, noninvasive 3D magnetic mapping of functional mammalian neuronal networks.

  18. Action potentials induce uniform calcium influx in mammalian myelinated optic nerves.

    PubMed

    Zhang, Chuan-Li; Wilson, J Adam; Williams, Justin; Chiu, Shing Yan

    2006-08-01

    The myelin sheath enables saltatory conduction by demarcating the axon into a narrow nodal region for excitation and an extended, insulated internodal region for efficient spread of passive current. This anatomical demarcation produces a dramatic heterogeneity in ionic fluxes during excitation, a classical example being the restriction of Na influx at the node. Recent studies have revealed that action potentials also induce calcium influx into myelinated axons of mammalian optic nerves. Does calcium influx in myelinated axons show spatial heterogeneity during nerve excitation? To address this, we analyzed spatial profiles of axonal calcium transients during action potentials by selectively staining axons with calcium indicators and subjected the data to theoretical analysis with parameters for axial calcium diffusion empirically determined using photolysis of caged compounds. The results show surprisingly that during action potentials, calcium influx occurs uniformly along an axon of a fully myelinated mouse optic nerve. PMID:16835363

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

    PubMed

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

    2016-08-01

    Electrode designs and strategies for electroneurogram recordings are often tested first by computer simulations and then by animal models, but they are rarely implanted for long-term evaluation in humans. The models show that the amplitude of the potential at the surface of an axon is higher in front of the nodes of Ranvier than at the internodes; however, this has not been investigated through in vivo measurements. An original experimental method is presented to emulate a single fiber action potential in an infinite conductive volume, allowing the potential of an axon to be recorded at both the nodes of Ranvier and the internodes, for a wide range of electrode-to-fiber radial distances. The paper particularly investigates the differences in the action potential amplitude along the longitudinal axis of an axon. At a short radial distance, the action potential amplitude measured in front of a node of Ranvier is two times larger than in the middle of two nodes. Moreover, farther from the phantom axon, the measured action potential amplitude is almost constant along the longitudinal axis. The results of this new method confirm the computer simulations, with a correlation of 97.6 %. PMID:27016364

  20. A Fast Na+/Ca2+-Based Action Potential in a Marine Diatom

    PubMed Central

    Taylor, Alison R.

    2009-01-01

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

  1. 49 CFR 655.52 - Substance abuse professional (SAP).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Substance abuse professional (SAP). 655.52 Section... OPERATIONS Drug and Alcohol Testing Procedures § 655.52 Substance abuse professional (SAP). The SAP must perform the functions in 49 CFR Part 40....

  2. 49 CFR 655.52 - Substance abuse professional (SAP).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Substance abuse professional (SAP). 655.52 Section... OPERATIONS Drug and Alcohol Testing Procedures § 655.52 Substance abuse professional (SAP). The SAP must perform the functions in 49 CFR Part 40....

  3. 49 CFR 655.52 - Substance abuse professional (SAP).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 7 2014-10-01 2014-10-01 false Substance abuse professional (SAP). 655.52 Section... OPERATIONS Drug and Alcohol Testing Procedures § 655.52 Substance abuse professional (SAP). The SAP must perform the functions in 49 CFR Part 40....

  4. 49 CFR 655.52 - Substance abuse professional (SAP).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Substance abuse professional (SAP). 655.52 Section... OPERATIONS Drug and Alcohol Testing Procedures § 655.52 Substance abuse professional (SAP). The SAP must perform the functions in 49 CFR Part 40....

  5. 49 CFR 655.52 - Substance abuse professional (SAP).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 7 2013-10-01 2013-10-01 false Substance abuse professional (SAP). 655.52 Section... OPERATIONS Drug and Alcohol Testing Procedures § 655.52 Substance abuse professional (SAP). The SAP must perform the functions in 49 CFR Part 40....

  6. The neuroendocrine action potential. Winner of the 2008 Frank Beach Award in Behavioral Neuroendocrinology.

    PubMed

    Hofmann, Hans A

    2010-09-01

    Animals are remarkably well equipped to respond to changes in their environment across different time scales and levels of biological organization. Here, I introduce a novel perspective that incorporates the three main processes the nervous system uses to integrate and process information: electrophysiological, genomic, and neuroendocrine action potentials. After discussing several examples of neuroendocrine action potentials, I lay out the commonalities of these temporally organized responses and how they might be interrelated with electrophysiological activity and genomic responses. This framework provides a novel outlook on longstanding questions in behavioral neuroendocrinology and suggests exciting new avenues for further research that will integrate across disciplines and levels of biological organization. PMID:20600047

  7. Effects of some heavy metals on the action potentials of an identified Helix pomatia photosensitive neuron.

    PubMed

    Kartelija, Gordana; Radenović, Lidija; Todorović, Natasa; Nedeljković, Miodrag

    2005-06-01

    In the photosensitive MB neuron in the left parietal ganglion of Helix pomatia, the onset of light prolongs significantly (by about 40%) the duration of the action potential. The broadening of the action potential after the onset of light was found to be due to its calcium component and could not be induced after blocking Ca(2+) channels by Cd(2+) and Pb(2+) and in absence of Ca(2+) in medium. The blocking effect of both compounds was reversible. It was found that CdCl(2) exhibited a more intense blocking effect than PbCl(2). PMID:16154952

  8. Euphorbia grandicornis Sap Keratouveitis: A Case Report

    PubMed Central

    Gómez-Valcárcel, María; Fuentes-Páez, Graciana

    2016-01-01

    Purpose To describe a case of keratouveitis caused by Euphorbia grandicornis sap, that resolved with topic steroids. Methods We report a case presentation of a patient with keratouveitis. Results A 70-year-old woman suffered from accidental ocular contact with E. grandicornis sap in her left eye. Two hours after the contact, she attended the clinic due to conjunctival hyperemia and pain. Best-corrected visual acuity (BCVA) was 20/25. The toxic conjunctivitis was treated with topical lubricant and steroid. After 24 h, she presented blurred vision. BCVA was 20/80. Toxic keratouveitis was diagnosed. Topical treatment with 1% cyclopentolate t.i.d., 5% sodium chloride, 1.14% dexamethasone phosphate each hour, and 4% sodium hyaluronate each hour was continued. Complete resolution was obtained 1 week later. Euphorbia sap content analysis was performed using dissolvent extraction spectrophotometry. Its contents included flavonoids, alkaloids, phenols and sesquiterpene lactones. Conclusion Corneal exposure to E. grandicornis sap is a cause of nonvisually threatening keratouveitis when adequately treated with corticosteroids. PMID:27293414

  9. Surface Absorption Polarization Sensors (SAPS), Final Technical Report, Laser Probing of Immobilized SAPS Actuators Component

    SciTech Connect

    Joseph I. Cline

    2010-04-22

    A novel hypothesized detection scheme for the detection of chemical agents was proposed: SAPS ``Surface-Adsorbed Polarization Sensors''. In this technique a thin layer of molecular rotors is adsorbed to a surface. The rotors can be energized by light absorption, but are otherwise locked in position or alternatively rotate slowly. Using polarized light, the adsorbed rotors are turned as an ensemble. Chemical agent (analyte) binding that alters the rotary efficiency would be detected by sensitive polarized absorption techniques. The mechanism of the SAPS detection can be mechanical, chemical, or photochemical: only a change in rotary efficiency is required. To achieve the goal of SAPS detection, new spectroscopic technique, polarized Normal Incidence Cavity Ringdown Spectroscopy (polarized NICRDS), was developed. The technique employs very sensitive and general Cavity Ringdown absorption spectroscopy along with the ability to perform polarized absorption measurements. Polarized absorption offers the ability to measure the angular position of molecular chromophores. In the new experiments a thin layer of SAPS sensors (roughly corresponding to a monolayer coverage on a surface) immobilized in PMMA. The PMMA layer is less than 100~nm thick and is spin-coated onto a flat fused-silica substrate. The new technique was applied to study the photoisomerization-driven rotary motion of a family of SAPS actuators based on a family of substituted dibenzofulvene rotors based upon 9-(2,2,2- triphenylethylidene)fluorene. By varying the substitution to include moieties such as nitro, amino, and cyano the absorption spectrum and the quantum efficiency of photoisomerization can be varied. This SAPS effect was readily detected by polarized NICRDS. The amino substituted SAPS actuator binds H+ to form an ammonium species which was shown to have a much larger quantum efficiency for photoisomerization. A thin layer of immobilized amino actuators were then shown by polarized NICRDS to have a

  10. Spatiotemporal pattern of action potential firing in developing inner hair cells of the mouse cochlea.

    PubMed

    Sendin, Gaston; Bourien, Jérôme; Rassendren, François; Puel, Jean-Luc; Nouvian, Régis

    2014-02-01

    Inner hair cells (IHCs) are the primary transducer for sound encoding in the cochlea. In contrast to the graded receptor potential of adult IHCs, immature hair cells fire spontaneous calcium action potentials during the first postnatal week. This spiking activity has been proposed to shape the tonotopic map along the ascending auditory pathway. Using perforated patch-clamp recordings, we show that developing IHCs fire spontaneous bursts of action potentials and that this pattern is indistinguishable along the basoapical gradient of the developing cochlea. In both apical and basal IHCs, the spiking behavior undergoes developmental changes, where the bursts of action potential tend to occur at a regular time interval and have a similar length toward the end of the first postnatal week. Although disruption of purinergic signaling does not interfere with the action potential firing pattern, pharmacological ablation of the α9α10 nicotinic receptor elicits an increase in the discharge rate. We therefore suggest that in addition to carrying place information to the ascending auditory nuclei, the IHCs firing pattern controlled by the α9α10 receptor conveys a temporal signature of the cochlear development. PMID:24429348

  11. CCA-1, EGL-19 and EXP-2 currents shape action potentials in the Caenorhabditis elegans pharynx

    PubMed Central

    Shtonda, Boris; Avery, Leon

    2005-01-01

    The pharynx of Caenorhabditis elegans is a tubular muscle controlled by its own set of neurons. We developed a technique to voltage clamp the pharyngeal muscle and demonstrate by analyzing mutants that the pharyngeal action potential is regulated by three major voltage-gated currents, conducted by a T-type calcium channel CCA-1, an L-type calcium channel EGL-19 and a potassium channel EXP-2. We show that CCA-1 exhibits T-type calcium channel properties: activation at −40 mV and rapid inactivation. Our results suggest that CCA-1’s role is to accelerate the action potential upstroke in the pharyngeal muscle in response to excitatory inputs. Similarly to other L-type channels, EGL-19 activates at high voltages and inactivates slowly; thus it may maintain the plateau phase of the action potential. EXP-2 is a potassium channel of the kV family that shows inward rectifier properties when expressed in Xenopus laevis oocytes. We show that endogenous EXP-2 is not a true inward rectifier – it conducts large outward currents at potentials up to +20 mV and is therefore well suited to trigger rapid repolarization at the end of the action potential plateau phase. Our results suggest that EXP-2 is a potassium channel with unusual properties that uses a hyperpolarization threshold to activate a regenerative hyperpolarizing current. PMID:15914661

  12. 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

  13. 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. PMID:27525414

  14. Wogonin potentiates the antitumor action of etoposide and ameliorates its adverse effects.

    PubMed

    Enomoto, Riyo; Koshiba, Chika; Suzuki, Chie; Lee, Eibai

    2011-05-01

    Wogonin, a flavone in the roots of Scutellaria baicalensis, reduced etoposide-induced apoptotic cell death in normal cells, such as bone marrow cells and thymocytes. On the other hand, wogonin potentiated the proapoptotic or cytotoxic action of etoposide in tumor cells, such as Jurkat, HL-60, A549, and NCI-H226. These contradictory actions of wogonin on apoptosis are distinguished by normal or cancer cell types. Wogonin had no effect on apoptosis induced by other anticancer agents in the tumor cells. Thus, the potentiation effect of wogonin was observed only in etoposide-induced apoptosis in tumor cells. In a functional assay for P-glycoprotein (P-gp), wogonin suppressed excretion of calcein, a substrate for P-gp, in these tumor cells. Moreover, wogonin decreased the excretion of radiolabeled etoposide and accordingly increased intracellular content of this agent in the cells. P-gp inhibitors showed a similar potentiation effect on etoposide-induced apoptosis in these tumor cells. Thus, wogonin is likely to potentiate the anticancer action of etoposide due to P-gp inhibition and accumulation of this agent. These findings suggest that wogonin may be a useful chemotherapeutic adjuvant to potentiate the pharmacological action of etoposide and ameliorate its adverse effects. PMID:20658136

  15. Naturalistic stimulation changes the dynamic response of action potential encoding in a mechanoreceptor

    PubMed Central

    Pfeiffer, Keram; French, Andrew S.

    2015-01-01

    Naturalistic signals were created from vibrations made by locusts walking on a Sansevieria plant. Both naturalistic and Gaussian noise signals were used to mechanically stimulate VS-3 slit-sense mechanoreceptor neurons of the spider, Cupiennius salei, with stimulus amplitudes adjusted to give similar firing rates for either stimulus. Intracellular microelectrodes recorded action potentials, receptor potential, and receptor current, using current clamp and voltage clamp. Frequency response analysis showed that naturalistic stimulation contained relatively more power at low frequencies, and caused increased neuronal sensitivity to higher frequencies. In contrast, varying the amplitude of Gaussian stimulation did not change neuronal dynamics. Naturalistic stimulation contained less entropy than Gaussian, but signal entropy was higher than stimulus in the resultant receptor current, indicating addition of uncorrelated noise during transduction. The presence of added noise was supported by measuring linear information capacity in the receptor current. Total entropy and information capacity in action potentials produced by either stimulus were much lower than in earlier stages, and limited to the maximum entropy of binary signals. We conclude that the dynamics of action potential encoding in VS-3 neurons are sensitive to the form of stimulation, but entropy and information capacity of action potentials are limited by firing rate. PMID:26578975

  16. Investigating a Potential Auxin-Related Mode of Hormetic/Inhibitory Action of the Phytotoxin Parthenin.

    PubMed

    Belz, Regina G

    2016-01-01

    Parthenin is a metabolite of Parthenium hysterophorus and is believed to contribute to the weed's invasiveness via allelopathy. Despite the potential of parthenin to suppress competitors, low doses stimulate plant growth. This biphasic action was hypothesized to be auxin-like and, therefore, an auxin-related mode of parthenin action was investigated using two approaches: joint action experiments with Lactuca sativa, and dose-response experiments with auxin/antiauxin-resistant Arabidopsis thaliana genotypes. The joint action approach comprised binary mixtures of subinhibitory doses of the auxin 3-indoleacetic acid (IAA) mixed with parthenin or one of three reference compounds [indole-3-butyric acid (IBA), 2,3,5-triiodobenzoic acid (TIBA), 2-(p-chlorophenoxy)-2-methylpropionic acid (PCIB)]. The reference compounds significantly interacted with IAA at all doses, but parthenin interacted only at low doses indicating that parthenin hormesis may be auxin-related, in contrast to its inhibitory action. The genetic approach investigated the response of four auxin/antiauxin-resistant mutants and a wildtype to parthenin or two reference compounds (IAA, PCIB). The responses of mutant plants to the reference compounds confirmed previous reports, but differed from the responses observed for parthenin. Parthenin stimulated and inhibited all mutants independent of resistance. This provided no indication for an auxin-related action of parthenin. Therefore, the hypothesis of an auxin-related inhibitory action of parthenin was rejected in two independent experimental approaches, while the hypothesis of an auxin-related stimulatory effect could not be rejected. PMID:26686984

  17. Groundwater sapping processes, Western Desert, Egypt.

    SciTech Connect

    Luo, W.; Arvidson, R.E.; Sultan, M.; Becker, R.; Crombie, M.K.; Sturchio, N.; El Alfy, Z.; Environmental Research; Washington Univ.; Egyptian Geological Survey and Mining Authority

    1997-01-01

    Depressions of the Western Desert of Egypt (specifically, Kharga, Farafra, and Kurkur regions) are mainly occupied by shales that are impermeable, but easily erodible by rainfall and runoff, whereas the surrounding plateaus are composed of limestones that are permeable and more resistant to fluvial erosion under semiarid to arid conditions. Scallop-shaped escarpment edges and stubby-looking channels that cut into the plateau units are suggestive of slumping of limestones by ground-water sapping at the limestone-shale interfaces, removal of slump blocks by weathering and fluvial erosion, and consequent scarp retreat. Spring-derived tufa deposits found near the limestone escarpments provide additional evidence for possible ground-water sapping during previous wet periods. A computer simulation model was developed to quantify the ground-water sapping processes, using a cellular automata algorithm with coupled surface runoff and ground-water flow for a permeable, resistant layer over an impermeable, friable unit. Erosion, deposition, slumping, and generation of spring-derived tufas were parametrically modeled. Simulations using geologically reasonable parameters demonstrate that relatively rapid erosion of the shales by surface runoff, ground-water sapping, and slumping of the limestones, and detailed control by hydraulic conductivity inhomogeneities associated with structures explain the depressions, escarpments, and associated landforms and deposits. Using episodic wet pulses, keyed by {delta}{sup 18}O deep-sea core record, the model produced tufa ages that are statistically consistent with the observed U/Th tufa ages. This result supports the hypothesis that northeastern African wet periods occurred during interglacial maxima. The {delta}{sup 18}O-forced model also replicates the decrease in fluvial and sapping activity over the past million years, as northeastern Africa became hyperarid. The model thus provides a promising predictive tool for studying long

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

    SciTech Connect

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

    2013-04-26

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

  19. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Reporting potential natural disasters and initial actions. 1945.19 Section 1945.19 Agriculture Regulations of the Department of Agriculture (Continued... AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) EMERGENCY...

  20. Viewing Objects and Planning Actions: On the Potentiation of Grasping Behaviours by Visual Objects

    ERIC Educational Resources Information Center

    Makris, Stergios; Hadar, Aviad A.; Yarrow, Kielan

    2011-01-01

    How do humans interact with tools? Gibson (1979) suggested that humans perceive directly what tools afford in terms of meaningful actions. This "affordances" hypothesis implies that visual objects can potentiate motor responses even in the absence of an intention to act. Here we explore the temporal evolution of motor plans afforded by common…

  1. Primary cortical representation of sounds by the coordination of action-potential timing

    NASA Astrophysics Data System (ADS)

    Decharms, R. Christopher; Merzenich, Michael M.

    1996-06-01

    CORTICAL population coding could in principle rely on either the mean rate of neuronal action potentials, or the relative timing of action potentials, or both. When a single sensory stimulus drives many neurons to fire at elevated rates, the spikes of these neurons become tightly synchronized1,2, which could be involved in 'binding' together individual firing-rate feature representations into a unified object percept3. Here we demonstrate that the relative timing of cortical action potentials can signal stimulus features themselves, a function even more basic than feature grouping. Populations of neurons in the primary auditory cortex can coordinate the relative timing of their action potentials such that spikes occur closer together in time during continuous stimuli. In this way cortical neurons can signal stimuli even when their firing rates do not change. Population coding based on relative spike timing can systematically signal stimulus features, it is topographically mapped, and it follows the stimulus time course even where mean firing rate does not.

  2. Youth Participatory Action Research and Educational Transformation: The Potential of Intertextuality as a Methodological Tool

    ERIC Educational Resources Information Center

    Bertrand, Melanie

    2016-01-01

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

  3. Optical recording of action potentials with second-harmonic generation microscopy.

    PubMed

    Dombeck, Daniel A; Blanchard-Desce, Mireille; Webb, Watt W

    2004-01-28

    Nonlinear microscopy has proven to be essential for neuroscience investigations of thick tissue preparations. However, the optical recording of fast (approximately 1 msec) cellular electrical activity has never until now been successfully combined with this imaging modality. Through the use of second-harmonic generation microscopy of primary Aplysia neurons in culture labeled with 4-[4-(dihexylamino)phenyl][ethynyl]-1-(4-sulfobutyl)pyridinium (inner salt), we optically recorded action potentials with 0.833 msec temporal and 0.6 microm spatial resolution on soma and neurite membranes. Second-harmonic generation response as a function of change in membrane potential was found to be linear with a signal change of approximately 6%/100 mV. The signal-to-noise ratio was approximately 1 for single-trace action potential recordings but was readily increased to approximately 6-7 with temporal averaging of approximately 50 scans. Photodamage was determined to be negligible by observing action potential characteristics, cellular resting potential, and gross cellular morphology during and after laser illumination. High-resolution (micrometer scale) optical recording of membrane potential activity by previous techniques has been limited to imaging depths an order of magnitude less than nonlinear methods. Because second-harmonic generation is capable of imaging up to approximately 400 microm deep into intact tissue with submicron resolution and little out-of-focus photodamage or bleaching, its ability to record fast electrical activity should prove valuable to future electrophysiology studies. PMID:14749445

  4. Sap flow measurements to determine the transpiration of facade greenings

    NASA Astrophysics Data System (ADS)

    Hölscher, Marie-Therese; Nehls, Thomas; Wessolek, Gerd

    2014-05-01

    Facade greening is expected to make a major contribution to the mitigation of the urban heat-island effect through transpiration cooling, thermal insulation and shading of vertical built structures. However, no studies are available on water demand and the transpiration of urban vertical green. Such knowledge is needed as the plants must be sufficiently watered, otherwise the posited positive effects of vertical green can turn into disadvantages when compared to a white wall. Within the framework of the German Research Group DFG FOR 1736 "Urban Climate and Heat Stress" this study aims to test the practicability of the sap flow technique for transpiration measurements of climbing plants and to obtain potential transpiration rates for the most commonly used species. Using sap flow measurements we determined the transpiration of Fallopia baldschuanica, Parthenocissus tricuspidata and Hedera helix in pot experiments (about 1 m high) during the hot summer period from August 17th to August 30th 2012 under indoor conditions. Sap flow measurements corresponded well to simultaneous weight measurement on a daily base (factor 1.19). Fallopia baldschuanica has the highest daily transpiration rate based on leaf area (1.6 mm d-1) and per base area (5.0 mm d-1). Parthenocissus tricuspidata and Hedera helix show transpiration rates of 3.5 and 0.4 mm d-1 (per base area). Through water shortage, transpiration strongly decreased and leaf temperature measured by infrared thermography increased by 1 K compared to a well watered plant. We transferred the technique to outdoor conditions and will present first results for facade greenings in the inner-city of Berlin for the hottest period in summer 2013.

  5. Cellular electrophysiology of canine pulmonary vein cardiomyocytes: action potential and ionic current properties

    PubMed Central

    Ehrlich, Joachim R; Cha, Tae-Joon; Zhang, Liming; Chartier, Denis; Melnyk, Peter; Hohnloser, Stefan H; Nattel, Stanley

    2003-01-01

    Pulmonary vein (PV) cardiomyocytes play an important role in atrial fibrillation; however, little is known about their specific cellular electrophysiological properties. We applied standard microelectrode recording and whole-cell patch-clamp to evaluate action potentials and ionic currents in canine PVs and left atrium (LA) free wall. Resting membrane potential (RMP) averaged −66 ± 1 mV in PVs and −74 ± 1 mV in LA (P < 0.0001) and action potential amplitude averaged 76 ± 2 mV in PVs vs. 95 ± 2 mV in LA (P < 0.0001). PVs had smaller maximum phase 0 upstroke velocity (Vmax: 98 ± 9 vs. 259 ± 16 V s−1, P < 0.0001) and action potential duration (APD): e.g. at 2 Hz, APD to 90 % repolarization in PVs was 84 % of LA (P < 0.05). Na+ current density under voltage-clamp conditions was similar in PV and LA, suggesting that smaller Vmax in PVs was due to reduced RMP. Inward rectifier current density in the PV cardiomyocytes was ˜58 % that in the LA, potentially accounting for the less negative RMP in PVs. Slow and rapid delayed rectifier currents were greater in the PV (by ˜60 and ˜50 %, respectively), whereas transient outward K+ current and L-type Ca2+ current were significantly smaller (by ˜25 and ˜30 %, respectively). Na+-Ca2+-exchange (NCX) current and T-type Ca2+ current were not significantly different. In conclusion, PV cardiomyocytes have a discrete distribution of transmembrane ion currents associated with specific action potential properties, with potential implications for understanding PV electrical activity in cardiac arrhythmias. PMID:12847206

  6. Sodium-calcium exchange during the action potential in guinea-pig ventricular cells.

    PubMed Central

    Egan, T M; Noble, D; Noble, S J; Powell, T; Spindler, A J; Twist, V W

    1989-01-01

    1. Slow inward tail currents attributable to electrogenic sodium-calcium exchange can be recorded by imposing hyperpolarizing voltage clamp pulses during the normal action potential of isolated guinea-pig ventricular cells. The hyperpolarizations return the membrane to the resting potential (between -65 and -88 m V) allowing an inward current to be recorded. This current usually has peak amplitude when repolarization is imposed during the first 50 ms after the action potential upstroke, but becomes negligible once the final phase of repolarization is reached. The envelope of peak current tail amplitudes strongly resembles that of the intracellular calcium transient recorded in other studies. 2. Repetitive stimulation producing normal action potentials at a frequency of 2 Hz progressively augments the tail current recorded immediately after the stimulus train. Conversely, if each action potential is prematurely terminated at 0.1 Hz, repetitive stimulation produces a tail current much smaller than the control value. The control amplitude of inward current is only maintained if interrupted action potentials are separated by at least one full 'repriming' action potential. These effects mimic those on cell contraction (Arlock & Wohlfart, 1986) and suggest that progressive changes in tail current are controlled by variations in the amplitude and time course of the intracellular calcium transient. 3. When intracellular calcium is buffered sufficiently to abolish contraction, the tail current is abolished. Substitution of calcium with strontium greatly reduces the tail current. 4. The inward tail current can also be recorded at more positive membrane potentials using standard voltage clamp pulse protocols. In this way it was found that temperature has a large effect on the tail current, which can change from net inward at 22 degrees C to net outward at 37 degrees C. The largest inward currents are usually recorded at about 30 degrees C. It is shown that this effect is

  7. The SAP, a new family of proteins, associate and function positively with the SIT4 phosphatase.

    PubMed Central

    Luke, M M; Della Seta, F; Di Como, C J; Sugimoto, H; Kobayashi, R; Arndt, K T

    1996-01-01

    SIT4 is the catalytic subunit of a type 2A-related protein phosphatase in Saccharomyces cerevisiae that is required for G1 cyclin transcription and for bud formation. SIT4 associates with several high-molecular-mass proteins in a cell cycle-dependent fashion. We purified two SIT4-associated proteins, SAP155 and SAP190, and cloned the corresponding genes. By sequence homology, we isolated two additional SAP genes, SAP185 and SAP4. Through such an association is not yet proven for SAP4, each of SAP155, SAP185, and SAP190 physically associates with SIT4 in separate complexes. The SAPs function positively with SIT4, and by several criteria, the loss of all four SAPs is equivalent to the loss of SIT4. The data suggest that the SAPs are not functional in the absence of SIT4 and likewise that SIT4 is not functional in the absence of the SAPs. The SAPs are hyperphoshorylated in cells lacking SIT4, raising the possibility that the SAPs are substrates of SIT4. By sequence similarity, the SAPs fall into two groups, the SAP4/SAP155 group and the SAP185/SAP190 group. Overexpression of a SAP from one group does not suppress the defects due to the loss of the other group. These findings and others indicate that the SAPs have distinct functions. PMID:8649382

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

  9. Toward a system to measure action potential on mice brain slices with local magnetoresistive probes

    SciTech Connect

    Amaral, J.; Cardoso, S.; Freitas, P. P.; Sebastiao, A. M.

    2011-04-01

    This work combines an electrophysiological system with a magnetoresistive chip to measure the magnetic field created by the synaptic/action potential currents. The chip, with 15 spin valve sensors, was designed to be integrated in a recording chamber for submerged mice brain slices used for synaptic potential measurements. Under stimulation (rectangular pulses of 0.1 ms every 10 s) through a concentric electrode placed near the CA3/CA1 border of the hippocampus, the spin valve sensor readout signals with 20 {mu}V amplitude and a pulse length of 20 to 30 ms were recorded only in the pyramidal cell bodies region and can be interpreted as being derived from action potentials/currents.

  10. Acute NMDA receptor antagonism disrupts synchronization of action potential firing in rat prefrontal cortex.

    PubMed

    Molina, Leonardo A; Skelin, Ivan; Gruber, Aaron J

    2014-01-01

    Antagonists of N-methyl-D-aspartate receptors (NMDAR) have psychotomimetic effects in humans and are used to model schizophrenia in animals. We used high-density electrophysiological recordings to assess the effects of acute systemic injection of an NMDAR antagonist (MK-801) on ensemble neural processing in the medial prefrontal cortex of freely moving rats. Although MK-801 increased neuron firing rates and the amplitude of gamma-frequency oscillations in field potentials, the synchronization of action potential firing decreased and spike trains became more Poisson-like. This disorganization of action potential firing following MK-801 administration is consistent with changes in simulated cortical networks as the functional connections among pyramidal neurons become less clustered. Such loss of functional heterogeneity of the cortical microcircuit may disrupt information processing dependent on spike timing or the activation of discrete cortical neural ensembles, and thereby contribute to hallucinations and other features of psychosis induced by NMDAR antagonists. PMID:24465743

  11. Synthesis and processing of sphingolipid activator protein-2 (SAP-2) in cultured human fibroblasts

    SciTech Connect

    Fujibayashi, S.; Wenger, D.A.

    1986-11-15

    Sphingolipid activator proteins (SAP) are relatively small molecular weight proteins that stimulate the enzymatic hydrolysis of sphingolipids in the presence of specific lysosomal hydrolases. SAP-2 has previously been demonstrated to activate the hydrolysis of glucosylceramide, galactosylceramide, and, possibly, sphingomyelin. Using monospecific rabbit antibodies against human spleen SAP-2, the synthesis and processing of SAP-2 were studied in cultured human fibroblasts. When (/sup 35/S)methionine was presented in the medium to control human cells for 4 h, five major areas of radiolabeling were found. These had apparent molecular weights of 73,000, 68,000, 50,000, 12,000, and 9000. Further studies indicated that the major extracellular product in normal cells given NH4Cl along with the (/sup 35/S)methionine and in medium from cultures from patients with I cell disease had an apparent molecular weight of 73,000. The Mr = 68,000 and 73,000 species can be converted to a species with an apparent molecular weight of 50,000 by the action of endoglycosidase F. After labeling cells for 1 h followed by a 1-h chase, the Mr = 12,000 and 9000 species appear. Treatment of the immunoprecipitated mixture with endoglycosidase F resulted in conversion of these species to one band with an apparent molecular weight of 7600. These studies indicate that this relatively low molecular weight protein is rapidly synthesized from a relatively large molecular weight highly glycosylated precursor.

  12. Understanding the cardiovascular actions of soy isoflavones: potential novel targets for antihypertensive drug development.

    PubMed

    Martin, Doug; Song, Jin; Mark, Connie; Eyster, Kathleen

    2008-12-01

    Interest in and use of "natural" remedies has grown exponentially in recent years. Compounds that have attracted considerable attention are the isoflavones, particular those found in soy. This review will provide a critical evaluation of our current understanding of the effects, mechanisms of action, and potential clinical applications of soy isoflavones in hypertension. Current data indicate that soy isoflavones, such as genistein and daidzein and equol, relax vascular smooth muscle both in vitro and in vivo via a combination of mechanisms including potentiation of endothelial-dependent and endothelial-independent vasodilator systems and inhibition of constrictor mechanisms. These effects involve both classical genomic as well non genomic actions. Isoflavone actions are mediated in part via interactions with estrogen receptors where soy isoflavones induce unique receptor conformations and exert tissue dependent effects similar to the selective estrogen receptor modulators. Signaling pathways such as ERK1/2, PI3-Kinase/Akt and cAMP contribute to isoflavone isoflavone activation of eNOS in the vasculature as well. Isoflavones also target the kidney to increase renal blood flow and sodium excretion. Finally, soy isoflavones interact with humoral systems such as the renin angiotensin. Data from animal studies show consistently that the aggregate effect of these actions is attenuation of hypertension. In contrast, studies in humans remain controversial. Recent data also suggest that analogues of isoflavones may possess unique vascular actions. Thus significant opportunity remains for study of the effects and mechanisms of action of soy isoflavones on hypertension in both animals and humans. PMID:19202595

  13. Spontaneous muscle action potentials fail to develop without fetal-type acetylcholine receptors

    PubMed Central

    Takahashi, Masazumi; Kubo, Tai; Mizoguchi, Akira; Carlson, C. George; Endo, Katsuaki; Ohnishi, Katsunori

    2002-01-01

    In mammals, two combinations of muscle nicotinic acetylcholine receptors (AChRs) are used: α2βγδ (γ-AChR) or α2βɛδ (ɛ-AChR). After birth, γ-AChRs are replaced by ɛ-AChRs (γ/ɛ-switch). The two receptors have different conductances and open times. During perinatal period, the long open time γ-AChRs generate random myofiber action potentials from uniquantal miniature end-plate potentials (mEPPs). ɛ-AChRs are suitable for strong adult muscle activities. Since the effect of the γ/ɛ-switch on neuromuscular development was unclear, despite the many differences in channel characteristics, we carried out this study to generate γ-subunit-deficient mice. Homozygotes born alive survived for 2 days in a stable condition, and were able to move their forelimbs. Endplate AChRs included ɛ-subunits, and muscle fibers had multiple neuromuscular junctions. Both pre- and postsynapses were abnormal and spontaneous action potentials generated from mEPPs were totally absent. Results suggest a requirement for γ-AChRs in mediating synaptically-induced action potential activity critical for neuromuscular development. PMID:12101101

  14. Event-related potentials reveal early activation of body part representations in action concept comprehension.

    PubMed

    Lu, Aitao; Liu, Jing; Zhang, John X

    2012-03-01

    With tasks involving action concept comprehension, many fMRI studies have reported brain activations in sensori-motor regions specific to effectors of the referent action. There is relatively less evidence whether such activations reflect early semantic access or late conceptual re-processing. Here we recorded event-related potentials when participants recognized noun-verb pairs. For Congruent pairs, the verb was the one most commonly associated with the noun (e.g., football-kick). Compared with a control condition, verbs in Congruent pairs showed priming effects in the time windows of 100-150 ms and 210-260 ms. Such activation seems to be specific to body part but not other aspects of the action as similar priming effect was also found when the noun and verb involved different actions though sharing the same body part (e.g., football-jump), documenting for the first time the early activation of body part representations in action concept comprehension. PMID:22306088

  15. Dynamics of Subauroral Polarization Stream (SAPS) Structures

    NASA Astrophysics Data System (ADS)

    Sazykin, S. Y.; Coster, A. J.; Huba, J.; Ridley, A. J.; Erickson, P. J.; Foster, J. C.; Baker, J. B. H.; Wolf, R.

    2015-12-01

    The Subauroral Polarization Stream (SAPS) flow structures are narrow ionospheric channels of fast (in excess of 100 m/s) westward drift just outside the equatorward edge of the diffuse aurora in the dusk-to-midnight local time sector. Other terms for this phenomenon include subauroral Ion Drift (SAID) events and Polarization Jets. SAPS structures represent a striking departure from the commonly-used two-cell convection pattern. They are thought to arise from the displacement of the downward region-2 Birkeland currents on the dusk side equatorward of the low-latitude boundary of the auroral oval during times of changing high-latitude convection. In this paper, we will use several event simulations with the SAMI3-RCM numerical model (a self-consistent ionosphere-inner magnetosphere model) and RCM-GITM (a self-consistent model of the ionosphere-thermosphere-inner magnetosphere) to analyze the relative roles of changes in the IMF Bz component, ionospheric electron density depletions, and thermospheric modifications in controlling the dynamics of SAPS. Simulation results will be compared to multi-instrument ionospheric observations.

  16. Potentiators of Defective ΔF508-CFTR Gating that Do Not Interfere with Corrector Action.

    PubMed

    Phuan, Puay-Wah; Veit, Guido; Tan, Joseph A; Finkbeiner, Walter E; Lukacs, Gergely L; Verkman, A S

    2015-10-01

    Combination drug therapies under development for cystic fibrosis caused by the ∆F508 mutation in cystic fibrosis transmembrane conductance regulator (CFTR) include a "corrector" to improve its cellular processing and a "potentiator" to improve its chloride channel function. Recently, it was reported that the approved potentiator N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (Ivacaftor) reduces ∆F508-CFTR cellular stability and the efficacy of investigational correctors, including 3-(6-[([1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl) amino]-3-methyl-2-pyridinyl)-benzoic acid and 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-(1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(2-hydroxy-1,1-dimethylethyl)-1H-indol-5-yl), which might contribute to the modest reported efficacy of combination therapy in clinical trials. Here, we report the identification and characterization of potentiators that do not interfere with ∆F508-CFTR stability or corrector action. High-throughput screening and structure-activity analysis identified several classes of potentiators that do not impair corrector action, including tetrahydrobenzothiophenes, thiooxoaminothiazoles, and pyrazole-pyrrole-isoxazoles. The most potent compounds have an EC(50) for ∆F508-CFTR potentiation down to 18 nM and do not reduce corrector efficacy in heterologous ∆F508-CFTR-expressing cells or primary cultures of ∆F508/∆F508 human bronchial epithelia. The ΔF508-CFTR potentiators also activated wild-type and G551D CFTR, albeit weakly. The efficacy of combination therapy for cystic fibrosis caused by the ∆F508 mutation may be improved by replacement of Ivacaftor with a potentiator that does not interfere with corrector action. PMID:26245207

  17. A Critical Role for the GluA1 Accessory Protein, SAP97, in Cocaine Seeking.

    PubMed

    White, Samantha L; Ortinski, Pavel I; Friedman, Shayna H; Zhang, Lei; Neve, Rachael L; Kalb, Robert G; Schmidt, Heath D; Pierce, R Christopher

    2016-02-01

    A growing body of evidence indicates that the transport of GluA1 subunit-containing calcium-permeable AMPA receptors (CP-AMPARs) to synapses in subregions of the nucleus accumbens promotes cocaine seeking. Consistent with these findings, the present results show that administration of the CP-AMPAR antagonist, Naspm, into the caudal lateral core or caudal medial shell of the nucleus accumbens attenuated cocaine priming-induced reinstatement of drug seeking. Moreover, viral-mediated overexpression of 'pore dead' GluA1 subunits (via herpes simplex virus (HSV) GluA1-Q582E) in the lateral core or medial shell attenuated the reinstatement of cocaine seeking. The overexpression of wild-type GluA1 subunits (via HSV GluA1-WT) in the medial shell, but not the lateral core, enhanced the reinstatement of cocaine seeking. These results indicate that activation of GluA1-containing AMPARs in subregions of the nucleus accumbens reinstates cocaine seeking. SAP97 and 4.1N are proteins involved in GluA1 trafficking to and stabilization in synapses; SAP97-GluA1 interactions also influence dendritic growth. We next examined potential roles of SAP97 and 4.1N in cocaine seeking. Viral-mediated expression of a microRNA that reduces SAP97 protein expression (HSV miSAP97) in the medial accumbens shell attenuated cocaine seeking. In contrast, a virus that overexpressed a dominant-negative form of a 4.1N C-terminal domain (HSV 4.1N-CTD), which prevents endogenous 4.1N binding to GluA1 subunits, had no effect on cocaine seeking. These results indicate that the GluA1 subunit accessory protein SAP97 may represent a novel target for pharmacotherapeutic intervention in the treatment of cocaine craving. PMID:26149358

  18. Tuning of Ranvier node and internode properties in myelinated axons to adjust action potential timing

    PubMed Central

    Ford, Marc C.; Alexandrova, Olga; Cossell, Lee; Stange-Marten, Annette; Sinclair, James; Kopp-Scheinpflug, Conny; Pecka, Michael; Attwell, David; Grothe, Benedikt

    2015-01-01

    Action potential timing is fundamental to information processing; however, its determinants are not fully understood. Here we report unexpected structural specializations in the Ranvier nodes and internodes of auditory brainstem axons involved in sound localization. Myelination properties deviated significantly from the traditionally assumed structure. Axons responding best to low-frequency sounds had a larger diameter than high-frequency axons but, surprisingly, shorter internodes. Simulations predicted that this geometry helps to adjust the conduction velocity and timing of action potentials within the circuit. Electrophysiological recordings in vitro and in vivo confirmed higher conduction velocities in low-frequency axons. Moreover, internode length decreased and Ranvier node diameter increased progressively along the distal axon segments, which simulations show was essential to ensure precisely timed depolarization of the giant calyx of Held presynaptic terminal. Thus, individual anatomical parameters of myelinated axons can be tuned to optimize pathways involved in temporal processing. PMID:26305015

  19. A reconstruction of charge movement during the action potential in frog skeletal muscle.

    PubMed Central

    Huang, C. L.; Peachey, L. D.

    1992-01-01

    The transfer of intramembrane charge during an action potential at 4 degrees C was reconstructed for a model representing the electrical properties of frog skeletal muscle by a cylindrical surface membrane and 16 concentric annuli ("shells") of transverse tubular membrane of equal radial thickness. The lumina of the transverse tubules were separated from extracellular fluid by a fixed series resistance. The quantity, geometrical distribution and steady-state and kinetic properties of charge movement components were described by equations incorporating earlier experimental results. Introducing such nonlinear charge into the distributed model for muscle membrane diminished the maximum amplitude of the action potential within the transverse tubules by 2 mV but increased the maximum size of the after-depolarization by 3-5 mV and also its duration. However, these changes were small in comparison to the 135-mV deflection represented by the action potential. They therefore did not justify altering the values of the electrical parameters adopted by Adrian R.H., and L.D. Peachey (1973. J. Physiol. [Lond.]. 235:103-131.) and used in the present calculations. Cable properties significantly affected the time course and extent of charge movement in each shell during action potential propagation into the tubular system. Q beta charge moved relatively rapidly in all annuli, and did so without significant latency (approximately 0.3 ms) after the surface action potential upstroke. Its peak displacement varied between 53 and 58% (the range representing the difference fiber edge/fiber axis) of the total Q beta charge. This was attained at 5.4-7.3 ms after the stimulus, depending on depth within the tubules. In contrast, q gamma moved after a 1.7-2.9 ms latency and achieved a peak displacement of up to 22-34% of available charge. Both charge movement species could be driven by repetitive (47.7 Hz) action potentials without buildup of charge transfer. Such stimulus frequencies would

  20. Iridium Oxide Nanotube Electrodes for Highly Sensitive and Prolonged Intracellular Measurement of Action Potentials

    PubMed Central

    Lin, Ziliang Carter; Xie, Chong; Osakada, Yasuko; Cui, Yi; Cui, Bianxiao

    2014-01-01

    Intracellular recording of action potentials is important to understand electrically-excitable cells. Recently, vertical nanoelectrodes have been developed to achieve highly sensitive, minimally invasive, and large scale intracellular recording. It has been demonstrated that the vertical geometry is crucial for the enhanced signal detection. Here we develop nanoelectrodes made up of nanotubes of iridium oxide. When cardiomyocytes are cultured upon those nanotubes, the cell membrane not only wraps around the vertical tubes but also protrudes deep into the hollow center. We show that this geometry enhances cell-electrode coupling and results in measuring much larger intracellular action potentials. The nanotube electrodes afford much longer intracellular access and are minimally invasive, making it possible to achieve stable recording up to an hour in a single session and more than 8 days of consecutive daily recording. This study suggests that the electrode performance can be significantly improved by optimizing the electrode geometry. PMID:24487777

  1. Real-time imaging of action potentials in nerves using changes in birefringence

    PubMed Central

    Badreddine, Ali H.; Jordan, Tomas; Bigio, Irving J.

    2016-01-01

    Polarized light can be used to measure the electrical activity associated with action potential propagation in nerves, as manifested in simultaneous dynamic changes in their intrinsic optical birefringence. These signals may serve as a tool for minimally invasive neuroimaging in various types of neuroscience research, including the study of neuronal activation patterns with high spatiotemporal resolution. A fast linear photodiode array was used to image propagating action potentials in an excised portion of the lobster walking leg nerve. We show that the crossed-polarized signal (XPS) can be reliably imaged over a ≥2 cm span in our custom nerve chamber, by averaging multiple-stimulation signals, and also in single-scan real-time “movies”. This demonstration paves the way toward utilizing changes in the optical birefringence to image more complex neuronal activity in nerve fibers and other organized neuronal tissue. PMID:27231635

  2. Real-time imaging of action potentials in nerves using changes in birefringence.

    PubMed

    Badreddine, Ali H; Jordan, Tomas; Bigio, Irving J

    2016-05-01

    Polarized light can be used to measure the electrical activity associated with action potential propagation in nerves, as manifested in simultaneous dynamic changes in their intrinsic optical birefringence. These signals may serve as a tool for minimally invasive neuroimaging in various types of neuroscience research, including the study of neuronal activation patterns with high spatiotemporal resolution. A fast linear photodiode array was used to image propagating action potentials in an excised portion of the lobster walking leg nerve. We show that the crossed-polarized signal (XPS) can be reliably imaged over a ≥2 cm span in our custom nerve chamber, by averaging multiple-stimulation signals, and also in single-scan real-time "movies". This demonstration paves the way toward utilizing changes in the optical birefringence to image more complex neuronal activity in nerve fibers and other organized neuronal tissue. PMID:27231635

  3. Tuning of Ranvier node and internode properties in myelinated axons to adjust action potential timing.

    PubMed

    Ford, Marc C; Alexandrova, Olga; Cossell, Lee; Stange-Marten, Annette; Sinclair, James; Kopp-Scheinpflug, Conny; Pecka, Michael; Attwell, David; Grothe, Benedikt

    2015-01-01

    Action potential timing is fundamental to information processing; however, its determinants are not fully understood. Here we report unexpected structural specializations in the Ranvier nodes and internodes of auditory brainstem axons involved in sound localization. Myelination properties deviated significantly from the traditionally assumed structure. Axons responding best to low-frequency sounds had a larger diameter than high-frequency axons but, surprisingly, shorter internodes. Simulations predicted that this geometry helps to adjust the conduction velocity and timing of action potentials within the circuit. Electrophysiological recordings in vitro and in vivo confirmed higher conduction velocities in low-frequency axons. Moreover, internode length decreased and Ranvier node diameter increased progressively along the distal axon segments, which simulations show was essential to ensure precisely timed depolarization of the giant calyx of Held presynaptic terminal. Thus, individual anatomical parameters of myelinated axons can be tuned to optimize pathways involved in temporal processing. PMID:26305015

  4. Experimental determination of compound action potential direction and propagation velocity from multi-electrode nerve cuffs.

    PubMed

    Rieger, R; Taylor, J; Comi, E; Donaldson, N; Russold, M; Mahony, C M O; McLaughlin, J A; McAdams, E; Demosthenous, A; Jarvis, J C

    2004-07-01

    Information extracted from whole-nerve electroneurograms, recorded using electrode cuffs, can provide signals to neuroprostheses. However, the amount of information that can be extracted from a single tripole is limited. This communication demonstrates how previously unavailable information about the direction of action potential propagation and velocity can be obtained using a multi-electrode cuff and that the arrangement acts as a velocity-selective filter. Results from in vitro experiments on frog nerves are presented. PMID:15234689

  5. An indirect component in the evoked compound action potential of the vagal nerve.

    PubMed

    Ordelman, Simone C M A; Kornet, Lilian; Cornelussen, Richard; Buschman, Hendrik P J; Veltink, Peter H

    2010-12-01

    The vagal nerve plays a vital role in the regulation of the cardiovascular system. It not only regulates the heart but also sends sensory information from the heart back to the brain. We hypothesize that the evoked vagal nerve compound action potential contains components that are indirect via the brain stem or coming via the neural network on the heart. In an experimental study of 15 pigs, we identified four components in the evoked compound action potentials. The fourth component was found to be an indirect component, which came from the periphery. The latency of the indirect component increased when heart rate and contractility were decreased by burst stimulation (P = 0.01; n = 7). When heart rate and contractility were increased by dobutamine administration, the latency of the indirect component decreased (P = 0.01; n = 9). This showed that the latency of the indirect component of the evoked compound action potentials may relate to the state of the cardiovascular system. PMID:20966537

  6. Concept of relative variability of cardiac action potential duration and its test under various experimental conditions.

