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Sample records for calcium transients delayed

  1. Measurement of calcium transients and slow calcium current in myotubes

    PubMed Central

    1994-01-01

    The purpose of this study was to characterize excitation-contraction (e- c) coupling in myotubes for comparison with e-c coupling of adult skeletal muscle. The whole cell configuration of the patch clamp technique was used in conjunction with the calcium indicator dye Fluo-3 to study the calcium transients and slow calcium currents elicited by voltage clamp pulses in cultured myotubes obtained from neonatal mice. Cells were held at -80 mV and stimulated with 15-20 ms test depolarizations preceded and followed by voltage steps designed to isolate the slow calcium current. The slow calcium current had a threshold for activation of about 0 mV; the peak amplitude of the current reached a maximum at 30 to 40 mV a and then declined for still stronger depolarizations. The calcium transient had a threshold of about -10 mV, and its amplitude increased as a sigmoidal function of test potential and did not decrease again even for test depolarizations sufficiently strong (> or = 50 mV) that the amplitude of the slow calcium current became very small. Thus, the slow calcium current in myotubes appears to have a negligible role in the process of depolarization-induced release of intracellular calcium and this process in myotubes is essentially like that in adult skeletal muscle. After repolarization, however, the decay of the calcium transient in myotubes was very slow (hundreds of ms) compared to adult muscle, particularly after strong depolarizations that triggered larger calcium transients. Moreover, when cells were repolarized after strong depolarizations, the transient typically continued to increase slowly for up to several tens of ms before the onset of decay. This continued increase after repolarization was abolished by the addition of 5 mM BAPTA to the patch pipette although the rapid depolarization-induced release was not, suggesting that the slow increase might be a regenerative response triggered by the depolarization-induced release of calcium. The addition of

  2. Transient amorphous calcium phosphate in forming enamel.

    PubMed

    Beniash, Elia; Metzler, Rebecca A; Lam, Raymond S K; Gilbert, P U P A

    2009-05-01

    Enamel, the hardest tissue in the body, begins as a three-dimensional network of nanometer size mineral particles, suspended in a protein gel. This mineral network serves as a template for mature enamel formation. To further understand the mechanisms of enamel formation we characterized the forming enamel mineral at an early secretory stage using X-ray absorption near-edge structure (XANES) spectromicroscopy, transmission electron microscopy (TEM), FTIR microspectroscopy and polarized light microscopy. We show that the newly formed enamel mineral is amorphous calcium phosphate (ACP), which eventually transforms into apatitic crystals. Interestingly, the size, shape and spatial organization of these amorphous mineral particles and older crystals are essentially the same, indicating that the mineral morphology and organization in enamel is determined prior to its crystallization. Mineralization via transient amorphous phases has been previously reported in chiton teeth, mollusk shells, echinoderm spicules and spines, and recent reports strongly suggest the presence of transient amorphous mineral in forming vertebrate bones. The present finding of transient ACP in murine tooth enamel suggests that this strategy might be universal. PMID:19217943

  3. Delayed transient post-traumatic quadriplegia.

    PubMed

    Al-Shaaibi, Khaloud; Kariyattil, Rajeev

    2015-03-01

    Transient neurological deficit following cervical trauma have been reported following sports injuries, and has been referred to as cervical cord neurapraxia. The so-called "whiplash injuries" following minor motor vehicle collisions usually do not produce any neurological deficit. Here we report the case of a whiplash type of injury presenting with a delayed onset neurological deficit, which was followed by rapid and complete recovery. The patient, an otherwise healthy 34-year-old male, attended the emergency department of Sultan Qaboos University Hospital following a rear-end motor vehicle collision. We present images showing degenerative disc disease causing spinal canal narrowing and mild cord compression in the patient, but no spinal instability. Differential diagnoses are also discussed. PMID:25960840

  4. CALCIUM-RICH GAP TRANSIENTS: SOLVING THE CALCIUM CONUNDRUM IN THE INTRACLUSTER MEDIUM

    SciTech Connect

    Mulchaey, John S.; Kollmeier, Juna A.; Kasliwal, Mansi M.