    PubMed

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

    2016-01-01

    Beat-to-beat variability of action potential duration (short-term variability, SV) is an intrinsic property of mammalian myocardium. Since the majority of agents and interventions affecting SV may modify also action potential duration (APD), we propose here the concept of relative SV (RSV), where changes in SV are normalized to changes in APD and these data are compared to the control SV-APD relationship obtained by lengthening or shortening of action potentials by inward and outward current injections. Based on this concept the influence of the several experimental conditions like stimulation frequency, temperature, pH, redox-state and osmolarity were examined on RSV in canine ventricular myocytes using sharp microelectrodes. RSV was increased by high stimulation frequency (cycle lengths <0.7 s), high temperature (above 37ºC), oxidative agents (H2O2), while it was decreased by reductive environment. RSV was not affected by changes in pH (within the range of 6.4-8.4) and osmolarity of the solution (between 250-350 mOsm). The results indicate that changes in beat-to-beat variability of APD must be evaluated exclusively in terms of RSV; furthermore, some experimental conditions, including the stimulation frequency, redox-state and temperature have to be controlled strictly when analyzing alterations in the short-term variability of APD. PMID:26492070

  7. Mechanisms of action potential propagation failure at sites of axon branching in the crayfish.

    PubMed Central

    Smith, D O

    1980-01-01

    1. The phenomena leading to action potential conduction block during repetitive stimulation of the excitor axon of the opener muscle in the crayfish walking leg were studied. 2. Action potentials, recorded extracellularly with micro-electrodes, failed to propagate past sites of axonal bifurcation following at least 3000 impulses; reduction of the rate or brief cessation of stimulation resulted in restored conduction. 3. Failure occurred initially at branch points located most peripherally and then more centrally as stimulation continued; this centripetal progression of the site of block resulted in a stepwise reduction of the number of synaptic terminals from which transmitter was released. 4. Prior to conduction failure, the conduction velocity and the sodium inward current of the action potentials decreased. 5. Local application of hyperpolarizing current or of physiological saline with low [K+] in the vicinity of a block can restore propagation; thus depolarization of the membrane most probably causes failure. 6. Soaking the preparation for as long as 2 hr in the metabolic inhibitor 2,4-dinitrophenol had no effect on the number of stimulus impulses before initial conduction block; however, the time required for recovery from the failure was prolonged. 7. The number of impulses prior to block was related directly to the temperature of the preparation; this had a Q10 calculated to be about 1 . 3. 8. It is suggested that during repetitive activity, the K+ gradient across the membrane is reduced, resulting in depolarization and eventually in conduction failure. PMID:7411430

  8. Shensong Yangxin capsules prevent ischemic arrhythmias by prolonging action potentials and alleviating Ca2+ overload.

    PubMed

    Zhao, Yixiu; Gao, Feng; Zhang, Yong; Wang, Hongtao; Zhu, Jiuxin; Chang, Liping; Du, Zhimin; Zhang, Yan

    2016-06-01

    Shensong Yangxin capsules (SSYX) are an effective traditional Chinese medicine that has been used to treat coronary heart disease clinically. The present study aimed to establish whether SSYX prevent ischemic arrhythmias in rats, and to explore the underlying mechanisms. Male rats were pretreated with distilled water, SSYX and amiodarone for one week. Acute myocardial ischemia (AMI) was performed to induce ischemic arrhythmias. The incidence and severity of ischemic arrhythmias were evaluated. The action potential, transient outward K+ current (Ito) and inward rectifier K+ current (IK1) of rat cardiomyocytes were measured using the patch‑clamp technique. The intracellular Ca2+ concentration of the cardiomyocytes was measured using a laser scanning confocal microscope. The results revealed that SSYX lowered the incidence of arrhythmia markedly during AMI. Furthermore, SSYX delayed the appearance, and reduced the severity, of ischemic arrhythmias compared with the control. In addition, SSYX markedly decreased the ratio of the myocardial infarction region to the whole heart. In an in vitro study, SSYX prolonged the action potential duration of rat cardiomyocytes, and inhibited Ito and IK1 markedly. Additionally, SSYX inhibited Ca2+ elevation induced by KCl in cardiomyocytes. These results suggested that SSYX prevents ischemic arrhythmia, and the underlying mechanism responsible for this process may include prolonging the action potential and alleviating Ca2+ overload. PMID:27122298

  9. Heart rate variability effect on the myocyte action potential duration restitution: insights from switched systems theory.

    PubMed

    Dvir, Hila; Zlochiver, Sharon

    2011-01-01

    The physiological heart rate presents a stochastic behavior known as heart rate variability (HRV). In this framework the influence of HRV on the action potential duration (APD) of the atrial myocyte is analyzed in a computer model. We have found that introducing HRV into the myocyte action potential model decreases the APD of the extra beat S2 in an S1-S2 protocol compared to constant heart rate. A possible theoretical explanation for this is also presented and is derived from switched systems theory. It is suggested to consider the myocyte action potential phase 4 and phase 2 as two operation modes of a switching system and analyze the stability of switching between them. Since random switching is known to have a stabilization effect on a switching system, this might explain why HRV has a stabilization effect on the myocyte APD restitution. Implications of this finding include reduced system stability for conditions with low HRV. A possible application for this phenomenon regards artificial pacemakers, where a preset added HRV is predicted to reduce susceptibility to arrhythmias. PMID:22254402

  10. Axon initial segment Ca2+ channels influence action potential generation and timing

    PubMed Central

    Bender, Kevin J.; Trussell, Laurence O.

    2009-01-01

    Summary Although action potentials are typically generated in the axon initial segment (AIS), the timing and pattern of action potentials is thought to depend on inward current originating in somatodendritic compartments. Using 2-photon imaging, we show that T- and R-type voltage-gated Ca2+ channels are co-localized with Na+ channels in the AIS of dorsal cochlear nucleus interneurons, and that activation of these Ca2+ channels is essential to the generation and timing of action potential bursts known as complex spikes. During complex spikes, where Na+-mediated spikelets fire atop slower depolarizing conductances, selective block of AIS Ca2+ channels delays spike timing and raises spike threshold. Furthermore, AIS Ca2+ channel block can decrease the number of spikelets within a complex spike, and even block single, simple spikes. Similar results were found in cortex and cerebellum. Thus, voltage-gated Ca2+ channels at the site of spike initiation play a key role in generating and shaping spike bursts. PMID:19186168

  11. Optical recording of action potentials in mammalian neurons using a microbial rhodopsin

    PubMed Central

    Kralj, Joel M.; Douglass, Adam D.; Hochbaum, Daniel R.; Maclaurin, Dougal; Cohen, Adam E.

    2011-01-01

    Reliable optical detection of single action potentials in mammalian neurons has been one of the longest-standing challenges in neuroscience. Here we achieve this goal by using the endogenous fluorescence of a microbial rhodopsin protein, Archaerhodopsin 3 (Arch) from Halorubrum sodomense, expressed in cultured rat hippocampal neurons. This genetically encoded voltage indicator exhibited an approximately 10-fold improvement in sensitivity and speed over existing protein-based voltage indicators, with a roughly linear two-fold increase in brightness between −150 mV and +150 mV and a sub-millisecond response time. Arch detected single electrically triggered action potentials with an optical signal-to-noise ratio > 10. The mutant Arch(D95N) lacked endogenous proton pumping and showed 50% greater sensitivity than wild-type, but had a slower response (41 ms). Nonetheless, Arch(D95N) also resolved individual action potentials. Microbial rhodopsin-based voltage indicators promise to enable optical interrogation of complex neural circuits, and electrophysiology in systems for which electrode-based techniques are challenging. PMID:22120467

  12. Impact of Laurel Wilt, Caused by Raffaelea lauricola, on Leaf Gas Exchange and Xylem Sap Flow in Avocado, Persea americana.

    PubMed

    Ploetz, Randy C; Schaffer, Bruce; Vargas, Ana I; Konkol, Joshua L; Salvatierra, Juanpablo; Wideman, Ronney

    2015-04-01

    Laurel wilt, caused by Raffaelea lauricola, is a destructive disease of avocado (Persea americana). The susceptibility of different cultivars and races was examined previously but more information is needed on how this host responds to the disease. In the present study, net CO2 assimilation (A), stomatal conductance of H2O (gs), transpiration (E), water use efficiency (WUE), and xylem sap flow rates were assessed in cultivars that differed in susceptibility. After artificial inoculation with R. lauricola, there was a close relationship between symptom development and reductions in A, gs, E, WUE, and mean daily sap flow in the most susceptible cultivar, 'Russell', and significantly greater disease and lower A, gs, E, WUE, and sap flow rates were usually detected after 15 days compared with the more tolerant 'Brogdon' and 'Marcus Pumpkin'. Significant differences in preinoculation A, gs, E, and WUE were generally not detected among the cultivars but preinoculation sap flow rates were greater in Russell than in Brogdon and Marcus Pumpkin. Preinoculation sap flow rates and symptom severity for individual trees were correlated at the end of an experiment (r=0.46), indicating that a plant's susceptibility to laurel wilt was related to its ability to conduct water. The potential management of this disease with clonal rootstocks that reduce sap flow rates is discussed. PMID:25496301

  13. Carbon nanotube multi-electrode array chips for noninvasive real-time measurement of dopamine, action potentials, and postsynaptic potentials.

    PubMed

    Suzuki, Ikuro; Fukuda, Mao; Shirakawa, Keiichi; Jiko, Hideyasu; Gotoh, Masao

    2013-11-15

    Multi-electrode arrays (MEAs) can be used for noninvasive, real-time, and long-term recording of electrophysiological activity and changes in the extracellular chemical microenvironment. Neural network organization, neuronal excitability, synaptic and phenotypic plasticity, and drug responses may be monitored by MEAs, but it is still difficult to measure presynaptic activity, such as neurotransmitter release, from the presynaptic bouton. In this study, we describe the development of planar carbon nanotube (CNT)-MEA chips that can measure both the release of the neurotransmitter dopamine as well as electrophysiological responses such as field postsynaptic potentials (fPSPs) and action potentials (APs). These CNT-MEA chips were fabricated by electroplating the indium-tin oxide (ITO) microelectrode surfaces. The CNT-plated ITO electrode exhibited electrochemical response, having much higher current density compared with the bare ITO electrode. Chronoamperometric measurements using these CNT-MEA chips detected dopamine at nanomolar concentrations. By placing mouse striatal brain slices on the CNT-MEA chip, we successfully measured synaptic dopamine release from spontaneous firings with a high S/N ratio of 62. Furthermore, APs and fPSPs were measured from cultured hippocampal neurons and slices with high temporal resolution and a 100-fold greater S/N ratio. Our CNT-MEA chips made it possible to measure neurotransmitter dopamine (presynaptic activities), postsynaptic potentials, and action potentials, which have a central role in information processing in the neuronal network. CNT-MEA chips could prove useful for in vitro studies of stem cell differentiation, drug screening and toxicity, synaptic plasticity, and pathogenic processes involved in epilepsy, stroke, and neurodegenerative diseases. PMID:23774164

  14. Liquid effluent Sampling and Analysis Plan (SAP) implementation summary report

    SciTech Connect

    Lueck, K.J.

    1995-04-26

    This report summarizes liquid effluent analytical data collected during the Sampling and Analysis Plan (SAP) Implementation Program, evaluates whether or not the sampling performed meets the requirements of the individual SAPs, compares the results to the WAC 173-200 Ground Water Quality Standards. Presented in the report are results from liquid effluent samples collected (1992-1994) from 18 of the 22 streams identified in the Consent Order (No. DE 91NM-177) requiring SAPs.

  15. Action-space Clustering of Tidal Streams to Infer the Galactic Potential

    NASA Astrophysics Data System (ADS)

    Sanderson, Robyn E.; Helmi, Amina; Hogg, David W.

    2015-03-01

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

  16. Environmental Asthma Reduction Potential Estimates for Selected Mitigation Actions in Finland Using a Life Table Approach

    PubMed Central

    Rumrich, Isabell Katharina; Hänninen, Otto

    2015-01-01

    Aims: To quantify the reduction potential of asthma in Finland achievable by adjusting exposures to selected environmental factors. Methods: A life table model for the Finnish population for 1986–2040 was developed and Years Lived with Disability caused by asthma and attributable to the following selected exposures were estimated: tobacco smoke (smoking and second hand tobacco smoke), ambient fine particles, indoor dampness and mould, and pets. Results: At baseline (2011) about 25% of the total asthma burden was attributable to the selected exposures. Banning tobacco was the most efficient mitigation action, leading to 6% reduction of the asthma burden. A 50% reduction in exposure to dampness and mould as well as a doubling in exposure to pets lead each to a 2% reduction. Ban of urban small scale wood combustion, chosen as a mitigation action to reduce exposure to fine particles, leads to a reduction of less than 1% of the total asthma burden. Combination of the most efficient mitigation actions reduces the total asthma burden by 10%. A more feasible combination of mitigation actions leads to 6% reduction of the asthma burden. Conclusions: The adjustment of environmental exposures can reduce the asthma burden in Finland by up to 10%. PMID:26067987

  17. Monophasic action potential recordings during acute changes in ventricular loading induced by the Valsalva manoeuvre.

    PubMed Central

    Taggart, P; Sutton, P; John, R; Lab, M; Swanton, H

    1992-01-01

    OBJECTIVE--The strong association between ventricular arrhythmia and ventricular dysfunction is unexplained. This study was designed to investigate a mechanism by which a change in ventricular loading could alter the time course of repolarisation and hence refractoriness. A possible mechanism may be a direct effect of an altered pattern of contraction on ventricular repolarisation and hence refractoriness. This relation has been termed contraction-excitation feedback or mechano-electric feedback. METHODS--Monophasic action potentials were recorded from the left ventricular endocardium as a measure of the time course of local repolarisation. The Valsalva manoeuvre was used to change ventricular loading by increasing the intrathoracic pressure and impeding venous return, and hence reducing ventricular pressure and volume (ventricular unloading). PATIENTS--23 patients undergoing routine cardiac catheterisation procedures: seven with no angiographic evidence of abnormal wall motion or history of myocardial infarction (normal), five with a history of myocardial infarction but with normal wall motion, and 10 with angiographic evidence of abnormal wall motion--with or without previous infarction. One patient was a transplant recipient and was analysed separately. SETTING--Tertiary referral centre for cardiology. RESULTS--In patients with normal ventricles during the unloading phase of the Valsalva manoeuvre (mean (SD)) monophasic action potential duration shortened from 311 (47) ms to 295 (47) ms (p less than 0.001). After release of the forced expiration as venous return was restored the monophasic action potential duration lengthened from 285 (44) ms to 304 (44) ms (p less than 0.0001). In the group with evidence of abnormal wall motion the direction of change of action potential duration during the strain phase was normal in 7/21 observations, abnormal in 6/21, and showed no clear change in 8/21. During the release phase 11/20 observations were normal, five abnormal

  18. Accounting for sap flow from different parts of the root system improves the prediction of xylem ABA concentration in plants grown with heterogeneous soil moisture

    PubMed Central

    Dodd, Ian C.; Egea, Gregorio; Davies, William J.

    2008-01-01

    When soil moisture is heterogeneous, sap flow from, and ABA status of, different parts of the root system impact on leaf xylem ABA concentration ([X-ABA]leaf). The robustness of a model for predicting [X-ABA]leaf was assessed. ‘Two root-one shoot’ grafted sunflower (Helianthus annuus L.) plants received either deficit irrigation (DI, each root system received the same irrigation volumes) or partial rootzone drying (PRD, only one root system was watered and the other dried the soil). Irrespective of whether relative sap flow was assessed using sap flow sensors in vivo or by pressurization of de-topped roots, each root system contributed similarly to total sap flow during DI, while sap flow from roots in drying soil declined linearly with soil water potential (Ψsoil) during PRD. Although Ψsoil of the irrigated pot determined the threshold Ψsoil at which sap flow from roots in drying soil decreased, the slope of this decrease was independent of the wet pot Ψsoil. Irrespective of whether sap was collected from the wet or dry root system of PRD plants, or a DI plant, root xylem ABA concentration increased as Ψsoil declined. The model, which weighted ABA contributions of each root system according to the sap flow from each, almost perfectly explained [X-ABA] immediately above the graft union. That the model overestimated measured [X-ABA]leaf may result from changes in [X-ABA] along the transport pathway or an artefact of collecting xylem sap from detached leaves. The implications of declining sap flow through partially dry roots during PRD for the control of stomatal behaviour and irrigation scheduling are discussed. PMID:18940933

  19. Plant fluid proteomics: Delving into the xylem sap, phloem sap and apoplastic fluid proteomes.

    PubMed

    Rodríguez-Celma, Jorge; Ceballos-Laita, Laura; Grusak, Michael A; Abadía, Javier; López-Millán, Ana-Flor

    2016-08-01

    The phloem sap, xylem sap and apoplastic fluid play key roles in long and short distance transport of signals and nutrients, and act as a barrier against local and systemic pathogen infection. Among other components, these plant fluids contain proteins which are likely to be important players in their functionalities. However, detailed information about their proteomes is only starting to arise due to the difficulties inherent to the collection methods. This review compiles the proteomic information available to date in these three plant fluids, and compares the proteomes obtained in different plant species in order to shed light into conserved functions in each plant fluid. Inter-species comparisons indicate that all these fluids contain the protein machinery for self-maintenance and defense, including proteins related to cell wall metabolism, pathogen defense, proteolysis, and redox response. These analyses also revealed that proteins may play more relevant roles in signaling in the phloem sap and apoplastic fluid than in the xylem sap. A comparison of the proteomes of the three fluids indicates that although functional categories are somewhat similar, proteins involved are likely to be fluid-specific, except for a small group of proteins present in the three fluids, which may have a universal role, especially in cell wall maintenance and defense. This article is part of a Special Issue entitled: Plant Proteomics--a bridge between fundamental processes and crop production, edited by Dr. Hans-Peter Mock. PMID:27033031

  20. 49 CFR 40.295 - May employees or employers seek a second SAP evaluation if they disagree with the first SAP's...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false May employees or employers seek a second SAP evaluation if they disagree with the first SAP's recommendations? 40.295 Section 40.295 Transportation Office... seek a second SAP evaluation if they disagree with the first SAP's recommendations? (a) As an...

  1. 49 CFR 40.295 - May employees or employers seek a second SAP evaluation if they disagree with the first SAP's...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false May employees or employers seek a second SAP evaluation if they disagree with the first SAP's recommendations? 40.295 Section 40.295 Transportation Office... seek a second SAP evaluation if they disagree with the first SAP's recommendations? (a) As an...

  2. 49 CFR 40.295 - May employees or employers seek a second SAP evaluation if they disagree with the first SAP's...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false May employees or employers seek a second SAP evaluation if they disagree with the first SAP's recommendations? 40.295 Section 40.295 Transportation Office... seek a second SAP evaluation if they disagree with the first SAP's recommendations? (a) As an...

  3. 49 CFR 40.295 - May employees or employers seek a second SAP evaluation if they disagree with the first SAP's...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false May employees or employers seek a second SAP evaluation if they disagree with the first SAP's recommendations? 40.295 Section 40.295 Transportation Office... seek a second SAP evaluation if they disagree with the first SAP's recommendations? (a) As an...

  4. 49 CFR 40.295 - May employees or employers seek a second SAP evaluation if they disagree with the first SAP's...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false May employees or employers seek a second SAP evaluation if they disagree with the first SAP's recommendations? 40.295 Section 40.295 Transportation Office... seek a second SAP evaluation if they disagree with the first SAP's recommendations? (a) As an...

  5. Effects of bath resistance on action potentials in the squid giant axon: myocardial implications.

    PubMed Central

    Wu, J; Wikswo, J P

    1997-01-01

    This study presents a simplified version of the quasi-one-dimensional theory (Wu, J., E. A. Johnson, and J. M. Kootsey. 1996. A quasi-one-dimensional theory for anisotropic propagation of excitation in cardiac muscle. Biophys. J. 71:2427-2439) with two components of the extracellular current, along and perpendicular to the axis, and a simulation and its experimental confirmation for the giant axon of the squid. By extending the one-dimensional core conductor cable equations, this theory predicts, as confirmed by the experiment, that the shapes of the intracellular and the extracellular action potentials are related to the resistance of the bath. Such a result was previously only expected by the field theories. The correlation between the shapes of the intracellular and the extracellular potentials of the giant axon of the squid resembles that observed during the anisotropic propagation of excitation in cardiac muscle. Therefore, this study not only develops a quasi-one-dimensional theory for a squid axon, but also provides one possible factor contributing to the anisotropic propagation of action potentials in cardiac muscle. PMID:9370430

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

    PubMed Central

    Pearman, Charles M.

    2014-01-01

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

  7. Phase Relationship between Alternans of Early and Late Phases of Ventricular Action Potentials

    PubMed Central

    Jing, Linyuan; Agarwal, Anuj; Chourasia, Sonam; Patwardhan, Abhijit

    2012-01-01

    Background: Alternans of early phase and of duration of action potential (AP) critically affect dispersion of refractoriness through their influence on conduction and repolarization. We investigated the phase relationship between the two alternans and its effect on conduction. Methods and Results: Transmembrane potentials recorded from ventricles of eight swine and three canines during paced activation intervals of ≤300 ms were used to quantify alternans of maximum rate of depolarization (|dv/dt|max) and of action potential duration (APD). Incidence of APD alternans was 62 and 76% in swine and canines. Alternans of APD was frequently accompanied with alternans of |dv/dt|max. Of these, 4 and 26% were out of phase in swine and canines, i.e., low |dv/dt|max preceded long APD. Computer simulations show that out of phase alternans attenuate variation of wavelength and thus minimize formation of spatially discordant alternans. Conclusion: The spontaneous switching of phase relationship between alternans of depolarization and repolarization suggests that mechanisms underlying these alternans may operate independent of each other. The phase between these alternans can critically impact spatial dispersion of refractoriness and thus stability of conduction, with the in phase relation promoting transition from concord to discord while out of phase preventing formation of discord. PMID:22701104

  8. NeuroGrid: recording action potentials from the surface of the brain

    PubMed Central

    Khodagholy, Dion; Gelinas, Jennifer N.; Thesen, Thomas; Doyle, Werner; Devinsky, Orrin; Malliaras, George G.; Buzsáki, György

    2014-01-01

    Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultra-conformable, biocompatible and scalable neural interface array (the ‘NeuroGrid’) that can record both LFP and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding one week. We also recorded LFP-modulated spiking activity intra-operatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders. PMID:25531570

  9. In vivo neuronal action potential recordings via three-dimensional microscale needle-electrode arrays

    PubMed Central

    Fujishiro, Akifumi; Kaneko, Hidekazu; Kawashima, Takahiro; Ishida, Makoto; Kawano, Takeshi

    2014-01-01

    Very fine needle-electrode arrays potentially offer both low invasiveness and high spatial resolution of electrophysiological neuronal recordings in vivo. Herein we report the penetrating and recording capabilities of silicon-growth-based three-dimensional microscale-diameter needle-electrodes arrays. The fabricated needles exhibit a circular-cone shape with a 3-μm-diameter tip and a 210-μm length. Due to the microscale diameter, our silicon needles are more flexible than other microfabricated silicon needles with larger diameters. Coating the microscale-needle-tip with platinum black results in an impedance of ~600 kΩ in saline with output/input signal amplitude ratios of more than 90% at 40 Hz–10 kHz. The needles can penetrate into the whisker barrel area of a rat's cerebral cortex, and the action potentials recorded from some neurons exhibit peak-to-peak amplitudes of ~300 μVpp. These results demonstrate the feasibility of in vivo neuronal action potential recordings with a microscale needle-electrode array fabricated using silicon growth technology. PMID:24785307

  10. In vivo neuronal action potential recordings via three-dimensional microscale needle-electrode arrays

    NASA Astrophysics Data System (ADS)

    Fujishiro, Akifumi; Kaneko, Hidekazu; Kawashima, Takahiro; Ishida, Makoto; Kawano, Takeshi

    2014-05-01

    Very fine needle-electrode arrays potentially offer both low invasiveness and high spatial resolution of electrophysiological neuronal recordings in vivo. Herein we report the penetrating and recording capabilities of silicon-growth-based three-dimensional microscale-diameter needle-electrodes arrays. The fabricated needles exhibit a circular-cone shape with a 3-μm-diameter tip and a 210-μm length. Due to the microscale diameter, our silicon needles are more flexible than other microfabricated silicon needles with larger diameters. Coating the microscale-needle-tip with platinum black results in an impedance of ~600 kΩ in saline with output/input signal amplitude ratios of more than 90% at 40 Hz-10 kHz. The needles can penetrate into the whisker barrel area of a rat's cerebral cortex, and the action potentials recorded from some neurons exhibit peak-to-peak amplitudes of ~300 μVpp. These results demonstrate the feasibility of in vivo neuronal action potential recordings with a microscale needle-electrode array fabricated using silicon growth technology.

  11. In vivo neuronal action potential recordings via three-dimensional microscale needle-electrode arrays.

    PubMed

    Fujishiro, Akifumi; Kaneko, Hidekazu; Kawashima, Takahiro; Ishida, Makoto; Kawano, Takeshi

    2014-01-01

    Very fine needle-electrode arrays potentially offer both low invasiveness and high spatial resolution of electrophysiological neuronal recordings in vivo. Herein we report the penetrating and recording capabilities of silicon-growth-based three-dimensional microscale-diameter needle-electrodes arrays. The fabricated needles exhibit a circular-cone shape with a 3-μm-diameter tip and a 210-μm length. Due to the microscale diameter, our silicon needles are more flexible than other microfabricated silicon needles with larger diameters. Coating the microscale-needle-tip with platinum black results in an impedance of ~600 kΩ in saline with output/input signal amplitude ratios of more than 90% at 40 Hz-10 kHz. The needles can penetrate into the whisker barrel area of a rat's cerebral cortex, and the action potentials recorded from some neurons exhibit peak-to-peak amplitudes of ~300 μVpp. These results demonstrate the feasibility of in vivo neuronal action potential recordings with a microscale needle-electrode array fabricated using silicon growth technology. PMID:24785307

  12. Protective effect of Acer mono Max. sap on water immersion restraint stress-induced gastric ulceration.

    PubMed

    Park, Chul-Hong; Son, Hyung-U; Son, Minsik; Lee, Sang-Han

    2011-09-01

    Acer mono Max. sap (AmMs) is called 'Gol-Li-Su' or 'Go-Lo-Soe' in Korean, which means 'water beneficial to the bones'. It is reported that the sap contains several types of minerals and sugars. In particular, the calcium concentration of the sap is 36.5 times higher than that of commercial mineral water. Apart from its anti-osteoporosis effect, no reports have addressed the biological activities of AmMs against degenerative diseases. In the present study, we investigated whether AmMs alleviates gastric ulcer-related symptoms in a stress-induced mouse model. To assess the effect of AmMs on gastric ulcer-like symptoms, we carried out a water immersion restraint (WIRE) test and found that AmMs has potential in alleviating gastric ulcers in a concentration-dependent manner. These results indicate that the nutritional factors of the sap mitigate the gastric ulcer-related symptoms caused by stress-induced gastric lesions in mice. AmMs-treated mice exhibited a significant decrease in the ulcer index as compared to those treated with omeprazole or L-arginine. To examine one potential mechanism underlying this effect, we performed reverse transcription-polymerase chain reaction to ascertain whether molecular markers were associated with the mitigation of the gastric lesions. Epithelial and/or tissue nitric oxide synthase (NOS) was assessed to determine whether or not the genes were down-regulated dose-dependently by the sap. The levels of these enzymes were found to be lower in the tissue samples treated with AmMs compared with the levels in the control samples. These findings collectively suggest that AmMs significantly protects the gastric mucosa against WIRE stress-induced gastric lesions, at least in part, by alleviating inducible NOS and/or neuronal NOS expression. PMID:22977586

  13. Carbon monoxide effects on human ventricle action potential assessed by mathematical simulations

    PubMed Central

    Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Rajamani, Sridharan; Belardinelli, Luiz; Giles, Wayne R.

    2013-01-01

    Carbon monoxide (CO) that is produced in a number of different mammalian tissues is now known to have significant effects on the cardiovascular system. These include: (i) vasodilation, (ii) changes in heart rate and strength of contractions, and (iii) modulation of autonomic nervous system input to both the primary pacemaker and the working myocardium. Excessive CO in the environment is toxic and can initiate or mediate life threatening cardiac rhythm disturbances. Recent reports link these ventricular arrhythmias to an increase in the slowly inactivating, or “late” component of the Na+ current in the mammalian heart. The main goal of this paper is to explore the basis of this pro-arrhythmic capability of CO by incorporating changes in CO-induced ion channel activity with intracellular signaling pathways in the mammalian heart. To do this, a quite well-documented mathematical model of the action potential and intracellular calcium transient in the human ventricular myocyte has been employed. In silico iterations based on this model provide a useful first step in illustrating the cellular electrophysiological consequences of CO that have been reported from mammalian heart experiments. Specifically, when the Grandi et al. model of the human ventricular action potential is utilized, and after the Na+ and Ca2+ currents in a single myocyte are modified based on the experimental literature, early after-depolarization (EAD) rhythm disturbances appear, and important elements of the underlying causes of these EADs are revealed/illustrated. Our modified mathematical model of the human ventricular action potential also provides a convenient digital platform for designing future experimental work and relating these changes in cellular cardiac electrophysiology to emerging clinical and epidemiological data on CO toxicity. PMID:24146650

  14. Monophasic action potentials and Ca2+ transients in ischaemically preconditioned rabbit ventricular muscle

    PubMed Central

    Dekker, L.R.C.; van Bavel, E.; Opthof, T.; Coronel, R.; Janse, M.J.

    2003-01-01

    Background ATP-sensitive K+ (KATP) channels play an important role in the protective mechanism underlying ischaemic preconditioning. Ample evidence indicates, however, that action potential shortening is not a prerequisite for the cardioprotective effect of preconditioning. Methods Monophasic action potential duration (MAPD), tissue resistance, intracellular Ca2+ (Indo-1) and mechanical activity were simultaneously assessed in arterially perfused rabbit papillary muscles. We studied four experimental protocols preceding sustained ischaemia: 1. control perfusion (n=6), 2. ischaemic preconditioning (PC; n=4), 3. pretreatment with a KATP channel blocker, glibenclamide (15 μmol/1), prior to ischaemic preconditioning (PC+glib; n=3), 4. glibenclamide pretreatment only (Glib; n=2). Results In the PC group an increase in the diastolic Ca2+ level and a prolongation of the Ca2+ transient just prior to the induction of sustained ischaemia correlate to the postponement of the onset of irreversible ischaemic damage, as established by a rise in [Ca2+]i, electrical uncoupling and contracture. Glibenclamide antagonised these changes in the Ca2+ transient and the cardioprotection induced by preconditioning. MAPD was equal in all experimental groups. Conclusions Prolongation of the Ca2+ transient and increase of diastolic [Ca2+]i just prior to the induction of sustained ischaemia and not action potential shortening are involved in the cardioprotective effect of ischaemic preconditioning. Therefore, a glibenclamide-sensitive mechanism, other than the sarcolemmal KATP channels, is involved in the protective effect of ischaemic preconditioning. Changes in Ca2+ metabolism may play a crucial role in ischaemic preconditioning. ImagesFigure 1 PMID:25696182

  15. Electrophysiological properties of rat spinal dorsal horn neurones in vitro: calcium-dependent action potentials.

    PubMed Central

    Murase, K; Randić, M

    1983-01-01

    1. The electrophysiological properties of dorsal horn neurones have been investigated in the immature rat in vitro spinal cord slice preparation. 2. Intracellular recordings from dorsal horn neurones show that direct or orthodromic stimulation generates action potentials followed by a brief after-hyperpolarization. Synaptic potentials were elicited by the activation of primary afferent fibres in the dorsal root. 3. Input resistance for dorsal horn neurones ranged from 48 to 267 M omega, and the membrane time constant was in the range of 4-19 ms. 4. In response to strong depolarizing currents dorsal horn neurones perfused with TTX and TEA frequently exhibit a slow regenerative depolarizing potential followed by a slow after-hyperpolarization. The depolarizing potential probably results from an influx of Ca. It is blocked by low concentration Ca, Co or Mn, and enhanced by high levels of extracellular Ca. 5. There is, in addition, a low-threshold Ca-dependent response which is activated at membrane potentials more negative than -65 mV and has a maximum rate of rise at the polarization level of about -80 mV. 6. The addition of Ba or TEA to the perfusing medium provided support for the Ca-dependence of the low- and high-threshold responses, and the lack of fast inactivation of the high-threshold Ca potential. Images Plate 1 PMID:6306228

  16. Dynamical speckles patterns of action potential transmission effects in squid giant axon membrane

    NASA Astrophysics Data System (ADS)

    Llovera-González, Juan J.; Moreno-Yeras, Alfredo B.; Muramatsu, Mikiya; Soga, Diogo; Serra-Toledo, Rolando L.; Magalhães, Daniel S. F.

    2013-11-01

    Undoubtedly the most important result of the investigations in physiology and biophysics was the discovery of the electrochemical mechanism of propagation of the action potential in nerves that was made by Hodgkin and Huxley during the first half of the past century. Since some decades ago diverse experiments about the electro optical properties of the axon membrane there was published using the most diverse optical experimental procedures6-10. In this paper some results of a dynamical speckle technique applied for obtaining microscopic images of a section of a squid giant axon membrane during the activation by electrical impulses and his digital process are presented.

  17. Simulation of ECG Repolarization Phase with Improved Model of Cell Action Potentials

    NASA Astrophysics Data System (ADS)

    Trobec, Roman; Depolli, Matjaž; Avbelj, Viktor

    An improved model of action potentials (AP) is proposed to increase the accuracy of simulated electrocardiograms (ECGs). ECG simulator is based on a spatial model of a left ventricle, composed of cubic cells. Three distinct APs, modeled with functions proposed by Wohlfard, have been assigned to the cells, forming epicardial, mid, and endocardial layers. Identification of exact parameter values for AP models has been done through optimization of the simulated ECGs. Results have shown that only through an introduction of a minor extension to the AP model, simulator is able to produce more realistic ECGs. The same extension also proves essential for achieving a better fit between the measured and modeled APs.

  18. A Quantitative Description of the Relationship between the Area of Rabbit Ventricular Action Potentials and the Pattern of Stimulation

    PubMed Central

    Gibbs, C. L.; Johnson, E. A.; Tille, J.

    1963-01-01

    Intracellular microelectrodes were used to record action potentials from fibres of the isolated rabbit right ventricle and the areas of the action potentials were measured. The action potential area was found to depend in a reproducible way on the preceding pattern of stimulation. A mathematical model reproducing all the observed changes in the action potential area was developed. In the model the action potential area is taken as a linear function of the product of two time and stimulation dependent variables, M and N. The behaviour of each variable between action potentials is described by the solution of a second order differential equation. During each action potential the variables are assumed to change discontinuously, the magnitudes of the discontinuous changes being given by a set of subsidiary equations. It was found that the behaviour of all the fibres tested was described by the same set of equations, each single fibre being characterized by a set of ten independent constants. ImagesFigure 5 PMID:14070359

  19. Creating "SMART" Supply Chain Scenarios Using SAP R/3

    ERIC Educational Resources Information Center

    Ragan, Joseph M.; McGettigan, Patrick J.; Storms, Michael R.; Rizman, Brian

    2004-01-01

    Pedagogical revisions to the undergraduate Haub School of Business curriculum at Saint Joseph's University employing the SAP R/3 system encompass the core accounting courses traversing the sophomore and junior years. The entire accounting curriculum was overhauled in order to integrate SAP R/3. Each course progressively builds upon and expands the…

  20. Stem sap flow in plants under low gravity conditions

    NASA Astrophysics Data System (ADS)

    Tokuda, Ayako; Hirai, Hiroaki; Kitaya, Yoshiaki

    2016-07-01

    A study was conducted to obtain a fundamental knowledge for plant functions in bio-regenerative life support systems in space. Stem sap flow in plants is important indicators for water transport from roots to atmosphere through leaves. In this study, stem sap flow in sweetpotato was assessed at gravity levels from 0.01 to 2 g for about 20 seconds each during parabolic airplane flights. Stem sap flow was monitored with a heat balance method in which heat generated with a tiny heater installed in the stem was transferred upstream and downstream by conduction and upstream by convection with the sap flow through xylems of the vascular tissue. Thermal images of stem surfaces near heated points were captured using infrared thermography and the internal heat convection corresponding to the sap flow was analyzed. In results, the sap flow in stems was suppressed more at lower gravity levels without forced air circulation. No suppression of the stem sap flow was observed with forced air circulation. Suppressed sap flow in stems would be caused by suppression of transpiration in leaves and would cause restriction of water and nutrient uptake in roots. The forced air movement is essential to culture healthy plants at a high growth rate under low gravity conditions in space.

  1. Flavonoids: a review of probable mechanisms of action and potential applications.

    PubMed

    Nijveldt, R J; van Nood, E; van Hoorn, D E; Boelens, P G; van Norren, K; van Leeuwen, P A

    2001-10-01

    The aim of this review, a summary of the putative biological actions of flavonoids, was to obtain a further understanding of the reported beneficial health effects of these substances. Flavonoids occur naturally in fruit, vegetables, and beverages such as tea and wine. Research in the field of flavonoids has increased since the discovery of the French paradox,ie, the low cardiovascular mortality rate observed in Mediterranean populations in association with red wine consumption and a high saturated fat intake. Several other potential beneficial properties of flavonoids have since been ascertained. We review the different groups of known flavonoids, the probable mechanisms by which they act, and the potential clinical applications of these fascinating natural substances. PMID:11566638

  2. Excitable Membranes and Action Potentials in Paramecia: An Analysis of the Electrophysiology of Ciliates.

    PubMed

    Schlaepfer, Charles H; Wessel, Ralf

    2015-01-01

    The ciliate Paramecium caudatum possesses an excitable cell membrane whose action potentials (APs) modulate the trajectory of the cell swimming through its freshwater environment. While many stimuli affect the membrane potential and trajectory, students can use current injection and extracellular ionic concentration changes to explore how APs cause reversal of the cell's motion. Students examine these stimuli through intracellular recordings, also gaining insight into the practices of electrophysiology. Paramecium's large size of around 150 µm, simple care, and relative ease to penetrate make them ideal model organisms for undergraduate students' laboratory study. The direct link between behavior and excitable membranes has thought provoking evolutionary implications for the study of paramecia. Recording from the cell, students note a small resting potential around -30 mV, differing from animal resting potentials. By manipulating ion concentrations, APs of the relatively long length of 20-30 ms up to several minutes with depolarizations maxing over 0 mV are observed. Through comparative analysis of membrane potentials and the APs induced by either calcium or barium, students can deduce the causative ions for the APs as well as the mechanisms of paramecium APs. Current injection allows students to calculate quantitative electric characteristics of the membrane. Analysis will follow the literature's conclusion in a V-Gated Ca(++) influx and depolarization resulting in feedback from intracellular Ca(++) that inactivates V-Gated Ca(++) channels and activates Ca-Dependent K(+) channels through a secondary messenger cascade that results in the K(+) efflux and repolarization. PMID:26557800

  3. Action of hallucinogens on raphe-evoked dorsal root potentials (DRPs) in the cat.

    PubMed

    Larson, A A; Anderson, E G

    1986-02-01

    The dorsal root potential (DRP) evoked by stimulation of the inferior central nucleus (ICN) of the cat is affected by administration of a variety of hallucinogenic agents. It has been previously shown that a single low dose of LSD is unique in that it potentiates this DRP, while injections of 5-methoxy-N,N- dimethyltryptamine (5-MeODMT), ketamine or phencyclidine (PCP) inhibit its production. Tolerance develops to the facilitatory effect of low doses of LSD on the DRP, but not to the inhibitory action of 5-MeODMT. Repeated injections of ketamine every 30 minutes also fail to produce tachyphylaxis to the inhibitory effect of this dissociative anesthetic. The raphe-evoked DRP is a long latency potential that is inhibited by a wide variety of putative serotonin antagonists and has therefore been traditionally thought to be mediated by serotonin. However, in light of the inability of either tryptophan or fluoxetine to potentiate this DRP, and the resistance of this DRP to blockade by parachlorophenylalanine, reserpine or intrathecally administered 5,7-dihydroxytryptamine, it appears that this potential may in fact be mediated, at least in part, by a non-serotonergic transmitter. PMID:3952125

  4. SAPS onset timing during substorms and the westward traveling surge

    NASA Astrophysics Data System (ADS)

    Mishin, Evgeny, V.

    2016-07-01

    We present multispacecraft observations in the magnetosphere and conjugate ionosphere of the onset time of subauroral polarization streams (SAPS) and tens of keV ring current injections on the duskside in three individual substorms. This is probably the first unequivocal determination of the substorm SAPS onset timing. The time lag between the SAPS and substorm onsets is much shorter than the gradient-curvature drift time of ˜10 keV ions in the plasmasphere. It seemingly depends on the propagation time of substorm-injected plasma from the dipolarization onset region to the plasmasphere, as well as on the SAPS position. These observations suggest that fast onset SAPS and ring current injections are causally related to the two-loop system of the westward traveling surge.

  5. Quantitative assessment of the distributions of membrane conductances involved in action potential backpropagation along basal dendrites.

    PubMed

    Acker, Corey D; Antic, Srdjan D

    2009-03-01

    Basal dendrites of prefrontal cortical neurons receive strong synaptic drive from recurrent excitatory synaptic inputs. Synaptic integration within basal dendrites is therefore likely to play an important role in cortical information processing. Both synaptic integration and synaptic plasticity depend crucially on dendritic membrane excitability and the backpropagation of action potentials. We carried out multisite voltage-sensitive dye imaging of membrane potential transients from thin basal branches of prefrontal cortical pyramidal neurons before and after application of channel blockers. We found that backpropagating action potentials (bAPs) are predominantly controlled by voltage-gated sodium and A-type potassium channels. In contrast, pharmacologically blocking the delayed rectifier potassium, voltage-gated calcium, or I(h) conductance had little effect on dendritic AP propagation. Optically recorded bAP waveforms were quantified and multicompartmental modeling was used to link the observed behavior with the underlying biophysical properties. The best-fit model included a nonuniform sodium channel distribution with decreasing conductance with distance from the soma, together with a nonuniform (increasing) A-type potassium conductance. AP amplitudes decline with distance in this model, but to a lesser extent than previously thought. We used this model to explore the mechanisms underlying two sets of published data involving high-frequency trains of APs and the local generation of sodium spikelets. We also explored the conditions under which I(A) down-regulation would produce branch strength potentiation in the proposed model. Finally, we discuss the hypothesis that a fraction of basal branches may have different membrane properties compared with sister branches in the same dendritic tree. PMID:19118105

  6. Interactions of ethanol and quinidine on contractility and myocyte action potential in the rat ventricle.

    PubMed

    Guthrie, S K; Wilde, D W; Brown, R A; Savage, A O; Bleske, B

    1995-01-01

    The combined effects of ethanol and quinidine on cardiac electromechanical coupling are unknown, but both drugs affect cardiac conduction and can cause myocardial depression. Isolated left ventricular papillary and ventricular myocytes were used to assess the combined effects of quinidine and ethanol on the electrophysiologic and mechanical properties of rat myocardium. The combination of quinidine (1-300 microM) and ethanol (120-240 mg/dL) depressed active papillary muscle tension within the clinically useful concentration range. In electrophysiologic studies of isolated ventricular myocytes, quinidine prolonged the action potential duration at 50% (APD50) and 90% (APD90) repolarization, the absolute refractory period, and the relative refractory period, but decreased the maximum rate of change of depolarization in phase 0 (Vmax). When cells were exposed to ethanol (240 mg/dL) and quinidine (1.5 microM) together, a significant decrease in the quinidine-induced prolongation of the absolute refractory and relative refractory periods was seen. Additional changes in action potential parameters from the quinidine values included slight reductions in Vmax and in APD50 and APD90, but these reductions were not consistently displayed, nor were they statistically significant. PMID:7897336

  7. Applications of Control Theory to the Dynamics and Propagation of Cardiac Action Potentials

    PubMed Central

    Muñoz, Laura M.; Stockton, Jonathan F.; Otani, Niels F.

    2011-01-01

    Sudden cardiac arrest is a widespread cause of death in the industrialized world. Most cases of sudden cardiac arrest are due to ventricular fibrillation (VF), a lethal cardiac arrhythmia. Electrophysiological abnormalities such as alternans (a beat-to-beat alternation in action potential duration) and conduction block have been suspected to contribute to the onset of VF. This study focuses on the use of control-systems techniques to analyze and design methods for suppressing these precursor factors. Control-systems tools, specifically controllability analysis and Lyapunov stability methods, were applied to a two-variable Karma model of the action-potential (AP) dynamics of a single cell, to analyze the effectiveness of strategies for suppressing AP abnormalities. State-feedback-integral (SFI) control was then applied to a Purkinje fiber simulated with the Karma model, where only one stimulating electrode was used to affect the system. SFI control converted both discordant alternans and 2:1 conduction block back toward more normal patterns, over a wider range of fiber lengths and pacing intervals compared with a Pyragas-type chaos controller. The advantages conferred by using feedback from multiple locations in the fiber, and using integral (i.e., memory) terms in the controller, are discussed. PMID:20407833

  8. Biorealistic cardiac cell culture platforms with integrated monitoring of extracellular action potentials

    PubMed Central

    Trantidou, Tatiana; Terracciano, Cesare M.; Kontziampasis, Dimitrios; Humphrey, Eleanor J.; Prodromakis, Themistoklis

    2015-01-01

    Current platforms for in vitro drug development utilize confluent, unorganized monolayers of heart cells to study the effect on action potential propagation. However, standard cell cultures are of limited use in cardiac research, as they do not preserve important structural and functional properties of the myocardium. Here we present a method to integrate a scaffolding technology with multi-electrode arrays and deliver a compact, off-the-shelf monitoring platform for growing biomimetic cardiac tissue. Our approach produces anisotropic cultures with conduction velocity (CV) profiles that closer resemble native heart tissue; the fastest impulse propagation is along the long axis of the aligned cardiomyocytes (CVL) and the slowest propagation is perpendicular (CVT), in contrast to standard cultures where action potential propagates isotropically (CVL ≈ CVT). The corresponding anisotropy velocity ratios (CVL/CVT = 1.38 – 2.22) are comparable with values for healthy adult rat ventricles (1.98 – 3.63). The main advantages of this approach are that (i) it provides ultimate pattern control, (ii) it is compatible with automated manufacturing steps and (iii) it is utilized through standard cell culturing protocols. Our platform is compatible with existing read-out equipment and comprises a prompt method for more reliable CV studies. PMID:26053434

  9. Supernormal Conduction and Suppression of Spatially Discordant Alternans of Cardiac Action Potentials

    PubMed Central

    Jing, Linyuan; Agarwal, Anuj; Patwardhan, Abhijit

    2016-01-01

    Spatially discordant alternans (DA) of action potential durations (APD) is thought to be more pro-arrhythmic than concordant alternans. Super normal conduction (SNC) has been reported to suppress formation of DA. An increase in conduction velocity (CV) as activation rate increases, i.e., a negative CV restitution, is widely considered as hallmark of SNC. Our aim in this study is to show that it is not an increase in CV for faster rates that prevents formation of DA, rather, it is the ratio of the CV for the short relative to the long activation that is critical in DA suppression. To illustrate this subtlety, we simulated this phenomenon using two approaches; (1) by using the standard, i.e., S1S2 protocol to quantify restitution and disabling the slow inactivation gate j of the sodium current (INa), and (2) by using the dynamic, i.e., S1S1 protocol for quantification of restitution and increasing INa at different cycle lengths (CL). Even though both approaches produced similar CV restitution curves, DA was suppressed only during the first approach, where the CV of the short of the long-short action potential (AP) pattern was selectively increased. These results show that negative CV restitution, which is considered characteristic of SNC, per se, is not causal in suppressing DA, rather, the critical factor is a change in the ratio of the velocities of the short and the long APs. PMID:26779035

  10. The effect of recording site on extracted features of motor unit action potential.

    PubMed

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

    2016-06-01

    Motor unit action potential (MUAP), which consists of individual muscle fiber action potentials (MFAPs), represents the electrical activity of the motor unit. The values of the MUAP features are changed by denervation and reinnervation in neurogenic involvement as well as muscle fiber loss with increased diameter variability in myopathic diseases. The present study is designed to investigate how increased muscle fiber diameter variability affects MUAP parameters in simulated motor units. In order to detect this variation, simulated MUAPs were calculated both at the innervation zone where the MFAPs are more synchronized, and near the tendon, where they show increased temporal dispersion. Reinnervation in neurogenic state increases MUAP amplitude for the recordings at both the innervation zone and near the tendon. However, MUAP duration and the number of peaks significantly increased in a case of myopathy for recordings near the tendon. Furthermore, of the new features, "number of peaks×spike duration" was found as the strongest indicator of MFAP dispersion in myopathy. MUAPs were also recorded from healthy participants in order to investigate the biological counterpart of the simulation data. MUAPs which were recorded near to tendon revealed significantly prolonged duration and decreased amplitude. Although the number of peaks was increased by moving the needle near to tendon, this was not significant. PMID:26817404

  11. Computational and Electronic Analog Implementation of the Hodgkin-Huxley Model of Action Potentials in Neurons

    NASA Astrophysics Data System (ADS)

    Smith, Peter; Link, Justin

    2012-02-01

    Alan Loyd Hodgkin and Andrew Huxley's mathematical model of action potential initiation and propagation in neurons is one of the greatest hallmarks of biophysics. Two techniques for implementing the Hodgkin-Huxley model were explored: computational and electronic analog. Computational modeling was done using NEURON 7.1. NEURON is a free, robust, and relatively user friendly simulation environment that enables quantitatively accurate computational modeling of neurons and neural networks. An analog electronic circuit was built using field-effect transistors (FETs) to simulate the non-linear, voltage-dependent (sodium and potassium) conductances that are responsible for membrane excitability. While the electronic analog qualitatively reproduces many of the key features of the action potential including overall shape, inactivation period, and propagation, it was difficult to quantitatively reproduce the Hodgkin-Huxley model. In addition, while the relative cost to build circuits equivalent to small membrane patches is minimal (˜50), implementation of larger cells or networks would prove uneconomical. Still, both techniques are viable avenues toward introducing interdisciplinary research into either a computational or electronics lab setting at the undergraduate level.

  12. Peripheral Hot Spots for Local Ca2+ Release after Single Action Potentials in Sympathetic Ganglion Neurons

    PubMed Central

    Cseresnyés, Zoltán; Schneider, Martin F.

    2004-01-01

    Ca2+ release from the endoplasmic reticulum (ER) contributes to Ca2+ transients in frog sympathetic ganglion neurons. Here we use video-rate confocal fluo-4 fluorescence imaging to show that single action potentials reproducibly trigger rapidly rising Ca2+ transients at 1–3 local hot spots within the peripheral ER-rich layer in intact neurons in fresh ganglia and in the majority (74%) of cultured neurons. Hot spots were located near the nucleus or the axon hillock region. Other regions exhibited either slower and smaller signals or no response. Ca2+ signals spread into the cell at constant velocity across the ER in nonnuclear regions, indicating active propagation, but spread with a (time)1/2 dependence within the nucleus, consistent with diffusion. 26% of cultured cells exhibited uniform Ca2+ signals around the periphery, but hot spots were produced by loading the cytosol with EGTA or by bathing such cells in low-Ca2+ Ringer's solution. Peripheral hot spots for Ca2+ release within the perinuclear and axon hillock regions provide a mechanism for preferential initiation of nuclear and axonal Ca2+ signals by single action potentials in sympathetic ganglion neurons. PMID:14695260

  13. 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

  14. Measurement of respirable superabsorbent polyacrylate (SAP) dust by ethanol derivatization using gas chromatography-mass spectrometry (GC-MS) detection.

    PubMed

    McCormack, Paul; Lemmo, John S; Macomber, Margaret; Holcomb, Mark L; Lieckfield, Robert

    2011-04-01

    Superabsorbent polyacrylate (SAP) is an important industrial chemical manufactured primarily as sodium polyacrylate but occasionally as potassium salt. It has many applications owing to its intrinsic physical property of very high water absorption, which can be more than 100 times it own weight. SAP is commonly used in disposable diapers and feminine hygiene products and is known by a number of synonyms-sodium polyacrylate, superabsorbent polyacrylate (SAP), polyacrylate absorbent (PA), and superabsorbent material (SAM). Germany and The Netherlands have adopted a nonbinding scientific guideline value 0.05 mg/m³ (8-hr time-weighted average, TWA) as the maximum allowable workplace concentration for the respirable dust of SAP (<10 μm particle diameter). Three industry associations representing Europe, the United States, and Asia have adopted the German scientific guideline value of 0.05 mg/m³ (8-hr TWA) as a voluntary guideline. A new test method based on alcohol derivatization of the acrylate was developed and validated for the analysis of respirable superabsorbent polyacrylate dust collected on filter cassettes in the workplace environment. This method is an alternative to the commonly used sodium-based method, which is limited owing to potential interference by other sources of sodium from the workplace and laboratory environments. The alcohol derivatization method effectively eliminates sodium interference from several classes of sodium compounds, as shown by their purposeful introduction at two and six times the equivalent amount of SAP present in reference samples. The accuracy of the method, as determined by comparison with sodium analysis of known reference samples, was greater than 80% over the study range of 5-50 μg of SAP dust. The lower reporting limit of the method is 3.0 μg of SAP per sample, which is equivalent to 3 (μg/m³) for an 8-hr sampling period at the recommended flow rate of 2.2 L/min. PMID:21416441

  15. Detection of cancer cells using SapC-DOPS nanovesicles.

    PubMed

    Davis, Harold W; Hussain, Nida; Qi, Xiaoyang

    2016-01-01

    Unlike normal cells, cancer cells express high levels of phosphatidylserine on the extracellular leaflet of their cell membrane. Exploiting this characteristic, our lab developed a therapeutic agent that consists of the fusogenic protein, saposin C (SapC) which is embedded in dioleoylphosphatidylserine (DOPS) vesicles. These nanovesicles selectively target cancer cells and induce apoptosis. Here we review the data supporting use of SapC-DOPS to locate tumors for surgical resection or for treatment. In addition, there is important evidence suggesting that SapC-DOPS may also prove to be an effective novel cancer therapeutic reagent. Given that SapC-DOPS is easily labeled with lipophilic dyes, it has been combined with the far-red fluorescent dye, CellVue Maroon (CVM), for tumor targeting studies. We also have used contrast agents incorporated in the SapC-DOPS nanovesicles for computed tomography and magnetic resonance imaging, and review that data here. Administered intravenously, the fluorescently labeled SapC-DOPS traversed the blood-brain tumor barrier enabling identification of brain tumors. SapC-DOPS-CVM also detected a variety of other mouse tumors in vivo, rendering them observable by optical imaging using IVIS and multi-angle rotational optical imaging. Dye is detected within 30 min and remains within tumor for at least 7 days, whereas non-tumor tissues were unstained (some dye observed in the liver was transient, likely representing degradation products). Additionally, labeled SapC-DOPS ex vivo delineated tumors in human histological specimens. SapC-DOPS can also be labeled with contrast reagents for computed tomography or magnetic resonance imaging. In conclusion, labeled SapC-DOPS provides a convenient, specific, and nontoxic method for detecting tumors while concurrently offering a therapeutic benefit. PMID:27160923

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

    PubMed Central

    Frey, Scott H.; Povinelli, Daniel J.

    2012-01-01

    The ability to adjust one's ongoing actions in the anticipation of forthcoming task demands is considered as strong evidence for the existence of internal action representations. Studies of action selection in tool use reveal that the behaviours that we choose in the present moment differ depending on what we intend to do next. Further, they point to a specialized role for mechanisms within the human cerebellum and dominant left cerebral hemisphere in representing the likely sensory costs of intended future actions. Recently, the question of whether similar mechanisms exist in other primates has received growing, but still limited, attention. Here, we present data that bear on this issue from a species that is a natural user of tools, our nearest living relative, the chimpanzee. In experiment 1, a subset of chimpanzees showed a non-significant tendency for their grip preferences to be affected by anticipation of the demands associated with bringing a tool's baited end to their mouths. In experiment 2, chimpanzees' initial grip preferences were consistently affected by anticipation of the forthcoming movements in a task that involves using a tool to extract a food reward. The partial discrepancy between the results of these two studies is attributed to the ability to accurately represent differences between the motor costs associated with executing the two response alternatives available within each task. These findings suggest that chimpanzees are capable of accurately representing the costs of intended future actions, and using those predictions to select movements in the present even in the context of externally directed tool use. PMID:22106426

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

    PubMed Central

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

    2014-01-01

    Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K+, inward rectifying K+, L-type Ca2+, and Na+/K+ pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally observed

  18. The Belem Framework for Action: Harnessing the Power and Potential of Adult Learning and Education for a Viable Future

    ERIC Educational Resources Information Center

    Adult Learning, 2012

    2012-01-01

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

  19. Regulation of Action Potential Waveforms by Axonal GABAA Receptors in Cortical Pyramidal Neurons

    PubMed Central

    Xia, Yang; Zhao, Yuan; Yang, Mingpo; Zeng, Shaoqun; Shu, Yousheng

    2014-01-01

    GABAA receptors distributed in somatodendritic compartments play critical roles in regulating neuronal activities, including spike timing and firing pattern; however, the properties and functions of GABAA receptors at the axon are still poorly understood. By recording from the cut end (bleb) of the main axon trunk of layer –5 pyramidal neurons in prefrontal cortical slices, we found that currents evoked by GABA iontophoresis could be blocked by picrotoxin, indicating the expression of GABAA receptors in axons. Stationary noise analysis revealed that single-channel properties of axonal GABAA receptors were similar to those of somatic receptors. Perforated patch recording with gramicidin revealed that the reversal potential of the GABA response was more negative than the resting membrane potential at the axon trunk, suggesting that GABA may hyperpolarize the axonal membrane potential. Further experiments demonstrated that the activation of axonal GABAA receptors regulated the amplitude and duration of action potentials (APs) and decreased the AP-induced Ca2+ transients at the axon. Together, our results indicate that the waveform of axonal APs and the downstream Ca2+ signals are modulated by axonal GABAA receptors. PMID:24971996

  20. External potassium and action potential propagation in rat fast and slow twitch muscles.

    PubMed

    Kössler, F; Lange, F; Caffier, G; Küchler, G

    1991-10-01

    The role of extracellular K+ concentration in the propagation velocity of action potential was tested in isolated rat skeletal muscles. Different K+ concentrations were produced by KCl additions to extracellular solution. Action potentials were measured extracellularly by means of two annular platinum electrodes. Fibre bundles of m. soleus (SOL), m. extensor digitorum longus (EDL), red (SMR) and white (SMW) part of m. sternomastoideus were maximum stimulated. The conduction velocity (c.v.) was calculated from the distance between the electrodes and the time delay of the potentials measured at 22 degrees C. In Tyrode solution containing 5 mmol/l K+, the c.v. was close to 1 m.s-1. Bundles of the fast muscle type seemed to have a somewhat higher c.v. The differences observed in these studies were not significant. At higher temperatures, the c.v. increased (Q10 of approx. 2) and a dissociation between SMR and SMW muscles appeared. An elevation of K+ concentration to 10 mmol/l induced a drop of the c.v. by approx. 25% and 15% in EDL and SOL muscles, respectively. After return to normal solution, the recovery was not complete within 30 min. In K+ free solution the c.v. of EDL and SM muscles rose by a factor of 1.5, but less in SOL muscles. The weaker response of SOL to K+ modification was related to the higher resistance of this muscle to fatigue. This suggestion was supported by experiments on fatigued fibre bundles. Immediately after a tetanic stimulation producing fatigue, the c.v. of EDL and SOL muscles dropped similarly as in 10 mmol/l K+; again, the drop was less for SOL muscles. Adrenaline (0.5-10.0 mumol/l) enhanced both the c.v. and the twitch amplitude. The results support the suggestion that extracellular K+ accumulation during activity is an essential factor of muscle fatigue. PMID:1816028

  1. Adjuvant-enhanced antibody and cellular responses to inclusion bodies expressing FhSAP2 correlates with protection of mice to Fasciola hepatica.

    PubMed

    Rivera, Francheska; Espino, Ana M

    2016-01-01

    Fasciola hepatica saposin-like protein-2 (FhSAP2) is a protein differentially expressed in various developmental stages of F. hepatica. Recombinant FhSAP2 has demonstrated the induction of partial protection in mice and rabbits when it is administered subcutaneously (SC) in Freund's adjuvant. Because FhSAP2 is overexpressed in bacteria in the form of inclusion bodies (IBs), we isolated IBs expressing FhSAP2 and tested their immunogenicity when administered SC in mice emulsified in two different adjuvants: QS-21 and Montanide TM ISA720. Animals received three injections containing 20 μg of protein two weeks apart and 4 weeks after the third injection, mice were infected with 10 F. hepatica metacercariae by oral route. The percentages of protection induced by FhSAP2-IBs were estimated to be between 60.0 and 62.5% when compared with adjuvant-vaccinated, infected controls. By determining the levels of IgG1 and IgG2a antibodies and IL-4 and IFNγ cytokines in the serum of experimental animals, it was found that both Th1 and Th2 immune responses were significantly increased in the FhSAP2-IBs vaccinated groups compared with the adjuvant-vaccinated, infected control groups. The adjuvant-vaccinated groups had significantly lower IgG1 to IgG2a ratios and lower IL-4 to IFNγ ratios than the FhSAP2-IBs vaccinated animals, which is indicative of higher levels of Th2 immune responses. Irrespective to the adjuvant used, animals vaccinated with FhSAP2-IBs exhibited significantly higher survival percentage and less liver damage than the adjuvant-control groups. This study suggests that FhSAP2 has potential as vaccine against F. hepatica and that the protection elicited by this molecule could be linked to a mechanism driven by the CD4-Th1 cells. PMID:26632503

  2. Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor.

    PubMed

    Duan, Xiaojie; Gao, Ruixuan; Xie, Ping; Cohen-Karni, Tzahi; Qing, Quan; Choe, Hwan Sung; Tian, Bozhi; Jiang, Xiaocheng; Lieber, Charles M

    2012-03-01

    The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be

  3. Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor

    NASA Astrophysics Data System (ADS)

    Duan, Xiaojie; Gao, Ruixuan; Xie, Ping; Cohen-Karni, Tzahi; Qing, Quan; Choe, Hwan Sung; Tian, Bozhi; Jiang, Xiaocheng; Lieber, Charles M.

    2012-03-01

    The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be

  4. Potential Mechanisms of Action in the Treatment of Social Impairment and Disorganization in Adolescents with ADHD

    PubMed Central

    Evans, Steven W.; Schultz, Brandon K.; Zoromski, Allison K.

    2014-01-01

    Two important domains that can be impaired in adolescents with ADHD are organization and social functioning; however, the development of interventions to target these areas in adolescents is in the early stages. Currently, small efficacy trials are beginning to be used to conduct preliminary tests on the proposed mechanisms of action for these interventions. These two studies examined the efficacy of organization and social functioning interventions for adolescents with ADHD, as well as the potential mechanisms of action for each intervention. Results from the organization intervention provide support for a significant relationship between performance on the organization checklist and overall GPA; however, there was no meaningful pattern of relationships between achieving mastery of the organization tasks and grades within quarter. Further, results from the social functioning intervention support a moderate relationship between performance on process measures of response to the intervention and outcome measures of social functioning. Results of this study provide implications for modifications to the measures and intervention procedures in future research. PMID:24748901

  5. A potential mode of action for Anakinra in patients with arthrofibrosis following total knee arthroplasty

    PubMed Central

    Dixon, David; Coates, Jonathon; del Carpio Pons, Alicia; Horabin, Joanna; Walker, Andrew; Abdul, Nicole; Kalson, Nicholas S.; Brewster, Nigel T.; Weir, David J.; Deehan, David J.; Mann, Derek A.; Borthwick, Lee A.

    2015-01-01

    Arthrofibrosis is a fibroproliferative disease characterised by excessive deposition of extracellular matrix components intra-articularly leading to pain and restricted range of movement. Although frequently observed following total knee arthroplasty (TKA) no therapeutic options exist. A pilot study demonstrated that intra-articular injection of Anakinra, an IL-1R antagonist, improved range of movement and pain in patients with arthrofibrosis however the mechanism of action is unknown. We hypothesise that IL-1α/β will drive an inflammatory phenotype in fibroblasts isolated from the knee, therefore identifying a potential mechanism of action for Anakinra in arthrofibrosis following TKA. Fibroblasts isolated from synovial membranes and infra-patellar fat pad of patients undergoing TKA express high levels of IL-1R1. Stimulation with IL-1α/β induced a pro-inflammatory phenotype characterised by increased secretion of GMCSF, IL-6 and IL-8. No significant difference in the inflammatory response was observed between fibroblasts isolated from synovial membrane or infra-patellar fat pad. IL-1α/β treatments induced a pro-inflammatory phenotype in fibroblasts from both synovial membrane and infra-patellar fat pad and therefore Anakinra can likely have an inhibitory effect on fibroblasts present in both tissues in vivo. It is also likely that fibroblast responses in the tissues are controlled by IL-1α/β availability and not their ability to respond to it. PMID:26553966

  6. Piloting the promotion of bamboo skirt barriers to prevent Nipah virus transmission through date palm sap in Bangladesh.

    PubMed

    Nahar, Nazmun; Mondal, Utpal Kumar; Hossain, M Jahangir; Khan, M Salah Uddin; Sultana, Rebeca; Gurley, Emily S; Luby, Stephen P

    2014-12-01

    Drinking raw date palm sap contaminated with infected fruit bat saliva or urine is an important mode of Nipah virus transmission to humans in Bangladesh. Bamboo skirts are an effective way to interrupt bat access to the sap. We conducted a study from November 2008 to March 2009 to explore the effectiveness of higher- and lower-intensity interventions by promoting bamboo skirt preparation and use among sap harvesters (gachhis). We spent 280 person-hours in two villages for the higher-intensity intervention and half that amount of time in two other villages for the lower-intensity intervention. To evaluate the interventions we followed up all gachhis once a month for three months. A high percentage of gachhis (83% in higher-, 65% in lower-intensity interventions) prepared and used a skirt of bamboo or other materials - jute stalk, dhoincha (Sesbania aculeata), or polythene - at least once after intervention. In general, 15% of gachhis consistently used skirts throughout the sap collection season. The intensive nature of this intervention is very expensive for a large-scale programme. Future efforts should focus on developing a low-cost behaviour change intervention and evaluate if it reduces the human exposure to potentially contaminated fresh date palm sap. PMID:24755262

  7. Transient response of sap flow to wind speed.

    PubMed

    Chu, Chia R; Hsieh, Cheng-I; Wu, Shen-Yuang; Phillips, Nathan G

    2009-01-01

    Transient responses of sap flow to step changes in wind speed were experimentally investigated in a wind tunnel. A Granier-type sap flow sensor was calibrated and tested in a cylindrical tube for analysis of its transient time response. Then the sensor was used to measure the transient response of a well-watered Pachira macrocarpa plant to wind speed variations. The transient response of sap flow was described using the resistance-capacitance model. The steady sap flow rate increased as the wind speed increased at low wind speeds. Once the wind speed exceeded 8.0 m s(-1), the steady sap flow rate did not increase further. The transpiration rate, measured gravimetrically, showed a similar trend. The response of nocturnal sap flow to wind speed variation was also measured and compared with the results in the daytime. Under the same wind speed, the steady sap flow rate was smaller than that in the daytime, indicating differences between diurnal and nocturnal hydraulic function, and incomplete stomatal closure at night. In addition, it was found that the temporal response of the Granier sensor is fast enough to resolve the transient behaviour of water flux in plant tissue. PMID:19022910

  8. Date palm sap collection: exploring opportunities to prevent Nipah transmission.

    PubMed

    Nahar, Nazmun; Sultana, Rebeca; Gurley, Emily S; Hossain, M Jahangir; Luby, Stephen P

    2010-06-01

    Nipah virus (NiV) infection is a seasonal disease in Bangladesh that coincides with the date palm sap collection season. Raw date palm sap is a delicacy to drink in Bengali culture. If fruit bats that are infected with NiV gain access to the sap for drinking, they might occasionally contaminate the sap through saliva and urine. In February 2007, we conducted a qualitative study in six villages, interviewing 27 date palm sap collectors (gachhis) within the geographical area where NiV outbreaks have occurred since 2001. Gachhis reported that bats pose a challenge to successful collection of quality sap, because bats drink and defecate into the sap which markedly reduces its value. They know some methods to prevent access by bats and other pests but do not use them consistently, because of lack of time and resources. Further studies to explore the effectiveness of these methods and to motivate gachhis to invest their time and money to use them could reduce the risk of human Nipah infection in Bangladesh. PMID:20617362

  9. Dynamics of action potential firing in electrically connected striatal fast-spiking interneurons

    PubMed Central

    Russo, Giovanni; Nieus, Thierry R.; Maggi, Silvia; Taverna, Stefano

    2013-01-01

    Fast-spiking interneurons (FSIs) play a central role in organizing the output of striatal neural circuits, yet functional interactions between these cells are still largely unknown. Here we investigated the interplay of action potential (AP) firing between electrically connected pairs of identified FSIs in mouse striatal slices. In addition to a loose coordination of firing activity mediated by membrane potential coupling, gap junctions (GJ) induced a frequency-dependent inhibition of spike discharge in coupled cells. At relatively low firing rates (2–20 Hz), some APs were tightly synchronized whereas others were inhibited. However, burst firing at intermediate frequencies (25–60 Hz) mostly induced spike inhibition, while at frequencies >50–60 Hz FSI pairs tended to synchronize. Spike silencing occurred even in the absence of GABAergic synapses or persisted after a complete block of GABAA receptors. Pharmacological suppression of presynaptic spike afterhyperpolarization (AHP) caused postsynaptic spikelets to become more prone to trigger spikes at near-threshold potentials, leading to a mostly synchronous firing activity. The complex pattern of functional coordination mediated by GJ endows FSIs with peculiar dynamic properties that may be critical in controlling striatal-dependent behavior. PMID:24294191

  10. Cancer Driver Log (CanDL): Catalog of Potentially Actionable Cancer Mutations.

    PubMed

    Damodaran, Senthilkumar; Miya, Jharna; Kautto, Esko; Zhu, Eliot; Samorodnitsky, Eric; Datta, Jharna; Reeser, Julie W; Roychowdhury, Sameek

    2015-09-01

    Massively parallel sequencing technologies have enabled characterization of genomic alterations across multiple tumor types. Efforts have focused on identifying driver mutations because they represent potential targets for therapy. However, because of the presence of driver and passenger mutations, it is often challenging to assign the clinical relevance of specific mutations observed in patients. Currently, there are multiple databases and tools that provide in silico assessment for potential drivers; however, there is no comprehensive resource for mutations with functional characterization. Therefore, we created an expert-curated database of potentially actionable driver mutations for molecular pathologists to facilitate annotation of cancer genomic testing. We reviewed scientific literature to identify variants that have been functionally characterized in vitro or in vivo as driver mutations. We obtained the chromosome location and all possible nucleotide positions for each amino acid change and uploaded them to the Cancer Driver Log (CanDL) database with associated literature reference indicating functional driver evidence. In addition to a simple interface, the database allows users to download all or selected genes as a comma-separated values file for incorporation into their own analysis pipeline. Furthermore, the database includes a mechanism for third-party contributions to support updates for novel driver mutations. Overall, this freely available database will facilitate rapid annotation of cancer genomic testing in molecular pathology laboratories for mutations. PMID:26320871

  11. Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles.

    PubMed

    Arnold, W David; Sheth, Kajri A; Wier, Christopher G; Kissel, John T; Burghes, Arthur H; Kolb, Stephen J

    2015-01-01

    Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the functional status of a motor unit pool in vivo. These measures can provide insight into the normal development and degeneration of the neuromuscular system. These measures have clear translational potential because they are routinely applied in diagnostic and clinical human studies. We present electrophysiological techniques similar to those employed in humans to allow recordings of mouse sciatic nerve function. The CMAP response represents the electrophysiological output from a muscle or group of muscles following supramaximal stimulation of a peripheral nerve. MUNE is an electrophysiological technique that is based on modifications of the CMAP response. MUNE is a calculated value that represents the estimated number of motor neurons or axons (motor control input) supplying the muscle or group of muscles being tested. We present methods for recording CMAP responses from the proximal leg muscles using surface recording electrodes following the stimulation of the sciatic nerve in mice. An incremental MUNE technique is described using submaximal stimuli to determine the average single motor unit potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to-peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques allow repeated measures in both neonatal and adult mice in such a manner that facilitates rapid analysis and data collection while reducing the number of animals required for experimental testing. Furthermore, these measures are similar to those recorded in human studies allowing more direct comparisons. PMID:26436455

  12. Neuronal adaptation involves rapid expansion of the action potential initiation site.

    PubMed

    Scott, Ricardo S; Henneberger, Christian; Padmashri, Ragunathan; Anders, Stefanie; Jensen, Thomas P; Rusakov, Dmitri A

    2014-01-01

    Action potential (AP) generation is the key to information-processing in the brain. Although APs are normally initiated in the axonal initial segment, developmental adaptation or prolonged network activity may alter the initiation site geometry thus affecting cell excitability. Here we find that hippocampal dentate granule cells adapt their spiking threshold to the kinetics of the ongoing dendrosomatic excitatory input by expanding the AP-initiation area away from the soma while also decelerating local axonal spikes. Dual-patch soma-axon recordings combined with axonal Na(+) and Ca(2+) imaging and biophysical modelling show that the underlying mechanism involves distance-dependent inactivation of axonal Na(+) channels due to somatic depolarization propagating into the axon. Thus, the ensuing changes in the AP-initiation zone and local AP propagation could provide activity-dependent control of cell excitability and spiking on a relatively rapid timescale. PMID:24851940

  13. Time course of Ca and Ca-dependent K currents during molluscan nerve cell action potentials.

    PubMed

    Gola, M; Hussy, N; Crest, M; Ducreux, C

    1986-10-20

    The time courses of Ca and Ca-dependent K currents during Ca-dependent action potentials were obtained by recording the membrane currents produced in response to spike-like voltage clamp pulses before and after selective blockade of channels. The Ca current had a biphasic waveform with a first surge and a late, large entry. The Ca-dependent K(Ca) current onset was relatively fast with a peak occurring at half spike repolarization. The fast activation of the K(Ca) current was consecutive to the first Ca entry. It is concluded that K(Ca) currents constitute a powerful spike repolarization mechanism in addition to the voltage-dependent K currents. PMID:2430243

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

    PubMed Central

    Li, Wentao; Xu, Haoliang; Testai, Fernando D.

    2016-01-01

    Fingolimod (FTY720) is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood–brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720’s mechanisms of action in stroke. PMID:27617002

  15. Synapse-Level Determination of Action Potential Duration by K(+) Channel Clustering in Axons.

    PubMed

    Rowan, Matthew J M; DelCanto, Gina; Yu, Jianqing J; Kamasawa, Naomi; Christie, Jason M

    2016-07-20

    In axons, an action potential (AP) is thought to be broadcast as an unwavering binary pulse over its arbor, driving neurotransmission uniformly at release sites. Yet by recording from axons of cerebellar stellate cell (SC) interneurons, we show that AP width varies between presynaptic bouton sites, even within the same axon branch. The varicose geometry of SC boutons alone does not impose differences in spike duration. Rather, axonal patching revealed heterogeneous peak conductance densities of currents mediated mainly by fast-activating Kv3-type potassium channels, with clustered hotspots at boutons and restricted expression at adjoining shafts. Blockade of Kv channels at individual boutons indicates that currents immediately local to a release site direct spike repolarization at that location. Thus, the clustered arrangement and variable expression density of Kv3 channels at boutons are key determinants underlying compartmentalized control of AP width in a near synapse-by-synapse manner, multiplying the signaling capacity of these structures. PMID:27346528

  16. Effects of lead acetate on guinea pig - cochear microphonics, action potential, and motor nerve conduction velocity

    SciTech Connect

    Yamamura, K.; Maehara, N.; Terayama, K.; Ueno, N.; Kohyama, A.; Sawada, Y.; Kishi, R.

    1987-04-01

    Segmental demyelination and axonal degeneration of motor nerves induced by lead exposure is well known in man, and animals. The effect of lead acetate exposure to man may involve the cranial nerves, since vertigo and sensory neuronal deafness have been reported among lead workers. However, there are few reports concerning the dose-effects of lead acetate both to the peripheral nerve and the cranial VII nerve with measurement of blood lead concentration. The authors investigated the effects of lead acetate to the cochlea and the VIII nerve using CM (cochlear microphonics) and AP (action potential) of the guinea pigs. The effects of lead acetate to the sciatic nerve were measured by MCV of the sciatic nerve with measurement of blood lead concentration.

  17. Neuronal adaptation involves rapid expansion of the action potential initiation site

    PubMed Central

    Scott, Ricardo S.; Henneberger, Christian; Padmashri, Ragunathan; Anders, Stefanie; Jensen, Thomas P.; Rusakov, Dmitri A.

    2014-01-01

    Action potential (AP) generation is the key to information-processing in the brain. Although APs are normally initiated in the axonal initial segment, developmental adaptation or prolonged network activity may alter the initiation site geometry thus affecting cell excitability. Here we find that hippocampal dentate granule cells adapt their spiking threshold to the kinetics of the ongoing dendrosomatic excitatory input by expanding the AP-initiation area away from the soma while also decelerating local axonal spikes. Dual-patch soma–axon recordings combined with axonal Na+ and Ca2+ imaging and biophysical modelling show that the underlying mechanism involves distance-dependent inactivation of axonal Na+ channels due to somatic depolarization propagating into the axon. Thus, the ensuing changes in the AP-initiation zone and local AP propagation could provide activity-dependent control of cell excitability and spiking on a relatively rapid timescale. PMID:24851940

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

    PubMed

    Li, Wentao; Xu, Haoliang; Testai, Fernando D

    2016-01-01

    Fingolimod (FTY720) is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood-brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720's mechanisms of action in stroke. PMID:27617002

  19. Anthropomorphizing the Mouse Cardiac Action Potential via a Novel Dynamic Clamp Method

    PubMed Central

    Ahrens-Nicklas, Rebecca C.; Christini, David J.

    2009-01-01

    Abstract Interspecies differences can limit the translational value of excitable cells isolated from model organisms. It can be difficult to extrapolate from a drug- or mutation-induced phenotype in mice to human pathophysiology because mouse and human cardiac electrodynamics differ greatly. We present a hybrid computational-experimental technique, the cell-type transforming clamp, which is designed to overcome such differences by using a calculated compensatory current to convert the macroscopic electrical behavior of an isolated cell into that of a different cell type. We demonstrate the technique's utility by evaluating drug arrhythmogenicity in murine cardiomyocytes that are transformed to behave like human myocytes. Whereas we use the cell-type transforming clamp in this work to convert between mouse and human electrodynamics, the technique could be adapted to convert between the action potential morphologies of any two cell types of interest. PMID:19917221

  20. Experimental and theoretical description of higher order periods in cardiac tissue action potential duration

    NASA Astrophysics Data System (ADS)

    Herndon, Conner; Fenton, Flavio; Uzelac, Ilija

    Much theoretical, experimental, and clinical research has been devoted to investigating the initiation of cardiac arrhythmias by alternans, the first period doubling bifurcation in the duration of cardiac action potentials. Although period doubling above alternans has been shown to exist in many mammalian hearts, little is understood about their emergence or behavior. There currently exists no physiologically correct theory or model that adequately describes and predicts their emergence in stimulated tissue. In this talk we present experimental data of period 2, 4, and 8 dynamics and a mathematical model that describes these bifurcations. This model extends current cell models through the addition of memory and includes spatiotemporal nonlinearities arising from cellular coupling by tissue heterogeneity.

  1. Na+ current in presynaptic terminals of the crayfish opener cannot initiate action potentials.

    PubMed

    Lin, Jen-Wei

    2016-01-01

    Action potential (AP) propagation in presynaptic axons of the crayfish opener neuromuscular junction (NMJ) was investigated by simultaneously recording from a terminal varicosity and a proximal branch. Although orthodromically conducting APs could be recorded in terminals with amplitudes up to 70 mV, depolarizing steps in terminals to -20 mV or higher failed to fire APs. Patch-clamp recordings did detect Na(+) current (INa) in most terminals. The INa exhibited a high threshold and fast activation rate. Local perfusion of Na(+)-free saline showed that terminal INa contributed to AP waveform by slightly accelerating the rising phase and increasing the peak amplitude. These findings suggest that terminal INa functions to "touch up" but not to generate APs. PMID:26561611

  2. Trichloroethanol alters action potentials in a subgroup of primary sensory neurones.

    PubMed

    Gruss, Marco; Hempelmann, Gunter; Scholz, Andreas

    2002-05-01

    We investigated the effects of 2,2,2-trichloroethanol (TCE), the active metabolite of chloral hydrate, on large-conductance calcium-activated K+ channels (BKCa channels) of dorsal root ganglion (DRG) neurones. In outside-out patches, 2 and 5 mM TCE increased the open probability of BKCa channels to 1.7-fold and 2.8-fold of control, respectively. In 50% of the cells investigated (group A) the action potential (AP) was shortened reversibly by TCE by 20% and the whole-cell outward-current was increased by 44%. Both effects could be antagonized by iberiotoxin. In a second group of neurone (group B), TCE prolonged the AP duration. The effects of TCE in group A, which was 20-fold more potent than ethanol on BKCa channels and AP might contribute to the described analgesic effect of chloral hydrate. PMID:11997700

  3. Control of action potential propagation by intracellular Ca2+ in cultured rat dorsal root ganglion cells.

    PubMed Central

    Lüscher, C; Lipp, P; Lüscher, H R; Niggli, E

    1996-01-01

    1. To assess the role of intracellular Ca2+ in action potential (AP) propagation, whole-cell recordings of cultured dorsal root ganglion (DRG) cells were carried out while Ca2+ was simultaneously measured with a laser-scanning confocal microscope. 2. Flash photolytic liberation of a Ca2+ buffer during trains of APs which partly failed to invade the DRG cell body immediately lowered intracellular Ca2+ and restored safe AP propagation. Furthermore, the speed of the propagated AP was reduced considerably when intracellular Ca2+ was increased by flash photolysis of caged Ca2+. 3. Both results suggest that intracellular Ca2+ regulates the safety factor for AP propagation and may thus provide a control mechanism for synaptic integration, which acts pre- as well as postsynaptically. Images Figure 1 Figure 3 PMID:8821131

  4. Effect of Cardiac Tissue Anisotropy on Three-Dimensional Electrical Action Potential Propagation

    NASA Astrophysics Data System (ADS)

    He, Zhi Zhu; Liu, Jing

    A three-dimensional (3D) electrical action potential propagation model is developed to characterize the integrated effect of cardiac tissue structure using a homogenous function with a spatial inhomogeneity. This method may be more effective for bridging the gap between computational models and experimental data for cardiac tissue anisotropy. A generalized 3D eikonal relation considering anisotropy and a self-similar evolution solution of such a relation are derived to identify the effect of anisotropy and predict the anisotropy-induced electrical wave propagation instabilities. Furthermore, the phase field equation is introduced to obtain the complex three-dimensional numerical solution of the new correlation. The present results are expected to be valuable for better understanding the physiological behavior of cardiac tissues.

  5. Excitable Membranes and Action Potentials in Paramecia: An Analysis of the Electrophysiology of Ciliates

    PubMed Central

    Schlaepfer, Charles H.; Wessel, Ralf

    2015-01-01

    The ciliate Paramecium caudatum possesses an excitable cell membrane whose action potentials (APs) modulate the trajectory of the cell swimming through its freshwater environment. While many stimuli affect the membrane potential and trajectory, students can use current injection and extracellular ionic concentration changes to explore how APs cause reversal of the cell’s motion. Students examine these stimuli through intracellular recordings, also gaining insight into the practices of electrophysiology. Paramecium’s large size of around 150 µm, simple care, and relative ease to penetrate make them ideal model organisms for undergraduate students’ laboratory study. The direct link between behavior and excitable membranes has thought provoking evolutionary implications for the study of paramecia. Recording from the cell, students note a small resting potential around −30 mV, differing from animal resting potentials. By manipulating ion concentrations, APs of the relatively long length of 20–30 ms up to several minutes with depolarizations maxing over 0 mV are observed. Through comparative analysis of membrane potentials and the APs induced by either calcium or barium, students can deduce the causative ions for the APs as well as the mechanisms of paramecium APs. Current injection allows students to calculate quantitative electric characteristics of the membrane. Analysis will follow the literature’s conclusion in a V-Gated Ca++ influx and depolarization resulting in feedback from intracellular Ca++ that inactivates V-Gated Ca++ channels and activates Ca-Dependent K+ channels through a secondary messenger cascade that results in the K+ efflux and repolarization. PMID:26557800

  6. Limited Role of Secreted Aspartyl Proteinases Sap1 to Sap6 in Candida albicans Virulence and Host Immune Response in Murine Hematogenously Disseminated Candidiasis▿

    PubMed Central

    Correia, Alexandra; Lermann, Ulrich; Teixeira, Luzia; Cerca, Filipe; Botelho, Sofia; Gil da Costa, Rui M.; Sampaio, Paula; Gärtner, Fátima; Morschhäuser, Joachim; Vilanova, Manuel; Pais, Célia

    2010-01-01

    Candida albicans secreted aspartyl proteinases (Saps) are considered virulence-associated factors. Several members of the Sap family were claimed to play a significant role in the progression of candidiasis established by the hematogenous route. This assumption was based on the observed attenuated virulence of sap-null mutant strains. However, the exclusive contribution of SAP genes to their attenuated phenotype was not unequivocally confirmed, as the Ura status of these mutant strains could also have contributed to the attenuation. In this study, we have reassessed the importance of SAP1 to SAP6 in a murine model of hematogenously disseminated candidiasis using sap-null mutant strains not affected in their URA3 gene expression and compared their virulence phenotypes with those of Ura-blaster sap mutants. The median survival time of BALB/c mice intravenously infected with a mutant strain lacking SAP1 to SAP3 was equivalent to that of mice infected with wild-type strain SC5314, while those infected with mutant strains lacking SAP5 showed slightly extended survival times. Nevertheless, no differences could be observed between the wild type and a Δsap456 mutant in their abilities to invade mouse kidneys. Likewise, a deficiency in SAP4 to SAP6 had no noticeable impact on the immune response elicited in the spleens and kidneys of C. albicans-infected mice. These results contrast with the behavior of equivalent Ura-blaster mutants, which presented a significant reduction in virulence. Our results suggest that Sap1 to Sap6 do not play a significant role in C. albicans virulence in a murine model of hematogenously disseminated candidiasis and that, in this model, Sap1 to Sap3 are not necessary for successful C. albicans infection. PMID:20679440

  7. SAP102 is a highly mobile MAGUK in spines

    PubMed Central

    Zheng, Chan-Ying; Petralia, Ronald S.; Wang, Ya-Xian; Kachar, Bechara; Wenthold, Robert J.

    2010-01-01

    Membrane associated guanylate kinases (MAGUKs), which are essential proteins in the postsynaptic density (PSD), cluster and anchor glutamate receptors and other proteins at synapses. The MAGUK family includes PSD-95, PSD-93, SAP102, and SAP97. Individual family members can compensate for one another in their ability to recruit and retain receptors at the postsynaptic membrane as shown through deletion and knockdown studies. SAP102 is highly expressed in both young and mature neurons, however, little is known about its localization and mobility at synapses. Here, we compared the distribution, mobility, and turnover times of SAP102 to the well-studied MAGUK, PSD-95. Using light and electron microscopy, we found that SAP102 shows a broader distribution as well as peak localization further away from the postsynaptic membrane than PSD-95. Using fluorescence recovery after photobleaching (FRAP), we found that 80% of SAP102 and 36% of PSD-95 are mobile in spines. Previous studies showed that PSD-95 was stabilized at the PSD by N-terminal palmitoylation. We found that stabilization of SAP102 at the PSD was dependent on its SH3/GK domains but not its PDZ interactions. Furthermore, we showed that stabilizing actin or blocking NMDA/AMPA receptors reduced the mobile pool of SAP102 but did not affect the mobile pool of PSD-95. Our results show significant differences in the localization, binding mechanism, and mobility of SAP102 and PSD-95. These differences and the compensatory properties of the MAGUKs point out an unrecognized versatility of the MAGUKs in their function in synaptic organization and plasticity. PMID:20357126

  8. Influence of auroral streamers on rapid evolution of SAPS flows

    NASA Astrophysics Data System (ADS)

    Gallardo-Lacourt, B.; Nishimura, T.; Lyons, L. R.; Ruohoniemi, J. M.; Donovan, E.; Angelopoulos, V.; Nishitani, N.

    2015-12-01

    An important manifestation of plasma transport in the ionosphere is Subauroral Polarization Streams or SAPS, which are strong westward flow lying just equatorward of the electron auroral oval and thus of enhanced ionospheric conductivities of the auroral oval. While SAPS are known to intensify due to substorm injections, recent studies showed that large variability of SAPS flow can occur well after substorm onset and even during non-substorm times. These SAPS enhancements have been suggested to occur in association with auroral streamers that propagate equatorward, a suggestion that would indicate that plasma sheet fast flows propagate into the inner magnetosphere and increase subauroral flows. We present auroral images from the THEMIS ground-based all-sky-imager array and 2-d line-of-sight flow observations from the SuperDARN radars that share fields of view with the imagers to investigate systematically the association between SAPS and auroral streamers. We surveyed events from December 2007 to April 2013 for which high or mid-latitude SuperDARN radars were available to measure the SAPS flows, and identified 60 events. For streamers observed near the equatorward boundary of the auroral oval, we find westward flow enhancements of ~200 m/s slightly equatorward of the streamers. A preliminary survey suggests that >90% of the streamers that reach close to the equatorward boundary lead to westward flow enhancements. We also characterize the SAPS flow channel width and timing relative to streamers reaching radar echo meridians. The strong influence of auroral streamers on rapid SAPS flow evolution suggests that transient fast earthward plasma sheet flows can lead to westward SAPS flow enhancements in the subauroral region, and that such enhancements are far more common than only during substorms because of the frequent occurrences of streamers under various geomagnetic conditions.

  9. Influence of auroral streamers on rapid evolution of SAPS flows

    NASA Astrophysics Data System (ADS)

    Gallardo-Lacourt, B.; Nishimura, T.; Lyons, L. R.; Angelopoulos, V.; Donovan, E.; Ruohoniemi, J. M.; McWilliams, K. A.; Nishitani, N.

    2014-12-01

    An important manifestation of plasma transport in the ionosphere is Subauroral Polarization Streams or SAPS, which are strong westward flow lying just equatorward of the electron auroral oval and thus of enhanced ionospheric conductivities of the auroral oval. While SAPS are known to intensify due to substorm injections, recent studies showed that large variability of SAPS flow can occur well after substorm onset and even during non-substorm times. These SAPS enhancements have been suggested to occur in association with auroral streamers that propagate equatorward and then turn azimuthally, a suggestion that would indicate that plasma sheet fast flows propagate into the inner magnetosphere and increase subauroral flows. We present auroral images from the THEMIS ground-based all-sky-imager array and 2-d line-of-sight flow observations from the SuperDARN radars that share fields of view with the imagers to investigate systematically the association between SAPS and auroral streamers. We surveyed events from December 2007 to April 2010 for which high or mid-latitude SuperDARN radars were available to measure the SAPS flows, and identified 30 events. For streamers observed near the equatorward boundary of the auroral oval either while turning, or after having turned, westward, we find westward flow enhancements of ~200 m/s slightly equatorward of the streamers. A preliminary survey suggests that >90% of the streamers that turn westward lead to westward flow enhancements. We also characterize the SAPS flow channel width and timing relative to streamers reaching radar echo meridians. The strong influence of auroral streamers on rapid evolution of SAPS flows suggests that transient fast earthward plasma sheet flows can lead to westward SAPS flow enhancements in the subauroral region, and that such enhancements are far more common than just during substorms because of the frequent occurrences of streamers under various geomagnetic conditions.

  10. In-vitro characterization of a cochlear implant system for recording of evoked compound action potentials

    PubMed Central

    2012-01-01

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

  11. Effects of 4-aminopyridine on action potentials generation in mouse sinoauricular node strips

    PubMed Central

    Golovko, Vladimir; Gonotkov, Mikhail; Lebedeva, Elena

    2015-01-01

    The physiological role of Ito has yet to be clarified. The goal of this study is to investigate the possible contribution of the transient outward current (Ito) on the generation of transmembrane action potentials (APs) and the sensitivity of mouse sinoauricular node (SAN) cells to a 4-aminopyridine (4AP) as Ito blocker. The electrophysiological identification of cells was performed in the sinoauricular node artery area (nstrips = 38) of the subendocardial surface using microelectrode technique. In this study, for the first time, it was observed that dependence duration of action potential at the level of 20% repolarization (APD20) level under a 4AP concentration in the pacemaker SAN and auricular cells corresponds to a curve predicted by Hill’s equation. APD20 raised by 70% and spike duration of AP increased by 15–25%, when 4AP concentration was increased from 0.1 to 5.0 mmol/L. Auricular cells were found to be more sensitive to 4AP than true pacemaker cells. This was accompanied by a decrease in the upstroke velocity as compared to the control. Our data and previous findings in the literature lead us to hypothesize that the 4AP-sensitive current participates in the repolarization formation of pacemaker and auricular type cells. Thus, study concerning the inhibitory effects of lidocaine and TTX on APD20 can explain the phenomenon of the decrease in upstroke velocity, which, for the first time, was observed after exposure to 4AP. Duration of AP at the level of 20% repolarization (APD20) under a 4-AP concentration 0.5 mmol/L in the true pacemaker cells lengthen by 60–70% with a control. PMID:26156968

  12. Effects of 4-aminopyridine on action potentials generation in mouse sinoauricular node strips.

    PubMed

    Golovko, Vladimir; Gonotkov, Mikhail; Lebedeva, Elena

    2015-07-01

    The physiological role of Ito has yet to be clarified. The goal of this study is to investigate the possible contribution of the transient outward current (Ito) on the generation of transmembrane action potentials (APs) and the sensitivity of mouse sinoauricular node (SAN) cells to a 4-aminopyridine (4AP) as Ito blocker. The electrophysiological identification of cells was performed in the sinoauricular node artery area (nstrips = 38) of the subendocardial surface using microelectrode technique. In this study, for the first time, it was observed that dependence duration of action potential at the level of 20% repolarization (APD20) level under a 4AP concentration in the pacemaker SAN and auricular cells corresponds to a curve predicted by Hill's equation. APD20 raised by 70% and spike duration of AP increased by 15-25%, when 4AP concentration was increased from 0.1 to 5.0 mmol/L. Auricular cells were found to be more sensitive to 4AP than true pacemaker cells. This was accompanied by a decrease in the upstroke velocity as compared to the control. Our data and previous findings in the literature lead us to hypothesize that the 4AP-sensitive current participates in the repolarization formation of pacemaker and auricular type cells. Thus, study concerning the inhibitory effects of lidocaine and TTX on APD20 can explain the phenomenon of the decrease in upstroke velocity, which, for the first time, was observed after exposure to 4AP. Duration of AP at the level of 20% repolarization (APD20) under a 4-AP concentration 0.5 mmol/L in the true pacemaker cells lengthen by 60-70% with a control. PMID:26156968

  13. Mannan Oligosaccharides in Nursery Pig Nutrition and Their Potential Mode of Action

    PubMed Central

    Halas, Veronika; Nochta, Imre

    2012-01-01

    Simple Summary The aim of the paper is to provide a review of mannan oligosaccharide products in relation to their growth promoting effect and mode of action. Mannan oligosaccharide products maintain intestinal integrity and the digestive and absorptive function of the gut in the post-weaning period in pigs and enhance disease resistance by promoting antigen presentation. We find that dietary supplementation has growth promoting effects in pigs kept in a poor hygienic environment, while the positive effect of MOS is not observed in healthy pig herds with high hygienic standards. Abstract Mannan oligosaccharides (MOSs) are often referred to as one of the potential alternatives for antimicrobial growth promoters. The aim of the paper is to provide a review of mannan oligosaccharide products in relation to their growth promoting effect and mode of action based on the latest publications. We discuss the dietary impact of MOSs on (1) microbial changes, (2) morphological changes of gut tissue and digestibility of nutrients, and (3) immune response of pigs after weaning. Dietary MOSs maintain the intestinal integrity and the digestive and absorptive function of the gut in the post-weaning period. Recent results suggest that MOS enhances the disease resistance in swine by promoting antigen presentation facilitating thereby the shift from an innate to an adaptive immune response. Accordingly, dietary MOS supplementation has a potential growth promoting effect in pigs kept in a poor hygienic environment, while the positive effect of MOS is not observed in healthy pig herds with high hygienic standards that are able to maintain a high growth rate after weaning. PMID:26486920

  14. Glutamine and glutamate limit the shortening of action potential duration in anoxia-challenged rabbit hearts

    PubMed Central

    Drake, Kenneth J; Shotwell, Matthew S; Wikswo, John P; Sidorov, Veniamin Y

    2015-01-01

    In clinical conditions, amino acid supplementation is applied to improve contractile function, minimize ischemia/reperfusion injury, and facilitate postoperative recovery. It has been shown that glutamine enhances myocardial ATP/APD (action potential duration) and glutathione/oxidized glutathione ratios, and can increase hexosamine biosynthesis pathway flux, which is believed to play a role in cardioprotection. Here, we studied the effect of glutamine and glutamate on electrical activity in Langendorff-perfused rabbit hearts. The hearts were supplied by Tyrode's media with or without 2.5 mmol/L glutamine and 150 μmol/L glutamate, and exposed to two 6-min anoxias with 20-min recovery in between. Change in APD was detected using a monophasic action potential probe. A nonlinear mixed-effects regression technique was used to evaluate the effect of amino acids on APD over the experiment. Typically, the dynamic of APD change encompasses three phases: short transient increase (more prominent in the first episode), slow decrease, and fast increase (starting with the beginning of recovery). The effect of both anoxic challenge and glutamine/glutamate was cumulative, being more pronounced in the second anoxia. The amino acids' protective effect became largest by the end of anoxia – 20.0% (18.9, 95% CI: [2.6 ms, 35.1 ms]), during the first anoxia and 36.6% (27.1, 95% CI: [7.7 ms, 46.6 ms]), during the second. Following the second anoxia, APD difference between control and supplemented hearts progressively increased, attaining 10.8% (13.6, 95% CI: [4.1 ms, 23.1 ms]) at the experiments' end. Our data reveal APD stabilizing and suggest an antiarrhythmic capacity of amino acid supplementation in anoxic/ischemic conditions. PMID:26333831

  15. 30 CFR 285.605 - What is a Site Assessment Plan (SAP)?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What is a Site Assessment Plan (SAP)? 285.605... Assessment Plan (SAP)? (a) A SAP describes the activities (e.g., installation of meteorological towers... project easement, or to test technology devices. (1) Your SAP must describe how you will conduct...

  16. Quantification of Transmembrane Currents during Action Potential Propagation in the Heart

    PubMed Central

    Gray, Richard A.; Mashburn, David N.; Sidorov, Veniamin Y.; Wikswo, John P.

    2013-01-01

    The measurement, quantitative analysis, theory, and mathematical modeling of transmembrane potential and currents have been an integral part of the field of electrophysiology since its inception. Biophysical modeling of action potential propagation begins with detailed ionic current models for a patch of membrane within a distributed cable model. Voltage-clamp techniques have revolutionized clinical electrophysiology via the characterization of the transmembrane current gating variables; however, this kinetic information alone is insufficient to accurately represent propagation. Other factors, including channel density, membrane area, surface/volume ratio, axial conductivities, etc., are also crucial determinants of transmembrane currents in multicellular tissue but are extremely difficult to measure. Here, we provide, to our knowledge, a novel analytical approach to compute transmembrane currents directly from experimental data, which involves high-temporal (200 kHz) recordings of intra- and extracellular potential with glass microelectrodes from the epicardial surface of isolated rabbit hearts during propagation. We show for the first time, to our knowledge, that during stable planar propagation the biphasic total transmembrane current (Im) dipole density during depolarization was ∼0.25 ms in duration and asymmetric in amplitude (peak outward current was ∼95 μA/cm2 and peak inward current was ∼140 μA/cm2), and the peak inward ionic current (Iion) during depolarization was ∼260 μA/cm2 with duration of ∼1.0 ms. Simulations of stable propagation using the ionic current versus transmembrane potential relationship fit from the experimental data reproduced these values better than traditional ionic models. During ventricular fibrillation, peak Im was decreased by 50% and peak Iion was decreased by 70%. Our results provide, to our knowledge, novel quantitative information that complements voltage- and patch-clamp data. PMID:23332079

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

    PubMed Central

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

    2012-01-01

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

  18. Antifungal and cytotoxicity activities of the fresh xylem sap of Hymenaea courbaril L. and its major constituent fisetin

    PubMed Central

    2014-01-01

    Background The great potential of plants as Hymenaea courbaril L (jatoba) has not yet been throughly explored scientifically and therefore it is very important to investigate their pharmacological and toxicological activities to establish their real efficacy and safety. This study investigated the cytotoxicity of xylem sap of Hymenaea courbaril L and its bioactivity against the fungi Cryptococcus neoformans species complex and dermatophytes. Methods The fresh xylem sap of H. courbaril was filtered resulting in an insoluble brown color precipitate and was identified as fisetin. In the filtrate was identified the mixture of fisetinediol, fustin, 3-O-methyl-2,3-trans-fustin and taxifolin, which were evaluated by broth microdilution antifungal susceptibility testing against C. neoformans species complex and dermatophytes. The fresh xylem sap and fisetin were screened for cytotoxicity against the 3T3-A31 cells of Balb/c using neutral red uptake (NRU) assay. Results The fresh xylem sap and the fisetin showed higher in vitro activity than the filtrate. The xylem sap of H. courbaril inhibited the growth of dermatophytes and of C. neoformans with minimal inhibition concentration (MIC) < 256 μg/mL, while the fisetin showed MIC < 128 μg/mL for these fungi. Fisetin showed lower toxicity (IC50 = 158 μg/mL) than the fresh xylem sap (IC50 = 109 μg/mL). Conclusion Naturally occurring fisetin can provide excellent starting points for clinical application and can certainly represent a therapeutic potential against fungal infections, because it showed in vitro antifungal activity and low toxicity on animal cells. PMID:25027026

  19. Simultaneous Optical Mapping of Intracellular Free Calcium and Action Potentials from Langendorff Perfused Hearts

    PubMed Central

    Salama, Guy; Hwang, Seong-min

    2015-01-01

    The cardiac action potential (AP) controls the rise and fall of intracellular free Ca2+ (Cai), and thus the amplitude and kinetics of force generation. Besides excitation-contraction coupling, the reverse process where Cai influences the AP through Cai-dependent ionic currents has been implicated as the mechanism underlying QT alternans and cardiac arrhythmias in heart failure, ischemia/reperfusion, cardiac myopathy, myocardial infarction, congenital and drug-induced long QT syndrome, and ventricular fibrillation. The development of dual optical mapping at high spatial and temporal resolution provides a powerful tool to investigate the role of Cai anomalies in eliciting cardiac arrhythmias. This unit describes experimental protocols to map APs and Cai transients from perfused hearts by labeling the heart with two fluorescent dyes, one to measure transmembrane potential (Vm), the other Cai transients. High spatial and temporal resolution is achieved by selecting Vm and Cai probes with the same excitation but different emission wavelengths, to avoid cross-talk and mechanical components. PMID:19575468

  20. Human neural tuning estimated from compound action potentials in normal hearing human volunteers

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  1. Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials.

    PubMed

    Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J

    2016-01-01

    A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs. PMID:27510732

  2. Variability of Action Potentials Within and Among Cardiac Cell Clusters Derived from Human Embryonic Stem Cells.

    PubMed

    Zhu, Renjun; Millrod, Michal A; Zambidis, Elias T; Tung, Leslie

    2016-01-01

    Electrophysiological variability in cardiomyocytes derived from pluripotent stem cells continues to be an impediment for their scientific and translational applications. We studied the variability of action potentials (APs) recorded from clusters of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using high-resolution optical mapping. Over 23,000 APs were analyzed through four parameters: APD30, APD80, triangulation and fractional repolarization. Although measures were taken to reduce variability due to cell culture conditions and rate-dependency of APs, we still observed significant variability in APs among and within the clusters. However, similar APs were found in spatial locations with close proximity, and in some clusters formed distinct regions having different AP characteristics that were reflected as separate peaks in the AP parameter distributions, suggesting multiple electrophysiological phenotypes. Using a recently developed automated method to group cells based on their entire AP shape, we identified distinct regions of different phenotypes within single clusters and common phenotypes across different clusters when separating APs into 2 or 3 subpopulations. The systematic analysis of the heterogeneity and potential phenotypes of large populations of hESC-CMs can be used to evaluate strategies to improve the quality of pluripotent stem cell-derived cardiomyocytes for use in diagnostic and therapeutic applications and in drug screening. PMID:26729331

  3. Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials

    PubMed Central

    Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J.

    2016-01-01

    A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs. PMID:27510732

  4. Calcium Transients Closely Reflect Prolonged Action Potentials in iPSC Models of Inherited Cardiac Arrhythmia

    PubMed Central

    Spencer, C. Ian; Baba, Shiro; Nakamura, Kenta; Hua, Ethan A.; Sears, Marie A.F.; Fu, Chi-cheng; Zhang, Jianhua; Balijepalli, Sadguna; Tomoda, Kiichiro; Hayashi, Yohei; Lizarraga, Paweena; Wojciak, Julianne; Scheinman, Melvin M.; Aalto-Setälä, Katriina; Makielski, Jonathan C.; January, Craig T.; Healy, Kevin E.; Kamp, Timothy J.; Yamanaka, Shinya; Conklin, Bruce R.

    2014-01-01

    Summary Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP). Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca2+]i) measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM). In myocytes carrying an LQT2 mutation (HERG-A422T), APs and [Ca2+]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca2+. Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca2+]i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na+-Ca2+ exchange. These results suggest that LQTS mutations act partly on cytosolic Ca2+ cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site. PMID:25254341

  5. Spatial dynamics of action potentials estimated by dendritic Ca(2+) signals in insect projection neurons.

    PubMed

    Ogawa, Hiroto; Mitani, Ruriko

    2015-11-13

    The spatial dynamics of action potentials, including their propagation and the location of spike initiation zone (SIZ), are crucial for the computation of a single neuron. Compared with mammalian central neurons, the spike dynamics of invertebrate neurons remain relatively unknown. Thus, we examined the spike dynamics based on single spike-induced Ca(2+) signals in the dendrites of cricket mechanosensory projection neurons, known as giant interneurons (GIs). The Ca(2+) transients induced by a synaptically evoked single spike were larger than those induced by an antidromic spike, whereas subthreshold synaptic potentials caused no elevation of Ca(2+). These results indicate that synaptic activity enhances the dendritic Ca(2+) influx through voltage-gated Ca(2+) channels. Stimulation of the presynaptic sensory afferents ipsilateral to the recording site evoked a dendritic spike with higher amplitude than contralateral stimulation, thereby suggesting that alteration of the spike waveform resulted in synaptic enhancement of the dendritic Ca(2+) transients. The SIZ estimated from the spatial distribution of the difference in the Ca(2+) amplitude was distributed throughout the right and left dendritic branches across the primary neurite connecting them in GIs. PMID:26456645

  6. Potential involvement of serotonergic signaling in ketamine's antidepressant actions: A critical review.

    PubMed

    du Jardin, Kristian Gaarn; Müller, Heidi Kaastrup; Elfving, Betina; Dale, Elena; Wegener, Gregers; Sanchez, Connie

    2016-11-01

    A single i.v. infusion of ketamine, classified as an N-methyl-d-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine's antidepressant effects. The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms responsible for ketamine's antidepressant activity do not appear to preclude the possibility that non-glutamate neurotransmitters are involved in the antidepressant effects. At multiple levels, the serotonergic and glutamatergic systems interact, and such crosstalk could support the notion that changes in serotonergic neurotransmission may impact ketamine's antidepressant potential. In line with these prospects, ketamine may increase 5-HT levels in the prefrontal cortex of rats, plausibly via hippocampal NMDA receptor inhibition and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In addition, a number of preclinical studies suggest that the antidepressant-like effects of ketamine may depend on endogenous activation of 5-HT receptors. Recent imaging and behavioral data predominantly support a role for 5-HT1A or 5-HT1B receptors, but the full range of 5-HT receptors has currently not been systematically investigated in this context. Furthermore, the nature of any 5-HT dependent mechanism in ketamine's antidepressant effect is currently not

  7. Whole-Genome Sequencing Reveals a New Genospecies of Methylobacterium sp. GXS13, Isolated from Vitis vinifera L. Xylem Sap

    PubMed Central

    Lai, Wan Xin; Gan, Han Ming; Hudson, André O.

    2016-01-01

    The whole-genome sequence of a new genospecies of Methylobacterium sp., named GXS13 and isolated from grapevine xylem sap, is reported and demonstrates potential for methylotrophy, cytokinin synthesis, and cell wall modification. In addition, biosynthetic gene clusters were identified for cupriachelin, carotenoid, and acyl-homoserine lactone using the antiSMASH server. PMID:26847900

  8. Averaging methods for extracting representative waveforms from motor unit action potential trains.

    PubMed

    Malanda, Armando; Navallas, Javier; Rodriguez-Falces, Javier; Rodriguez-Carreño, Ignacio; Gila, Luis

    2015-08-01

    In the context of quantitative electromyography (EMG), it is of major interest to obtain a waveform that faithfully represents the set of potentials that constitute a motor unit action potential (MUAP) train. From this waveform, various parameters can be determined in order to characterize the MUAP for diagnostic analysis. The aim of this work was to conduct a thorough, in-depth review, evaluation and comparison of state-of-the-art methods for composing waveforms representative of MUAP trains. We evaluated nine averaging methods: Ensemble (EA), Median (MA), Weighted (WA), Five-closest (FCA), MultiMUP (MMA), Split-sweep median (SSMA), Sorted (SA), Trimmed (TA) and Robust (RA) in terms of three general-purpose signal processing figures of merit (SPMF) and seven clinically-used MUAP waveform parameters (MWP). The convergence rate of the methods was assessed as the number of potentials per MUAP train (NPM) required to reach a level of performance that was not significantly improved by increasing this number. Test material comprised 78 MUAP trains obtained from the tibialis anterioris of seven healthy subjects. Error measurements related to all SPMF and MWP parameters except MUAP amplitude descended asymptotically with increasing NPM for all methods. MUAP amplitude showed a consistent bias (around 4% for EA and SA and 1-2% for the rest). MA, TA and SSMA had the lowest SPMF and MWP error figures. Therefore, these methods most accurately preserve and represent MUAP physiological information of utility in clinical medical practice. The other methods, particularly WA, performed noticeably worse. Convergence rate was similar for all methods, with NPM values averaged among the nine methods, which ranged from 10 to 40, depending on the waveform parameter evaluated. PMID:25962870

  9. Decoupling structural and environmental determinants of sap velocity

    NASA Astrophysics Data System (ADS)

    Caylor, K. K.; Dragoni, D.

    2007-12-01

    Characterization of transpiration based on the water use of individual tress has the advantage of preserving vital information on the plant-environment functional links and flux partitioning between species and landscape areas. Whole-tree transpiration has been estimated by means of sap velocity probes, which offer the dual advantages of practicality and repeatability. However, the assumptions underlying the technique require careful verification in order to determine total sap flow from point-based estimates of sap velocity. Our work presents a novel theoretical framework for the study of individual tree sap flow that incorporates both spatial and temporal variability in sap velocities. The instantaneous sap velocity at any point in the radial profile of xylem tissue is defined as the product of two components: (1) a time-invariant sap velocity distribution linked to the species- specific anatomical and structural properties of the conducting xylem, and (2) a time-varying term linked to the dynamics of the atmospheric water demand and available soil moisture. The separation of structural and temporal variation in sap velocity observations provides a direct mechanism for investigating how sap flow is governed by variation in environmental conditions as well as a means for comparing characteristic rates of plant water use among individuals of varying size. Most critically, this approach allows for a consistent and physically meaningful method for extrapolating point observations of sap velocity across the entire depth of conducting xylem. Experimental evidence supports our theoretical framework in the case of a population of sugar maples in a mixed deciduous forest, where observations were taken from a wide range of tree sizes, under varying soil water availability and atmospheric transpiration demand. We have also applied our approach to a small homogeneous sample of dwarf apple trees in a managed orchard, with favorable results. While these results require further

  10. Hair waving natural product: Dillenia indica seed sap.

    PubMed

    Saikia, Jyoti Prasad

    2013-02-01

    Knowing keratin is the main component and mechanical strength of hair a study was performed to evaluate whether Dillenia indica seed sap can affect molecular strength of hair or not. In the present study the human hair collected from barber shop waste were subjected to purified sap for 12 h and then analysed using Fourier transform infrared spectroscopy (FTIR) for documenting evidence for keratin degradation. Further the deterioration was confirmed by thermo gravimetric analysis (TGA) and scanning electron microscopy (SEM). PMID:23124020

  11. Antidiarrhoeal Activity of Musa paradisiaca Sap in Wistar Rats

    PubMed Central

    Yakubu, Musa T.; Nurudeen, Quadri O.; Salimon, Saoban S.; Yakubu, Monsurat O.; Jimoh, Rukayat O.; Nafiu, Mikhail O.; Akanji, Musbau A.; Oladiji, Adenike T.; Williams, Felicia E.

    2015-01-01

    The folkloric claim of Musa paradisiaca sap in the management of diarrhoea is yet to be substantiated or refuted with scientific data. Therefore, the aim of the current study was to screen the sap of M. paradisiaca for both its secondary metabolites and antidiarrhoeal activity at 0.25, 0.50, and 1.00 mL in rats. Secondary metabolites were screened using standard methods while the antidiarrhoeal activity was done by adopting the castor oil-induced diarrhoeal, castor oil-induced enteropooling, and gastrointestinal motility models. The sap contained flavonoids, phenolics, saponins, alkaloids, tannins, and steroids while cardiac glycosides, anthraquinones, triterpenes, cardenolides, and dienolides were not detected. In the castor oil-induced diarrhoeal model, the sap significantly (P < 0.05) prolonged the onset time of diarrhoea, decreased the number, fresh weight, and water content of feaces, and increased the inhibition of defecations. Na+-K+-ATPase activity in the small intestine increased significantly whereas nitric oxide content decreased. The decreases in the masses and volumes of intestinal fluid by the sap were accompanied by increase in inhibition of intestinal fluid content in the enteropooling model. The sap decreased the charcoal meal transit in the gastrointestinal motility model. In all the models, the 1.00 mL of the sap produced changes that compared well with the reference drugs. Overall, the antidiarrhoeal activity of Musa paradisiaca sap attributed to the presence of alkaloids, phenolics, flavonoids, and/or saponins which may involve, among others, enhancing fluid and electrolyte absorption through de novo synthesis of the sodium potassium ATPase and/or reduced nitric oxide levels. PMID:25893000

  12. Effect of microgravity on sap flow in plant stems

    NASA Astrophysics Data System (ADS)

    Kitaya, Yoshiaki; Hirai, Hiroaki; Nobol Ikeda, MR..

    2012-07-01

    A fundamental study was conducted to assess the possibility of plant growth suppression caused by poor movement of air in closed plant growth facilities in space farming. Sap water flow in plant stems, which plays an important role to transport fluid and nutrients from roots to leaves, will be suppressed through suppression of transpiration because of little natural convection of air under microgravity conditions. In this study, the sap flow in tomato stems was examined using a heat flow method at 0.01 and 1.0 g for 20 seconds each during parabolic airplane flights in order to clarify the effect of microgravity on the sap flow in stems. Heat generated with a tiny heater installed in the stem was transferred upstream and downstream by conduction and upstream by the sap flow through xylems of the vascular tissue. The internal heat convection corresponding to the sap flow was analyzed with thermal images captured on stems near heated points. In results, the sap flow in stems at 0.01 g was suppressed under a retarded air condition at a wind speed of 0.1 m s-1 compared with that at 1 g. No suppression of the sap flow was observed under a stirred air condition at a wind speed of 0.5 m s-1. Suppressed sap water flow in stems would be caused by suppression of transpiration in leaves and would cause restriction of water and nutrient uptake in roots. The forced air movement is, therefore, essential to culture healthy plants at a high growth rate under microgravity conditions in space.

  13. Novel Transabdominal Motor Action Potential (TaMAP) Neuromonitoring System for Spinal Surgery

    PubMed Central

    Feldman, Erica; Gabel, Brandon C; Taylor, Natalie; Gharib, James; Lee, Yu-Po; Taylor, William

    2016-01-01

    Introduction Minimally invasive lateral lumbar interbody fusion (LLIF) approaches to the lumbar spine reduce patient morbidity compared to anterior or posterior alternatives. This approach, however, decreases direct anatomical visualization, creating the need for highly sensitive and specific neurophysiological monitoring. We seek to determine feasibility in 'transabdominal motor action potential (TaMAP)' monitoring as an assessment for the integrity of the neural elements during lateral-approach surgeries to the lumbar spine.  Methods Cathode and anode leads were placed on the posterior and anterior surfaces of two porcine subjects. Currents of varying degrees were transmitted across, from front to back. Motor responses were monitored and recorded by needle electrodes in specific distal muscle groups of the lower extremity. Lastly, the cathode and anode were placed anterior and posterior to the chest wall and stimulated to the maximum of 1500 mA to determine any effect on cardiac rhythm. Results Responses were seen by measuring vertical height differences between peaks of corresponding evoked potentials. Recruitment began at 200 mA in the lower extremities. Stimulation at 450 mA recruited a reliable and distinguishable electrographic response from most muscle groups. Responses were recorded and reliably measured and increased in proportion to the graduation of transabdominal stimulation current; no responses were seen in the arms or face. 1500 mA across the chest wall failed to stimulate or induce cardiac arrhythmia on repeated stimulation, indicating safety of stimulation. Conclusion TaMAPs seen in the animal model provide a potential alternative to standard transcranial motor evoked potentials done in the lateral approach of LLIFs. TaMAP recordings in most muscle groups were recordable and reliable, though some muscle groups failed to stimulate. Safety of transabdominal motor evoked potentials was confirmed in this porcine study. Future studies

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

    PubMed Central

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

    2008-01-01

    The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the difference between the fast, step-like onset of APs in rat neocortical neurons and the gradual, exponential-like AP onset in identified snail neurons. The quantitative measure of the AP onset dynamics, provided by the method, allows us to perform quantitative analyses of factors influencing the dynamics. PMID:18398478

  15. Effect of stem water content on sap flow from dormant maple and butternut stems: induction of sap flow in butternut.

    PubMed

    Johnson, R W; Tyree, M T

    1992-10-01

    Sap flow from excised maple stems collected over the winter (1986/87) was correlated with stem water content. Stem water content was high in the fall (>0.80) and decreased rapidly during 2 weeks of continuous freezing temperatures in late winter (<0.60). Exudation of sap from stem segments subjected to freeze/thaw cycles was small (<10 mL/kg) in the fall, but substantial exudation (45-50 mL/kg) occurred following the decline in water content. These observations are consistent with Milburn's and O'Malley's models (J.A. Milburn, P.E.R. O'Malley [1984] Can J Bot 62: 2101-2106; P.E.R. O'Malley, J.A. Milburn [1983] Can J Bot 61:3100-3106) of sap absorption into gas-filled fibers during freezing. Exudation volume was increased 200 to 300% in maple stems originally at high water content (>0.80) after perfusion with sucrose and dehydration at -12 degrees C. Sap flow was also induced in butternut stem segments after the same treatment. Thus, sap flow may not be unique to maples. Sap flow could not be increased in stem segments dehydrated at 4 degrees C. Migration of water molecules from small ice crystals in fibers to larger crystals in vessels while stems were frozen may account for increase exudation after dehydration at -12 degrees C. This would result in preferential dehydration of fibers and a distribution of gas and sap favorable for stem-based sap flow. PMID:16653067

  16. Antifungal potential of Sideroxylon obtusifolium and Syzygium cumini and their mode of action against Candida albicans.

    PubMed

    Pereira, Jozinete Vieira; Freires, Irlan Almeida; Castilho, Aline Rogéria; da Cunha, Marcos Guilherme; Alves, Harley da Silva; Rosalen, Pedro Luiz

    2016-10-01

    Context The emergence of resistant pathogens and toxicity of antifungals have encouraged an active search for novel candidates to manage Candida biofilms. Objective In this study, the little known species Sideroxylon obtusifolium T.D. Penn (Sapotacea) and Syzygium cumini (L.) Skeels (Myrtaceae), from the Caatinga biome in Brazil were chemically characterized and explored for their antifungal potential against C. albicans. Materials and methods We determined the effects of hydroalcoholic extracts/fractions upon fungal growth (minimum inhibitory and fungicidal concentrations, MIC/MFC), biofilm morphology (scanning electron microscopy) and viability (confocal laser scanning microscopy), proposed their mode of action (sorbitol and ergosterol assays), and finally investigated their effects against macrophage and keratinocyte cells in a cell-based assay. Data were analysed using one-way analysis of variance with Tukey-Kramer post-test (α = 0.05). Results The n-butanol (Nb) fraction from S. obtusifolium and S. cumini extract (Sc) showed flavonoids (39.11 ± 6.62 mg/g) and saponins (820.35 ± 225.38 mg/g), respectively, in their chemical composition and demonstrated antifungal activity, with MICs of 62.5 and 125 μg/mL, respectively. Nb and Sc may complex with ergosterol as there was a 4-16-fold increase in MICs in the presence of exogenous ergosterol, leading to disrupted permeability of cell membrane. Deleterious effects were observed on morphology and viability of treated biofilms from concentrations as low as their MICs and higher. Sc was not toxic to macrophages and keratinocytes at these concentrations (p > 0.05), unlike Nb. Conclusions Nb and Sc demonstrated considerable antifungal activity and should be further investigated as potential alternative candidates to treat Candida biofilms. PMID:26987037

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

    PubMed

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

    2016-02-01

    Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na(+)-rich animal and nutrition for the plant. PMID:26804557

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

    PubMed Central

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

    2016-01-01

    Summary Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na+-rich animal and nutrition for the plant. Video Abstract PMID:26804557

  19. Action potential amplitude as a noninvasive indicator of motor unit-specific hypertrophy.

    PubMed

    Pope, Zachary K; Hester, Garrett M; Benik, Franklin M; DeFreitas, Jason M

    2016-05-01

    Skeletal muscle fibers hypertrophy in response to strength training, with type II fibers generally demonstrating the greatest plasticity in regards to cross-sectional area (CSA). However, assessing fiber type-specific CSA in humans requires invasive muscle biopsies. With advancements in the decomposition of surface electromyographic (sEMG) signals recorded using multichannel electrode arrays, the firing properties of individual motor units (MUs) can now be detected noninvasively. Since action potential amplitude (APSIZE) has a documented relationship with muscle fiber size, as well as with its parent MU's recruitment threshold (RT) force, our purpose was to examine if MU APSIZE, as a function of its RT (i.e., the size principle), could potentially be used as a longitudinal indicator of MU-specific hypertrophy. By decomposing the sEMG signals from the vastus lateralis muscle of 10 subjects during maximal voluntary knee extensions, we noninvasively assessed the relationship between MU APSIZE and RT before and immediately after an 8-wk strength training intervention. In addition to significant increases in muscle size and strength (P < 0.02), our data show that training elicited an increase in MU APSIZE of high-threshold MUs. Additionally, a large portion of the variance (83.6%) in the change in each individual's relationship between MU APSIZE and RT was explained by training-induced changes in whole muscle CSA (obtained via ultrasonography). Our findings suggest that the noninvasive, electrophysiological assessment of longitudinal changes to MU APSIZE appears to reflect hypertrophy specific to MUs across the RT continuum. PMID:26936975

  20. Wavelet Transform for Real-Time Detection of Action Potentials in Neural Signals

    PubMed Central

    Quotb, Adam; Bornat, Yannick; Renaud, Sylvie

    2011-01-01

    We present a study on wavelet detection methods of neuronal action potentials (APs). Our final goal is to implement the selected algorithms on custom integrated electronics for on-line processing of neural signals; therefore we take real-time computing as a hard specification and silicon area as a price to pay. Using simulated neural signals including APs, we characterize an efficient wavelet method for AP extraction by evaluating its detection rate and its implementation cost. We compare software implementation for three methods: adaptive threshold, discrete wavelet transform (DWT), and stationary wavelet transform (SWT). We evaluate detection rate and implementation cost for detection functions dynamically comparing a signal with an adaptive threshold proportional to its SD, where the signal is the raw neural signal, respectively: (i) non-processed; (ii) processed by a DWT; (iii) processed by a SWT. We also use different mother wavelets and test different data formats to set an optimal compromise between accuracy and silicon cost. Detection accuracy is evaluated together with false negative and false positive detections. Simulation results show that for on-line AP detection implemented on a configurable digital integrated circuit, APs underneath the noise level can be detected using SWT with a well-selected mother wavelet, combined to an adaptive threshold. PMID:21811455

  1. Dopaminergic modulation of axonal potassium channels and action potential waveform in pyramidal neurons of prefrontal cortex.

    PubMed

    Yang, Jing; Ye, Mingyu; Tian, Cuiping; Yang, Mingpo; Wang, Yonghong; Shu, Yousheng

    2013-07-01

    Voltage-gated K(+) (KV) channels play critical roles in shaping neuronal signals. KV channels distributed in the perisomatic regions and thick dendrites of cortical pyramidal neurons have been extensively studied. However, the properties and regulation of KV channels distributed in the thin axons remain unknown. In this study, by performing somatic and axonal patch-clamp recordings from layer 5 pyramidal neurons of prefrontal cortical slices, we showed that the rapidly inactivating A-currents mediated the transient K(+) currents evoked by action potential (AP) waveform command (KAP) at the soma, whereas the rapidly activating but slowly inactivating KV1-mediated D-currents dominated the KAP at the axon. In addition, activation of D1-like receptors for dopamine decreased the axonal K(+) currents, as a result of an increase in the activity of cAMP-PKA pathway. In contrast, activation of D2-like receptors showed an opposite effect on the axonal K(+) currents. Further experiments demonstrated that functional D1-like receptors were expressed at the main axon trunk and their activation could broaden the waveforms of axonal APs. Together, these results show that axonal KV channels were subjected to dopamine modulation, and this modulation could regulate the waveforms of propagating APs at the axon, suggesting an important role of dopaminergic modulation of axonal KV channels in regulating neuronal signalling. PMID:23568892

  2. Skeletal muscle atrophy: Potential therapeutic agents and their mechanisms of action.

    PubMed

    Dutt, Vikas; Gupta, Sanjeev; Dabur, Rajesh; Injeti, Elisha; Mittal, Ashwani

    2015-09-01

    Over the last two decades, new insights into the etiology of skeletal muscle wasting/atrophy under diverse clinical settings including denervation, AIDS, cancer, diabetes, and chronic heart failure have been reported in the literature. However, the treatment of skeletal muscle wasting remains an unresolved challenge to this day. About nineteen potential drugs that can regulate loss of muscle mass have been reported in the literature. This paper reviews the mechanisms of action of all these drugs by broadly classifying them into six different categories. Mechanistic data of these drugs illustrate that they regulate skeletal muscle loss either by down-regulating myostatin, cyclooxygenase2, pro-inflammatory cytokines mediated catabolic wasting or by up-regulating cyclic AMP, peroxisome proliferator-activated receptor gamma coactivator-1α, growth hormone/insulin-like growth factor1, phosphatidylinositide 3-kinases/protein kinase B(Akt) mediated anabolic pathways. So far, five major proteolytic systems that regulate loss of muscle mass have been identified, but the majority of these drugs control only two or three proteolytic systems. In addition to their beneficial effect on restoring the muscle loss, many of these drugs show some level of toxicity and unwanted side effects such as dizziness, hypertension, and constipation. Therefore, further research is needed to understand and develop treatment strategies for muscle wasting. For successful management of skeletal muscle wasting either therapeutic agent which regulates all five known proteolytic systems or new molecular targets/proteolytic systems must be identified. PMID:26048279

  3. Multifocal fluorescence microscope for fast optical recordings of neuronal action potentials.

    PubMed

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

    2015-02-01

    In recent years, optical sensors for tracking neural activity have been developed and offer great utility. However, developing microscopy techniques that have several kHz bandwidth necessary to reliably capture optically reported action potentials (APs) at multiple locations in parallel remains a significant challenge. To our knowledge, we describe a novel microscope optimized to measure spatially distributed optical signals with submillisecond and near diffraction-limit resolution. Our design uses a spatial light modulator to generate patterned illumination to simultaneously excite multiple user-defined targets. A galvanometer driven mirror in the emission path streaks the fluorescence emanating from each excitation point during the camera exposure, using unused camera pixels to capture time varying fluorescence at rates that are ∼1000 times faster than the camera's native frame rate. We demonstrate that this approach is capable of recording Ca(2+) transients resulting from APs in neurons labeled with the Ca(2+) sensor Oregon Green Bapta-1 (OGB-1), and can localize the timing of these events with millisecond resolution. Furthermore, optically reported APs can be detected with the voltage sensitive dye DiO-DPA in multiple locations within a neuron with a signal/noise ratio up to ∼40, resolving delays in arrival time along dendrites. Thus, the microscope provides a powerful tool for photometric measurements of dynamics requiring submillisecond sampling at multiple locations. PMID:25650920

  4. Kv3.1 uses a timely resurgent K+ current to secure action potential repolarization

    PubMed Central

    Labro, Alain J.; Priest, Michael F.; Lacroix, Jérôme J.; Snyders, Dirk J.; Bezanilla, Francisco

    2015-01-01

    High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K+ currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na+ and K+ currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3–S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission. PMID:26673941

  5. Glucocorticoids: mechanisms of action and anti-inflammatory potential in asthma.

    PubMed Central

    van der Velden, V H

    1998-01-01

    GLUCOCORTICOIDS are potent inhibitors of inflammatory processes and are widely used in the treatment of asthma. The anti-inflammatory effects are mediated either by direct binding of the glucocorticoid/glucocorticoid receptor complex to glucocorticoid responsive elements in the promoter region of genes, or by an interaction of this complex with other transcription factors, in particular activating protein-1 or nuclear factor-kappaB. Glucocorticoids inhibit many inflammation-associated molecules such as cytokines, chemokines, arachidonic acid metabolites, and adhesion molecules. In contrast, anti-inflammatory mediators often are up-regulated by glucocorticoids. In vivo studies have shown that treatment of asthmatic patients with inhaled glucocorticoids inhibits the bronchial inflammation and simultaneously improves their lung function. In this review, our current knowledge of the mechanism of action of glucocorticoids and their anti-inflammatory potential in asthma is described. Since bronchial epithelial cells may be important targets for glucocorticoid therapy in asthma, the effects of glucocorticoids on epithelial expressed inflammatory genes will be emphasized. PMID:9792333

  6. Do Resin Cements Alter Action Potentials of Isolated Rat Sciatic Nerve?

    PubMed Central

    Ertan, Ahmet Atila; Beriat, Nilufer Celebi; Onur, Mehmet Ali; Tan, Gamze; Cehreli, Murat Cavit

    2011-01-01

    Objectives: The purpose of this study was to explore the effects dual-cure resin cements on nerve conduction. Methods: Panavia F, RelyX ARC, and Variolink II polymerized either by light-emitting diode (LED) or quartz tungsten halogen (QTH) were used in the study (n=10). The conductance of sciatic nerves of 50 rats were measured before and after contact with the specimens for 1 h. Results: The time-dependent change in nerve conductance and the comparison of LED versus QTH showed that differences between groups are significant (P<.05). For both polymerization techniques, pair-wise comparisons of resin cements showed that the nerve conductance between groups is different (P<.05). RelyX ARC elicited irreversible inhibition of compound action potentials (more than 50% change) and Panavia F and Variolink II polymerized by LED and QTH did not alter nerve conduction beyond physiologic limits. Conclusions: Resin cements may alter nerve conductance and even lead to neurotoxic effects. PMID:21494389

  7. Sensitivity analysis of potential events affecting the double-shell tank system and fallback actions

    SciTech Connect

    Knutson, B.J.

    1996-09-27

    Sensitivity analyses were performed for fall-back positions (i.e., management actions) to accommodate potential off-normal and programmatic change events overlaid on the waste volume projections and their uncertainties. These sensitivity analyses allowed determining and ranking tank system high-risk parameters and fall- back positions that will accommodate the respective impacts. This quantification of tank system impacts shows periods where tank capacity is sensitive to certain variables that must be carefully managed and/or evaluated. Identifying these sensitive variables and quantifying their impact will allow decision makers to prepare fall-back positions and focus available resources on the highest impact parameters where technical data are needed to reduce waste projection uncertainties. For noncomplexed waste, the period of capacity vulnerability occurs during the years of single-shell tank (SST) retrieval (after approximately 2009) due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate and 200-East SST solids transfer volume. For complexed waste, the period of capacity vulnerability occurs during the period after approximately 2005 due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate. 200-East SST solids transfer volume. complexed waste reduction factor using evaporation, and 200-west saltwell liquid porosity.

  8. A novel analysis of excitatory currents during an action potential from suprachiasmatic nucleus neurons

    PubMed Central

    2013-01-01

    A new application of the action potential (AP) voltage-clamp technique is described based on computational analysis. An experimentally recorded AP is digitized. The resulting Vi vs. ti data set is applied to mathematical models of the ionic conductances underlying excitability for the cell from which the AP was recorded to test model validity. The method is illustrated for APs from suprachiasmatic nucleus (SCN) neurons and the underlying tetrodotoxin-sensitive Na+ current, INa, and the Ca2+ current, ICa. Voltage-step recordings have been made for both components from SCN neurons (Jackson et al. 2004). The combination of voltage-step and AP clamp results provides richer constraints for mathematical models of voltage-gated ionic conductances than either set of results alone, in particular the voltage-step results. For SCN neurons the long-term goal of this work is a realistic mathematical model of the SCN AP in which the equations for INa and ICa obtained from this analysis will be a part. Moreover, the method described in this report is general. It can be applied to any excitable cell. PMID:24047903

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

    PubMed

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

    2010-01-01

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

  10. Motor Unit Number Estimation and Motor Unit Action Potential Analysis in Carpal Tunnel Syndrome

    PubMed Central

    Sohn, Min Kyun; Jee, Sung Ju; Kim, Young-Jae; Shin, Hyun-Dae

    2011-01-01

    Objective To evaluate the clinical significance of motor unit number estimation (MUNE) and quantitative analysis of motor unit action potential (MUAP) in carpal tunnel syndrome (CTS) according to electrophysiologic severity, ultrasonographic measurement and clinical symptoms. Method We evaluated 78 wrists of 45 patients, who had been diagnosed with CTS and 42 wrists of 21 healthy controls. Median nerve conduction studies, amplitude and duration of MUAP, and the MUNE of the abductor pollicis brevis were measured. The cross sectional area (CSA) of the median nerve at the pisiform and distal radioulnar joint level was determined by high resolution ultrasonography. Clinical symptom of CTS was assessed using the Boston Carpal Tunnel Questionnaire (BCTQ). Results The MUNE, the amplitude and the duration of MUAP of the CTS group were significantly different from those found in the control group. The area under the ROC curve was 0.944 for MUNE, 0.923 for MUAP amplitude and 0.953 for MUAP duration. MUNE had a negative correlation with electrophysiologic stage of CTS, amplitude and duration of MUAP, CSA at pisiform level, and the score of BCTQ. The amplitude and duration of MUAP had a positive correlation with the score of BCTQ. The electrophysiologic stage was correlated with amplitude but not with the duration of MUAP. Conclusion MUNE, amplitude and duration of MUAP are useful tests for diagnosis of CTS. In addition, the MUNE serves as a good indicator of CTS severity. PMID:22506210

  11. Efficacy of action potential simulation and interferential therapy in the rehabilitation of patients with knee osteoarthritis

    PubMed Central

    Eftekharsadat, Bina; Habibzadeh, Afshin; Kolahi, Babak

    2015-01-01

    Objective: Knee osteoarthritis (OA) is the main cause of pain, physical impairment and chronic disability in older people. Electrotherapeutic modalities such as interferential therapy (IFT) and action potential simulation (APS) are used for the treatment of knee OA. In this study, we aim to evaluate the therapeutic effects of APS and IFT on knee OA. Methods: In this randomized clinical trial, 67 patients (94% female and 6% male with mean age of 52.80 ± 8.16 years) with mild and moderate knee OA were randomly assigned to be treated with APS (n = 34) or IFT (n = 33) for 10 sessions in 4 weeks. Baseline and post-treatment Western Ontario and McMaster Universities Osteoarthritis (WOMAC) subscales, visual analogue scale (VAS) and timed up and go (TUG) test were measured in all patients. Results: VAS and WOMAC subscales were significantly improved after treatment in APS and IFT groups (p < 0.001 for all). TUG was also significantly improved after treatment in APS group (p < 0.001), but TUG changes in IFT was not significant (p = 0.09). There was no significant difference in VAS, TUG and WOMAC subscales values before and after treatment as well as the mean improvement in VAS, TUG and WOMAC subscales during study between groups. Conclusion: Short-term treatment with both APS and IFT could significantly reduce pain and improve physical function in patients with knee OA. PMID:26029268

  12. Variety of the Wave Change in Compound Muscle Action Potential in an Animal Model

    PubMed Central

    Ito, Zenya; Ando, Kei; Muramoto, Akio; Kobayashi, Kazuyoshi; Hida, Tetsuro; Ito, Kenyu; Ishikawa, Yoshimoto; Tsushima, Mikito; Matsumoto, Akiyuki; Tanaka, Satoshi; Morozumi, Masayoshi; Matsuyama, Yukihiro; Ishiguro, Naoki

    2015-01-01

    Study Design Animal study. Purpose To review the present warning point criteria of the compound muscle action potential (CMAP) and investigate new criteria for spinal surgery safety using an animal model. Overview of Literature Little is known about correlation palesis and amplitude of spinal cord monitoring. Methods After laminectomy of the tenth thoracic spinal lamina, 2-140 g force was delivered to the spinal cord with a tension gage to create a bilateral contusion injury. The study morphology change of the CMAP wave and locomotor scale were evaluated for one month. Results Four different types of wave morphology changes were observed: no change, amplitude decrease only, morphology change only, and amplitude and morphology change. Amplitude and morphology changed simultaneously and significantly as the injury force increased (p<0.05) Locomotor scale in the amplitude and morphology group worsened more than the other groups. Conclusions Amplitude and morphology change of the CMAP wave exists and could be the key of the alarm point in CMAP. PMID:26713129

  13. Action potential generation in an anatomically constrained model of medial superior olive axons.

    PubMed

    Lehnert, Simon; Ford, Marc C; Alexandrova, Olga; Hellmundt, Franziska; Felmy, Felix; Grothe, Benedikt; Leibold, Christian

    2014-04-01

    Neurons in the medial superior olive (MSO) encode interaural time differences (ITDs) with sustained firing rates of >100 Hz. They are able to generate such high firing rates for several hundred milliseconds despite their extremely low-input resistances of only few megaohms and high synaptic conductances in vivo. The biophysical mechanisms by which these leaky neurons maintain their excitability are not understood. Since action potentials (APs) are usually assumed to be generated in the axon initial segment (AIS), we analyzed anatomical data of proximal MSO axons in Mongolian gerbils and found that the axon diameter is <1 μm and the internode length is ∼100 μm. Using a morphologically constrained computational model of the MSO axon, we show that these thin axons facilitate the excitability of the AIS. However, for ongoing high rates of synaptic inputs the model generates a substantial fraction of APs in its nodes of Ranvier. These distally initiated APs are mediated by a spatial gradient of sodium channel inactivation and a strong somatic current sink. The model also predicts that distal AP initiation increases the dynamic range of the rate code for ITDs. PMID:24719114

  14. Mechanism of Action of IL-7 and Its Potential Applications and Limitations in Cancer Immunotherapy

    PubMed Central

    Gao, Jianbao; Zhao, Lintao; Wan, Yisong Y.; Zhu, Bo

    2015-01-01

    Interleukin-7 (IL-7) is a non-hematopoietic cell-derived cytokine with a central role in the adaptive immune system. It promotes lymphocyte development in the thymus and maintains survival of naive and memory T cell homeostasis in the periphery. Moreover, it is important for the organogenesis of lymph nodes (LN) and for the maintenance of activated T cells recruited into the secondary lymphoid organs (SLOs). The immune capacity of cancer patients is suppressed that is characterized by lower T cell counts, less effector immune cells infiltration, higher levels of exhausted effector cells and higher levels of immunosuppressive cytokines, such as transforming growth factor β (TGF-β). Recombinant human IL-7 (rhIL-7) is an ideal solution for the immune reconstitution of lymphopenia patients by promoting peripheral T cell expansion. Furthermore, it can antagonize the immunosuppressive network. In animal models, IL-7 has been proven to prolong the survival of tumor-bearing hosts. In this review, we will focus on the mechanism of action and applications of IL-7 in cancer immunotherapy and the potential restrictions for its usage. PMID:25955647

  15. Correlates of a single cortical action potential in the epidural EEG

    PubMed Central

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

    2015-01-01

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

  16. 'Action potential-like' ST elevation following pseudo-Wellens' electrocardiogram.

    PubMed

    Oksuz, Fatih; Sensoy, Baris; Sen, Fatih; Celik, Ethem; Ozeke, Ozcan; Maden, Orhan

    2015-01-01

    Coronary artery vasospasm is an important cause of chest pain syndromes that can lead to myocardial infarction, ventricular arrhythmias, and sudden death. In 1959, Prinzmetal et al described a syndrome of nonexertional chest pain with ST-segment elevation on electrocardiography. Persistent angina is challenging, and repeated coronary angioplasty may be required in this syndrome. Calcium antagonists are extremely effective in treating and preventing coronary spasm, and may provide long-lasting relief for the patient. Whereas the Wellens' syndrome is characterized by symmetrically inverted T-waves with preserved R waves in the precordial leads suggestive of impending myocardial infarction due to a critical proximal left anterior descending stenosis, the pseudo-Wellens' syndrome caused by coronary artery spasm has also rarely been reported in literature. We present a pseudo-Wellens syndrome as a cause of vasospastic angina, and a diffuse ST segment elavation on electrocardiogram resembling the Greek letter lambda, called also 'action potential-like' ECG in a patient with vasospastic-type Printzmetal angina. PMID:26432739

  17. A Hybrid Classifier for Characterizing Motor Unit Action Potentials in Diagnosing Neuromuscular Disorders

    PubMed Central

    Kamali, T; Boostani, R; Parsaei, H

    2013-01-01

    Background: The time and frequency features of motor unit action potentials (MUAPs) extracted from electromyographic (EMG) signal provide discriminative information for diagnosis and treatment of neuromuscular disorders. However, the results of conventional automatic diagnosis methods using MUAP features is not convincing yet. Objective: The main goal in designing a MUAP characterization system is obtaining high classification accuracy to be used in clinical decision system. For this aim, in this study, a robust classifier is proposed to improve MUAP classification performance in estimating the class label (myopathic, neuropathic and normal) of a given MUAP. Method: The proposed scheme employs both time and time–frequency features of a MUAP along with an ensemble of support vector machines (SVMs) classifiers in hybrid serial/parallel architecture. Time domain features includes phase, turn, peak to peak amplitude, area, and duration of the MUAP. Time–frequency features are discrete wavelet transform coefficients of the MUAP. Results: Evaluation results of the developed system using EMG signals of 23 subjects (7 with myopathic, 8 with neuropathic and 8 with no diseases)  showed that the system estimated the class label of MUAPs extracted from these signals with average of accuracy of 91% which is at least 5% higher than the accuracy of two previously presented methods. Conclusion: Using different optimized subsets of features along with the presented hybrid classifier results in a classification accuracy that is encouraging to be used in clinical applications for MUAP characterization.  PMID:25505761

  18. Motor unit action potential conduction velocity estimated from surface electromyographic signals using image processing techniques.

    PubMed

    Soares, Fabiano Araujo; Carvalho, João Luiz Azevedo; Miosso, Cristiano Jacques; de Andrade, Marcelino Monteiro; da Rocha, Adson Ferreira

    2015-01-01

    In surface electromyography (surface EMG, or S-EMG), conduction velocity (CV) refers to the velocity at which the motor unit action potentials (MUAPs) propagate along the muscle fibers, during contractions. The CV is related to the type and diameter of the muscle fibers, ion concentration, pH, and firing rate of the motor units (MUs). The CV can be used in the evaluation of contractile properties of MUs, and of muscle fatigue. The most popular methods for CV estimation are those based on maximum likelihood estimation (MLE). This work proposes an algorithm for estimating CV from S-EMG signals, using digital image processing techniques. The proposed approach is demonstrated and evaluated, using both simulated and experimentally-acquired multichannel S-EMG signals. We show that the proposed algorithm is as precise and accurate as the MLE method in typical conditions of noise and CV. The proposed method is not susceptible to errors associated with MUAP propagation direction or inadequate initialization parameters, which are common with the MLE algorithm. Image processing -based approaches may be useful in S-EMG analysis to extract different physiological parameters from multichannel S-EMG signals. Other new methods based on image processing could also be developed to help solving other tasks in EMG analysis, such as estimation of the CV for individual MUs, localization and tracking of innervation zones, and study of MU recruitment strategies. PMID:26384112

  19. 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

  20. Kv3.1 uses a timely resurgent K(+) current to secure action potential repolarization.

    PubMed

    Labro, Alain J; Priest, Michael F; Lacroix, Jérôme J; Snyders, Dirk J; Bezanilla, Francisco

    2015-01-01

    High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K(+) currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na(+) and K(+) currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3-S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission. PMID:26673941

  1. Multifocal Fluorescence Microscope for Fast Optical Recordings of Neuronal Action Potentials

    PubMed Central

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

    2015-01-01

    In recent years, optical sensors for tracking neural activity have been developed and offer great utility. However, developing microscopy techniques that have several kHz bandwidth necessary to reliably capture optically reported action potentials (APs) at multiple locations in parallel remains a significant challenge. To our knowledge, we describe a novel microscope optimized to measure spatially distributed optical signals with submillisecond and near diffraction-limit resolution. Our design uses a spatial light modulator to generate patterned illumination to simultaneously excite multiple user-defined targets. A galvanometer driven mirror in the emission path streaks the fluorescence emanating from each excitation point during the camera exposure, using unused camera pixels to capture time varying fluorescence at rates that are ∼1000 times faster than the camera’s native frame rate. We demonstrate that this approach is capable of recording Ca2+ transients resulting from APs in neurons labeled with the Ca2+ sensor Oregon Green Bapta-1 (OGB-1), and can localize the timing of these events with millisecond resolution. Furthermore, optically reported APs can be detected with the voltage sensitive dye DiO-DPA in multiple locations within a neuron with a signal/noise ratio up to ∼40, resolving delays in arrival time along dendrites. Thus, the microscope provides a powerful tool for photometric measurements of dynamics requiring submillisecond sampling at multiple locations. PMID:25650920

  2. On the use of phloem sap δ13C to estimate canopy carbon discrimination

    NASA Astrophysics Data System (ADS)

    Rascher, Katherine; Máguas, Cristina; Werner, Christiane

    2010-05-01

    Although the carbon stable isotope composition (d13C) of bulk leaf material is a good integrative parameter of photosynthetic discrimination and can be used as a reliable ecological index of plant functioning; it is not a good tracer of short-term changes in photosynthetic discrimination. In contrast, d13C of phloem sap is potentially useful as an indicator of short-term changes in canopy photosynthetic discrimination. However, recent research indicates that d13C signatures may be substantially altered by metabolic processes downstream of initial leaf-level carbon fixation (e.g. post-photosynthetic fractionation). Accordingly, before phloem sap d13C can be used as a proxy for canopy level carbon discrimination an understanding of factors influencing the degree and magnitude of post-photosynthetic fractionation and how these vary between species is of paramount importance. In this study, we measured the d13C signature along the basipetal transport pathway in two co-occurring tree species in the field - an understory invasive exotic legume, Acacia longifolia, and a native pine, Pinus pinaster. We measured d13C of bulk leaf and leaf water soluble organic matter (WSOM), phloem sap sampled at two points along the plant axis and leaf and root dark respiration. In general, species differences in photosynthetic discrimination resulted in more enriched d13C values in the water-conserving P. pinaster relative to the water-spending A. longifolia. Post-photosynthetic fractionation led to differences in d13C of carbon pools along the plant axis with progressively more depleted d13C from the canopy to the trunk (~6.5 per mil depletion in A. longifolia and ~0.8per mil depletion in P. pinaster). Leaf and root respiration, d13C, were consistently enriched relative to putative substrates. We hypothesize that the pronounced enrichment of leaf respired CO2 relative to leaf WSOM may have left behind relatively depleted carbon to be loaded into the phloem resulting in d13C depletion

  3. Modeling the action-potential-sensitive nonlinear-optical response of myelinated nerve fibers and short-term memory

    NASA Astrophysics Data System (ADS)

    Shneider, M. N.; Voronin, A. A.; Zheltikov, A. M.

    2011-11-01

    The Goldman-Albus treatment of the action-potential dynamics is combined with a phenomenological description of molecular hyperpolarizabilities into a closed-form model of the action-potential-sensitive second-harmonic response of myelinated nerve fibers with nodes of Ranvier. This response is shown to be sensitive to nerve demyelination, thus enabling an optical diagnosis of various demyelinating diseases, including multiple sclerosis. The model is applied to examine the nonlinear-optical response of a three-neuron reverberating circuit—the basic element of short-term memory.

  4. 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

  5. Cloning and characterization of E-dlg, a novel splice variant of mouse homologue of the Drosophila discs large tumor suppressor binds preferentially to SAP102

    PubMed Central

    Mao, Peizhong; Tao, Yuan-Xiang; Fukaya, Masahiro; Tao, Feng; Li, Dechun; Watanabe, Masahiko; Johns, Roger A.

    2009-01-01

    Summary Membrane-associated guanylate kinases (MAGUKs) act as scaffolds to coordinate signaling events through their multiple domains at the plasma membrane. The MAGUK SH3 domain is noncanonical and its function remains unclear. To identify potential binding partners of MAGUK SH3, the synapse-associated protein 102 (SAP102) SH3 domain was used as bait in a yeast two-hybrid screen of a mouse embryonic cDNA library. A mouse homologue of the Drosophila discs large tumor suppressor (Dlg, also known as SAP97) bound preferentially to SAP102 SH3. The 4347bp cDNA sequence encoded an 893 amino acid protein with 94% identity to mouse SAP97. A deleted region (33-aa) strongly suggests this is a novel splice variant, which we call Embryonic-dlg/SAP97 (E-dlg). The interaction of SAP102 and E-dlg was confirmed in mammalian cells. E-dlg can also bind to potassium channel Kv1.4 in a pull-down assay. E-dlg was highly expressed in embryonic and some adult mouse tissues, such as brain, kidney and ovary. Furthermore, in situ hybridization showed that E-dlg was mostly expressed in olfactory bulb and cerebellum. PMID:18618587

  6. Activity of sap from Croton lechleri on rat vascular and gastric smooth muscles.

    PubMed

    Froldi, G; Zagotto, G; Filippini, R; Montopoli, M; Dorigo, P; Caparrotta, L

    2009-08-01

    The effects of red sap from Croton lechleri (SdD), Euphorbiaceae, on vascular and gastric smooth muscles were investigated. SdD, from 10 to 1000 microg/ml, induced concentration-dependent vasoconstriction in rat caudal arteries, which was endothelium-independent. In arterial preparations pre-constricted by phenylephrine (0.1 microM) or KCl (30 mM), SdD also produced concentration-dependent vasoconstriction. To study the mechanisms implicated in this effect we used selective inhibitors such as prazosin (0.1 microM), an antagonist of alpha(1)-adrenoceptors, atropine (0.1 microM), an antagonist of muscarinic receptors, and ritanserin (50 nM), a 5-HT(2A) antagonist; none of these influenced vasoconstriction caused by SdD. Likewise, nifedipine (50 nM), an inhibitor of L-type calcium channels, did not modify the action of SdD. Capsaicin (100 nM), an agonist of vanilloid receptors, also did not affect vasoconstriction by SdD. We also investigated the action of SdD (10-1000 microg/ml) on rat gastric fundus; per se the sap slightly increased contractile tension. When the gastric fundus was pre-treated with SdD (100 microg/ml) the contraction induced by carbachol (1 microM) was increased, whereas that by KCl (60mM) or capsaicin (100 nM) were unchanged. The data shows that SdD increased contractile tension in a concentration-dependent way, both on vascular and gastric smooth muscles. The vasoconstriction is unrelated to alpha(1), M, 5-HT(2A) and vanilloid receptors as well as L-type calcium channels. SdD increased also contraction by carbachol on rat gastric fundus. Thus for the first time, experimental data provides evidence that sap from C. lechleri owns constricting activity on smooth muscles. PMID:19406630

  7. Toxicity, sublethal effects, and potential modes of action of select fungicides on freshwater fish and invertebrates

    USGS Publications Warehouse

    Elskus, Adria A.

    2012-01-01

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

  8. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids.

    PubMed

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

    2016-06-01

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

  9. Facilitating Youth to Take Sustainability Actions: The Potential of Peer Education

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  10. Bacteriocins: modes of action and potentials in food preservation and control of food poisoning.

    PubMed

    Abee, T; Krockel, L; Hill, C

    1995-12-01

    Lactic acid bacteria (LAB) play an essential role in the majority of food fermentations, and a wide variety of strains are routinely employed as starter cultures in the manufacture of dairy, meat, vegetable and bakery products. One of the most important contributions of these microorganisms is the extended shelf life of the fermented product by comparison to that of the raw substrate. Growth of spoilage and pathogenic bacteria in these foods is inhibited due to competition for nutrients and the presence of starter-derived inhibitors such as lactic acid, hydrogen peroxide and bacteriocins (Ray and Daeschel, 1992). Bacteriocins, are a heterogenous group of anti-bacterial proteins that vary in spectrum of activity, mode of action, molecular weight, genetic origin and biochemical properties. Currently, artificial chemical preservatives are employed to limit the number of microorganisms capable of growing within foods, but increasing consumer awareness of potential health risks associated with some of these substances has led researchers to examine the possibility of using bacteriocins produced by LAB as biopreservatives. The major classes of bacteriocins produced by LAB include: (I) lantibiotics, (II) small heat stable peptides, (III) large heat labile proteins, and (IV) complex proteins whose activity requires the association of carbohydrate or lipid moieties (Klaenhammer, 1993). Significantly however, the inhibitory activity of these substances is confined to Gram-positive bacteria and inhibition of Gram-negatives by these bacteriocins has not been demonstrated, an observation which can be explained by a detailed analysis and comparison of the composition of Gram-positive and Gram-negative bacterial cell walls (Fig. 1). In both types the cytoplasmic membrane which forms the border between the cytoplasm and the external environment, is surrounded by a layer of peptidoglycan which is significantly thinner in Gram-negative bacteria than in Gram-positive bacteria. Gram

  11. Effect of temperature on isoprenaline- and barium-induced slow action potentials in guinea-pig ventricular strips.

    PubMed

    Manzini, S; Parlani, M; Martucci, E; Maggi, C A; Meli, A

    1986-01-01

    The effect of variation in temperature (37-32 and 27 degrees C) on electrical and mechanical activity of depolarized and isoprenaline- or barium-reactivated guinea pig ventricular strips was studied. Lowering the temperature brings a marked prolongation of isoprenaline-induced slow action potentials. In addition the maximal rate of depolarization was strongly reduced at lower temperatures. These effects were observed at an extracellular Ca2+ concentration of either 0.9 or 2.5 mM. The accompanying mechanical activities was significantly increased by reduction in temperature. Barium-induced slow action potentials were similarly affected by temperature variations. These observations suggest that hypothermia exert a sort of calcium antagonistic action probably coupled to a reduction of repolarizing outward potassium currents. PMID:2430855

  12. Effect of knockout of α2δ-1 on action potentials in mouse sensory neurons.

    PubMed

    Margas, Wojciech; Ferron, Laurent; Nieto-Rostro, Manuela; Schwartz, Arnold; Dolphin, Annette C

    2016-08-01

    Gene deletion of the voltage-gated calcium channel auxiliary subunit α2δ-1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in α2δ-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from α2δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α2δ-1 knockout are involved in setting the duration of individual APs and their firing frequency. Our main findings are that there is reduced Ca(2+) entry on single AP stimulation, particularly in the axon proximal segment, reduced AP duration and reduced firing frequency to a 400 ms stimulation in α2δ-1 knockout neurons, consistent with the expected role of voltage-gated calcium channels in these events. Furthermore, lower intracellular Ca(2+) buffering also resulted in reduced AP duration, and a lower frequency of AP firing in WT neurons, mimicking the effect of α2δ-1 knockout. By contrast, we did not obtain any consistent evidence for the involvement of Ca(2+)-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca(2+) elevation as a result of single AP stimulation is likely to result from the reduced duration of the AP in α2δ-1 knockout sensory neurons.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377724

  13. Effect of knockout of α2δ-1 on action potentials in mouse sensory neurons

    PubMed Central

    Margas, Wojciech; Ferron, Laurent; Nieto-Rostro, Manuela; Schwartz, Arnold; Dolphin, Annette C.

    2016-01-01

    Gene deletion of the voltage-gated calcium channel auxiliary subunit α2δ-1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in α2δ-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from α2δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α2δ-1 knockout are involved in setting the duration of individual APs and their firing frequency. Our main findings are that there is reduced Ca2+ entry on single AP stimulation, particularly in the axon proximal segment, reduced AP duration and reduced firing frequency to a 400 ms stimulation in α2δ-1 knockout neurons, consistent with the expected role of voltage-gated calcium channels in these events. Furthermore, lower intracellular Ca2+ buffering also resulted in reduced AP duration, and a lower frequency of AP firing in WT neurons, mimicking the effect of α2δ-1 knockout. By contrast, we did not obtain any consistent evidence for the involvement of Ca2+-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca2+ elevation as a result of single AP stimulation is likely to result from the reduced duration of the AP in α2δ-1 knockout sensory neurons. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377724

  14. Action potential processing in a detailed Purkinje cell model reveals a critical role for axonal compartmentalization

    PubMed Central

    Masoli, Stefano; Solinas, Sergio; D'Angelo, Egidio

    2015-01-01

    The Purkinje cell (PC) is among the most complex neurons in the brain and plays a critical role for cerebellar functioning. PCs operate as fast pacemakers modulated by synaptic inputs but can switch from simple spikes to complex bursts and, in some conditions, show bistability. In contrast to original works emphasizing dendritic Ca-dependent mechanisms, recent experiments have supported a primary role for axonal Na-dependent processing, which could effectively regulate spike generation and transmission to deep cerebellar nuclei (DCN). In order to account for the numerous ionic mechanisms involved (at present including Nav1.6, Cav2.1, Cav3.1, Cav3.2, Cav3.3, Kv1.1, Kv1.5, Kv3.3, Kv3.4, Kv4.3, KCa1.1, KCa2.2, KCa3.1, Kir2.x, HCN1), we have elaborated a multicompartmental model incorporating available knowledge on localization and gating of PC ionic channels. The axon, including initial segment (AIS) and Ranvier nodes (RNs), proved critical to obtain appropriate pacemaking and firing frequency modulation. Simple spikes initiated in the AIS and protracted discharges were stabilized in the soma through Na-dependent mechanisms, while somato-dendritic Ca channels contributed to sustain pacemaking and to generate complex bursting at high discharge regimes. Bistability occurred only following Na and Ca channel down-regulation. In addition, specific properties in RNs K currents were required to limit spike transmission frequency along the axon. The model showed how organized electroresponsive functions could emerge from the molecular complexity of PCs and showed that the axon is fundamental to complement ionic channel compartmentalization enabling action potential processing and transmission of specific spike patterns to DCN. PMID:25759640

  15. Halothane diminishes changes in cardiac fiber action potential duration induced by hypocarbia and hypercarbia.

    PubMed

    Stowe, D F; Bosnjak, Z J; Kampine, J P

    1984-09-01

    Both halothane (HAL) and acid-base changes produce cardiac arrhythmias in humans. The authors' aim was to determine if HAL alters the effects of hypercapnic acidosis and hypocapnic alkalosis on action potential (AP) properties of ventricular muscle fibers. They superfused the paced right ventricle of 15 guinea pig hearts with non-HCO3- buffered salt solution and recorded transmembrane APs with 3 M KCl microelectrodes in 35 subendocardial cells. Random changes in the fractions of HAL were made during low (12% CO2 in O2), normal (5% CO2 in O2), and high (0% CO2 in O2) pH. Compared with controls at pH 7.44, AP duration (APD) and effective refractory period (ERP) significantly decreased by 7 and 4% at pH 8.08 and increased by 7 and 9% at pH 7.09. At pH 7.44, 0.7-2.1% HAL produced no change in APD; but 2.1% increased ERP, while 3.5% HAL decreased ERP. At pH 8.08, the decrease in ERP induced with alkalosis alone was converted to an increase with 1.4 and 2.1% HAL. At pH 7.09, 0.7-1.4% HAL had no additional effect on the acidosis-induced increases in APD and ERP, but 2.1 and 2.8% HAL greatly reduced these responses. At HAL fractions greater than 1.4% the marked inverse changes in APD and ERP, induced alone by acidosis and alkalosis, were no longer significantly different from control. This study shows that the opposing effects of alkalosis to shorten and of acidosis to lengthen APD and ERP were attenuated at low levels and abolished at high levels of HAL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6433748

  16. Natural cures for type 1 diabetes: a review of phytochemicals, biological actions, and clinical potential.

    PubMed

    Chang, C L T; Chen, Yi-Ching; Chen, Hui-Ming; Yang, Ning-Sun; Yang, Wen-Chin

    2013-01-01

    Autoimmune diseases are the third largest category of illness in the industrialized world, following cardiovascular diseases and cancers. Among them, type 1 diabetes, also named autoimmune diabetes, afflicts 10 million people worldwide. This disease is caused by autoimmunity-mediated destruction of pancreatic β-cells, leading to insulin deficiency, hyperglycemia and complications. Currently, there is no cure for type 1 diabetes. Insulin injection is the only medication; however, it accompanies serious medical complications. Current strategies to cure type 1 diabetes include immunotherapy, replacement therapy, and combination therapy. Despite recent advances in anti-diabetic strategies, no strategy is clinically successful. How to cure type 1 diabetes without undesirable side effects still remains a formidable challenge in drug research and development. Plants provide an extraordinary source of natural medicines for different diseases. Moreover, secondary metabolites of plant origin serve as an invaluable chemical library for drug discovery and current medicinal chemistry in the pharmaceutical industry. Over the past 25 years, 50% of prescription drugs have been developed from natural products and their derivatives. In this article, we review more than 20 plant compounds and extracts reported in the literature to prevent and treat type-1 diabetes. Emphasis is placed on their chemistry and biology in terms of regulation of immune cells and pancreatic β-cells. We summarize recent progress in understanding the biological actions, mechanisms and therapeutic potential of the compounds and extracts of plant origin in type 1 diabetes. New views on phytocompound-based strategies for prevention and treatment of type 1 diabetes are also discussed. PMID:23210779

  17. A potential role for cannabinoid receptors in the therapeutic action of fenofibrate.

    PubMed

    Priestley, Richard S; Nickolls, Sarah A; Alexander, Stephen P H; Kendall, David A

    2015-04-01

    Cannabinoids are reported to have actions through peroxisome proliferator-activated receptors (PPARs), which led us to investigate PPAR agonists for activity at the cannabinoid receptors. Radio-ligand binding and functional assays were conducted using human recombinant cannabinoid type 1 (CB1) or cannabinoid type 2 (CB2) receptors, as well as the guinea pig isolated ileum, using the full agonist CP55940 as a positive control. The PPAR-α agonist fenofibrate exhibited submicromolar affinity for both receptors (pKi CB1, 6.3 ± 0.1; CB2, 7.7 ± 0.1). Functionally, fenofibrate acted as an agonist at the CB2 receptor (pEC50, 7.7 ± 0.1) and a partial agonist at the CB1 receptor, although with a decrease in functional response at higher concentrations, producing bell-shaped concentration-response curves. High concentrations of fenofibrate were able to increase the dissociation rate constant for [(3)H]-CP55940 at the CB1 receptor, (kfast without: 1.2 ± 0.2/min; with: 3.8 ± 0.1 × 10(-2)/min) and decrease the maximal response to CP55940 (Rmax, 86 ± 2%), which is consistent with a negative allosteric modulator. Fenofibrate also reduced electrically induced contractions in isolated guinea pig ileum via CB1 receptors (pEC50, 6.0 ± 0.4). Fenofibrate is thus identified as an example of a new class of cannabinoid receptor ligand and allosteric modulator, with the potential to interact therapeutically with cannabinoid receptors in addition to its primary PPAR target. PMID:25550466

  18. Contribution of auditory nerve fibers to compound action potential of the auditory nerve.

    PubMed

    Bourien, Jérôme; Tang, Yong; Batrel, Charlène; Huet, Antoine; Lenoir, Marc; Ladrech, Sabine; Desmadryl, Gilles; Nouvian, Régis; Puel, Jean-Luc; Wang, Jing

    2014-09-01

    Sound-evoked compound action potential (CAP), which captures the synchronous activation of the auditory nerve fibers (ANFs), is commonly used to probe deafness in experimental and clinical settings. All ANFs are believed to contribute to CAP threshold and amplitude: low sound pressure levels activate the high-spontaneous rate (SR) fibers, and increasing levels gradually recruit medium- and then low-SR fibers. In this study, we quantitatively analyze the contribution of the ANFs to CAP 6 days after 30-min infusion of ouabain into the round window niche. Anatomic examination showed a progressive ablation of ANFs following increasing concentration of ouabain. CAP amplitude and threshold plotted against loss of ANFs revealed three ANF pools: 1) a highly ouabain-sensitive pool, which does not participate in either CAP threshold or amplitude, 2) a less sensitive pool, which only encoded CAP amplitude, and 3) a ouabain-resistant pool, required for CAP threshold and amplitude. Remarkably, distribution of the three pools was similar to the SR-based ANF distribution (low-, medium-, and high-SR fibers), suggesting that the low-SR fiber loss leaves the CAP unaffected. Single-unit recordings from the auditory nerve confirmed this hypothesis and further showed that it is due to the delayed and broad first spike latency distribution of low-SR fibers. In addition to unraveling the neural mechanisms that encode CAP, our computational simulation of an assembly of guinea pig ANFs generalizes and extends our experimental findings to different species of mammals. Altogether, our data demonstrate that substantial ANF loss can coexist with normal hearing threshold and even unchanged CAP amplitude. PMID:24848461

  19. 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

  20. Recording Single Neurons' Action Potentials from Freely Moving Pigeons Across Three Stages of Learning

    PubMed Central

    Güntürkün, Onur

    2014-01-01

    While the subject of learning has attracted immense interest from both behavioral and neural scientists, only relatively few investigators have observed single-neuron activity while animals are acquiring an operantly conditioned response, or when that response is extinguished. But even in these cases, observation periods usually encompass only a single stage of learning, i.e. acquisition or extinction, but not both (exceptions include protocols employing reversal learning; see Bingman et al.1 for an example). However, acquisition and extinction entail different learning mechanisms and are therefore expected to be accompanied by different types and/or loci of neural plasticity. Accordingly, we developed a behavioral paradigm which institutes three stages of learning in a single behavioral session and which is well suited for the simultaneous recording of single neurons' action potentials. Animals are trained on a single-interval forced choice task which requires mapping each of two possible choice responses to the presentation of different novel visual stimuli (acquisition). After having reached a predefined performance criterion, one of the two choice responses is no longer reinforced (extinction). Following a certain decrement in performance level, correct responses are reinforced again (reacquisition). By using a new set of stimuli in every session, animals can undergo the acquisition-extinction-reacquisition process repeatedly. Because all three stages of learning occur in a single behavioral session, the paradigm is ideal for the simultaneous observation of the spiking output of multiple single neurons. We use pigeons as model systems, but the task can easily be adapted to any other species capable of conditioned discrimination learning. PMID:24961391

  1. Disruption of action potential and calcium signaling properties in malformed myofibers from dystrophin-deficient mice

    PubMed Central

    Hernández-Ochoa, Erick O; Pratt, Stephen J P; Garcia-Pelagio, Karla P; Schneider, Martin F; Lovering, Richard M

    2015-01-01

    Duchenne muscular dystrophy (DMD), the most common and severe muscular dystrophy, is caused by the absence of dystrophin. Muscle weakness and fragility (i.e., increased susceptibility to damage) are presumably due to structural instability of the myofiber cytoskeleton, but recent studies suggest that the increased presence of malformed/branched myofibers in dystrophic muscle may also play a role. We have previously studied myofiber morphology in healthy wild-type (WT) and dystrophic (MDX) skeletal muscle. Here, we examined myofiber excitability using high-speed confocal microscopy and the voltage-sensitive indicator di-8-butyl-amino-naphthyl-ethylene-pyridinium-propyl-sulfonate (di-8-ANEPPS) to assess the action potential (AP) properties. We also examined AP-induced Ca2+ transients using high-speed confocal microscopy with rhod-2, and assessed sarcolemma fragility using elastimetry. AP recordings showed an increased width and time to peak in malformed MDX myofibers compared to normal myofibers from both WT and MDX, but no significant change in AP amplitude. Malformed MDX myofibers also exhibited reduced AP-induced Ca2+ transients, with a further Ca2+ transient reduction in the branches of malformed MDX myofibers. Mechanical studies indicated an increased sarcolemma deformability and instability in malformed MDX myofibers. The data suggest that malformed myofibers are functionally different from myofibers with normal morphology. The differences seen in AP properties and Ca2+ signals suggest changes in excitability and remodeling of the global Ca2+ signal, both of which could underlie reported weakness in dystrophic muscle. The biomechanical changes in the sarcolemma support the notion that malformed myofibers are more susceptible to damage. The high prevalence of malformed myofibers in dystrophic muscle may contribute to the progressive strength loss and fragility seen in dystrophic muscles. PMID:25907787

  2. Inter-Subject Variability in Human Atrial Action Potential in Sinus Rhythm versus Chronic Atrial Fibrillation

    PubMed Central

    Sánchez, Carlos; Bueno-Orovio, Alfonso; Wettwer, Erich; Loose, Simone; Simon, Jana; Ravens, Ursula; Pueyo, Esther; Rodriguez, Blanca

    2014-01-01

    Aims Human atrial electrophysiology exhibits high inter-subject variability in both sinus rhythm (SR) and chronic atrial fibrillation (cAF) patients. Variability is however rarely investigated in experimental and theoretical electrophysiological studies, thus hampering the understanding of its underlying causes but also its implications in explaining differences in the response to disease and treatment. In our study, we aim at investigating the ability of populations of human atrial cell models to capture the inter-subject variability in action potential (AP) recorded in 363 patients both under SR and cAF conditions. Methods and Results Human AP recordings in atrial trabeculae (n = 469) from SR and cAF patients were used to calibrate populations of computational SR and cAF atrial AP models. Three populations of over 2000 sampled models were generated, based on three different human atrial AP models. Experimental calibration selected populations of AP models yielding AP with morphology and duration in range with experimental recordings. Populations using the three original models can mimic variability in experimental AP in both SR and cAF, with median conductance values in SR for most ionic currents deviating less than 30% from their original peak values. All cAF populations show similar variations in GK1, GKur and Gto, consistent with AF-related remodeling as reported in experiments. In all SR and cAF model populations, inter-subject variability in IK1 and INaK underlies variability in APD90, variability in IKur, ICaL and INaK modulates variability in APD50 and combined variability in Ito and IKur determines variability in APD20. The large variability in human atrial AP triangulation is mostly determined by IK1 and either INaK or INaCa depending on the model. Conclusion Experimentally-calibrated human atrial AP models populations mimic AP variability in SR and cAF patient recordings, and identify potential ionic determinants of inter-subject variability in

  3. Mathematical simulations of ligand-gated and cell-type specific effects on the action potential of human atrium

    PubMed Central

    Maleckar, Mary M.; Greenstein, Joseph L.; Trayanova, Natalia A.; Giles, Wayne R.

    2010-01-01

    In the mammalian heart, myocytes and fibroblasts can communicate via gap junction, or connexin-mediated current flow. Some of the effects of this electrotonic coupling on the action potential waveform of the human ventricular myocyte have been analyzed in detail. The present study employs a recently developed mathematical model of the human atrial myocyte to investigate the consequences of this heterogeneous cell–cell interaction on the action potential of the human atrium. Two independent physiological processes which alter the physiology of the human atrium have been studied. i) The effects of the autonomic transmitter acetylcholine on the atrial action potential have been investigated by inclusion of a time-independent, acetylcholine-activated K+ current in this mathematical model of the atrial myocyte. ii) A non-selective cation current which is activated by natriuretic peptides has been incorporated into a previously published mathematical model of the cardiac fibroblast. These results identify subtle effects of acetylcholine, which arise from the nonlinear interactions between ionic currents in the human atrial myocyte. They also illustrate marked alterations in the action potential waveform arising from fibroblast–myocyte source–sink principles when the natriuretic peptide-mediated cation conductance is activated. Additional calculations also illustrate the effects of simultaneous activation of both of these cell-type specific conductances within the atrial myocardium. This study provides a basis for beginning to assess the utility of mathematical modeling in understanding detailed cell–cell interactions within the complex paracrine environment of the human atrial myocardium. PMID:19186188

  4. The effect of stimulation frequency on the transmural ventricular monophasic action potential in yellowfin tuna Thunnus albacares.

    PubMed

    Patrick, S M; White, E; Brill, R W; Shiels, H A

    2011-02-01

    Monophasic action potentials (MAPs) were recorded from the spongy and compact layers of the yellowfin tuna Thunnus albacares ventricle as stimulation frequency was increased. MAP duration decreased with increase in stimulation frequency in both the spongy and compact myocardial layers, but no significant difference in MAP duration was observed between the layers. PMID:21284642

  5. Postnatal maturation of rat hypothalamoneurohypophysial neurons: evidence for a developmental decrease in calcium entry during action potentials.

    PubMed

    Widmer, H; Amerdeil, H; Fontanaud, P; Desarménien, M G

    1997-01-01

    Action potentials and voltage-gated currents were studied in acutely dissociated neurosecretory cells from the rat supraoptic nucleus during the first three postnatal weeks (PW1-PW3), a period corresponding to the final establishment of neuroendocrine relationships. Action potential duration (at half maximum) decreased from 2.7 to 1.8 ms; this was attributable to a decrease in decay time. Application of cadmium (250 microM) reduced the decay time by 43% at PW1 and 21% at PW3, indicating that the contribution of calcium currents to action potentials decreased during postnatal development. The density of high-voltage-activated calcium currents increased from 4.4 to 10.1 pA/pF at postnatal days 1-5 and 11-14, respectively. The conductance density of sustained potassium current, measured at +20 mV, increased from 0.35 (PW1) to 0.53 (PW3) nS/pF. The time to half-maximal amplitude did not change. Conductance density and time- and voltage-dependent inactivation of the transient potassium current were stable from birth. At PW1, the density and time constant of decay (measured at 0 mV) were 0.29 nS/pF (n = 12) and 17.9 ms (n = 10), respectively. Voltage-dependent properties and density (1.1 nS/pF) of the sodium current did not change postnatally. During PW1, fitting the mean activation data with a Boltzmann function gave a half-activation potential of -25 mV. A double Boltzman equation was necessary to adequately fit the inactivation data, suggesting the presence of two populations of sodium channels. One population accounted for approximately 14% of the channels, with a half-inactivation potential of -86 mV; the remaining population showed a half-inactivation potential of -51 mV. A mathematical model, based on Hodgkin-Huxley equations, was used to assess the respective contributions of individual currents to the action potential. When the densities of calcium and sustained potassium currents were changed from immature to mature values, the decay time of the action

  6. Adaptive SAR ATR problem set (AdaptSAPS)

    NASA Astrophysics Data System (ADS)

    Wise, Angela R.; Fitzgerald, Donna; Ross, Timothy D.

    2004-09-01

    A strong and growing interest in systems that adapt to changing circumstances was evident in panel discussions at the "Algorithms for SAR Imagery" Conference of the AeroSense Symposium in April 2003, with DARPA, Air Force, industry and academia participation. As a result, Conference Co-Chair Mr. Ed Zelnio suggested producing a dynamic model to create problem sets suitable for adaptive system research and development. Such a problem set provides a framework for the overall problem, including organization of operating conditions, performance measures and specific test cases. It is hoped that this AdaptSAPS framework will help provide the community with a more concrete base for discussing adaptation in SAR imagery exploitation. AdaptSAPS Version 1.0 was produced by the AFRL COMPASE and SDMS organizations and posted on 5 August 2003. AdaptSAPS consists of over a dozen MatLab programs that allow the user to create "missions" with SAR data of varying complexities and then present that test data one image at a time, first as unexploited imagery and then later with the exploitation results that an ATR could use for adaptation in an operational environment. AdaptSAPS keeps track of performance results and reports performance measures. This paper describes AdaptSAPS - its application process and possible improvements as a problem set.

  7. SAP- FORTRAN STATIC SOURCE CODE ANALYZER PROGRAM (DEC VAX VERSION)

    NASA Technical Reports Server (NTRS)

    Merwarth, P. D.

    1994-01-01

    The FORTRAN Static Source Code Analyzer program, SAP, was developed to automatically gather statistics on the occurrences of statements and structures within a FORTRAN program and to provide for the reporting of those statistics. Provisions have been made for weighting each statistic and to provide an overall figure of complexity. Statistics, as well as figures of complexity, are gathered on a module by module basis. Overall summed statistics are also accumulated for the complete input source file. SAP accepts as input syntactically correct FORTRAN source code written in the FORTRAN 77 standard language. In addition, code written using features in the following languages is also accepted: VAX-11 FORTRAN, IBM S/360 FORTRAN IV Level H Extended; and Structured FORTRAN. The SAP program utilizes two external files in its analysis procedure. A keyword file allows flexibility in classifying statements and in marking a statement as either executable or non-executable. A statistical weight file allows the user to assign weights to all output statistics, thus allowing the user flexibility in defining the figure of complexity. The SAP program is written in FORTRAN IV for batch execution and has been implemented on a DEC VAX series computer under VMS and on an IBM 370 series computer under MVS. The SAP program was developed in 1978 and last updated in 1985.

  8. SAP- FORTRAN STATIC SOURCE CODE ANALYZER PROGRAM (IBM VERSION)

    NASA Technical Reports Server (NTRS)

    Manteufel, R.

    1994-01-01

    The FORTRAN Static Source Code Analyzer program, SAP, was developed to automatically gather statistics on the occurrences of statements and structures within a FORTRAN program and to provide for the reporting of those statistics. Provisions have been made for weighting each statistic and to provide an overall figure of complexity. Statistics, as well as figures of complexity, are gathered on a module by module basis. Overall summed statistics are also accumulated for the complete input source file. SAP accepts as input syntactically correct FORTRAN source code written in the FORTRAN 77 standard language. In addition, code written using features in the following languages is also accepted: VAX-11 FORTRAN, IBM S/360 FORTRAN IV Level H Extended; and Structured FORTRAN. The SAP program utilizes two external files in its analysis procedure. A keyword file allows flexibility in classifying statements and in marking a statement as either executable or non-executable. A statistical weight file allows the user to assign weights to all output statistics, thus allowing the user flexibility in defining the figure of complexity. The SAP program is written in FORTRAN IV for batch execution and has been implemented on a DEC VAX series computer under VMS and on an IBM 370 series computer under MVS. The SAP program was developed in 1978 and last updated in 1985.

  9. Pharmacological and biochemical actions of simple coumarins: natural products with therapeutic potential.

    PubMed

    Hoult, J R; Payá, M

    1996-06-01

    1. More than 300 coumarins have been identified from natural sources, especially green plants. The pharmacological and biochemical properties and therapeutic applications of simple coumarins depend upon the pattern of substitution. More complex related compounds based on the coumarin nucleus include the dicoumarol/warfarin anticoagulants, aflatoxins and the psoralens (photosensitizing agents). 2. Coumarin itself (1,2-benzopyrone) has long-established efficacy in slow-onset long-term reduction of lymphoedema in man, as confirmed in recent double-blind trials against elephantiasis and postmastectomy swelling of the arm. The mechanism of action is uncertain, but may involve macrophage-induced proteolysis of oedema protein. However, coumarin has low absolute bioavailability in man (< 5%), due to extensive first-pass hepatic conversion to 7-hydroxycoumarin followed by glucuronidation. It may, therefore, be a prodrug. 3. Scoparone (6,7-dimethoxycoumarin) has been purified from the hypolipidaemic Chinese herb Artemisia scoparia and shown to reduce the proliferative responses of human peripheral mononuclear cells, to relax smooth muscle, to reduce total cholesterol and triglycerides and to retard the characteristic pathomorphological changes in hypercholesterolaemic diabetic rabbits. Various properties of scoparone were suggested to account for these findings, including ability to scavenge reactive oxygen species, inhibition of tyrosine kinases and potentiation of prostaglandin generation. 4. Osthole (7-methoxy-8-[3-methylpent-2-enyl]coumarin) from Angelica pubescens, used also in Chinese medicine, causes hypotension in vivo, and inhibits platelet aggregation and smooth muscle contraction in vitro. It may interfere with calcium influx and with cyclic nucleotide phosphodiesterases. 5. Cloricromene, a synthetic coumarin derivative, also possesses antithrombotic antiplatelet actions, inhibits PMN neutrophil function and causes vasodilatation. Some of these properties of

  10. Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi-Challenge

    PubMed Central

    Resende, Lucilene Aparecida; Aguiar-Soares, Rodrigo Dian de Oliveira; Gama-Ker, Henrique; Roatt, Bruno Mendes; de Mendonça, Ludmila Zanandreis; Alves, Marina Luiza Rodrigues; da Silveira-Lemos, Denise; Corrêa-Oliveira, Rodrigo; Martins-Filho, Olindo Assis; Araújo, Márcio Sobreira Silva; Fujiwara, Ricardo Toshio; Gontijo, Nelder Figueiredo; Reis, Alexandre Barbosa; Giunchetti, Rodolfo Cordeiro

    2016-01-01

    Dogs represent the most important domestic reservoir of L. chagasi (syn. L. infantum). A vaccine against canine visceral leishmaniasis (CVL) would be an important tool for decreasing the anxiety related to possible L. chagasi infection and for controlling human visceral leishmaniasis (VL). Because the sand fly salivary proteins are potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in past decades. We investigated the immunogenicity of the “LbSapSal” vaccine (L. braziliensis antigens, saponin as adjuvant, and Lutzomyia longipalpis salivary gland extract) in dogs at baseline (T0), during the post-vaccination protocol (T3rd) and after early (T90) and late (T885) times following L. chagasi-challenge. Our major data indicated that immunization with “LbSapSal” is able to induce biomarkers characterized by enhanced amounts of type I (tumor necrosis factor [TNF]-α, interleukin [IL]-12, interferon [IFN]-γ) cytokines and reduction in type II cytokines (IL-4 and TGF-β), even after experimental challenge. The establishment of a prominent pro-inflammatory immune response after “LbSapSal” immunization supported the increased levels of nitric oxide production, favoring a reduction in spleen parasitism (78.9%) and indicating long-lasting protection against L. chagasi infection. In conclusion, these results confirmed the hypothesis that the “LbSapSal” vaccination is a potential tool to control the Leishmania chagasi infection. PMID:27556586

  11. Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi-Challenge.

    PubMed

    Resende, Lucilene Aparecida; Aguiar-Soares, Rodrigo Dian de Oliveira; Gama-Ker, Henrique; Roatt, Bruno Mendes; Mendonça, Ludmila Zanandreis de; Alves, Marina Luiza Rodrigues; Silveira-Lemos, Denise da; Corrêa-Oliveira, Rodrigo; Martins-Filho, Olindo Assis; Araújo, Márcio Sobreira Silva; Fujiwara, Ricardo Toshio; Gontijo, Nelder Figueiredo; Reis, Alexandre Barbosa; Giunchetti, Rodolfo Cordeiro

    2016-01-01

    Dogs represent the most important domestic reservoir of L. chagasi (syn. L. infantum). A vaccine against canine visceral leishmaniasis (CVL) would be an important tool for decreasing the anxiety related to possible L. chagasi infection and for controlling human visceral leishmaniasis (VL). Because the sand fly salivary proteins are potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in past decades. We investigated the immunogenicity of the "LbSapSal" vaccine (L. braziliensis antigens, saponin as adjuvant, and Lutzomyia longipalpis salivary gland extract) in dogs at baseline (T0), during the post-vaccination protocol (T3rd) and after early (T90) and late (T885) times following L. chagasi-challenge. Our major data indicated that immunization with "LbSapSal" is able to induce biomarkers characterized by enhanced amounts of type I (tumor necrosis factor [TNF]-α, interleukin [IL]-12, interferon [IFN]-γ) cytokines and reduction in type II cytokines (IL-4 and TGF-β), even after experimental challenge. The establishment of a prominent pro-inflammatory immune response after "LbSapSal" immunization supported the increased levels of nitric oxide production, favoring a reduction in spleen parasitism (78.9%) and indicating long-lasting protection against L. chagasi infection. In conclusion, these results confirmed the hypothesis that the "LbSapSal" vaccination is a potential tool to control the Leishmania chagasi infection. PMID:27556586

  12. Water Deficit-Induced Changes in Concentrations in Proline and Some Other Amino Acids in the Phloem Sap of Alfalfa.

    PubMed Central

    Girousse, C.; Bournoville, R.; Bonnemain, J. L.

    1996-01-01

    Changes in amino acid composition of alfalfa (Medicago sativa L.) phloem sap were studies in response to a water deficit. Sap was collected by stylectomy. As the leaf water potential ([psi]) decreased from -0.4 to -2.0 MPa, there was significant increase of the total amino acid concentration, due to that of some amino acids: proline, valine, isoleucine, leucine, glutamic acid, aspartic acid, and threonine. Asparagine concentration, which is the main amino acid assayed in the phloem sap of alfalfa (it accounts for 70% of the total content), did not vary with the plant water status. The other amino acid concentrations remained stable as [psi] varied; in particular, [gamma]-amino butyric acid concentration remained unchanged, whereas it varied in response to wounding. The more striking change in the sieve tubes was the accumulation of proline, which was observed below a [psi] threshold value of about -0.9 MPa (concentration x60 for a decrease of [psi] from -0.9 to -2.0 MPa). The role of such changes in phloem sap amino acid concentration in osmotic adjustment of growing tissues is discussed. PMID:12226278

  13. Evaluating potential changes in salmonid rearing capacity from alternative sets of rehabilitation actions in the Trinity River, California

    NASA Astrophysics Data System (ADS)

    Beechie, T. J.; Pess, G. R.; Imaki, H.; Martin, A.; Alvarez, J.; Goodman, D.

    2013-12-01

    River restoration plans often propose numerous rehabilitation actions to address key habitat impairments for salmonids. However, restoration plans rarely propose alternative sets of actions or attempt to quantify the potential benefits to targeted biota. In this paper we use geomorphic and biological analyses to estimate restoration potential for each of 37 reaches in a 64-km section of Trinity River, California from the North Fork Trinity River to Lewiston Dam (the focus of habitat rehabilitation efforts under the Trinity River Restoration Program). We first predicted the channel pattern that might develop based in each reach on slope-discharge criteria, and then used these potential patterns along with floodplain width to estimate the maximum sinuosity that restoration actions could likely achieve, as well as a maximum side-channel length that might be created in each reach. For each scenario, we then used existing stream habitat and juvenile salmonid data from previous studies in the Trinity River and other watersheds to determine current and restored carrying capacity. Potential increases in Chinook and steelhead carrying capacity range from 39% for a relatively realistic estimate of increasing habitat quality (more low velocity areas with cover) to 67% for a more optimistic scenario that increases both sinuosity and habitat quality. Only the most optimistic scenario that increases habitat quality, increases sinuosity, and constructs tens of kilometers of side channels more than doubles potential juvenile salmonid production (140% increase). These quantitative predictions provide a frame of reference for evaluating alternative restoration options, and for setting measurable restoration goals.

  14. [Radial variation and time lag of sap flow of Populus gansuensis in Minqin Oasis, Northwest].

    PubMed

    Dang, Hong-Zhong; Yang, Wen-Bin; Li, Wei; Zhang, You-Yan; Li, Chang-Long

    2014-09-01

    Sap flow of tree trunk is very important to reflect the dynamics of physiological activities, as well as to estimate the water consumption of individual plant. In the present study, we used the thermal dissipation technique to monitor the sap flow velocity (J) at four depth loci (i. e. 2 cm, 3 cm, 5 cm, 8 cm) of three Populus gansuensis trees (30 year-old) in Minqin Oasis for two consecutive growing seasons. The results showed that there were significant differences among J values at four depth loci under tree trunk cambium. J value at the 3 cm depth locus (J3) of the tree trunk was the highest, and then in sequences, were 2 cm, 5 cm and 8 cm depth loci (J2, J5 and J8). J value (J3) on typical sunny days in June with the highest atmospheric potential evapotranspiration (ET0) was up to 28.53 g · cm(-2) · h(-1), which was 1.42, 2.74 and 4.4 times of J2, J5 and J8, respectively. In the process of diurnal variation of sap flow velocity, the peak value time of J at the four depth loci of the tree trunk was different, but the differences among them were within 20 min. Furthermore, the peak value time of sap flow velocity was very different to that of solar radiation (Rs) and air vapour pressure deficit (VPD). The time lag between J and Rs was from 55 to 88 min on typical sunny days during the main growing seasons (from June to August), and, positively related to the depth of the locus under tree trunk cambium, while the time lag between J and VPD reached 60-96 min, and was negatively related to the depth of the locus. The seasonal variation patterns of J were consistent with ET0. With the increase of tree physiological activities, there was a trend that the major water transportation layer extended to the interior sapwood. The most important meteorological factor was the solar radiation, which primarily drove sap flow at different depths of tree trunk. However, the secondary factor changed along with the depth, and VPD became increasingly important with increasing the

  15. Simulation of the undiseased human cardiac ventricular action potential: model formulation and experimental validation.

    PubMed

    O'Hara, Thomas; Virág, László; Varró, András; Rudy, Yoram

    2011-05-01

    Cellular electrophysiology experiments, important for understanding cardiac arrhythmia mechanisms, are usually performed with channels expressed in non myocytes, or with non-human myocytes. Differences between cell types and species affect results. Thus, an accurate model for the undiseased human ventricular action potential (AP) which reproduces a broad range of physiological behaviors is needed. Such a model requires extensive experimental data, but essential elements have been unavailable. Here, we develop a human ventricular AP model using new undiseased human ventricular data: Ca(2+) versus voltage dependent inactivation of L-type Ca(2+) current (I(CaL)); kinetics for the transient outward, rapid delayed rectifier (I(Kr)), Na(+)/Ca(2+) exchange (I(NaCa)), and inward rectifier currents; AP recordings at all physiological cycle lengths; and rate dependence and restitution of AP duration (APD) with and without a variety of specific channel blockers. Simulated APs reproduced the experimental AP morphology, APD rate dependence, and restitution. Using undiseased human mRNA and protein data, models for different transmural cell types were developed. Experiments for rate dependence of Ca(2+) (including peak and decay) and intracellular sodium ([Na(+)](i)) in undiseased human myocytes were quantitatively reproduced by the model. Early afterdepolarizations were induced by I(Kr) block during slow pacing, and AP and Ca(2+) alternans appeared at rates >200 bpm, as observed in the nonfailing human ventricle. Ca(2+)/calmodulin-dependent protein kinase II (CaMK) modulated rate dependence of Ca(2+) cycling. I(NaCa) linked Ca(2+) alternation to AP alternans. CaMK suppression or SERCA upregulation eliminated alternans. Steady state APD rate dependence was caused primarily by changes in [Na(+)](i), via its modulation of the electrogenic Na(+)/K(+) ATPase current. At fast pacing rates, late Na(+) current and I(CaL) were also contributors. APD shortening during restitution was

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

    PubMed

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

    2014-03-01

    Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na(v)) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these K(v)7 channels and the functional impact of colocalization with Na(v) channels remain poorly understood. Here, we quantitatively examined K(v)7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. K(v)7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ~12 (proximal) to 150 pS μm(-2) (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by K(v)7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (~15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic K(v)7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal K(v)7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains K(v)7.2/7.3 channels were found to increase Na(v) channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, K(v)7 clustering near axonal Na(v) channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential. PMID:24599470

  17. Heteromeric Kv7.2/7.3 Channels Differentially Regulate Action Potential Initiation and Conduction in Neocortical Myelinated Axons

    PubMed Central

    Battefeld, Arne; Tran, Baouyen T.; Gavrilis, Jason; Cooper, Edward C.

    2014-01-01

    Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of Kv7 potassium channels and voltage-gated sodium (Nav) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these Kv7 channels and the functional impact of colocalization with Nav channels remain poorly understood. Here, we quantitatively examined Kv7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. Kv7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ∼12 (proximal) to 150 pS μm−2 (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by Kv7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (∼15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic Kv7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal Kv7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains Kv7.2/7.3 channels were found to increase Nav channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, Kv7 clustering near axonal Nav channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential. PMID:24599470

  18. Comparative Statistical Study of Some SAP UI Technologies

    NASA Astrophysics Data System (ADS)

    Berdie, Adela; Osaci, Mihaela; Dan Lemle, Ludovic

    2011-09-01

    The goal of this paper is to present a comparative study on some web UI (User Interface) technologies that involve the creation of web applications on the platform SAP Net Weaver AS 7.01 of the integrated SAP (System Application Products) system. The attention will be directed mainly to the ABAP (Advanced Business Application Programing) development environment and to the Web Dynpro (WD) technologies, Floor Plan Manager (FPM) and Web Client UI. Through this study, we make an assesment regarding the decision of choosing a technology for the realisation of a project which consists of a web application.

  19. Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential for insect control.

    PubMed

    Bravo, Alejandra; Gill, Sarjeet S; Soberón, Mario

    2007-03-15

    Bacillus thuringiensis Crystal (Cry) and Cytolitic (Cyt) protein families are a diverse group of proteins with activity against insects of different orders--Lepidoptera, Coleoptera, Diptera and also against other invertebrates such as nematodes. Their primary action is to lyse midgut epithelial cells by inserting into the target membrane and forming pores. Among this group of proteins, members of the 3-Domain Cry family are used worldwide for insect control, and their mode of action has been characterized in some detail. Phylogenetic analyses established that the diversity of the 3-Domain Cry family evolved by the independent evolution of the three domains and by swapping of domain III among toxins. Like other pore-forming toxins (PFT) that affect mammals, Cry toxins interact with specific receptors located on the host cell surface and are activated by host proteases following receptor binding resulting in the formation of a pre-pore oligomeric structure that is insertion competent. In contrast, Cyt toxins directly interact with membrane lipids and insert into the membrane. Recent evidence suggests that Cyt synergize or overcome resistance to mosquitocidal-Cry proteins by functioning as a Cry-membrane bound receptor. In this review we summarize recent findings on the mode of action of Cry and Cyt toxins, and compare them to the mode of action of other bacterial PFT. Also, we discuss their use in the control of agricultural insect pests and insect vectors of human diseases. PMID:17198720

  20. Preparing Social Justice Oriented Teachers: The Potential Role of Action Research in the PDS

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  1. The Potential of General Classroom Observation: Turkish EFL Teachers' Perceptions, Sentiments, and Readiness for Action

    ERIC Educational Resources Information Center

    Merç, Ali

    2015-01-01

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

  2. Xylem sap collection and extraction methodologies to determine in vivo concentrations of ABA and its bound forms by gas chromatography-mass spectrometry (GC-MS)

    PubMed Central

    2012-01-01

    Background Accurate quantification of xylem sap ABA concentrations is important to underpin models of root-to-shoot ABA signalling to predict the physiological effects of soil drying. Growing tomato plants in a whole plant pressure chamber allowed sequential xylem sap collection from a detached leaf, the petiole stub of an otherwise intact plant and finally the de-topped root system of the same plant, to determine the impact of xylem sap sampling methodology on xylem ABA concentration. Since xylem sap can contain bound forms of ABA, a novel gas chromatography-mass spectrometry (GC-MS) procedure was developed to chemically separate free ABA from two in planta bound ABA forms known as Adducts I and II and ABA-glucose-ester (ABA-GE). Results Xylem sap ABA concentrations were highly dependent on the sampling methodology used: the highest concentrations were detected in sap collected by applying an overpressure to detached leaves following the measurement of leaf water potential. Irrespective of xylem sap source, the wild-type cultivars Ailsa Craig and Rheinlands Ruhm had higher free ABA concentrations than a range of ABA-deficient mutants (notabilis, flacca and sitiens). However, in the mutants, concentrations of bound forms of ABA were similar to wild-type plants, and similar to free ABA concentrations. Conclusions Although xylem concentrations of these bound ABA forms and ABA-GE suggest they have a limited physiological impact on ABA homeostasis in tomato, the methods developed here will allow a more complete understanding of ABA biochemistry and root-to-shoot signalling in species known to have higher concentrations of these compounds. PMID:22439865

  3. [Hardware Implementation of Numerical Simulation Function of Hodgkin-Huxley Model Neurons Action Potential Based on Field Programmable Gate Array].

    PubMed

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

    2015-12-01

    Neuron is the basic unit of the biological neural system. The Hodgkin-Huxley (HH) model is one of the most realistic neuron models on the electrophysiological characteristic description of neuron. Hardware implementation of neuron could provide new research ideas to clinical treatment of spinal cord injury, bionics and artificial intelligence. Based on the HH model neuron and the DSP Builder technology, in the present study, a single HH model neuron hardware implementation was completed in Field Programmable Gate Array (FPGA). The neuron implemented in FPGA was stimulated by different types of current, the action potential response characteristics were analyzed, and the correlation coefficient between numerical simulation result and hardware implementation result were calculated. The results showed that neuronal action potential response of FPGA was highly consistent with numerical simulation result. This work lays the foundation for hardware implementation of neural network. PMID:27079105

  4. 49 CFR Appendix E to Part 40 - SAP Equivalency Requirements for Certification Organizations

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false SAP Equivalency Requirements for Certification... TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Pt. 40, App. E Appendix E to Part 40—SAP Equivalency... of knowledge must be of sufficient quantity to ensure a high quality of SAP evaluation and...

  5. 30 CFR 585.607 - How do I submit my SAP?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 2 2012-07-01 2012-07-01 false How do I submit my SAP? 585.607 Section 585.607 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE RENEWABLE ENERGY... my SAP? You must submit one paper copy and one electronic version of your SAP to BOEM at the...

  6. 30 CFR 585.606 - What must I demonstrate in my SAP?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 2 2012-07-01 2012-07-01 false What must I demonstrate in my SAP? 585.606 Section 585.606 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE... What must I demonstrate in my SAP? (a) Your SAP must demonstrate that you have planned and are...

  7. 30 CFR 585.607 - How do I submit my SAP?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 2 2013-07-01 2013-07-01 false How do I submit my SAP? 585.607 Section 585.607 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE RENEWABLE ENERGY... my SAP? You must submit one paper copy and one electronic version of your SAP to BOEM at the...

  8. 30 CFR 285.614 - When may I begin conducting activities under my approved SAP?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... approved SAP? 285.614 Section 285.614 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE... Plans and Information Requirements Activities Under An Approved Sap § 285.614 When may I begin conducting activities under my approved SAP? (a) You may begin conducting the activities approved in your...

  9. 49 CFR Appendix E to Part 40 - SAP Equivalency Requirements for Certification Organizations

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false SAP Equivalency Requirements for Certification... TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Pt. 40, App. E Appendix E to Part 40—SAP Equivalency... of knowledge must be of sufficient quantity to ensure a high quality of SAP evaluation and...

  10. 30 CFR 285.607 - How do I submit my SAP?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false How do I submit my SAP? 285.607 Section 285.607... Leases § 285.607 How do I submit my SAP? You must submit one paper copy and one electronic version of your SAP to MMS at the address listed in § 285.110(a)....

  11. 30 CFR 285.614 - When may I begin conducting activities under my approved SAP?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... approved SAP? 285.614 Section 285.614 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION, AND... OUTER CONTINENTAL SHELF Plans and Information Requirements Activities Under An Approved Sap § 285.614 When may I begin conducting activities under my approved SAP? (a) You may begin conducting...

  12. 30 CFR 585.614 - When may I begin conducting activities under my approved SAP?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... approved SAP? 585.614 Section 585.614 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF... CONTINENTAL SHELF Plans and Information Requirements Activities Under An Approved Sap § 585.614 When may I begin conducting activities under my approved SAP? (a) You may begin conducting the activities...

  13. 30 CFR 585.606 - What must I demonstrate in my SAP?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 2 2013-07-01 2013-07-01 false What must I demonstrate in my SAP? 585.606 Section 585.606 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE... What must I demonstrate in my SAP? (a) Your SAP must demonstrate that you have planned and are...

  14. 30 CFR 285.606 - What must I demonstrate in my SAP?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What must I demonstrate in my SAP? 285.606 Section 285.606 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE... demonstrate in my SAP? (a) Your SAP must demonstrate that you have planned and are prepared to conduct...

  15. 30 CFR 585.614 - When may I begin conducting activities under my approved SAP?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... approved SAP? 585.614 Section 585.614 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF... CONTINENTAL SHELF Plans and Information Requirements Activities Under An Approved Sap § 585.614 When may I begin conducting activities under my approved SAP? (a) You may begin conducting the activities...

  16. 30 CFR 285.606 - What must I demonstrate in my SAP?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false What must I demonstrate in my SAP? 285.606 Section 285.606 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION, AND ENFORCEMENT... Commercial Leases § 285.606 What must I demonstrate in my SAP? (a) Your SAP must demonstrate that you...

  17. 49 CFR Appendix E to Part 40 - SAP Equivalency Requirements for Certification Organizations

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false SAP Equivalency Requirements for Certification... TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Pt. 40, App. E Appendix E to Part 40—SAP Equivalency... of knowledge must be of sufficient quantity to ensure a high quality of SAP evaluation and...

  18. 49 CFR Appendix E to Part 40 - SAP Equivalency Requirements for Certification Organizations

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false SAP Equivalency Requirements for Certification... TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Pt. 40, App. E Appendix E to Part 40—SAP Equivalency... of knowledge must be of sufficient quantity to ensure a high quality of SAP evaluation and...

  19. 30 CFR 585.606 - What must I demonstrate in my SAP?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 2 2014-07-01 2014-07-01 false What must I demonstrate in my SAP? 585.606 Section 585.606 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE... What must I demonstrate in my SAP? (a) Your SAP must demonstrate that you have planned and are...

  20. 30 CFR 585.607 - How do I submit my SAP?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 2 2014-07-01 2014-07-01 false How do I submit my SAP? 585.607 Section 585.607 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE RENEWABLE ENERGY... my SAP? You must submit one paper copy and one electronic version of your SAP to BOEM at the...

  1. 30 CFR 585.614 - When may I begin conducting activities under my approved SAP?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... approved SAP? 585.614 Section 585.614 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF... CONTINENTAL SHELF Plans and Information Requirements Activities Under An Approved Sap § 585.614 When may I begin conducting activities under my approved SAP? (a) You may begin conducting the activities...

  2. Contribution of BK channels to action potential repolarisation at minimal cytosolic Ca2+ concentration in chromaffin cells.

    PubMed

    Scott, Ricardo S; Bustillo, Diego; Olivos-Oré, Luis Alcides; Cuchillo-Ibañez, Inmaculada; Barahona, Maria Victoria; Carbone, Emilio; Artalejo, Antonio R

    2011-10-01

    BK channels modulate cell firing in excitable cells in a voltage-dependent manner regulated by fluctuations in free cytosolic Ca(2+) during action potentials. Indeed, Ca(2+)-independent BK channel activity has ordinarily been considered not relevant for the physiological behaviour of excitable cells. We employed the patch-clamp technique and selective BK channel blockers to record K(+) currents from bovine chromaffin cells at minimal intracellular (about 10 nM) and extracellular (free Ca(2+)) Ca(2+) concentrations. Despite their low open probability under these conditions (V(50) of +146.8 mV), BK channels were responsible for more than 25% of the total K(+) efflux during the first millisecond of a step depolarisation to +20 mV. Moreover, BK channels activated about 30% faster (τ = 0.55 ms) than the rest of available K(+) channels. The other main source of fast voltage-dependent K(+) efflux at such a low Ca(2+) was a transient K(+) (I(A)-type) current activating with V (50) = -14.2 mV. We also studied the activation of BK currents in response to action potential waveforms and their contribution to shaping action potentials both in the presence and the absence of extracellular Ca(2+). Our results show that BK channels activate during action potentials and accelerate cell repolarisation even at minimal Ca(2+) concentration, and suggest that they could do so also in the presence of extracellular Ca(2+), before Ca(2+) entering the cell facilitates their activity. PMID:21755285

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

    INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P < 0.0001) and correspondingly decreased average apparent surface conduction velocity by 16%+/- 7% (P = 0.007). Ventricular loading did not significantly alter action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P < 0.0001). The dispersion of APD20 was decreased with loading from 19 +/- 2 msec to 13 +/- 2 msec (P = 0.024), whereas the dispersion of APD80 was not significantly changed. These electrophysiologic changes with ventricular loading were not affected by the nonspecific stretch-activated channel blocker streptomycin (200 microM) and were not attributable to changes in myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. CONCLUSION: Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

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

    NASA Astrophysics Data System (ADS)

    Salzberg, Brian M.

    2008-03-01

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

  5. Effect of depth of general anesthesia on the threshold of electrically evoked compound action potential in cochlear implantation.

    PubMed

    Eftekharian, Ali; Amizadeh, Maryam; Mottaghi, Kamran; Safari, Farhad; Mahani, Mozhgan Hosseinerezai; Ranjbar, Leila Azadeh; Abdi, Ali; Mokari, Nooshin

    2015-10-01

    The purpose of the present study was to evaluate effect of depth of general anesthesia on the threshold of electrically evoked compound action potential in cochlear implantation. A prospective clinical study in a single-subject design was conducted in the cochlear implant center of a tertiary care University-based hospital. Sixty-one cochlear-implanted children with bilateral, severe to profound sensory neural hearing loss were enrolled in the study. During the operation electrically evoked compound action potentials (e-ECAP) were measured in two phase of general anesthesia; in deep and in light anesthesia. Thresholds of e-ECAP in these two phases of anesthesia were compared. Thirty-one children received HiRes90k1j prosthesis and 30 children received CI24RE prosthesis. Thresholds difference of electrically evoked compound action potential between light and deep anesthesia in all tested electrodes in either group were statistically significant (P < 0.001). Non-measurable e-ECAP in some electrodes at deep anesthesia was measurable in light phase of anesthesia. Depth of anesthesia can have significant influence on e-ECAP threshold and it is important to reduce the depth of anesthesia to achieve better results. PMID:25145642

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

    PubMed Central

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

    2010-01-01

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

  7. 46 CFR 16.203 - Employer, MRO, and SAP responsibilities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... meet the training requirements and follow the procedures in 49 CFR Part 40. (2) MROs may report... and follow the procedures in 49 CFR Part 40. ... 46 Shipping 1 2013-10-01 2013-10-01 false Employer, MRO, and SAP responsibilities. 16.203...

  8. 46 CFR 16.203 - Employer, MRO, and SAP responsibilities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... meet the training requirements and follow the procedures in 49 CFR Part 40. (2) MROs may report... and follow the procedures in 49 CFR Part 40. ... 46 Shipping 1 2012-10-01 2012-10-01 false Employer, MRO, and SAP responsibilities. 16.203...

  9. 46 CFR 16.203 - Employer, MRO, and SAP responsibilities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... meet the training requirements and follow the procedures in 49 CFR Part 40. (2) MROs may report... and follow the procedures in 49 CFR Part 40. ... 46 Shipping 1 2011-10-01 2011-10-01 false Employer, MRO, and SAP responsibilities. 16.203...

  10. 46 CFR 16.203 - Employer, MRO, and SAP responsibilities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... meet the training requirements and follow the procedures in 49 CFR Part 40. (2) MROs may report... and follow the procedures in 49 CFR Part 40. ... 46 Shipping 1 2010-10-01 2010-10-01 false Employer, MRO, and SAP responsibilities. 16.203...

  11. Faculty Performance Evaluation: The CIPP-SAPS Model.

    ERIC Educational Resources Information Center

    Mitcham, Maralynne

    1981-01-01

    The issues of faculty performance evaluation for allied health professionals are addressed. Daniel Stufflebeam's CIPP (content-imput-process-product) model is introduced and its development into a CIPP-SAPS (self-administrative-peer- student) model is pursued. (Author/CT)

  12. 46 CFR 16.203 - Employer, MRO, and SAP responsibilities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... meet the training requirements and follow the procedures in 49 CFR Part 40. (2) MROs may report... and follow the procedures in 49 CFR Part 40. ... 46 Shipping 1 2014-10-01 2014-10-01 false Employer, MRO, and SAP responsibilities. 16.203...

  13. Accounting Control Technology Using SAP: A Case-Based Approach

    ERIC Educational Resources Information Center

    Ragan, Joseph; Puccio, Christopher; Talisesky, Brandon

    2014-01-01

    The Sarbanes-Oxley Act (SOX) revolutionized the accounting and audit industry. The use of preventative and process controls to evaluate the continuous audit process done via an SAP ERP ECC 6.0 system is key to compliance with SOX and managing costs. This paper can be used in a variety of ways to discuss issues associated with auditing and testing…

  14. Diosgenin, 4-hydroxyisoleucine, and fiber from fenugreek: mechanisms of actions and potential effects on metabolic syndrome.

    PubMed

    Fuller, Scott; Stephens, Jacqueline M

    2015-03-01

    Metabolic syndrome and its complications continue to rise in prevalence and show no signs of abating in the immediate future. Therefore, the search for effective treatments is a high priority in biomedical research. Products derived from botanicals have a time-honored history of use in the treatment of metabolic diseases including type 2 diabetes. Trigonella foenum-graecum, commonly known as fenugreek, is an annual herbaceous plant that has been a staple of traditional herbal medicine in many cultures. Although fenugreek has been studied in both clinical and basic research settings, questions remain about its efficacy and biologic mechanisms of action. Diosgenin, 4-hydroxyisoleucine, and the fiber component of the plant are the most intensively studied bioactive constituents present in fenugreek. These compounds have been demonstrated to exert beneficial effects on several physiologic markers including glucose tolerance, inflammation, insulin action, liver function, blood lipids, and cardiovascular health. Although insights into the molecular mechanisms underlying the favorable effects of fenugreek have been gained, we still do not have definitive evidence establishing its role as a therapeutic agent in metabolic disease. This review aims to summarize the currently available evidence on the physiologic effects of the 3 best-characterized bioactive compounds of fenugreek, with particular emphasis on biologic mechanisms of action relevant in the context of metabolic syndrome. PMID:25770257

  15. Complex Dynamic Thresholds and Generation of the Action Potentials in the Neural-Activity Model

    NASA Astrophysics Data System (ADS)

    Kirillov, S. Yu.; Nekorkin, V. I.

    2016-05-01

    This work is devoted to studying the processes of activation of the neurons whose excitation thresholds are not constant and vary in time (the so-called dynamic thresholds). The neuron dynamics is described by the FitzHugh-Nagumo model with nonlinear behavior of the recovery variable. The neuron response to the external pulsed activating action in the presence of a slowly varying synaptic current is studied within the framework of this model. The structure of the dynamic threshold is studied and its properties depending on the external-action parameters are established. It is found that the formation of the "folds" in the separatrix threshold manifold in the model phase space is a typical feature of the complex dynamic threshold. High neuron sensitivity to the action of the comparatively weak slow control signals is established. This explains the capability of the neurons to perform flexible tuning of their selective properties for detecting various external signals in sufficiently short times (of the order of duration of several spikes).

  16. Complex Dynamic Thresholds and Generation of the Action Potentials in the Neural-Activity Model

    NASA Astrophysics Data System (ADS)

    Kirillov, S. Yu.; Nekorkin, V. I.

    2016-06-01

    This work is devoted to studying the processes of activation of the neurons whose excitation thresholds are not constant and vary in time (the so-called dynamic thresholds). The neuron dynamics is described by the FitzHugh-Nagumo model with nonlinear behavior of the recovery variable. The neuron response to the external pulsed activating action in the presence of a slowly varying synaptic current is studied within the framework of this model. The structure of the dynamic threshold is studied and its properties depending on the external-action parameters are established. It is found that the formation of the "folds" in the separatrix threshold manifold in the model phase space is a typical feature of the complex dynamic threshold. High neuron sensitivity to the action of the comparatively weak slow control signals is established. This explains the capability of the neurons to perform flexible tuning of their selective properties for detecting various external signals in sufficiently short times (of the order of duration of several spikes).

  17. Artesunate ameliorates severe acute pancreatitis (SAP) in rats by inhibiting expression of pro-inflammatory cytokines and Toll-like receptor 4.

    PubMed

    Cen, Yanyan; Liu, Chao; Li, Xiaoli; Yan, Zifei; Kuang, Mei; Su, Yujie; Pan, Xichun; Qin, Rongxin; Liu, Xin; Zheng, Jiang; Zhou, Hong

    2016-09-01

    Severe acute pancreatitis (SAP) is a severe clinical condition with significant morbidity and mortality. Multiple organs dysfunction (MOD) is the leading cause of SAP-related death. The over-release of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α is the underlying mechanism of MOD; however, there is no effective agent against the inflammation. Herein, artesunate (AS) was found to increase the survival of SAP rats significantly when injected with 3.5% sodium taurocholate into the biliopancreatic duct in a retrograde direction, improving their pancreatic pathology and decreasing serum amylase and pancreatic lipase activities along with substantially reduced pancreatic IL-1β and IL-6 release. In vitro, AS-pretreatment strongly inhibited IL-1β and IL-6 release and their mRNA expressions in the pancreatic acinar cells treated with lipopolysaccharide (LPS) but exerted little effect on TNF-α release. Additionally, AS reduced the mRNA expressions of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) p65 as well as their protein expressions in the pancreatic acinar cells. In conclusion, our results demonstrated that AS could significantly protect SAP rats, and this protection was related to the reduction of digestive enzyme activities and pro-inflammatory cytokine expressions via inhibition of TLR4/NF-κB signaling pathway. Therefore, AS may be considered as a potential therapeutic agent against SAP. PMID:27318790

  18. Quantifying environmental controls on sap flow in Great Basin tree species and their possible significance for mountain groundwater recharge under anthropogenic climate change

    NASA Astrophysics Data System (ADS)

    Johnson, B. G.; Jasoni, R. L.; Arnone, J.

    2011-12-01

    Transpiration of trees in mountain recharge zones may significantly limit the input of water to groundwater systems in Great Basin mountain ranges. This removal of vadose zone soil water eventually constrains the bioavailability of water for both agriculture and human consumption. The objective of this study is to develop a quantitative understanding of the response of sap flow to key modulating environmental factors. Quantifying the interaction between these factors will determine which have greatest influence on transpiration rates and how rates may be affected by shifts in these factors under anthropogenic climate change. Data recorded from mature trees growing at a montane site (2,730 m) on the western slope of the Snake Range in eastern Nevada measured during a precipitation-free month (July 2011) indicated that photosynthetically active radiation (PAR), and covarying air temperature and vapor pressure deficit (VPD), most strongly modulated diurnal patterns of sap flow in all species studied (Abies concolor, Pinus flexilis, Pseudotsuga menziesii and Cercocarpus ledifolius). Daily sap flow sums were also closely correlated with daily PAR sums. Declines in topsoil (0-30 cm) volumetric water content during the month by 5-10% appeared to have no effect on sap flow. This suggests that soil water potentials remained in a range that still enabled trees to extract water easily. Although species differed from each other in actual sap fluxes, temporal responses to variability in these control factors were similar among species. Anticipated higher VPDs under projected climate scenarios may further increase transpirational water losses.

  19. Potential of rapid adjustment of brief interceptive action using predicted information.

    PubMed

    Ikudome, Sachi; Nakamoto, Hiroki; Yotani, Kengo; Unenaka, Satoshi; Mori, Shiro

    2015-07-01

    Interceptive actions, such as hitting a ball in baseball or tennis, feature a moving target whose parameters (i.e., velocity or trajectory) differ across trials. This means that players are required to make rapid trial-by-trial adjustments. The purpose of this study was to determine whether a brief interceptive action could be adjusted using predicted sensory consequence of movement (pSCM) information, even under severe time constraints where the participants could not adjust their movement using only visual feedback. Participants performed an interceptive action for targets with two different velocities with different occurrence probabilities (20%, 50%, and 80%). Prior to movement onset, we applied transcranial magnetic stimulation (TMS) to the supplementary motor area (SMA), as TMS of the SMA is known to disrupt pSCM activity. We hypothesized that if pSCM information were used to adjust the motor parameters of a brief interception, then TMS would significantly increase the constant temporal error (i.e., the difference between the sum of reaction time and movement time and the total target visible time) for a target velocity with a low probability (20%). This hypothesis is based on the previous findings that the pSCM plays an important role in the adjustment of relatively brief interception. We found that while interceptions that lasted about 250 ms after movement onset were unaffected, interceptions that lasted about 350 ms after movement onset could be influenced by TMS. However, TMS interfered with performance provided that the delivery of the pulse occurred 100 ms before movement onset. This finding suggests that pSCM information that is used for a rapid adjustment is generated only in that specific time interval. PMID:26010202

  20. Conservation laws of wave action and potential enstrophy for Rossby waves in a stratified atmosphere

    NASA Technical Reports Server (NTRS)

    Straus, D. M.

    1983-01-01

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

  1. Conservation laws of wave action and potential enstrophy for Rossby waves in a stratified atmosphere

    NASA Technical Reports Server (NTRS)

    Straus, D. M.

    1983-01-01

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

  2. Mechanism of irradiation-induced mammary cancer metastasis: A role for SAP-dependent Mkl1 signaling.

    PubMed

    Asparuhova, Maria B; Secondini, Chiara; Rüegg, Curzio; Chiquet-Ehrismann, Ruth

    2015-10-01

    Radiotherapy is a standard treatment after conservative breast cancer surgery. However, cancers relapsing within a previously irradiated area have an increased probability to metastasize. The mechanisms responsible for this aggressiveness remain unclear. Here, we used the clinically relevant 4T1 breast cancer model mimicking aggressive local relapse after radiotherapy to identify differences between tumors grown in untreated versus preirradiated mammary glands. Tumors grown within preirradiated beds were highly enriched in transcripts encoding collagens and other proteins building or modifying the extracellular matrix, such as laminin-332, tenascins, lysyl oxidases and matrix metalloproteinases. Type I collagen, known to directly contribute to tissue stiffening, and the pro-metastatic megakaryoblastic leukemia-1 (Mkl1) target gene tenascin-C were further investigated. Mammary tissue preirradiation induced Mkl1 nuclear translocation in the tumor cells in vivo, indicating activation of Mkl1 signaling. Transcript profiling of cultured 4T1 cells revealed that the majority of the Mkl1 target genes, including tenascin-C, required serum response factor (SRF) for their expression. However, application of dynamic strain or matrix stiffness to 4T1 cells converted the predominant SRF/Mkl1 action into SAP domain-dependent Mkl1 signaling independent of SRF, accompanied by a switch to SAP-dependent tumor cell migration. 4T1 tumors overexpressing intact Mkl1 became more metastatic within preirradiated beds, while tumors expressing Mkl1 lacking the SAP domain exhibited impaired growth and metastatic spread, and decreased Mkl1 target gene expression. Thus, we identified SAP-dependent Mkl1 signaling as a previously unrecognized mediator of aggressive progression of mammary tumors locally relapsing after radiotherapy, and provide a novel signaling pathway for therapeutic intervention. PMID:25999144

  3. Comparison of genetically encoded calcium indicators for monitoring action potentials in mammalian brain by two-photon excitation fluorescence microscopy

    PubMed Central

    Podor, Borbala; Hu, Yi-ling; Ohkura, Masamichi; Nakai, Junichi; Croll, Roger; Fine, Alan

    2015-01-01

    Abstract. Imaging calcium transients associated with neuronal activity has yielded important insights into neural physiology. Genetically encoded calcium indicators (GECIs) offer conspicuous potential advantages for this purpose, including exquisite targeting. While the catalogue of available GECIs is steadily growing, many newly developed sensors that appear promising in vitro or in model cells appear to be less useful when expressed in mammalian neurons. We have, therefore, evaluated the performance of GECIs from two of the most promising families of sensors, G-CaMPs [Nat. Biotechnol. 19(2), 137–141 (2001)11175727] and GECOs [Science 333(6051), 1888–1891 (2011)21903779], for monitoring action potentials in rat brain. Specifically, we used two-photon excitation fluorescence microscopy to compare calcium transients detected by G-CaMP3; GCaMP6f; G-CaMP7; Green-GECO1.0, 1.1 and 1.2; Blue-GECO; Red-GECO; Rex-GECO0.9; Rex-GECO1; Carmine-GECO; Orange-GECO; and Yellow-GECO1s. After optimizing excitation wavelengths, we monitored fluorescence signals associated with increasing numbers of action potentials evoked by current injection in CA1 pyramidal neurons in rat organotypic hippocampal slices. Some GECIs, particularly Green-GECO1.2, GCaMP6f, and G-CaMP7, were able to detect single action potentials with high reliability. By virtue of greatest sensitivity and fast kinetics, G-CaMP7 may be the best currently available GECI for monitoring calcium transients in mammalian neurons. PMID:26158004

  4. NuSAP governs chromosome oscillation by facilitating the Kid-generated polar ejection force.

    PubMed

    Li, Chenyu; Xue, Chenyi; Yang, Qiaoyun; Low, Boon Chuan; Liou, Yih-Cherng

    2016-01-01

    In vertebrate cells, chromosomes oscillate to align precisely during metaphase. NuSAP, a microtubule-associated protein, plays a critical role in stabilizing spindle microtubules. In this study, we utilize 3D time-lapse live-cell imaging to monitor the role of NuSAP in chromosome oscillation and identify NuSAP as a novel regulator of the chromokinesin, Kid. Depletion of NuSAP significantly suppresses the amplitude and velocity of chromosome oscillation. We analyse the effects of NuSAP and Kid depletion in monopolar and bipolar cells with or without kinetochore microtubule depletion. Twelve postulated conditions are deciphered to reveal the contribution of NuSAP to the polar force generated at kinetochore microtubules and to the regulation of the polar ejection force generated by Kid, thus revealing a pivotal role of NuSAP in chromosome oscillation. PMID:26839278

  5. The FORTRAN static source code analyzer program (SAP) user's guide, revision 1

    NASA Technical Reports Server (NTRS)

    Decker, W.; Taylor, W.; Eslinger, S.

    1982-01-01

    The FORTRAN Static Source Code Analyzer Program (SAP) User's Guide (Revision 1) is presented. SAP is a software tool designed to assist Software Engineering Laboratory (SEL) personnel in conducting studies of FORTRAN programs. SAP scans FORTRAN source code and produces reports that present statistics and measures of statements and structures that make up a module. This document is a revision of the previous SAP user's guide, Computer Sciences Corporation document CSC/TM-78/6045. SAP Revision 1 is the result of program modifications to provide several new reports, additional complexity analysis, and recognition of all statements described in the FORTRAN 77 standard. This document provides instructions for operating SAP and contains information useful in interpreting SAP output.

  6. NuSAP governs chromosome oscillation by facilitating the Kid-generated polar ejection force

    PubMed Central

    Li, Chenyu; Xue, Chenyi; Yang, Qiaoyun; Low, Boon Chuan; Liou, Yih-Cherng

    2016-01-01

    In vertebrate cells, chromosomes oscillate to align precisely during metaphase. NuSAP, a microtubule-associated protein, plays a critical role in stabilizing spindle microtubules. In this study, we utilize 3D time-lapse live-cell imaging to monitor the role of NuSAP in chromosome oscillation and identify NuSAP as a novel regulator of the chromokinesin, Kid. Depletion of NuSAP significantly suppresses the amplitude and velocity of chromosome oscillation. We analyse the effects of NuSAP and Kid depletion in monopolar and bipolar cells with or without kinetochore microtubule depletion. Twelve postulated conditions are deciphered to reveal the contribution of NuSAP to the polar force generated at kinetochore microtubules and to the regulation of the polar ejection force generated by Kid, thus revealing a pivotal role of NuSAP in chromosome oscillation. PMID:26839278

  7. A model of the magnetic fields created by single motor unit compound action potentials in skeletal muscle.

    PubMed

    Parker, K K; Wikswo, J P

    1997-10-01

    We have developed a computationally simple model for calculating the magnetic-field strength at a point due to a single motor unit compound action potential (SMUCAP). The motor unit is defined only in terms of its anatomical features, and the SMUCAP is approximated using the tripole model. The distributed current density J is calculated within the volume defined by the motor unit. The law of Biot and Savart can then be cast in a form necessitating that J be integrated only over the region containing current sources or conductivity boundaries. The magnetic-field strength is defined as the summation of the contributions to the field made by every muscle fiber in the motor unit. Applying this model to SMUCAP measurements obtained using a high-resolution SUper Conducting Quantum Interference Device (SQUID) magnetometer may yield information regarding the distribution of action currents (AC's) and the anatomical properties of single motor units within a muscle bundle. PMID:9311164

  8. The potential for multi-disciplinary primary health care services to take action on the social determinants of health: actions and constraints

    PubMed Central

    2013-01-01

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

  9. Computational modeling of inhibition of voltage-gated Ca channels: identification of different effects on uterine and cardiac action potentials

    PubMed Central

    Tong, Wing-Chiu; Ghouri, Iffath; Taggart, Michael J.

    2014-01-01

    The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs). Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models—of uterine smooth muscle cells (USMC), cardiac sinoatrial node cells (SAN), and ventricular cells—to investigate the relative effects of reducing two important voltage-gated Ca currents—the L-type (ICaL) and T-type (ICaT) Ca currents. Reduction of ICaL (10%) alone, or ICaT (40%) alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine specificity of action

  10. Potential mechanisms of action of lithium in bipolar disorder. Current understanding.

    PubMed

    Malhi, Gin S; Tanious, Michelle; Das, Pritha; Coulston, Carissa M; Berk, Michael

    2013-02-01

    Lithium has been used for over half a century for the treatment of bipolar disorder as the archetypal mood stabilizer, and has a wealth of empirical evidence supporting its efficacy in this role. Despite this, the specific mechanisms by which lithium exerts its mood-stabilizing effects are not well understood. Given the inherently complex nature of the pathophysiology of bipolar disorder, this paper aims to capture what is known about the actions of lithium ranging from macroscopic changes in mood, cognition and brain structure, to its effects at the microscopic level on neurotransmission and intracellular and molecular pathways. A comprehensive literature search of databases including MEDLINE, EMBASE and PsycINFO was conducted using relevant keywords and the findings from the literature were then reviewed and synthesized. Numerous studies report that lithium is effective in the treatment of acute mania and for the long-term maintenance of mood and prophylaxis; in comparison, evidence for its efficacy in depression is modest. However, lithium possesses unique anti-suicidal properties that set it apart from other agents. With respect to cognition, studies suggest that lithium may reduce cognitive decline in patients; however, these findings require further investigation using both neuropsychological and functional neuroimaging probes. Interestingly, lithium appears to preserve or increase the volume of brain structures involved in emotional regulation such as the prefrontal cortex, hippocampus and amygdala, possibly reflecting its neuroprotective effects. At a neuronal level, lithium reduces excitatory (dopamine and glutamate) but increases inhibitory (GABA) neurotransmission; however, these broad effects are underpinned by complex neurotransmitter systems that strive to achieve homeostasis by way of compensatory changes. For example, at an intracellular and molecular level, lithium targets second-messenger systems that further modulate neurotransmission. For

  11. 30 CFR 285.617 - What activities require a revision to my SAP, and when will MMS approve the revision?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false What activities require a revision to my SAP... Activities Under An Approved Sap § 285.617 What activities require a revision to my SAP, and when will MMS... your approved SAP, describing in detail the type of activities you propose to conduct. We...

  12. Analytical solutions of the Frankenhaeuser-Huxley equations I: minimal model for backpropagation of action potentials in sparsely excitable dendrites.

    PubMed

    Poznanski, Roman R

    2004-09-01

    Hodgkin and Huxley's ionic theory of the nerve impulse embodies principles, applicable also to the impulses in vertebrate nerve fibers, as demonstrated by Bernhard Frankenhaeuser and Andrew Huxley 40 years ago. Frankenhaeuser and Huxley reformulated the classical Hodgkin-Huxley equations, in terms of electrodiffusion theory, and computed action potentials specifically for saltatory conduction in myelinated axons. In this paper, we obtain analytical solutions to the most difficult nonlinear partial differential equations in classical neurophysiology. We solve analytically the Frankenhaeuser-Huxley equations pertaining to a model of sparsely excitable, nonlinear dendrites with clusters of transiently activating, TTX-sensitive Na(+) channels, discretely distributed as point sources of inward current along a continuous (non-segmented) leaky cable structure. Each cluster or hot-spot, corresponding to a mesoscopic level description of Na(+) ion channels, includes known cumulative inactivation kinetics observed at the microscopic level. In such a third-order system, the 'recovery' variable is an electrogenic sodium-pump imbedded in the passive membrane, and the system is stabilized by the presence of a large leak conductance mediated by a composite number of ligand-gated channels permeable to monovalent cations Na(+) and K(+). In order to reproduce antidromic propagation and attenuation of action potentials, a nonlinear integral equation must be solved (in the presence of suprathreshold input, and a constant-field equation of electrodiffusion at each hot-spot with membrane gates controlling the flow of current). A perturbative expansion of the non-dimensional membrane potential (Phi) is used to obtain time-dependent analytical solutions, involving a voltage-dependent Na(+) activation (micro) and a state-dependent inactivation (eta) gating variables. It is shown that action potentials attenuate in amplitude in accordance with experimental findings, and that the spatial

  13. Cardiovascular Actions and Therapeutic Potential of Tetramethylpyrazine (Active Component Isolated from Rhizoma Chuanxiong): Roles and Mechanisms

    PubMed Central

    Guo, Ming; Liu, Yue; Shi, Dazhuo

    2016-01-01

    Tetramethylpyrazine (TMP), a pharmacologically active component isolated from the rhizome of the Chinese herb Rhizoma Chuanxiong (Chuanxiong), has been clinically used in China and Southeast Asian countries for the prevention and treatment of cardiovascular diseases (CVDs) for about fifty years. The pharmacological effects of TMP on the cardiovascular system have attracted great interest. Emerging experimental studies and clinical trials have demonstrated that TMP prevents atherosclerosis as well as ischemia-reperfusion injury. The cardioprotective effects of TMP are mainly related to its antioxidant, anti-inflammatory, or calcium-homeostasis effects. This review focuses on the roles and mechanisms of action of TMP in the cardiovascular system and provides a novel perspective on TMP's clinical use. PMID:27314011

  14. Larval therapy from antiquity to the present day: mechanisms of action, clinical applications and future potential

    PubMed Central

    Whitaker, Iain S; Twine, Christopher; Whitaker, Michael J; Welck, Mathew; Brown, Charles S; Shandall, Ahmed

    2007-01-01

    When modern medicine fails, it is often useful to draw ideas from ancient treatments. The therapeutic use of fly larvae to debride necrotic tissue, also known as larval therapy, maggot debridement therapy or biosurgery, dates back to the beginnings of civilisation. Despite repeatedly falling out of favour largely because of patient intolerance to the treatment, the practice of larval therapy is increasing around the world because of its efficacy, safety and simplicity. Clinical indications for larval treatment are varied, but, in particular, are wounds infected with multidrug‐resistant bacteria and the presence of significant co‐morbidities precluding surgical intervention. The flies most often used in larval therapy are the facultative calliphorids, with the greenbottle blowfly (Lucilia sericata) being the most widely used species. This review summarises the fascinating and turbulent history of larval therapy from its origin to the present day, including mechanisms of action and evidence for its clinical applications. It also explores future research directions. PMID:17551073

  15. Assessing potential targets of calcium action in light-modulated gravitropism

    NASA Technical Reports Server (NTRS)

    Roux, S. J.

    1995-01-01

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

  16. Metal-organic frameworks: mechanisms of antibacterial action and potential applications.

    PubMed

    Wyszogrodzka, Gabriela; Marszałek, Bartosz; Gil, Barbara; Dorożyński, Przemysław

    2016-06-01

    The growing resistance of pathogens to conventional antibiotics has become a public health problem and raises the need to seek new effective solutions. Metal-organic frameworks (MOFs) are porous, hybrid materials comprising metal ions linked by organic binding ligands. The possibility of using a variety of chemical building components in MOFs enables the formation of structures with desired properties. They can act as a reservoir of metal ions, providing their gradual release and resulting in a sustained antibacterial action analogous to that proposed for metal/metal oxide nanoparticles (NPs) but different to that of antibiotics. These features make MOFs promising candidates for pharmaceutical and biomedical applications, as illustrated by examples discussed in this review. PMID:27091434

  17. Nuclear Targeting with an Auger Electron Emitter Potentiates the Action of a Widely Used Antineoplastic Drug.

    PubMed

    Imstepf, Sebastian; Pierroz, Vanessa; Raposinho, Paula; Bauwens, Matthias; Felber, Michael; Fox, Thomas; Shapiro, Adam B; Freudenberg, Robert; Fernandes, Célia; Gama, Sofia; Gasser, Gilles; Motthagy, Felix; Santos, Isabel R; Alberto, Roger

    2015-12-16

    We present the combination of the clinically well-proven chemotherapeutic agent, Doxorubicin, and (99m)Tc, an Auger and internal conversion electron emitter, into a dual-action agent for therapy. Chemical conjugation of Doxorubicin to (99m)Tc afforded a construct which autonomously ferries a radioactive payload into the cell nucleus. At this site, damage is exerted by dose deposition from Auger radiation. The (99m)Tc-conjugate exhibited a dose-dependent inhibition of survival in a selected panel of cancer cells and an in vivo study in healthy mice evidenced a biodistribution which is comparable to that of the parent drug. The homologous Rhenium conjugate was found to effectively bind to DNA, inhibited human Topoisomerase II, and exhibited cytotoxicity in vitro. The collective in vitro and in vivo data demonstrate that the presented metallo-conjugates closely mimic native Doxorubicin. PMID:26473388

  18. Spatial and temporal variations in sap flux density in Japanese cedar (Cryptomeria japonica) trees, central Taiwan

    NASA Astrophysics Data System (ADS)

    Tseng, Han; Chiu, Chen-Wei; Wey, Tsong-Huei; Kume, Tomonori

    2013-04-01

    Sap flow measurement method is a technique widely used for measuring forest transpiration. However, variations in sap flow distribution can make accurately estimating individual tree-scale transpiration difficult. Significant spatial variations in sap flow across the sapwood within tree have been reported in many studies. In contrast, few studies have discussed azimuthal variations in sap flow, and even fewer have examined their seasonal change characteristics. This study was undertaken to clarify within-tree special and temporal variations in sap flow, and to propose an appropriate design for individual-tree scale transpiration estimates for Japanese cedar trees. The measurement was conducted in a Japanese cedar plantation located in Central Taiwan. Spatial distribution of sap flux density through the sapwood cross-section was measured using Granier's thermal dissipation technique. Sensors were installed at 1.3 m high on the east, west, north and south sides of the stem at 0-2 cm in 8 trees, and at 2-4 cm in the 6 larger trees. We found, in radial profile analysis, that sap flux densities measured at the depth of 2-4 cm were 50 % in average of those measured at depth of 0-2 cm. In azimuthal profile analysis, we found significant azimuthal variations in sap flux density. In one individual tree, the ratio of sap flux density on one aspect to another could be approximately 40-190 %, with no dependency on directions. Both radial and azimuthal profiles in most sample trees were fairly consistent throughout the measurement period. We concluded that radial and azimuthal variations in sap flow across sapwood might introduce significant errors in individual tree-scale transpiration estimations based on single point sap flow measurement, and seasonal change of within-tree spatial variations in sap flow could have insignificant impacts on accuracy of long-term individual tree-scale transpiration estimates. Keywords: transpiration, sap flow measurement, scaling up, sap flow

  19. Rearrangement of sapA homologs with conserved and variable regions in Campylobacter fetus.

    PubMed

    Tummuru, M K; Blaser, M J

    1993-08-01

    The Campylobacter fetus surface-layer (S-layer) proteins mediate both complement resistance and antigenic variation in mammalian hosts. Wild-type strain 23D possesses the sapA gene, which encodes a 97-kDa S-layer protein, and several sapA homologs are present in both wild-type and mutant strains. Here we report that a cloned silent gene (sapA1) in C. fetus can express a functional full-length S-layer protein in Escherichia coli. Analysis of sapA and sapA1 and partial analysis of sapA2 indicate that a block of approximately 600 bp beginning upstream and continuing into the open reading frames is completely conserved, and then the sequences diverge completely, but immediately downstream of each gene is another conserved 50-bp sequence. Conservation of sapA1 among strains, the presence of a putative Chi (RecBCD recognition) site upstream of sapA, sapA1, and sapA2, and the sequence identities of the sapA genes suggest a system for homologous recombination. Comparison of the wild-type strain (23D) with a phenotypic variant (23D-11) indicates that variation is associated with removal of the divergent region of sapA from the expression locus and exchange with a corresponding region from a sapA homolog. We propose that site-specific reciprocal recombination between sapA homologs leads to expression of divergent S-layer proteins as one of the mechanisms that C. fetus uses for antigenic variation. PMID:8346244

  20. Mosquito larvicidal and pupaecidal potential of prodigiosin from Serratia marcescens and understanding its mechanism of action.

    PubMed

    Suryawanshi, Rahul K; Patil, Chandrashekhar D; Borase, Hemant P; Narkhede, Chandrakant P; Salunke, Bipinchandra K; Patil, Satish V

    2015-09-01

    Mosquitoes spread lethal diseases like malaria and dengue fever to humans. Considering mosquito vector control as one of the best alternatives to reduce new infections, here we have analyzed the effect of purified pigment prodigiosin extracted from Serratia marcescens (NMCC 75) against larval and pupal stages of Aedes aegypti and Anopheles stephensi mosquitoes. Mosquito larvicidal activities of purified prodigiosin revealed LC50 values of 14 ± 1.2, 15.6 ± 1.48, 18 ± 1.3, 21 ± 0.87 µg/ml against early IInd, IIIrd, IVth instar and pupal stages of Ae. aegypti, respectively. LC50 values for An. stephensi were found to be 19.7 ± 1.12, 24.7 ± 1.47, 26.6 ± 1.67, 32.2 ± 1.79 µg/ml against early IInd, IIIrd, IVth instar and pupae of An. stephensi, respectively. Further investigations toward understanding modes of action revealed variations in the activities of esterases, acetylcholine esterases, phosphatases, proteases and total proteins in the fourth instar larvae of Ae. aegypti indicating intrinsic difference in biochemical features due to prodigiosin treatment. Although there was no inhibition of enzymes like catalase and oxidase but may have profound inhibitory effect on carbonic anhydrase or H(+)-V-ATPase which is indicated by change in the pH of midgut and caeca of mosquito larvae. This reduced pH may be possibly due to the proton pump inhibitory activity of prodigiosin. Pure prodigiosin can prove to be an important molecule for mosquito control at larval and pupal stages of Ae. aegypti and An. stephensi. This is the first report on the mosquito pupaecidal activity of prodigiosin and its possible mechanism of action. PMID:26267052

  1. HMGB1 Inhibition During Zymosan-Induced Inflammation: The Potential Therapeutic Action of Riboflavin.

    PubMed

    Mazur-Bialy, Agnieszka Irena; Pocheć, Ewa

    2016-04-01

    Sepsis, also known as systemic inflammatory response syndrome, is a life-threatening condition caused by a pathogenic agent and leading to multiple organ dysfunction syndrome. One of the factors responsible for the excessive intensification of the inflammatory response in the course of inflammation is high-mobility group protein B1 (HMGB1). HMG-1 is a nuclear protein which, after being released to the intercellular space, has a highly pro-inflammatory effect and acts as a late mediator of lethal damage. The purpose of this study was to examine whether the anti-inflammatory action of riboflavin is accompanied by inhibition of HMGB1 release during peritoneal inflammation and zymosan stimulation of macrophages. Peritonitis was induced in male BALB/c and C57BL/6J mice via intraperitoneal injection of zymosan (40 mg/kg). RAW 264.7 macrophages were activated with zymosan (250 µg/ml). Riboflavin (mice, 50 mg/kg; RAW 264.7, 25 µg/ml) was administered 30 min before zymosan, simultaneously with, or 2, 4, 6 h after zymosan. Additionally, mRNA expression of HMGB1 and its intracellular and serum levels were evaluated. The research showed that riboflavin significantly reduces both the expression and the release of HMGB1; however, the effect of riboflavin was time-dependent. The greatest efficacy was found when riboflavin was given 30 min prior to zymosan, and also 2 and 4 h (C57BL/6J; RAW 264.7) or 4 and 6 h (BALB/c) after zymosan. Research showed that riboflavin influences the level of HMGB1 released in the course of inflammation; however, further study is necessary to determine its mechanisms of action. PMID:26445809

  2. Generation of slow wave type action potentials in the mouse small intestine involves a non-L-type calcium channel.

    PubMed

    Malysz, J; Richardson, D; Farraway, L; Christen, M O; Huizinga, J D

    1995-10-01

    Intrinsic electrical activities in various isolated segments of the mouse small intestine were recorded (i) to characterize action potential generation and (ii) to obtain a profile on the ion channels involved in initiating the slow wave type action potentials (slow waves). Gradients in slow wave frequency, resting membrane potential, and occurrence of spiking activity were found, with the proximal intestine exhibiting the highest frequency, the most hyperpolarized cell membrane, and the greatest occurrence of spikes. The slow waves were only partially sensitive to L-type calcium channel blockers. Nifedipine, verapamil, and pinaverium bromide abolished spikes that occurred on the plateau phase of the slow waves in all tissues. The activity that remained in the presence of L-type calcium channel blockers, the upstroke potential, retained a similar amplitude to the original slow wave and was of identical frequency. The upstroke potential was not sensitive to a reduction in extracellular chloride or to the sodium channel blockers tetrodotoxin and mexiletine. Abolishment of the Na+ gradient by removal of 120 mM extracellular Na+ reduced the upstroke potential frequency by 13 - 18% and its amplitude by 50 - 70% in the ileum. The amplitude was similarly reduced by Ni2+ (up to 5 mM), and by flufenamic acid (100 mu M), a nonspecific cation and chloride channel blocker. Gadolinium, a nonspecific blocker of cation and stretch-activated channels, had no effect. Throughout these pharmacological manipulations, a robust oscillation remained at 5 - 10 mV. This oscillation likely reflects pacemaker activity. It was rapidly abolished by removal of extracellular calcium but not affected by L-type calcium channel blockers. In summary, the mouse small intestine has been established as a model for research into slow wave generation and electrical pacemaker activity. The upstroke part of the slow wave has two components, the pacemaker component involves a non-L-type calcium channel

  3. Impacts of Hydrological Alterations to the Tonle Sap Ecosystem of the Mekong River Basin

    NASA Astrophysics Data System (ADS)

    Arias, M. E.; Cochrane, T. A.

    2013-12-01

    The Tonle Sap is the largest and most important natural wetland in Southeast Asia. It covers an area of more than 15,000 km2 with a unique mosaic of natural and agricultural floodplain habitats that coexist with the largest fishery in the Mekong Basin. Accelerating hydropower development and climate change, however, are altering the Mekong's hydrology, which could negatively affect downstream ecosystems. The Tonle Sap is facing a two-fold problem. First, the link between its hydrology and ecosystem properties is not well understood. Second, potential ecological changes caused by future hydrological disruptions related to hydropower and climate change are unknown. Thus, the main objective of this study was to quantify how alterations to the Mekong hydrology could affect the Tonle Sap ecosystem. An assessment of landscape patterns revealed a distinct relationship between inundation and vegetation. Habitats in the Tonle Sap were divided into five groups based on annual flood duration, as well as physiognomic factors and human activity: (1) open water, (2) gallery forest, (3) seasonally flooded habitats, (4) transitional habitats, and (5) rainfed habitats. Large shifts could occur as a result of hydropower development scenarios by the 2030s; areas optimal for gallery forest could decrease by 82% from baseline conditions, whereas areas of rainfed habitats could increase by 10-13 % (813-1061 km2). An assessment of habitat patterns demonstrated that despite the complexity and intense human use of this ecosystem, the Mekong flood-pulse hydrology is the underlying driver of habitat characteristics by (1) determining inundation depth and duration, (2) creating the main soils gradient, (3) limiting the area cleared for agriculture, (4) influencing vegetation structure and water quality, and (5) shaping the composition of plant species. A numerical model was used to estimate aquatic net primary production (NPP) as a function of hydrology, sediments, and habitat characteristics

  4. Bursting regimes in a reaction-diffusion system with action potential-dependent equilibrium.

    PubMed

    Meier, Stephen R; Lancaster, Jarrett L; Starobin, Joseph M

    2015-01-01

    The equilibrium Nernst potential plays a critical role in neural cell dynamics. A common approximation used in studying electrical dynamics of excitable cells is that the ionic concentrations inside and outside the cell membranes act as charge reservoirs and remain effectively constant during excitation events. Research into brain electrical activity suggests that relaxing this assumption may provide a better understanding of normal and pathophysiological functioning of the brain. In this paper we explore time-dependent ionic concentrations by allowing the ion-specific Nernst potentials to vary with developing transmembrane potential. As a specific implementation, we incorporate the potential-dependent Nernst shift into a one-dimensional Morris-Lecar reaction-diffusion model. Our main findings result from a region in parameter space where self-sustaining oscillations occur without external forcing. Studying the system close to the bifurcation boundary, we explore the vulnerability of the system with respect to external stimulations which disrupt these oscillations and send the system to a stable equilibrium. We also present results for an extended, one-dimensional cable of excitable tissue tuned to this parameter regime and stimulated, giving rise to complex spatiotemporal pattern formation. Potential applications to the emergence of neuronal bursting in similar two-variable systems and to pathophysiological seizure-like activity are discussed. PMID:25823018

  5. Bursting Regimes in a Reaction-Diffusion System with Action Potential-Dependent Equilibrium

    PubMed Central

    Meier, Stephen R.; Lancaster, Jarrett L.; Starobin, Joseph M.

    2015-01-01

    The equilibrium Nernst potential plays a critical role in neural cell dynamics. A common approximation used in studying electrical dynamics of excitable cells is that the ionic concentrations inside and outside the cell membranes act as charge reservoirs and remain effectively constant during excitation events. Research into brain electrical activity suggests that relaxing this assumption may provide a better understanding of normal and pathophysiological functioning of the brain. In this paper we explore time-dependent ionic concentrations by allowing the ion-specific Nernst potentials to vary with developing transmembrane potential. As a specific implementation, we incorporate the potential-dependent Nernst shift into a one-dimensional Morris-Lecar reaction-diffusion model. Our main findings result from a region in parameter space where self-sustaining oscillations occur without external forcing. Studying the system close to the bifurcation boundary, we explore the vulnerability of the system with respect to external stimulations which disrupt these oscillations and send the system to a stable equilibrium. We also present results for an extended, one-dimensional cable of excitable tissue tuned to this parameter regime and stimulated, giving rise to complex spatiotemporal pattern formation. Potential applications to the emergence of neuronal bursting in similar two-variable systems and to pathophysiological seizure-like activity are discussed. PMID:25823018

  6. The spatio-temporal characteristics of action potential initiation in layer 5 pyramidal neurons: a voltage imaging study.

    PubMed

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

    2011-09-01

    The spatial pattern of Na(+) channel clustering in the axon initial segment (AIS) plays a critical role in tuning neuronal computations, and changes in Na(+) channel distribution have been shown to mediate novel forms of neuronal plasticity in the axon. However, immunocytochemical data on channel distribution may not directly predict spatio-temporal characteristics of action potential initiation, and prior electrophysiological measures are either indirect (extracellular) or lack sufficient spatial resolution (intracellular) to directly characterize the spike trigger zone (TZ). We took advantage of a critical methodological improvement in the high sensitivity membrane potential imaging (V(m) imaging) technique to directly determine the location and length of the spike TZ as defined in functional terms. The results show that in mature axons of mouse cortical layer 5 pyramidal cells, action potentials initiate in a region ∼20 μm in length centred between 20 and 40 μm from the soma. From this region, the AP depolarizing wave invades initial nodes of Ranvier within a fraction of a millisecond and propagates in a saltatory fashion into axonal collaterals without failure at all physiologically relevant frequencies. We further demonstrate that, in contrast to the saltatory conduction in mature axons, AP propagation is non-saltatory (monotonic) in immature axons prior to myelination. PMID:21669974

  7. Potentiation of bradykinin action on smooth muscle by a scorpion venom extract.

    PubMed

    Araujo, R L; Gomez, M V

    1976-08-01

    Gel filtration of the water extract of the venom of the scorpion T. serrulatus showed four peaks; the first peak (P1) is devoid of toxic activity but increases the bradykinin-induced contraction of isolated rat uterus and guinea-pig ileum. The stepwise fractionation of the pooled P1 peak was performed in a DEAE-cellulose column and the bradykinin potentiating activity was found in the second protein peak. Finger-printing of this material showed that the bradykinin potentiating material migrates to the anode, giving two spots when submitted to chromatography, the activity being found in the spot that presents the greatest Rf. The potentiator is destroyed by heating at 97 degrees C, is not dialysable and is destroyed by incubation with pronase. Some of these properties differentiate it from the BPF's from snake venoms. PMID:976731

  8. 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. PMID:26414356

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

    PubMed Central

    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. PMID:26414356

  10. Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro

    PubMed Central

    Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C.

    2015-01-01

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

  11. 4-bromopropofol decreases action potential generation in spinal neurons by inducing a glycine receptor‐mediated tonic conductance

    PubMed Central

    Eckle, V S; Grasshoff, C; Mirakaj, V; O'Neill, P M; Berry, N G; Leuwer, M; Antkowiak, B

    2014-01-01

    Background and Purpose Impaired function of spinal strychnine-sensitive glycine receptors gives rise to chronic pain states and movement disorders. Therefore, increased activity of glycine receptors should help to treat such disorders. Although compounds targeting glycine receptors with a high selectivity are lacking, halogenated analogues of propofol have recently been considered as potential candidates. Therefore we asked whether 4-bromopropofol attenuated the excitability of spinal neurons by promoting glycine receptor-dependent inhibition. Experimental Approach The actions of sub-anaesthetic concentrations of propofol and 4-bromopropofol were investigated in spinal tissue cultures prepared from mice. Drug-induced alterations in action potential firing were monitored by extracellular multi-unit recordings. The effects on GABAA and glycine receptor-mediated inhibition were quantified by whole-cell voltage-clamp recordings. Key Results Low concentrations of 4-bromopropofol (50 nM) reduced action potential activity of ventral horn neurons by about 30%, compared with sham-treated slices. This effect was completely abolished by strychnine (1 μM). In voltage-clamped neurons, 4-bromopropofol activated glycine receptors, generating a tonic current of 65 ± 10 pA, while GABAA- and glycine receptor-mediated synaptic transmission remained unaffected. Conclusions and Implications The highest glycine levels in the CNS are found in the ventral horn of the spinal cord, a region mediating pain-induced motor reflexes and participating in the control of muscle tone. 4-Bromopropofol may serve as a starting point for the development of non-sedative, non-addictive, muscle relaxants and analgesics to be used to treat low back pain. PMID:25131750

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

    PubMed Central

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

    2015-01-01

    Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line. Expression of hBKα had minimal effects on expression levels of other ion channels with the exception of a small but significant reduction in Kv11.1. Patch-clamped hBKα expressing HL-1 cells exhibited an outward voltage- and Ca2+-sensitive K+ current, which was inhibited by the BK channel blocker iberiotoxin (100 nM). This BK current phenotype was not detected in untransfected HL-1 cells or in HL-1 null cells sham-transfected with an empty vector. Importantly, APD in hBKα-expressing HL-1 cells averaged 14.3 ± 2.8 ms (n = 10), which represented a 53% reduction in APD compared to HL-1 null cells lacking BKα expression. APD in the latter cells averaged 31.0 ± 5.1 ms (n = 13). The shortened APD in hBKα-expressing cells was restored to normal duration by 100 nM iberiotoxin, suggesting that a repolarizing K+ current attributed to BK channels accounted for action potential shortening. These findings provide initial proof-of-concept that the introduction of hBKα channels into a cardiac cell line can shorten APD, and raise the possibility that gene-based interventions to increase hBKα channels in cardiac cells may hold promise as a therapeutic strategy for long QT syndrome. PMID:26091273

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

    PubMed

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

    2016-02-01

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

  14. Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease.

    PubMed

    Kolko, Miriam; Vosborg, Fia; Henriksen, Ulrik L; Hasan-Olive, Md Mahdi; Diget, Elisabeth Holm; Vohra, Rupali; Gurubaran, Iswariya Raja Sridevi; Gjedde, Albert; Mariga, Shelton Tendai; Skytt, Dorte M; Utheim, Tor Paaske; Storm-Mathisen, Jon; Bergersen, Linda H

    2016-06-01

    In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions, such as excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina, where the retinal ganglion cells die, notably glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies reveal high GPR81 mRNA in retina and indicate GPR81 localization in Müller cells and retinal ganglion cells. Moreover, monocarboxylate transporters are expressed in retinal cells. We envision that lactate receptors and transporters could be useful future targets of novel therapeutic strategies to protect neurons and prevent or counteract glaucoma as well as other retinal diseases. PMID:26677077

  15. Immunomodulatory effects of fluoxetine: A new potential pharmacological action for a classic antidepressant drug?

    PubMed

    Di Rosso, María Emilia; Palumbo, María Laura; Genaro, Ana María

    2016-07-01

    Selective serotonin reuptake inhibitors are frequently used antidepressants. In particular, fluoxetine is usually chosen for the treatment of the symptoms of depression, obsessive-compulsive, panic attack and bulimia nervosa. Antidepressant therapy has been associated with immune dysfunction. However, there is contradictory evidence about the effect of fluoxetine on the immune system. Experimental findings indicate that lymphocytes express the serotonin transporter. Moreover it has been shown that fluoxetine is able to modulate the immune function through a serotonin-dependent pathway and through a novel independent mechanism. In addition, several studies have shown that fluoxetine can alter tumor cell viability. Thus, it was recently demonstrated in vivo that chronic fluoxetine treatment inhibits tumor growth by increasing antitumor T-cell activity. Here we briefly review some of the literature referring to how fluoxetine is able to modify, for better or worse, the functionality of the immune system. These results of our analysis point to the relevance of the novel pharmacological action of this drug as an immunomodulator helping to treat several pathologies in which immune deficiency and/or deregulation is present. PMID:26644208

  16. [Environmental investigation of ground water contamination at Wright-Patterson Air Force Base, Ohio]. Volume 3, Sampling and analysis plan (SAP): Phase 1, Task 4, Field Investigation: Draft

    SciTech Connect

    Not Available

    1991-10-01

    In April 1990, Wright-Patterson Air Force Base (WPAFB), initiated an investigation to evaluate a potential Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) removal action to prevent, to the extent practicable, the offsite migration of contaminated ground water from WPAFB. WPAFB retained the services of the Environmental Management Operations (EMO) and its principle subcontractor, International Technology Corporation (IT) to complete Phase 1 of the environmental investigation of ground-water contamination at WPAFB. Phase 1 of the investigation involves the short-term evaluation and potential design for a program to remove ground-water contamination that appears to be migrating across the western boundary of Area C, and across the northern boundary of Area B along Springfield Pike. Primarily, Task 4 of Phase 1 focuses on collection of information at the Area C and Springfield Pike boundaries of WPAFB. This Sampling and Analysis Plan (SAP) has been prepared to assist in completion of the Task 4 field investigation and is comprised of the Quality Assurance Project Plan (QAPP) and the Field Sampling Plan (FSP).

  17. Anti-atherogenic potential of jujube, saffron and barberry: anti-diabetic and antioxidant actions.

    PubMed

    Hemmati, Mina; Zohoori, Elham; Mehrpour, Omid; Karamian, Mehdi; Asghari, Somaye; Zarban, Asghar; Nasouti, Roya

    2015-01-01

    Atherogenic dyslipidemia, characterized by an increased level of lipoprotein (a) and a decreased level of adiponectin, is a major risk factor for cardiovascular diseases in diabetic patients. To reduce cardiovascular risk in diabetic patients, use of agents with antidiabetic and anti-atherogenic potential is required. Using an animal model of diabetes, we investigated the antiatherogenic potential of extracts of three medicinal plants: jujube, barberry, and saffron. For this, serum level of fasting blood glucose, lipid profile, malondialdehyde, total antioxidant capacity, adiponectin and lipoprotein (a) in diabetic control and extract treated groups were measured. Statistical analysis of measurements showed that serum levels of fasting blood glucose, triglyceride, and VLDL decreased significantly (P < 0.05) in all treated groups. Treatment with all extracts reduced lipid peroxidation and increased antioxidant capacity of the experimental diabetic groups. Serum adiponectin levels increased in all treated groups, whereas lipoprotein (a) levels decreased, most markedly when treated with jujube extract. Jujube, saffron, and barberry extracts are beneficial in ameliorating oxidative stress and atherogenic risk of diabetic rats. This highlights the benefits of further investigating the cardio-protective potential of medicinal plant extracts and evaluating their usefulness as cardio protective agents in clinical practice. PMID:26600752

  18. Direct inhibition of arcuate proopiomelanocortin neurons: a potential mechanism for the orexigenic actions of dynorphin

    PubMed Central

    Zhang, Xiaobing; van den Pol, Anthony N

    2013-01-01

    Dynorphin, an endogenous ligand of kappa (κ) opioid receptors, has multiple roles in the brain, and plays a positive role in energy balance and food intake. However, the mechanism for this is unclear. With immunocytochemistry, we find that axonal dynorphin immunoreactivity in the arcuate nucleus is strong, and that a large number of dynorphin-immunoreactive boutons terminate on or near anorexigenic proopiomelanocortin (POMC) cells. Here we provide evidence from whole-cell patch-clamp recording that dynorphin-A (Dyn-A) directly and dose-dependently inhibits arcuate nucleus POMC neurons. Dyn-A inhibition was eliminated by the κ opioid receptor antagonist nor-BNI, but not by the μ receptor antagonist CTAP. The inhibitory effect was mimicked by the κ2 receptor agonist GR89696, but not by the κ1 receptor agonist U69593. No presynaptic effect of κ2 agonists was found. These results suggest that Dyn-A inhibits POMC neurons through activation of the κ2 opioid receptor. In whole-cell voltage clamp, Dyn-A opened G-protein-coupled inwardly rectifying potassium (GIRK)-like channels on POMC neurons. Dynorphin attenuated glutamate and GABA neurotransmission to POMC neurons. In contrast to the strong inhibition of POMC neurons by Dyn-A, we found a weaker direct inhibitory effect of Dyn-A on arcuate nucleus neuropeptide Y (NPY) neurons mediated by both κ1 and κ2 receptors. Taken together, these results indicate a direct inhibitory effect of Dyn-A on POMC neurons through activation of the κ2 opioid receptor and GIRK channels. A number of orexigenic hypothalamic neurons release dynorphin along with other neuropeptides. The inhibition of anorexigenic POMC neurons may be one mechanism underlying the orexigenic actions of dynorphin. PMID:23318874

  19. Ground-water sapping processes, Western Desert, Egypt

    SciTech Connect

    Luo, W.; Arvidson, R.E.; Sultan, M.; Becker, R.; Crombie, M.K.; Sturchio, N.; Alfy, Z.E.

    1997-01-01

    Depressions of the Western Desert of Egypt (specifically, Kharga, Farafra, and Kurkur regions) are mainly occupied by shales that are impermeable, but easily erodible by rainfall and runoff, whereas the surrounding plateaus are composed of limestones that are permeable and more resistant to fluvial erosion under semiarid to arid conditions. A computer simulation model was developed to quantify the ground-water sapping processes, using a cellular automata algorithm with coupled surface runoff and ground-water flow for a permeable, resistant layer over an impermeable, friable unit. Erosion, deposition, slumping, and generation of spring-derived tufas were parametrically modeled. Simulations using geologically reasonable parameters demonstrate that relatively rapid erosion of the shales by surface runoff, ground-water sapping, and slumping of the limestones, and detailed control by hydraulic conductivity inhomogeneities associated with structures explain the depressions, escarpments, and associated landforms and deposits. Using episodic wet pulses, keyed by {delta}{sup 18}O deep-sea core record, the model produced tufa ages that are statistically consistent with the observed U/Th tufa ages. This result supports the hypothesis that northeastern African wet periods occurred during interglacial maxima. This {delta}{sup 18}O-forced model also replicates the decrease in fluvial and sapping activity over the past million years. 65 refs., 21 figs., 2 tabs.

  20. In vitro antimalarial activity and chloroquine potentiating action of two bisbenzylisoquinoline enantiomer alkaloids isolated from Strychnopsis thouarsii and Spirospermum penduliflorum.

    PubMed

    Ratsimamanga-Urverg, S; Rasoanaivo, P; Ramiaramanana, L; Milijaona, R; Rafatro, H; Verdier, F; Rakoto-Ratsimamanga, A; Le Bras, J

    1992-12-01

    The bisbenzylisoquinolines 7-O-demethyltetrandrine and limacine, respectively, isolated from Strychnopsis thouarsii Baill. and Spirospermum penduliflorum Thou. were evaluated for their intrinsic antimalarial activity in vitro and chloroquine potentiating action against the chloroquine-resistant Plasmodium falciparum FCM 29 originating from Cameroon. They both showed significant antiplasmodial potency in vitro with very similar IC50 values of respectively, 740 nM and 789 nM (IC50 = 214 nM for chloroquine used as standard drug), which demonstrated that the stereochemistry of the C-1 and C-1' configuration likely plays a role in the chloroquine potentiating effect of these drugs. If confirmed in vivo, these results may account for the traditional use of the two plants as antimalarials and adjuvant to chloroquine in Madagascan folklore remedies. PMID:1484894

  1. A comprehensive strategy for identifying long-distance mobile peptides in xylem sap.

    PubMed

    Okamoto, Satoru; Suzuki, Takamasa; Kawaguchi, Masayoshi; Higashiyama, Tetsuya; Matsubayashi, Yoshikatsu

    2015-11-01

    There is a growing awareness that secreted pemediate organ-to-organ communication in higher plants. Xylem sap peptidomics is an effective but challenging approach for identifying long-distance mobile peptides. In this study we developed a simple, gel-free purification system that combines o-chlorophenol extraction with HPLC separation. Using this system, we successfully identified seven oligopeptides from soybean xylem sap exudate that had one or more post-transcriptional modifications: glycosylation, sulfation and/or hydroxylation. RNA sequencing and quantitative PCR analyses showed that the peptide-encoding genes are expressed in multiple tissues. We further analyzed the long-distance translocation of four of the seven peptides using gene-encoding peptides with single amino acid substitutions, and identified these four peptides as potential root-to-shoot mobile oligopeptides. Promoter-GUS analysis showed that all four peptide-encoding genes were expressed in the inner tissues of the root endodermis. Moreover, we found that some of these peptide-encoding genes responded to biotic and/or abiotic factors. These results indicate that our purification system provides a comprehensive approach for effectively identifying endogenous small peptides and reinforce the concept that higher plants employ various peptides in root-to-shoot signaling. PMID:26333921

  2. Contribution of ion currents to beat-to-beat variability of action potential duration in canine ventricular myocytes.

    PubMed

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

    2015-07-01

    Although beat-to-beat variability (short-term variability, SV) of action potential duration (APD) is considered as a predictor of imminent cardiac arrhythmias, the underlying mechanisms are still not clear. In the present study, therefore, we aimed to determine the role of the major cardiac ion currents, APD, stimulation frequency, and changes in the intracellular Ca(2+) concentration ([Ca(2+)]i) on the magnitude of SV. Action potentials were recorded from isolated canine ventricular cardiomyocytes using conventional microelectrode techniques. SV was an exponential function of APD, when APD was modified by current injections. Drug effects were characterized as relative SV changes by comparing the drug-induced changes in SV to those in APD according to the exponential function obtained with current pulses. Relative SV was increased by dofetilide, HMR 1556, nisoldipine, and veratridine, while it was reduced by BAY K8644, tetrodotoxin, lidocaine, and isoproterenol. Relative SV was also increased by increasing the stimulation frequency and [Ca(2+)]i. In summary, relative SV is decreased by ion currents involved in the negative feedback regulation of APD (I Ca, I Ks, and I Kr), while it is increased by I Na and I to. We conclude that drug-induced effects on SV should be evaluated in relation with the concomitant changes in APD. Since relative SV was decreased by ion currents playing critical role in the negative feedback regulation of APD, blockade of these currents, or the beta-adrenergic pathway, may carry also some additional proarrhythmic risk in addition to their well-known antiarrhythmic action. PMID:25081243

  3. Changes in intracellular calcium concentration influence beat-to-beat variability of action potential duration in canine ventricular myocytes.

    PubMed

    Kistamas, K; Szentandrassy, N; Hegyi, B; Vaczi, K; Ruzsnavszky, F; Horvath, B; Banyasz, T; Nanasi, P P; Magyar, J

    2015-02-01

    The aim of the present work was to study the influence of changes in intracellular calcium concentration ([Ca(2+)]i) on beat-to-beat variability (short term variability, SV) of action potential duration (APD) in isolated canine ventricular cardiomyocytes. Series of action potentials were recorded from enzymatically isolated canine ventricular cells using conventional microelectrode technique. Drug effects on SV were evaluated as relative SV changes determined by plotting the drug-induced changes in SV against corresponding changes in APD and comparing these data to the exponential SV-APD function obtained with inward and outward current injections. Exposure of myocytes to the Ca(2+) chelator BAPTA-AM (5 μM) decreased, while Ca(2+) ionophore A23187 (1 μM) increased the magnitude of relative SV. Both effects were primarily due to the concomitant changes in APD. Relative SV was reduced by BAPTA-AM under various experimental conditions including pretreatment with veratridine, BAY K8644, dofetilide or E-4031. Contribution of transient changes of [Ca(2+)]i due to Ca(2+) released from the sarcoplasmic reticulum (SR) was studied using 10 μM ryanodine and 1 μM cyclopiazonic acid: relative SV was reduced by both agents. Inhibition of the Na(+)-Ca(2+) exchanger by 1 μM SEA0400 increased relative SV. It is concluded that elevation of [Ca(2+)]i increases relative SV significantly. More importantly, Ca(2+) released from the SR is an important component of this effect. PMID:25716967

  4. Combined electric field and gap junctions on propagation of action potentials in cardiac muscle and smooth muscle in PSpice simulation.

    PubMed

    Sperelakis, Nicholas

    2003-10-01

    Propagation of action potentials in cardiac muscle and smooth muscle were simulated using the PSpice program. Excitation was transmitted from cell to cell along a strand of 6 cells (cardiac muscle) or 10 cells (smooth muscle) either not connected (control) or connected by low-resistance tunnels (gap-junction connexons). A significant negative cleft potential (V(jv) ) develops in the narrow junctional cleft when the pre-JM fires. V(jc) depolarizes the postjunctional membrane (post-JM) to threshold by a patch-clamp action. With few connecting tunnels, cell-to-cell transmission by the EF mechanism was facilitated. With many tunnels, propagation was dominated by the low-resistance mechanism, and propagation velocity (theta) became very fast and nonphysiological. In conclusion, when the 2 mechanisms for cell-to-cell transfer of excitation were combined, the two mechanisms facilitated each other in a synergistic manner. When there were many connecting tunnels, the tunnel mechanism was dominant. PMID:14661164

  5. The energy cost of action potential propagation in dopamine neurons: clues to susceptibility in Parkinson's disease

    PubMed Central

    Pissadaki, Eleftheria K.; Bolam, J. Paul

    2013-01-01

    Dopamine neurons of the substantia nigra pars compacta (SNc) are uniquely sensitive to degeneration in Parkinson's disease (PD) and its models. Although a variety of molecular characteristics have been proposed to underlie this sensitivity, one possible contributory factor is their massive, unmyelinated axonal arbor that is orders of magnitude larger than other neuronal types. We suggest that this puts them under such a high energy demand that any stressor that perturbs energy production leads to energy demand exceeding supply and subsequent cell death. One prediction of this hypothesis is that those dopamine neurons that are selectively vulnerable in PD will have a higher energy cost than those that are less vulnerable. We show here, through the use of a biology-based computational model of the axons of individual dopamine neurons, that the energy cost of axon potential propagation and recovery of the membrane potential increases with the size and complexity of the axonal arbor according to a power law. Thus SNc dopamine neurons, particularly in humans, whose axons we estimate to give rise to more than 1 million synapses and have a total length exceeding 4 m, are at a distinct disadvantage with respect to energy balance which may be a factor in their selective vulnerability in PD. PMID:23515615

  6. A wavelet-like filter based on neuron action potentials for analysis of human scalp electroencephalographs.

    PubMed

    Glassman, Elena L

    2005-11-01

    This paper describes the development and testing of a wavelet-like filter, named the SNAP, created from a neural activity simulation and used, in place of a wavelet, in a wavelet transform for improving EEG wavelet analysis, intended for brain-computer interfaces. The hypothesis is that an optimal wavelet can be approximated by deriving it from underlying components of the EEG. The SNAP was compared to standard wavelets by measuring Support Vector Machine-based EEG classification accuracy when using different wavelets/filters for EEG analysis. When classifying P300 evoked potentials, the error, as a function of the wavelet/filter used, ranged from 6.92% to 11.99%, almost twofold. Classification using the SNAP was more accurate than that with any of the six standard wavelets tested. Similarly, when differentiating between preparation for left- or right-hand movements, classification using the SNAP was more accurate (10.03% error) than for four out of five of the standard wavelets (9.54% to 12.00% error) and internationally competitive (7% error) on the 2001 NIPS competition test set. Phenomena shown only in maps of discriminatory EEG activity may explain why the SNAP appears to have promise for improving EEG wavelet analysis. It represents the initial exploration of a potential family of EEG-specific wavelets. PMID:16285389

  7. Adjuvant potential of resiquimod with inactivated Newcastle disease vaccine and its mechanism of action in chicken.

    PubMed

    Sachan, Swati; Ramakrishnan, Saravanan; Annamalai, Arunsaravanakumar; Sharma, Bal Krishan; Malik, Hina; Saravanan, B C; Jain, Lata; Saxena, Meeta; Kumar, Ajay; Krishnaswamy, Narayanan

    2015-08-26

    Resiquimod (R-848), an imidazoquinoline compound, is a potent synthetic Toll-like receptor (TLR) 7 agonist. Although the solitary adjuvant potential of R-848 is well established in mammals, such reports are not available in avian species hitherto. Hence, the adjuvant potential of R-848 was tested in SPF chicken in this study. Two week old chicks were divided into four groups (10 birds/group) viz., control (A), inactivated Newcastle disease virus (NDV) vaccine prepared from velogenic strain (B), commercial oil adjuvanted inactivated NDV vaccine prepared from lentogenic strain (C) and inactivated NDV vaccine prepared from velogenic strain with R-848 (D). Booster was given two weeks post primary vaccination. Humoral immune response was assessed by haemagglutination inhibition (HI) test and ELISA while the cellular immune response was quantified by lymphocyte transformation test (LTT) and flow cytometry post-vaccination. Entire experiment was repeated twice to check the reproducibility. Highest HI titre was observed in group D at post booster weeks 1 and 2 that corresponds to mean log2 HI titre of 6.4 ± 0.16 and 6.8 ± 0.13, respectively. The response was significantly higher than that of group B or C (P<0.01). LTT stimulation index (P ≤ 0.01) as well as CD4(+) and CD8(+) cells in flow cytometry (P<0.05) were significantly high and maximum in group D. Group D conferred complete protection against virulent NDV challenge, while it was only 80% in group B and C. To understand the effects of R-848, the kinetics of immune response genes in spleen were analyzed using quantitative real-time PCR after R-848 administration (50 μg/bird, i.m. route). Resiquimod significantly up-regulated the expression of IFN-α, IFN-β, IFN-γ, IL-1β, IL-4, iNOS and MHC-II genes (P<0.01). In conclusion, the study demonstrated the adjuvant potential of R-848 when co-administered with inactivated NDV vaccine in SPF chicken which is likely due to the up-regulation of immune response genes

  8. Dipeptidyl Peptidase IV as a Potential Target for Selective Prodrug Activation and Chemotherapeutic Action in Cancers

    PubMed Central

    2015-01-01

    The efficacy of chemotherapeutic drugs is often offset by severe side effects attributable to poor selectivity and toxicity to normal cells. Recently, the enzyme dipeptidyl peptidase IV (DPPIV) was considered as a potential target for the delivery of chemotherapeutic drugs. The purpose of this study was to investigate the feasibility of targeting chemotherapeutic drugs to DPPIV as a strategy to enhance their specificity. The expression profile of DPPIV was obtained for seven cancer cell lines using DNA microarray data from the DTP database, and was validated by RT-PCR. A prodrug was then synthesized by linking the cytotoxic drug melphalan to a proline-glycine dipeptide moiety, followed by hydrolysis studies in the seven cell lines with a standard substrate, as well as the glycyl-prolyl-melphalan (GP-Mel). Lastly, cell proliferation studies were carried out to demonstrate enzyme-dependent activation of the candidate prodrug. The relative RT-PCR expression levels of DPPIV in the cancer cell lines exhibited linear correlation with U95Av2 Affymetrix data (r2 = 0.94), and with specific activity of a standard substrate, glycine-proline-p-nitroanilide (r2 = 0.96). The significantly higher antiproliferative activity of GP-Mel in Caco-2 cells (GI50 = 261 μM) compared to that in SK-MEL-5 cells (GI50 = 807 μM) was consistent with the 9-fold higher specific activity of the prodrug in Caco-2 cells (5.14 pmol/min/μg protein) compared to SK-MEL-5 cells (0.68 pmol/min/μg protein) and with DPPIV expression levels in these cells. Our results demonstrate the great potential to exploit DPPIV as a prodrug activating enzyme for efficient chemotherapeutic drug targeting. PMID:25365774

  9. K+ accumulation and K+ conductance inactivation during action potential trains in giant axons of the squid Sepioteuthis.

    PubMed Central

    Inoue, I; Tsutsui, I; Brown, E R

    1997-01-01

    1. During action potential trains in giant axons from the squid Sepioteuthis, decline of the peak level of the undershoot potential was observed. The time course of the decline of the undershoot could be fitted with a three-exponential function with time constants of approximately 25, approximately 400 and approximately 7,000 ms, respectively. 2. When the osmolarity of the external solution was doubled by adding glucose (1.2 M), the fast component of undershoot decline, but not the medium and slow components, was significantly reduced. 3. Under voltage clamp in high osmolarity solutions where K+ accumulation was completely removed, repeated depolarizing pulses at 40 Hz (designed to mimic a train of action potentials) elicited K+ currents whose peak value declined. The decline is consistent with inactivation of the K+ conductance (gK). The decline of gK was fitted by a two-exponential function with time constants of approximately 400 and approximately 7,000 ms, respectively. 4. Interventions designed to modify Schwann cell physiology, such as high frequency stimulation (100 Hz, 2 min), externally applied ouabain (100-500 microM), L-glutamate (100 microM), ACh (100 microM), Co2+ (5mM), Ba2+ (2mM), or removal of external Ca2+ by EGTA, had no significant effects on the fast, medium or slow components of undershoot decline. 5. The results suggest that the fast component of undershoot decline represents K+ accumulation in the space between Schwann cell and axolemma. The medium and slow components are the result of axonal gK inactivation. Schwann cells appear to be involved in K+ clearance only to the extent that they provide an efficient physical pathway for the clearance of K+ by extracellular diffusion. PMID:9147323

  10. Phosphorylated SAP155, the spliceosomal component, is localized to chromatin in postnatal mouse testes

    SciTech Connect

    Eto, Ko; Sonoda, Yoshiyuki; Jin, Yuji; Abe, Shin-ichi

    2010-03-19

    SAP155 is an essential component of the spliceosome and its phosphorylation is required for splicing catalysis, but little is known concerning its expression and regulation during spermatogenesis in postnatal mouse testes. We report that SAP155 is ubiquitously expressed in nuclei of germ and Sertoli cells within the seminiferous tubules of 6- and 35-day postpartum (dpp) testes. Analyses by fractionation of testes revealed that (1) phosphorylated SAP155 was found in the fraction containing nuclear structures at 6 dpp in amounts much larger than that at other ages; (2) non-phosphorylated SAP155 was detected in the fraction containing nucleoplasm; and (3) phosphorylated SAP155 was preferentially associated with chromatin. Our findings suggest that the active spliceosome, containing phosphorylated SAP155, performs pre-mRNA splicing on chromatin concomitant with transcription during testicular development.

  11. Groundwater sapping channels: Summary of effects of experiments with varied stratigraphy

    NASA Technical Reports Server (NTRS)

    Kochel, R. Craig; Simmons, David W.

    1987-01-01

    Experiments in the recirculating flume sapping box have modeled valley formation by groundwater sapping processes in a number of settings. The effects of the following parameters on sapping channel morphology were examined: surface slope; stratigraphic variations in permeability cohesion and dip; and structure of joints and dikes. These kinds of modeling experiments are particularly good for: testing concepts; developing a suite of distinctive morphologies and morphometries indicative of sapping; helping to relate process to morphology; and providing data necessary to assess the relative importance of runoff, sapping, and mass wasting processes on channel development. The observations from the flume systems can be used to help interpret features observed in terrestrial and Martian settings where sapping processes are thought to have played an important role in the development of valley networks.

  12. Reactivity of anti-human C-reactive protein (CRP) and serum amyloid P component (SAP) monoclonal antibodies with limulin and pentraxins of other species.

    PubMed Central

    Ying, S C; Marchalonis, J J; Gewurz, A T; Siegel, J N; Jiang, H; Gewurz, B E; Gewurz, H

    1992-01-01

    Limulus polyphemus C-reactive protein (CRP) (limulin) has approximately 30% amino acid sequence homology and shares at least one idiotypic determinant associated with ligand-binding activity with human CRP (hCRP); limulin also shares amino acid sequence homology and lectin activity with human serum amyloid P component (hSAP). In the present study panels of 14 anti-hCRP monoclonal antibodies (mAb) directed to distinct hCRP epitopes and 11 anti-hSAP mAb directed to distinct epitopes of hSAP were tested for reactivity with limulin and pentraxins of other species including rabbit CRP (raCRP), rat CRP and hamster female protein (FP) by ELISA and Western blot analyses. None of the anti-human pentraxin mAb showed strong cross-reactivity with limulin; only five mAb reacted with limulin at all, and cross-reactivities of these mAb with the other pentraxins, when present, also were weak. Cross-reactivity of limulin with hCRP and hSAP was similar, and in light of comparable amino acid sequence homology, suggests this molecule can be considered the limulus SAP as well as the limulus CRP. Several anti-hCRP mAb cross-reacted strongly with rabbit CRP and rat CRP; a few anti-hSAP cross-reacted strongly with FP; and weak cross-reactions were observed between hCRP and hSAP, but cross-reactivities between the pentraxins generally were limited and weak. A rabbit polyclonal antibody raised to highly conserved limulin peptide 141-156 and strongly reactive with limulin reacted weakly with hCRP and raCRP but failed to react with rat CRP, hSAP or FP. These studies emphasize a limited but distinct antigenic similarity between limulin, hCRP and other pentraxins, and identify mAb reactive with potential regions of shared structure and/or function between pentraxins of different species. Images Figure 1 Figure 2 PMID:1378818

  13. Control of Postharvest Bacterial Soft Rot by Gamma Irradiation and its Potential Modes of Action

    PubMed Central

    Jeong, Rae-Dong; Chu, Eun-Hee; Park, Duck Hwan; Park, Hae-Jun

    2016-01-01

    Gamma irradiation was evaluated for its in vitro and in vivo antibacterial activity against a postharvest bacterial pathogen, Erwinia carotovora subsp. carotovora (Ecc). Gamma irradiation in a bacteria cell suspension resulted in a dramatic reduction of the viable counts as well as an increase in the amounts of DNA and protein released from the cells. Gamma irradiation showed complete inactivation of Ecc, especially at a dose of 0.6 kGy. In addition, scanning electron microscopy of irradiated cells revealed severe damage on the surface of most bacterial cells. Along with the morphological changes of cells by gamma irradiation, it also affected the membrane integrity in a dose-dependent manner. The mechanisms by which the gamma irradiation decreased the bacterial soft rot can be directly associated with the disruption of the cell membrane of the bacterial pathogen, along with DNA fragmentation, results in dose-dependent cell inactivation. These findings suggest that gamma irradiation has potential as an antibacterial approach to reduce the severity of the soft rot of paprika. PMID:27147935

  14. Screening a panel of drugs with diverse mechanisms of action yields potential therapeutic agents against neuroblastoma

    PubMed Central

    Gheeya, Jinesh S.; Chen, Qing-Rong; Benjamin, Christopher D.; Cheuk, Adam T.; Tsang, Patricia; Chung, Joon-Yong; Metaferia, Belhu B.; Badgett, Thomas C.; Johansson, Peter; Wei, Jun S.; Hewitt, Stephen M.

    2009-01-01

    Neuroblastoma (NB) is the most common extracranial solid tumor in children. Despite current aggressive therapy, the survival rate for high risk NB remains less than 40%. To identify novel effective chemo-agents against NB, we screened a panel of 96 drugs against two NB cell lines, SK-N-AS and SH-SY5Y. We found 30 compounds that were active against NB cell lines at ≤ 10 µM concentration. More interestingly, 17 compounds are active at ≤ 1 µM concentration, and they act through a wide spectrum of diverse mechanisms such as mitotic inhibition, topoisomerase inhibition, targeting various biological pathways, and unknown mechanisms. The majority of these active compounds also induced caspase 3/7 by more than 2-fold. Of these 17 active compounds against NB cell lines at sub-micromolar concentration, 11 compounds are not currently used to treat NB. Among them, 9 are FDA approved compounds, and 3 agents are undergoing clinical trials for various malignancies. Furthermore, we identified 4 agents active against these NB cell lines that have not yet been tested in the clinical setting. Finally we demonstrated that Cucurbitacin I inhibits neuroblastoma cell growth through inhibition of STAT3 pathway. These drugs thus represent potential novel therapeutic agents for patients with NB, and further validation studies are needed to translate them to the clinic. PMID:19946221

  15. Anthocyanins in obesity-associated thrombogenesis: a review of the potential mechanism of action.

    PubMed

    Thompson, Kiara; Pederick, Wayne; Santhakumar, Abishek Bommannan

    2016-05-18

    Platelet dysfunction, oxidative stress and dyslipidemia are important contributors to pro-thrombotic progression particularly in obese and hyper-cholesterolemic populations. Becoming an increasingly widespread endemic, obesity causes a dysfunction in the metabolic system by initiating endothelial dysfunction; increasing free radical production; lipid peroxidation; platelet hyperactivity and aggregation; thereby accelerating thrombogenesis. In the event of increased free radical generation under pro-thrombotic conditions, antioxidants act as scavengers in reducing physiological oxidative stress; free radical-mediated thrombosis and hemostatic function. Anthocyanin, a subclass of the polyphenol family flavonoids has been shown to exhibit anti-dyslipidemic and anti-thrombotic properties by virtue of its antioxidant activity. Current anti-platelet/coagulant therapeutics target specific receptor pathways to relieve the extent of dysfunction and plaque acceleration in pro-thrombotic individuals. Though effective, they have been associated with high bleeding risk and increased response variability. The following review focuses on the potential role of natural dietary anthocyanins in targeting simultaneous mechanistic pathways in alleviating platelet activation, dyslipidemia, and oxidative stress-associated thrombus acceleration in obese pro-thrombotic populations. PMID:27043127

  16. Differential effects and glucocorticoid potentiation of bone morphogenetic protein action during rat osteoblast differentiation in vitro.

    PubMed

    Boden, S D; McCuaig, K; Hair, G; Racine, M; Titus, L; Wozney, J M; Nanes, M S

    1996-08-01

    Bone morphogenetic proteins (BMPs) induce cartilage and bone differentiation in vivo and promote osteoblast differentiation from calvarial and marrow stromal cell preparations. Functional differences between BMP-2, -4, and -6 are not well understood. Recent investigations find that these three closely related osteoinductive proteins may exert different effects in primary rat calvarial cell cultures, suggesting the possibility of unique functions in vivo. In this study, we use a fetal rat secondary calvarial cell culture system to examine the differential effects of BMP-2, -4, and -6 on early osteoblast differentiation. These cells do not spontaneously differentiate into osteoblasts, as do cells in primary calvarial cultures, but rather require exposure to a differentiation initiator such as glucocorticoid or BMP. We determined that BMP-6 is a 2- to 2.5-fold more potent inducer of osteoblast differentiation than BMP-2 or -4. BMP-6 induced the formation of more and larger bone nodules as well as increased osteocalcin secretion. The effects of all three of these BMPs were potentiated up to 10-fold by cotreatment or pretreatment with the glucocorticoid triamcinolone (Trm). The Trm effects were synergistic with those of BMP-2 or -4, suggesting that this glucocorticoid may increase the cell responsiveness to these BMPs. Finally, BMP-6 did not require either cotreatment or pretreatment with Trm to achieve greater amounts of osteoblast differentiation than seen with BMP-2 or BMP-4 treatment, suggesting that BMP-6 may act at an earlier stage of cell differentiation. PMID:8754767

  17. Control of Postharvest Bacterial Soft Rot by Gamma Irradiation and its Potential Modes of Action.

    PubMed

    Jeong, Rae-Dong; Chu, Eun-Hee; Park, Duck Hwan; Park, Hae-Jun

    2016-04-01

    Gamma irradiation was evaluated for its in vitro and in vivo antibacterial activity against a postharvest bacterial pathogen, Erwinia carotovora subsp. carotovora (Ecc). Gamma irradiation in a bacteria cell suspension resulted in a dramatic reduction of the viable counts as well as an increase in the amounts of DNA and protein released from the cells. Gamma irradiation showed complete inactivation of Ecc, especially at a dose of 0.6 kGy. In addition, scanning electron microscopy of irradiated cells revealed severe damage on the surface of most bacterial cells. Along with the morphological changes of cells by gamma irradiation, it also affected the membrane integrity in a dose-dependent manner. The mechanisms by which the gamma irradiation decreased the bacterial soft rot can be directly associated with the disruption of the cell membrane of the bacterial pathogen, along with DNA fragmentation, results in dose-dependent cell inactivation. These findings suggest that gamma irradiation has potential as an antibacterial approach to reduce the severity of the soft rot of paprika. PMID:27147935

  18. Next-generation sequencing identifies high frequency of mutations in potentially clinically actionable genes in sebaceous carcinoma.

    PubMed

    Tetzlaff, Michael T; Singh, Rajesh R; Seviour, Elena G; Curry, Jonathan L; Hudgens, Courtney W; Bell, Diana; Wimmer, Daniel A; Ning, Jing; Czerniak, Bogdan A; Zhang, Li; Davies, Michael A; Prieto, Victor G; Broaddus, Russell R; Ram, Prahlad; Luthra, Rajyalakshmi; Esmaeli, Bita

    2016-09-01

    Sebaceous carcinoma (SC) is a rare but aggressive malignancy with frequent recurrence and metastases. Surgery is the mainstay of therapy, but effective systemic therapies are lacking because the molecular alterations driving SC remain poorly understood. To identify these, we performed whole-exome next-generation sequencing of 409 cancer-associated genes on 27 SCs (18 primary/locally recurrent ocular, 5 paired metastatic ocular, and 4 primary extraocular) from 20 patients. In ocular SC, we identified 139 non-synonymous somatic mutations (median/lesion 3; range 0-23). Twenty-five of 139 mutations (18%) occurred in potentially clinically actionable genes in 6 of 16 patients. The most common mutations were mutations in TP53 (n = 9), RB1 (n = 6), PIK3CA (n = 2), PTEN (n = 2), ERBB2 (n = 2), and NF1 (n = 2). TP53 and RB1 mutations were restricted to ocular SC and correlated with aberrant TP53 and RB protein expression. Systematic pathway analyses demonstrated convergence of these mutations to activation of the PI3K signalling cascade, and PI3K pathway activation was confirmed in tumours with PTEN and/or PIK3CA mutations. Considerable inter-tumoural heterogeneity was observed between paired primary and metastatic ocular SCs. In primary extraocular SC, we identified 77 non-synonymous somatic mutations (median/lesion 22.5; range 3-29). This overall higher mutational load was attributed to a microsatellite instability phenotype in three of four patients and somatically acquired mutations in mismatch repair genes in two of four patients. Eighteen of 77 mutations (23%) were in potentially clinically actionable genes in three of four patients, including BTK, FGFR2, PDGFRB, HRAS, and NF1 mutations. Identification of potentially clinically actionable mutations in 9 of 20 SC patients (45%) underscores the importance of next-generation sequencing to expand the spectrum of genotype-matched targeted therapies. Frequent activation of PI3K signalling pathways provides a strong

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

    PubMed

    Sellebjerg, Finn; Cadavid, Diego; Steiner, Deborah; Villar, Luisa Maria; Reynolds, Richard; Mikol, Daniel

    2016-01-01

    Multiple sclerosis (MS) is a common and chronic central nervous system (CNS) demyelinating disease and a leading cause of permanent disability. Patients most often present with a relapsing-remitting disease course, typically progressing over time to a phase of relentless advancement in secondary progressive MS (SPMS), for which approved disease-modifying therapies are limited. In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. In both forms of MS, active brain-tissue injury is associated with inflammation; but in SPMS, the inflammatory response occurs at least partly behind the blood-brain barrier and is followed by a cascade of events, including persistent microglial activation that may lead to chronic demyelination and neurodegeneration associated with irreversible disability. In patients with relapsing forms of MS, natalizumab therapy is known to significantly reduce intrathecal inflammatory responses which results in reductions in brain lesions and brain atrophy as well as beneficial effects on clinical measures, such as reduced frequency and severity of relapse and reduced accumulation of disability. Natalizumab treatment also reduces levels of cerebrospinal fluid chemokines and other biomarkers of intrathecal inflammation, axonal damage and demyelination, and has demonstrated the ability to reduce innate immune activation and intrathecal immunoglobulin synthesis in patients with MS. The efficacy of natalizumab therapy in SPMS is currently being investigated in a randomized, double-blind, placebo-controlled trial. PMID:26788129

  20. Microelectrode array recordings of cardiac action potentials as a high throughput method to evaluate pesticide toxicity.

    PubMed

    Natarajan, A; Molnar, P; Sieverdes, K; Jamshidi, A; Hickman, J J

    2006-04-01

    The threat of environmental pollution, biological warfare agent dissemination and new diseases in recent decades has increased research into cell-based biosensors. The creation of this class of sensors could specifically aid the detection of toxic chemicals and their effects in the environment, such as pyrethroid pesticides. Pyrethroids are synthetic pesticides that have been used increasingly over the last decade to replace other pesticides like DDT. In this study we used a high-throughput method to detect pyrethroids by using multielectrode extracellular recordings from cardiac cells. The data from this cell-electrode hybrid system was compared to published results obtained with patch-clamp electrophysiology and also used as an alternative method to further understand pyrethroid effects. Our biosensor consisted of a confluent monolayer of cardiac myocytes cultured on microelectrode arrays (MEA) composed of 60 substrate-integrated electrodes. Spontaneous activity of these beating cells produced extracellular field potentials in the range of 100 microV to nearly 1200 microV with a beating frequency of 0.5-4 Hz. All of the tested pyrethroids; alpha-Cypermethrin, Tetramethrin and Tefluthrin, produced similar changes in the electrophysiological properties of the cardiac myocytes, namely reduced beating frequency and amplitude. The sensitivity of our toxin detection method was comparable to earlier patch-clamp studies, which indicates that, in specific applications, high-throughput extracellular methods can replace single-cell studies. Moreover, the similar effect of all three pyrethroids on the measured parameters suggests, that not only detection of the toxins but, their classification might also be possible with this method. Overall our results support the idea that whole cell biosensors might be viable alternatives when compared to current toxin detection methods. PMID:16198528

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

    PubMed Central

    Sellebjerg, Finn; Cadavid, Diego; Steiner, Deborah; Villar, Luisa Maria; Reynolds, Richard; Mikol, Daniel

    2016-01-01

    Multiple sclerosis (MS) is a common and chronic central nervous system (CNS) demyelinating disease and a leading cause of permanent disability. Patients most often present with a relapsing–remitting disease course, typically progressing over time to a phase of relentless advancement in secondary progressive MS (SPMS), for which approved disease-modifying therapies are limited. In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. In both forms of MS, active brain-tissue injury is associated with inflammation; but in SPMS, the inflammatory response occurs at least partly behind the blood–brain barrier and is followed by a cascade of events, including persistent microglial activation that may lead to chronic demyelination and neurodegeneration associated with irreversible disability. In patients with relapsing forms of MS, natalizumab therapy is known to significantly reduce intrathecal inflammatory responses which results in reductions in brain lesions and brain atrophy as well as beneficial effects on clinical measures, such as reduced frequency and severity of relapse and reduced accumulation of disability. Natalizumab treatment also reduces levels of cerebrospinal fluid chemokines and other biomarkers of intrathecal inflammation, axonal damage and demyelination, and has demonstrated the ability to reduce innate immune activation and intrathecal immunoglobulin synthesis in patients with MS. The efficacy of natalizumab therapy in SPMS is currently being investigated in a randomized, double-blind, placebo-controlled trial. PMID:26788129

  2. 30 CFR 285.607 - How do I submit my SAP?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false How do I submit my SAP? 285.607 Section 285.607... Assessment Plan and Information Requirements for Commercial Leases § 285.607 How do I submit my SAP? You must submit one paper copy and one electronic version of your SAP to MMS at the address listed in § 285.110(a)....

  3. Ribavirin Potentiates Interferon Action by Augmenting Interferon-Stimulated Gene Induction in Hepatitis C Virus Cell Culture Models

    PubMed Central

    Thomas, Emmanuel; Feld, Jordan J.; Li, Qisheng; Hu, Zongyi; Fried, Michael W.; Liang, T. Jake

    2012-01-01

    The combination of pegylated interferon (PEG-IFN) and ribavirin is the standard treatment for chronic hepatitis C. Our recent clinical study suggests that ribavirin augments the induction of interferon-stimulated genes (ISGs) in patients treated for hepatitis C virus (HCV) infection. In order to further characterize the mechanisms of action of ribavirin, we examined the effect of ribavirin treatment on ISG induction in cell culture. In addition, the effect of ribavirin on infectious HCV cell culture systems was studied. Similar to interferon (IFN)-α, ribavirin potently inhibits JFH-1 infection of Huh7.5.1 cells in a dose-dependent manner, which spans the physiological concentration of ribavirin in vivo. Microarray analysis and subsequent quantitative polymerase chain reaction assays demonstrated that ribavirin treatment resulted in the induction of a distinct set of ISGs. These ISGs, including IFN regulatory factors 7 and 9, are known to play an important role in anti-HCV responses. When ribavirin is used in conjunction with IFN-α, induction of specific ISGs is synergistic when compared with either drug applied separately. Direct up-regulation of these antiviral genes by ribavirin is mediated by a novel mechanism different from those associated with IFN signaling and intracellular double-stranded RNA sensing pathways such as RIG-I and MDA5. RNA interference studies excluded the activation of the Toll-like receptor and nuclear factor κB pathways in the action of ribavirin. Conclusion Our study suggests that ribavirin, acting by way of a novel innate mechanism, potentiates the anti-HCV effect of IFN. Understanding the mechanism of action of ribavirin would be valuable in identifying novel antivirals PMID:21254160

  4. [SapM-induced fusion blocking of autophagosome-lysosome is depended on interaction with Rab7].

    PubMed

    Hu, Dong; Wang, Wan; Zhao, Runpeng; Xu, Xuewei; Xing, Yingru; Ni, Shengfa; Xu, Congjing; Tie, Baoxian; Zhang, Rongbo; Wu, Jing

    2016-09-01

    Objective To study the role of Rab7 in the blockage of autophagosome-lysosome fusion induced by secretory acid phosphatase (SapM), a virulence factor of mycobacterium tuberculosis. Methods The Raw264.7 cells were transfected with siRab7, and the P62 was detected using Western blotting. After transfected with mCherry-SapM, the co-localization of SapM and Rab7 in Raw264.7 cells was detected by immunofluorescence cytochemistry and the interaction of SapM with Rab7 was determined by co-immunoprecipitation. SapM mutants including SapM(δ ARCA), SapM(δ FRED) and SapM(δ CT) were used to transfect Raw264.7 cells, and their associations with Rab7 were analyzed. Results The treatment of siRab7 induced a significant increase of P62 in these cells. Immunofluorescence cytochemistry showed the intracellular co-localization of SapM and Rab7. Co-immunoprecipitation showed that SapM and Rab7 were precipitated by each other. Only SapM(δ CT) failed to interact with Rab7 among the three SapM mutants. Conclusion The inhibition of autophagosome-lysosome fusion induced by SapM is dependent on the interaction between SapM and Rab7. PMID:27609571

  5. HGF-independent Potentiation of EGFR Action by c-Met

    PubMed Central

    Dulak, Austin M.; Gubish, Christopher T.; Stabile, Laura P.; Henry, Cassandra; Siegfried, Jill M.

    2011-01-01

    The c-Met receptor is a potential therapeutic target for non-small cell lung cancer (NSCLC). Signaling interactions between c-Met and the mutant Epidermal Growth Factor Receptor (EGFR) have been studied extensively, but signaling intermediates and biological consequences of lateral signaling to c-Met in EGFR wild-type tumors is minimally understood. Our observations indicate that delayed c-Met activation in NSCLC cell lines is initiated by wild-type EGFR, the receptor most often found in NSCLC tumors. EGFR ligands induce accumulation of activated c-Met which begins at 8 h continues for 48 h. This effect is accompanied by an increase in c-Met expression and phosphorylation of critical c-Met tyrosine residues without activation of MAPK or Akt. Gene transcription is required for delayed c-Met activation; however, phosphorylation of c-Met by EGFR occurs without production of HGF or another secreted factor, supporting a ligand-independent mechanism. Lateral signaling is blocked by two selective c-Met tyrosine kinase inhibitors (TKIs), PF2341066 and SU11274, or with gefitinib, an EGFR TKI, suggesting kinase activity of both receptors is required for this effect. Prolonged c-Src phosphorylation is observed, and c-Src pathway is essential for EGFR to c-Met communication. Pre-treatment with pan-SFK inhibitors, PP2 and dasatinib, abolishes delayed c-Met phosphorylation. A c-Src dominant-negative construct reduces EGF-induced c-Met phosphorylation compared to control, further, confirming a c-Src requirement. Inhibition of c-Met with PF2341066 and siRNA decreases EGF-induced phenotypes of invasion by ~86% and motility by ~81%, suggesting that a novel form of c-Met activation is utilized by EGFR to maximize these biological effects. Combined targeting of c-Met and EGFR leads to increased xenograft anti-tumor activity, demonstrating that inhibition of downstream and lateral signaling from the EGFR-c-Src-c-Met axis might be effective in treatment of NSCLC. PMID:21423210

  6. Single unit action potentials in humans and the effect of seizure activity

    PubMed Central

    Merricks, Edward M.; Smith, Elliot H.; McKhann, Guy M.; Goodman, Robert R.; Bateman, Lisa M.; Emerson, Ronald G.

    2015-01-01

    Spike-sorting algorithms have been used to identify the firing patterns of isolated neurons (‘single units’) from implanted electrode recordings in patients undergoing assessment for epilepsy surgery, but we do not know their potential for providing helpful clinical information. It is important therefore to characterize both the stability of these recordings and also their context. A critical consideration is where the units are located with respect to the focus of the pathology. Recent analyses of neuronal spiking activity, recorded over extended spatial areas using microelectrode arrays, have demonstrated the importance of considering seizure activity in terms of two distinct spatial territories: the ictal core and penumbral territories. The pathological information in these two areas, however, is likely to be very different. We investigated, therefore, whether units could be followed reliably over prolonged periods of times in these two areas, including during seizure epochs. We isolated unit recordings from several hundred neurons from four patients undergoing video-telemetry monitoring for surgical evaluation of focal neocortical epilepsies. Unit stability could last in excess of 40 h, and across multiple seizures. A key finding was that in the penumbra, spike stereotypy was maintained even during the seizure. There was a net tendency towards increased penumbral firing during the seizure, although only a minority of units (10–20%) showed significant changes over the baseline period, and notably, these also included neurons showing significant reductions in firing. In contrast, within the ictal core territories, regions characterized by intense hypersynchronous multi-unit firing, our spike sorting algorithms failed as the units were incorporated into the seizure activity. No spike sorting was possible from that moment until the end of the seizure, but recovery of the spike shape was rapid following seizure termination: some units reappeared within tens of

  7. Cordycepin Decreases Compound Action Potential Conduction of Frog Sciatic Nerve In Vitro Involving Ca (2+) -Dependent Mechanisms.

    PubMed

    Yao, Li-Hua; Yu, Hui-Min; Xiong, Qiu-Ping; Sun, Wei; Xu, Yan-Liang; Meng, Wei; Li, Yu-Ping; Liu, Xin-Ping; Yuan, Chun-Hua

    2015-01-01

    Cordycepin has been widely used in oriental countries to maintain health and improve physical performance. Compound nerve action potential (CNAP), which is critical in signal conduction in the peripheral nervous system, is necessary to regulate physical performance, including motor system physiological and pathological processes. Therefore, regulatory effects of cordycepin on CNAP conduction should be elucidated. In this study, the conduction ability of CNAP in isolated frog sciatic nerves was investigated. Results revealed that cordycepin significantly decreased CNAP amplitude and conductive velocity in a reversible and concentration-dependent manner. At 50 mg/L cordycepin, CNAP amplitude and conductive velocity decreased by 62.18 ± 8.06% and 57.34% ± 6.14% compared with the control amplitude and conductive velocity, respectively. However, the depressive action of cordycepin on amplitude and conductive velocity was not observed in Ca(2+)-free medium or in the presence of Ca(2+) channel blockers (CdCl2/LaCl3). Pretreatment with L-type Ca(2+) channel antagonist (nifedipine/deltiazem) also blocked cordycepin-induced responses; by contrast, T-type and P-type Ca(2+) channel antagonists (Ni(2+)) failed to block such responses. Therefore, cordycepin decreased the conduction ability of CNAP in isolated frog sciatic nerves via L-type Ca(2+) channel-dependent mechanism. PMID:26078886

  8. Effect of DSPE-PEG on compound action potential, injury potential and ion concentration following compression in ex vivo spinal cord.

    PubMed

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

    2016-05-01

    It has been shown that polyethylene glycol (PEG) can reseal membrane disruption on the spinal cord, but only high concentrations of PEG have been shown to have this effect. Therefore, the effect of PEG is somewhat limited, and it is necessary to investigate a new approach to repair spinal cord injury. This study assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological function and attenuate the injury-induced influx of extracellular ions in ex vivo spinal cord injury. Isolated spinal cords were subjected to compression injury and treated with PEG or DSPE-PEG immediately after injury. The compound action potential (CAP) was recorded before and after injury to assess the functional recovery. Furthermore, injury potential, the difference in gap potentials before and after compression, and the concentration of intracellular ions were used to evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the injury potential and ion concentration of the untreated, PEG and DSPE-PEG group, without significant difference among them, are remarkably higher than those of the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated spinal cords was significantly greater than that of the untreated spinal cords. The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same, but the concentration of DSPE-PEG used was much lower than the concentration of PEG. These results suggest that instant application of DSPE-PEG could effectively repair functional disturbance in SCI at a much lower concentration than PEG. PMID:27021025

  9. Regulation of natural cytotoxicity by the adaptor SAP and the Src-related kinase Fyn

    PubMed Central

    Bloch-Queyrat, Coralie; Fondanèche, Marie-Claude; Chen, Riyan; Yin, Luo; Relouzat, Francis; Veillette, André; Fischer, Alain; Latour, Sylvain

    2005-01-01

    SAP is an adaptor protein that is expressed in NK and T cells. It is mutated in humans who have X-linked lymphoproliferative (XLP) disease. By interacting with SLAM family receptors, SAP enables tyrosine phosphorylation signaling of these receptors by its ability to recruit the Src-related kinase, Fyn. Here, we analyzed the role of SAP in NK cell functions using the SAP-deficient mouse model. Our results showed that SAP was required for the ability of NK cells to eliminate tumor cells in vitro and in vivo. This effect strongly correlated with expression of CD48 on tumor cells, the ligand of 2B4, a SLAM-related receptor expressed in NK cells. In keeping with earlier reports that studied human NK cells, we showed that SAP was necessary for the ability of 2B4 to trigger cytotoxicity and IFN-γ secretion. In the absence of SAP, 2B4 function was shifted toward inhibition of NK cell–mediated cytotoxicity. By analyzing mice lacking Fyn, we showed that similarly to SAP, Fyn was strictly required for 2B4 function. Taken together, these results provide evidence that the 2B4-SAP-Fyn cascade defines a potent activating pathway of natural cytotoxicity. They also could help to explain the high propensity of patients who have XLP disease to develop lymphoproliferative disorders. PMID:15998796

  10. NuSAP modulates the dynamics of kinetochore microtubules by attenuating MCAK depolymerisation activity

    PubMed Central

    Li, Chenyu; Zhang, Yajun; Yang, Qiaoyun; Ye, Fan; Sun, Stella Ying; Chen, Ee Sin; Liou, Yih-Cherng

    2016-01-01

    Nucleolar and spindle-associated protein (NuSAP) is a microtubule-associated protein that functions as a microtubule stabiliser. Depletion of NuSAP leads to severe mitotic defects, however the mechanism by which NuSAP regulates mitosis remains elusive. In this study, we identify the microtubule depolymeriser, mitotic centromere-associated kinesin (MCAK), as a novel binding partner of NuSAP. We show that NuSAP regulates the dynamics and depolymerisation activity of MCAK. Phosphorylation of MCAK by Aurora B kinase, a component of the chromosomal passenger complex, significantly enhances the interaction of NuSAP with MCAK and modulates the effects of NuSAP on the depolymerisation activity of MCAK. Our results reveal an underlying mechanism by which NuSAP controls kinetochore microtubule dynamics spatially and temporally by modulating the depolymerisation function of MCAK in an Aurora B kinase-dependent manner. Hence, this study provides new insights into the function of NuSAP in spindle formation during mitosis. PMID:26733216

  11. Biochemical and Genetic Evidence for a SAP-PKC-θ Interaction Contributing to IL-4 Regulation

    PubMed Central

    Cannons, Jennifer L.; Wu, Julie Z.; Gomez-Rodriguez, Julio; Zhang, Jinyi; Dong, Baoxia; Liu, Yin; Shaw, Stephen; Siminovitch, Katherine A.; Schwartzberg, Pamela L.

    2012-01-01

    SAP, an adaptor molecule that recruits Fyn to the SLAM-family of immunomodulatory receptors, is mutated in X-linked lymphoproliferative disease. CD4+ T cells from SAP-deficient mice have defective TCR-induced IL-4 production and impaired T cell-mediated help for germinal center formation; however, the downstream intermediates contributing to these defects remain unclear. We previously found that SAP-deficient CD4+ T cells exhibit decreased PKC-θ recruitment upon TCR stimulation. We demonstrate here using GST-pulldowns and co-immunoprecipitation studies that SAP constitutively associates with PKC-θ in T cells. SAP-PKC-θ interactions required R78 of SAP, a residue previously implicated in Fyn recruitment, yet SAP’s interactions with PKC-θ occurred independent of phosphotyrosine binding and Fyn. Overexpression of SAP in T cells increased and sustained PKC-θ recruitment to the immune synapse and elevated IL-4 production in response to TCR plus SLAM-mediated stimulation. Moreover, PKC-θ, like SAP, was required for SLAM-mediated increases in IL-4 production and conversely, membrane-targeted PKC-θ mutants rescued IL-4 expression in SAP−/− CD4+ T cells, providing genetic evidence that PKC-θ is a critical component of SLAM/SAP-mediated pathways that influence TCR-driven IL-4 production. PMID:20668219

  12. LINEAR RELATIONS BETWEEN STIMULUS AMPLITUDES AND AMPLITUDES OF RETINAL ACTION POTENTIALS FROM THE EYE OF THE WOLF SPIDER.

    PubMed

    DEVOE, R D

    1963-09-01

    Incremental photic stimuli have been used to elicit small amplitude retinal action potentials from light-adapted ocelli of the wolf spider, Lycosa baltimoriana (Keyserling) in order to see whether or not the amplitudes of these potentials are linearly related to the stimulus amplitudes. Sine wave variations of light intensity around a mean elicit sine wave variations in potential which contain inappreciable harmonics of the stimulus frequency and whose amplitudes are linearly related to the stimulus amplitudes. Likewise, the responses to the first two periodic Fourier components of incremental rectangular wave stimuli of variable duty cycle are directly proportional to the amplitudes of these components and have phases dependent only on the frequencies and phases of these components. Thirdly, a linear transfer function can be found which describes the amplitudes and phases of responses recorded at different frequencies of sine wave stimulation and this transfer function is sufficient to predict the responses to incremental step stimuli. Finally, it is shown that flash response amplitudes are linearly related to incremental flash intensities at all levels of adaptation. The relations of these linear responses to non-linear responses and to physiological mechanisms of the eye are discussed. PMID:14060442

  13. Frequency Analysis of Atrial Action Potential Alternans: A Sensitive Clinical Index of Individual Propensity to Atrial Fibrillation

    PubMed Central

    Lalani, Gautam G.; Schricker, Amir A.; Clopton, Paul; Krummen, David E.; Narayan, Sanjiv M.

    2013-01-01

    Background Few clinical indices identify the propensity of patients to atrial fibrillation (AF) when not in AF. Repolarization alternans has been shown to indicate AF vulnerability, but is limited in its sensitivity to detect changes in action potential duration (APD), that may be subtle. We hypothesized that spectral analysis would be a more sensitive and robust marker of action potential (AP) alternans and thus a better clinical index of individual propensity to AF than APD alternans. Methods and Results In 31 patients (12 persistent AF, 15 paroxysmal AF, 4 controls with no AF), we recorded left (n=27) and right (n=6) atrial monophasic APs during incremental pacing from cycle length (CL) 500 ms (120 bpm) to AF onset. Alternans was measured by APD and spectral analysis. At baseline pacing [median CL 500 (IQR 500,500) ms], APD alternans was detected in only 7/27 AF patients (no controls), while spectral AP alternans was detected in 18/27 AF patients (no controls; p=0.003); AP alternans was more prevalent in persistent than paroxysmal AF, and absent in controls (p=0.018 APD, p=0.042 spectral). Spectral AP alternans magnitude at baseline was highest in persistent AF, with modest rate-dependent amplification, then in paroxysmal AF, with marked rate-dependence, and was undetectable in controls until just before induced AF. Conclusions Spectral AP alternans near baseline rates can identify patients with, versus those without, clinical histories and pathophysiological substrates for AF. Future studies should examine whether the presence of spectral AP alternans during sinus rhythm may obviate the need to actually demonstrate AF, such as on ambulatory ECG monitoring. PMID:23995250

  14. Nerve-released acetylcholine contracts urinary bladder smooth muscle by inducing action potentials independently of IP3-mediated calcium release.

    PubMed

    Nausch, Bernhard; Heppner, Thomas J; Nelson, Mark T

    2010-09-01

    Nerve-released ACh is the main stimulus for contraction of urinary bladder smooth muscle (UBSM). Here, the mechanisms by which ACh contracts UBSM are explored by determining Ca(2+) and electrical signals induced by nerve-released ACh. Photolysis of caged inositol 1,4,5-trisphosphate (IP(3)) evoked Ca(2+) release from the sarcoplasmic reticulum. Electrical field stimulation (20 Hz) induced Ca(2+) waves within the smooth muscle that were present only during stimulus application. Ca(2+) waves were blocked by inhibition of muscarinic ACh receptors (mAChRs) with atropine and depletion of sarcoplasmic reticulum Ca(2+) stores with cyclopiazonic acid (CPA), and therefore likely reflect activation of IP(3) receptors (IP(3)Rs). Electrical field stimulation also increased excitability to induce action potentials (APs) that were accompanied by Ca(2+) flashes, reflecting Ca(2+) entry through voltage-dependent Ca(2+) channels (VDCCs) during the action potential. The evoked Ca(2+) flashes and APs occurred as a burst with a lag time of approximately 1.5 s after onset of stimulation. They were not inhibited by blocking IP(3)-mediated Ca(2+) waves, but by blockers of mAChRs (atropine) and VDCCs (diltiazem). Nerve-evoked contractions of UBSM strips were greatly reduced by blocking VDCCs, but not by preventing IP(3)-mediated Ca(2+) signaling with cyclopiazonic acid or inhibition of PLC with U73122. These results indicate that ACh released from nerve varicosities induces IP(3)-mediated Ca(2+) waves during stimulation; but contrary to expectations, these signals do not appear to participate in contraction. In addition, our data provide compelling evidence that UBSM contractions evoked by nerve-released ACh depend on increased excitability and the resultant Ca(2+) entry through VDCCs during APs. PMID:20573989

  15. Effect of mental challenge induced by movie clips on action potential duration in normal human subjects independent of heart rate

    PubMed Central

    Child, Nicholas; Hanson, Ben; Bishop, Martin; Rinaldi, Christopher A; Bostock, Julian; Western, David; Cooklin, Michael; O’Neil, Mark; Wright, Matthew; Razavi, Reza; Gill, Jaswinder; Taggart, Peter

    2014-01-01

    Background Mental stress and emotion have long been associated with ventricular arrhythmias and sudden death in animal models and humans. The effect of mental challenge on ventricular action potential duration (APD) in conscious healthy humans has not been reported. Methods and Results Activation recovery intervals (ARI) measured from unipolar electrograms as a surrogate for APD (n=19) were recorded from right and left ventricular endocardium during steady state pacing while subjects watched an emotionally charged film clip. To assess the possible modulating role of altered respiration on APD, the subjects then repeated the same breathing pattern they had during the stress, but without the movie clip. Haemodynamic parameters (mean, systolic, and diastolic blood pressure, and rate of pressure increase) and respiration rate increased during the stressful part of the film clip (p=0.001). APD decreased during the stressful parts of the film clip, eg for global RV ARI at end of film clip 193.8ms (SD 14) vs 198.0ms (SD13) during the matched breathing control (end film LV 199.8ms (SD16) vs control 201.6ms (SD15), p=0.004. Respiration rate increased during the stressful part of the film clip (by 2 breaths/minute), and was well matched in the respective control period without any haemodynamic or ARI changes. Conclusions Our results document for the first time direct recordings of the effect of a mental challenge protocol on ventricular action potential duration in conscious humans. The effect of mental challenge on APD was not secondary to emotionally-induced altered respiration or heart rate. PMID:24833641

  16. Critical factors in the limited occurrence of the Japanese tree sap mite Hericia sanukiensis (Acari: Astigmata: Algophagidae) inhabiting the sap of the oak Quercus acutissima.

    PubMed

    Hayashi, Kyohei; Ichikawa, Toshihide; Yasui, Yukio

    2011-08-01

    Hericia sanukiensis (Astigmata: Algophagidae) is a semi-aquatic mite inhabiting fermented sap flux of the Japanese sawtooth oak (Quercus acutissima) and utilizes Nitidulidae (Coleoptera) as the dispersal (phoretic) carrier. Although nitidulid beetles are commonly found in sap flux, the occurrence of H. sanukiensis has been extremely limited to a few trees in Shikoku Island, Kagawa Prefecture, Japan. To elucidate the critical factors limiting the occurrence of this species, we compared several physical and biological characteristics of sap-exudation points, including the structure and temperature of tree trunks, period and abundance of sap exudation, and seasonal occurrence and dispersal behavior of nitidulid beetles between environments with and without mites. During the two consecutive years of field research, we found that only sap-exudation points with obvious tree holes (ringent area >10 cm², depth >10 cm) had sustained mite populations throughout the observation period. In contrast, for the sap-exudation points lacking tree holes, H. sanukiensis temporally (from spring to autumn) colonized only when the sap production was considerably high. Thus, we suggest that the settlement of H. sanukiensis populations requires tree holes as an overwintering habitat. Nitidulid beetles also concentrated in areas with high sap production and did not disperse from such habitats during the sap flow season. This indicates that H. sanukiensis mites may only disperse and colonize new habitats at very limited opportunities, such as drastic habitat deterioration, which may promote the movement of their carrier. Taken together, these findings may explain the limited occurrence of this mite species. PMID:21479774

  17. The Effects of Propofol on Local Field Potential Spectra, Action Potential Firing Rate, and Their Temporal Relationship in Humans and Felines

    PubMed Central

    Hanrahan, Sara J.; Greger, Bradley; Parker, Rebecca A.; Ogura, Takahiro; Obara, Shinju; Egan, Talmage D.; House, Paul A.

    2013-01-01

    Propofol is an intravenous sedative hypnotic, which, acting as a GABAA agonist, results in neocortical inhibition. While propofol has been well studied at the molecular and clinical level, less is known about the effects of propofol at the level of individual neurons and local neocortical networks. We used Utah Electrode Arrays (UEAs) to investigate the effects of propofol anesthesia on action potentials (APs) and local field potentials (LFPs). UEAs were implanted into the neocortex of two humans and three felines. The two human patients and one feline received propofol by bolus injection, while the other two felines received target-controlled infusions. We examined the changes in LFP power spectra and AP firing at different levels of anesthesia. Increased propofol concentration correlated with decreased high-frequency power in LFP spectra and decreased AP firing rates, and the generation of large-amplitude spike-like LFP activity; however, the temporal relationship between APs and LFPs remained relatively consistent at all levels of propofol. The probability that an AP would fire at this local minimum of the LFP increased with propofol administration. The propofol-induced suppression of neocortical network activity allowed LFPs to be dominated by low-frequency spike-like activity, and correlated with sedation and unconsciousness. As the low-frequency spike-like activity increased and the AP–LFP relationship became more predictable firing rate encoding capacity is impaired. This suggests a mechanism for decreased information processing in the neocortex that accounts for propofol-induced unconsciousness. PMID:23576977

  18. Auditory steady-state evoked potentials vs. compound action potentials for the measurement of suppression tuning curves in the sedated dog puppy.

    PubMed

    Markessis, Emily; Poncelet, Luc; Colin, Cécile; Hoonhorst, Ingrid; Collet, Grégory; Deltenre, Paul; Moore, Brian C J

    2010-06-01

    Auditory steady-state evoked potential (ASSEP) tuning curves were compared to compound action potential (CAP) tuning curves, both measured at 2 Hz, using sedated beagle puppies. The effect of two types of masker (narrowband noise and sinusoidal) on the tuning curve parameters was assessed. Whatever the masker type, CAP tuning curve parameters were qualitatively and quantitatively similar to the ASSEP ones, with a similar inter-subject variability, but with a greater incidence of upward tip displacement. Whatever the procedure, sinusoidal maskers produced sharper tuning curves than narrow-band maskers. Although these differences are not likely to have significant implications for clinical work, from a fundamental point of view, their origin requires further investigations. The same amount of time was needed to record a CAP and an ASSEP 13-point tuning curve. The data further validate the ASSEP technique, which has the advantages of having a smaller tendency to produce upward tip shifts than the CAP technique. Moreover, being non invasive, ASSEP tuning curves can be easily repeated over time in the same subject for clinical and research purposes. PMID:20482293

  19. Changes in cochlear responses in guinea pig with changes in perilymphatic K+. Part I: summating potentials, compound action potentials and DPOAEs.

    PubMed

    Marcon, Simon; Patuzzi, Robert

    2008-03-01

    We have measured the effects of changing perilymphatic K+ by perfusing scala tympani in guinea pigs with salt solutions high or low in K+, while monitoring the distortion product otoacoustic emissions (DPOAEs) in the ear canal (a measure of mechanical vibration of the organ of Corti), the summating potential (SP) evoked by high-frequency tone-bursts (taken to be a measure of pre-synaptic electrical activity of the inner hair cells) and the compound action potential (CAP) of the auditory nerve (taken to be a measure of post-synaptic neural activity). We have attempted to investigate the osmotic effects of our perfusates by comparison with simple hyperosmotic sucrose perfusates and iso-osmotic versions of perfusates, and for the effects of changes in other ions (e.g. Na+ and Cl-) by keeping these constant in some perfusates while elevating K+. We have found that changing the K+ concentration over the range 0-30mM elevated the SP and CAP thresholds almost equally in normal animals, and not at all in animals devoid of outer hair cells (OHCs), showing that OHCs are sensitive to the perfusates we have used, but the inner hair cells (IHCs) and the type I afferent dendrites are not, presumably because IHCs are shielded from perilymph by supporting cells, and the membranes of the afferent dendrite membranes exposed directly to our perfusates are dominated by Cl(-) permeability, rather than by K+ permeability. This view is supported by experiments in which the perilymphatic Cl(-) concentration was reduced, producing a large elevation in CAP threshold, but a much smaller elevation of SP threshold, suggesting disruption of action potential initiation. The view that threshold elevations with changes in perilymphatic K+ are due almost solely to a disruption of OHC function and a consequent change in the mechanical sensitivity of the organ of Corti was supported by measurements of amplitude of the 2f1-f2 distortion product otoacoustic emission. During elevations in K+, DPOAEs

  20. Sap Flow Estimate Of Watershed-Scale Transpiration

    NASA Astrophysics Data System (ADS)

    Kumagai, T.; Aoki, S.; Shimizu, T.; Otsuki, K.

    2006-12-01

    The present study examined how to obtain sufficient information to extrapolate watershed-scale transpiration in a Japanese cedar (Cryptomeria japonica D. Don) forest from sap flow measurements of available individual trees. In this study, we conducted measurements of tree biometrics and tree-to-tree and radial variations in xylem sap flux density (Fd) in two different stand plots, an upper slope plot (UP) and lower slope plot (LP), during the growing season with significant variations in environmental factors. The manner in which the mean stand sap flux density (JS) and tree stem allometric relationship (diameter at breast height (DBH) versus sapwood area (AS_tree)) vary between the two stands along the slope of the watershed was then investigated. After these analyses, appropriate sample sizes for estimations of representative JS values in the stand were also determined. The results demonstrated that a unique or general function allowed description of the allometric relationship along the slope, but the data for its formulation needed to be obtained in both UP and LP. They also revealed that JS in UP and LP were almost the same during the study period despite differences in tree density and size between the two plots. This implies that JS measured in a partial stand within a watershed is a reasonable estimator of the values of other stands, and that stand sapwood area calculated by AS_tree is a strong determinant of water-use in a forest watershed. To estimate JS in both an UP and LP, at least 10 trees should be sampled, but not necessarily more than this.

  1. A ground-water sapping landscape in the Florida Panhandle

    NASA Astrophysics Data System (ADS)

    Schumm, S. A.; Boyd, K. F.; Wolff, C. G.; Spitz, W. J.

    1995-07-01

    Drainage networks that have formed by ground-water sapping are developed in the highly permeable sands of the Citronelle Formation in the Florida Panhandle. The valleys resemble those formed on Hawaii, the Colorado Plateau and on Mars, but they have developed without significant lithologic controls. Drainage patterns range from trellis to dentritic depending on the effect of beach ridges and relative relief. Many of the drainage networks are not fully developed, and the adjacent uplands have been modified by marine, aeolian, and to a limited extent fluvial processes. Extension of the networks appears to be episodic, as a result of fires, hurricanes, and human activities, which damage or destroy vegetation.

  2. Ternary complex factors SAP-1 and Elk-1, but not net, are functionally equivalent in thymocyte development.

    PubMed

    Costello, Patrick; Nicolas, Robert; Willoughby, Jane; Wasylyk, Bohdan; Nordheim, Alfred; Treisman, Richard

    2010-07-15

    The ternary complex factors (TCFs; SAP-1, Elk-1, and Net) are serum response factor cofactors that share many functional properties and are coexpressed in many tissues. SAP-1, the predominant thymus TCF, is required for thymocyte positive selection. In this study, we assessed whether the different TCFs are functionally equivalent. Elk-1 deletion, but not the hypomorphic Net(delta) mutation, exacerbated the SAP-1 positive selection phenotype, but triply deficient thymocytes were no more defective than SAP-1(-/-) Elk-1(-/-) cells. Inactivation of the other TCFs did not affect SAP-1-independent processes, including beta-selection, regulatory T cell selection, and negative selection, although reduced marginal zone B cells were observed in SAP-1(-/-) Elk-1(-/-) animals. Ectopic expression of Elk-1, but not Net, rescued positive selection of SAP-1(-/-) thymocytes; thus, SAP-1 and Elk-1 are functionally equivalent in this system, and the SAP-1 null selection phenotype reflects only its high expression in the thymus. Array analysis of TCR-stimulated double-positive cells identified SAP-1-dependent inducible genes whose transcription was further impaired in SAP-1(-/-) Elk-1(-/-) cells; thus, these genes, which include Egr-1 and Egr-2, represent candidate mediators of positive selection. Chromatin immunoprecipitation revealed subtly different promoter targeting between the different TCFs. Ectopic expression of Egr-1 restored positive selection in SAP-1 null thymocytes, establishing it (and possibly other Egr family members) as the major effector for ERK-SAP-1 signaling in thymocyte positive selection. PMID:20554967

  3. [Electrophysiologic analysis of the lumbosacral radiculopathy using nerve root conduction velocity (NRCV) and cauda equina action potentials (CEAP)].

    PubMed

    Kamitani, K; Baba, H; Shimada, T; Chiba, H

    1993-07-01

    Nerve root conduction velocity (NRCV) and cauda equina action potential (CEAP) have been measured to assess the severity of lumbosacral radiculopathy, the level-specific diagnosis of the symptomatic roots, and to predict the outcome. This study included 71 patients (40 males, 31 females, average age of 54 years at the time of surgery) who underwent decompressive surgery for lumbar radiculopathy. The NRCV and CEAP were directly measured during the operation. The NRCV decreased significantly with progression of radicular symptoms. The NRCV showed a marked reduction in the nerve roots of the patients with a two years or longer history of radicular symptoms; or those with compression of the nerve roots on the imaging examinations; or nerve roots that were considered to have been subjected to persistent compression over a prolonged period with severe inflammation and adhesions. Multivariative analyses suggested that the NRCV correlated closely to the postoperative neurologic recovery, and the outcome of the lumbosacral radiculopathy could be predicted to some extent by measurements of NRCV. The level-specific diagnosis of the radiculopathy could be determined when the CEAP showed a more than 30% left-right potentials difference. PMID:8409633

  4. On-Chip Multichannel Action Potential Recording System for Electrical Measurement of Single Neurites of Neuronal Network

    NASA Astrophysics Data System (ADS)

    Suzuki, Ikurou; Hattori, Akihiro; Yasuda, Kenji

    2007-11-01

    We have developed a multielectrode array recording system for single-neurite-firing measurement using an artificially constructed neuronal network on a chip, which has a 10 μm diameter array with electrodes spaced at 50 μm, for noninvasive 64-channel 100 kHz multirecording and the stimulation of a plurality of neurites extending from a single neuron. To improve the signal/noise ratio, the ground plane was set on the multi-electrode-array plane and platinum black was set on each of the 10 μm electrodes. Using this system, we performed a multisite recording of neurites of a single neuron of a rat hippocampal network in cases of both spontaneous firing and evoked responses to electrical stimulations, and estimated the velocity of action potential propagation among neurites of a single neuron from six recording sites. This demonstrated the potential use of our low-noise chip and our high-speed measurement system for the analysis of neuronal network activities at the single-neuron level.

  5. Effects of calcium channel antagonists on action potential conduction and transmitter release in the guinea-pig vas deferens.

    PubMed Central

    Beattie, D. T.; Cunnane, T. C.; Muir, T. C.

    1986-01-01

    The effects of the Ca2+ channel antagonists amlodipine, cobalt, diltiazem, nifedipine and verapamil and the local anaesthetic lignocaine were investigated on action potential conduction in and on evoked transmitter release from sympathetic nerves in the guinea-pig isolated vas deferens. Transmitter release was investigated by measurement of evoked (trains of pulses at 1 and 2 Hz, 0.1-0.5 ms supramaximal voltage) excitatory junction potentials (e.j.ps) using microelectrodes; tension was recorded simultaneously; tritium [3H] overflow from vasa preincubated (37 degrees C, 30 min) in Krebs solution containing either [3H]-noradrenaline (NA, 25 microCi ml-1, 2 X 10(-6) M NA) or [3H]-adenosine (50 microCi ml-1, 1 X 10(-6) M adenosine). Amlodipine (0.5-2 X 10(-4) M), verapamil (0.5-2 X 10(-4) M), diltiazem (1-8 X 10(-4) M), lignocaine (0.1-2 X 10(-3) M) and cobalt (2-6 X 10(-2) M) in descending order of potency, but not nifedipine (1-5 X 10(-3) M), increased the latency and inhibited, then abolished, the amplitude and number of action potentials in a concentration-dependent manner. Amlodipine (0.5-1 X 10(-4) M), verapamil (1-2 X 10(-4) M), diltiazem (1-5 X 10(-4) M) and cobalt (1 X 10(-3) M), in descending order of potency, but not nifedipine (5 X 10(-4) M), inhibited then abolished evoked e.j.ps in a concentration-dependent manner. Cobalt inhibited e.j.ps at a lower concentration than that (2-6 X 10(-2) M) required to block action potential conduction. In unstimulated tissues, the resting [3H] overflow following preincubation with [3H]-NA consisted largely of 4-hydroxy 3-methoxymandelic acid (VMA), 4-hydroxy 3-methoxy phenylglycol (MOPEG), 3,4 dihydroxyphenylglycol (DOPEG) and NA; stimulated tissues (300 pulses at 20 Hz, 0.5 ms supramaximal voltage) released mainly NA. Verapamil (0.1-1 X 10(-4) M), amlodipine (0.05-1 X 10(-4) M) and nifedipine (1-5 X 10(-4) M), but not cobalt (2 X 10(-3) M), increased, significantly, the resting overflow of 3H comprising mainly DOPEG

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

    PubMed Central

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

    2013-01-01

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

  7. Effect of gender on sap-flux-scaled transpiration in a dominant riparian tree species: Box elder (Acer negundo)

    NASA Astrophysics Data System (ADS)

    Hultine, K. R.; Bush, S. E.; West, A. G.; Ehleringer, J. R.

    2007-09-01

    Acer negundo is a dioecious riparian tree species with a spatial segregation of the sexes along soil moisture gradients. Females are typically more common in wet sites along streams (typically F/M ≈ 1.6), whereas males are more common in drier sites away from streams (typically F/M ≈ 0.6). Spatial segregation between sexes may develop because of the higher reproductive cost in females compared to males. If so, female Acer negundo trees would be under stronger selection to maximize resource uptake, and would therefore likely occur at greater frequencies in high resources sites (i.e., along streamsides), and increase rates of resource acquisition (i.e., water and nutrients). The spatial segregation of the sexes leads to the hypothesis that male and female individuals have varying influence on ecosystem evapotranspiration. To address this, stem sap flux was measured on mature streamside (≤1 m from stream channel) and nonstreamside (>1 m from stream channel) male and female Acer negundo trees occurring in Red Butte Canyon near Salt Lake City, Utah, during the 2004 growing season. Despite having similar predawn and midday water potentials, sap flux density was 76% higher in streamside female trees than in males (P < 0.0001), while sap flux density was 19% greater in nonstreamside female trees compared to males (P < 0.0001). Mean daily sap flux density of all A. negundo populations was highly correlated with mean daily vapor pressure deficit (P < 0.0001), and was moderately correlated with mean daily photosynthetic active radiation (P = 0.0263). At the watershed scale, nonstreamside male and female A. negundo trees contributed 20 and 21% respectively to the estimated 1.7 mm d-1 transpiration flux from dominant riparian vegetation away from streamsides (estimated from scaled sap flux measurements of all dominant riparian tree species in Red Butte Canyon). Male and female A. negundo trees contributed 31 and 46% respectively of the estimated 8.0 mm d-1 transpiration

  8. Evapotranspiration in a cottonwood (Populus fremontii) restoration plantation estimated by sap flow and remote sensing methods

    USGS Publications Warehouse

    Nagler, P.; Jetton, A.; Fleming, J.; Didan, K.; Glenn, E.; Erker, J.; Morino, K.; Milliken, J.; Gloss, S.

    2007-01-01

    Native tree plantations have been proposed for the restoration of wildlife habitat in human-altered riparian corridors of western U.S. rivers. Evapotranspiration (ET) by riparian vegetation is an important, but poorly quantified, term in river water budgets. Native tree restoration plots will potentially increase ET. We used sap flow sensors and satellite imagery to estimate ET in a 8 ha, cottonwood (Populus fremontii) restoration plot on the Lower Colorado River. Biometric methods were used to scale leaf area to whole trees and stands of trees. This technique was used to validate our estimates of ET obtained by scaling from branch level to stand (or plot) level measurements of ET. Cottonwood trees used 6-10 mm day-1 of water during the peak of the growing season as determined by sap flow sensors, and annual rates scaled by time-series MODIS satellite imagery were approximately 1.2 m year-1. Although irrigation was not quantified, the field had been flood irrigated at 2 week intervals during the 3 years prior to the study, receiving approximately 2 m year-1 of water. A frequency-domain electromagnetic induction survey of soil moisture content showed that the field was saturated (26-28% gravimetric water content) at the 90-150 cm soil depth under the field. Trees were apparently rooted into the saturated soil, and considerable saving of water could potentially be achieved by modifying the irrigation regime to take into account that cottonwoods are phreatophytes. The study showed that cottonwood ET can be monitored by remote sensing methods calibrated with ground measurements with an accuracy or uncertainty of 20-30% in western riparian corridors. ?? 2007 Elsevier B.V. All rights reserved.

  9. Nickel affects xylem Sap RNase a and converts RNase A to a urease

    PubMed Central

    2013-01-01

    Background Nickel (Ni) is an essential micronutrient; however, its metabolic or physiological functions in plants and animals are largely uncharacterized. The ribonucleases (RNase, e.g., RNase A) are a large family of hydrolases found in one form or many forms facilitating nitrogen (N) cycling. It is currently unknown how either a deficiency or excess of Ni influences the functionality of ribonucleases, like RNase A. This is especially true for perennial crops possessing relatively high Ni requirements. Results We report that the 'rising’ xylem sap of pecan [Carya illinoinensis (Wangenh.) K. Koch, a long-lived tree] at bud break contains a 14 kDa RNase A (aka, RNase 1), which amount has a 33% greater in Ni-deficient as in Ni-sufficient trees when exposed to Ni ions exhibits ureolytic activity. The homologous 13.4 kDa bovine pancreatic RNase A likewise exhibits ureolytic activity upon exposure to Ni ions. Ni therefore affects enzymatic function of a typically non-metalloenzyme, such as it transforms to an enzyme capable of hydrolyzing a linear amide; thus, converting an endonuclease esterase into a urease. Conclusions We conclude that Ni potentially affects the level and activity of RNase A present in the spring xylem sap of pecan trees, and probably in other crops, it has the same influence. The catalytic property of RNase A appears to shift from a nuclease to a urease relying on Ni exposure. This is suggestive that RNase A might possess novel metabolic functionality regarding N-metabolism in perennial plants. The ability of Ni to convert the activity of plant and animal RNase A from that of a ribonuclease to a urease indicates a possible unrecognized beneficial metabolic function of Ni in organisms, while also identifying a potential detrimental effect of excessive Ni on N related metabolic activity if there is sufficient disruption of Ni homeostasis. PMID:24320827

  10. Action Learning: Avoiding Conflict or Enabling Action

    ERIC Educational Resources Information Center

    Corley, Aileen; Thorne, Ann

    2006-01-01

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

  11. Action potentials in parasympathetic and sympathetic efferent fibres to the trachea and lungs of dogs and cats

    PubMed Central

    Widdicombe, J. G.

    1966-01-01

    1. Action potentials were recorded from seventy-four single and twenty-nine small multifibre nerve strands efferent to the trachea and lungs of cats and dogs. From the pathway (vagal or sympathetic), spontaneous activity, conduction velocity and responses to various interventions the efferent fibres were classified in the following way. 2. Group I, vagal. These had a mean conduction velocity of 9·7 m/sec, and had a respiratory but seldom a cardiac rhythm. Their discharge was inhibited during hypertension caused by injections of adrenaline and during inflation of the lungs, but was increased during tracheal occlusion, stimulation of peripheral chemoreceptors and irritation of the larynx. The fibres are thought to be constrictor to the airways. 3. Group II, sympathetic. These had a mean conduction velocity of 0·85 m/sec and usually had inspiratory and cardiac rhythms. Their discharge usually responded qualitatively as that of group I fibres to the various interventions, but with clear quantitative differences. They are divided into three subgroups on the basis of their responses to injections of adrenaline and to asphyxial stimuli. 4. Group III, vagal and sympathetic. These had a mean conduction velocity of 9·0 m/sec, very slow discharge rates and often an expiratory and cardiac modulation. They were activated during hypertension due to adrenaline and often by tracheal occlusion, chemoreceptor stimulation, laryngeal irritation and lung inflation. Their motor action is unknown. 5. Group IV, vagal and sympathetic. These had conspicuous cardiac rhythms resembling those of vascular baroreceptors, but their discharge could not be correlated with arterial blood pressure. Their mean conduction velocity was 6·6 m/sec. Some were active after combined vagotomy and sympathectomy. Together with some unclassified fibres, those of group IV are thought to be aberrant afferent nerves or collateral afferent branches, and possibly to subserve local reflexes. 6. The results are

  12. 49 CFR 40.299 - What is the SAP's role and what are the limits on a SAP's discretion in referring employees for...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... TESTING PROGRAMS Substance Abuse Professionals and the Return-to-Duty Process § 40.299 What is the SAP's... insurance program (e.g., the single substance abuse in-patient treatment program made available by...

  13. 49 CFR 40.299 - What is the SAP's role and what are the limits on a SAP's discretion in referring employees for...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... TESTING PROGRAMS Substance Abuse Professionals and the Return-to-Duty Process § 40.299 What is the SAP's... insurance program (e.g., the single substance abuse in-patient treatment program made available by...

  14. 49 CFR 40.299 - What is the SAP's role and what are the limits on a SAP's discretion in referring employees for...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... TESTING PROGRAMS Substance Abuse Professionals and the Return-to-Duty Process § 40.299 What is the SAP's... insurance program (e.g., the single substance abuse in-patient treatment program made available by...

  15. 49 CFR 40.299 - What is the SAP's role and what are the limits on a SAP's discretion in referring employees for...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... TESTING PROGRAMS Substance Abuse Professionals and the Return-to-Duty Process § 40.299 What is the SAP's... insurance program (e.g., the single substance abuse in-patient treatment program made available by...

  16. 49 CFR 40.299 - What is the SAP's role and what are the limits on a SAP's discretion in referring employees for...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... TESTING PROGRAMS Substance Abuse Professionals and the Return-to-Duty Process § 40.299 What is the SAP's... insurance program (e.g., the single substance abuse in-patient treatment program made available by...

  17. Voltage-gated sodium channels contribute to action potentials and spontaneous contractility in isolated human lymphatic vessels.

    PubMed

    Telinius, Niklas; Majgaard, Jens; Kim, Sukhan; Katballe, Niels; Pahle, Einar; Nielsen, Jørn; Hjortdal, Vibeke; Aalkjaer, Christian; Boedtkjer, Donna Briggs

    2015-07-15

    Voltage-gated sodium channels (VGSC) play a key role for initiating action potentials (AP) in excitable cells. VGSC in human lymphatic vessels have not been investigated. In the present study, we report the electrical activity and APs of small human lymphatic collecting vessels, as well as mRNA expression and function of VGSC in small and large human lymphatic vessels. The VGSC blocker TTX inhibited spontaneous contractions in six of 10 spontaneously active vessels, whereas ranolazine, which has a narrower VGSC blocking profile, had no influence on spontaneous activity. TTX did not affect noradrenaline-induced contractions. The VGSC opener veratridine induced contractions in a concentration-dependent manner (0.1-30 μm) eliciting a stable tonic contraction and membrane depolarization to -18 ± 0.6 mV. Veratridine-induced depolarizations and contractions were reversed ∼80% by TTX, and were dependen