    2014-01-10

    X-ray measurements suggest that the abundance of calcium in the intracluster medium is higher than can be explained using favored models for core-collapse and Type Ia supernovae alone. We investigate whether the ''calcium conundrum'' in the intracluster medium can be alleviated by including a contribution from the recently discovered subclass of supernovae known as calcium-rich gap transients. Although the calcium-rich gap transients make up only a small fraction of all supernovae events, we find that their high calcium yields are sufficient to reproduce the X-ray measurements found for nearby rich clusters. We find the χ{sup 2} goodness-of-fit metric improves from 84 to 2 by including this new class. Moreover, calcium-rich supernovae preferentially occur in the outskirts of galaxies making it easier for the nucleosynthesis products of these events to be incorporated in the intracluster medium via ram-pressure stripping. The discovery of calcium-rich gap transients in clusters and groups far from any individual galaxy suggests that supernovae associated with intracluster stars may play an important role in enriching the intracluster medium. Calcium-rich gap transients may also help explain anomalous calcium abundances in many other astrophysical systems including individual stars in the Milky Way, the halos of nearby galaxies, and the circumgalactic medium. Our work highlights the importance of considering the diversity of supernovae types and corresponding yields when modeling the abundance of the intracluster medium and other gas reservoirs.

  5. Variable-time-delay optical coherent transient signal processing.

    PubMed

    Merkel, K D; Babbitt, W R; Anderson, K E; Wagner, K H

    1999-10-15

    A technique is proposed and experimentally demonstrated that achieves simultaneous optical pattern waveform storage and programmable time delay for continuous real-time signal processing by use of optical coherent transient technology. We achieve variable-time-delay and broadband signal processing by frequency shifting of two chirped programming pulses, the chirp rate of one being twice that of the other, without using brief reference pulses and without changing the timing of the programming sequence. We demonstrate the technique experimentally in Tm(3+): YAG at 5 K for 40-MHz chirps by performing temporal signal convolution with true-time delays that vary over a 250-ns range.

  6. Photonic Nonlinear Transient Computing with Multiple-Delay Wavelength Dynamics

    NASA Astrophysics Data System (ADS)

    Martinenghi, Romain; Rybalko, Sergei; Jacquot, Maxime; Chembo, Yanne K.; Larger, Laurent

    2012-06-01

    We report on the experimental demonstration of a hybrid optoelectronic neuromorphic computer based on a complex nonlinear wavelength dynamics including multiple delayed feedbacks with randomly defined weights. This neuromorphic approach is based on a new paradigm of a brain-inspired computational unit, intrinsically differing from Turing machines. This recent paradigm consists in expanding the input information to be processed into a higher dimensional phase space, through the nonlinear transient response of a complex dynamics excited by the input information. The computed output is then extracted via a linear separation of the transient trajectory in the complex phase space. The hyperplane separation is derived from a learning phase consisting of the resolution of a regression problem. The processing capability originates from the nonlinear transient, resulting in nonlinear transient computing. The computational performance is successfully evaluated on a standard benchmark test, namely, a spoken digit recognition task.

  7. Understanding anomalous delays in a model of intracellular calcium dynamics

    NASA Astrophysics Data System (ADS)

    Harvey, Emily; Kirk, Vivien; Osinga, Hinke M.; Sneyd, James; Wechselberger, Martin

    2010-12-01

    In many cell types, oscillations in the concentration of free intracellular calcium ions are used to control a variety of cellular functions. It has been suggested [J. Sneyd et al., "A method for determining the dependence of calcium oscillations on inositol trisphosphate oscillations," Proc. Natl. Acad. Sci. U.S.A. 103, 1675-1680 (2006)] that the mechanisms underlying the generation and control of such oscillations can be determined by means of a simple experiment, whereby a single exogenous pulse of inositol trisphosphate (IP3) is applied to the cell. However, more detailed mathematical investigations [M. Domijan et al., "Dynamical probing of the mechanisms underlying calcium oscillations," J. Nonlinear Sci. 16, 483-506 (2006)] have shown that this is not necessarily always true, and that the experimental data are more difficult to interpret than first thought. Here, we use geometric singular perturbation techniques to study the dynamics of models that make different assumptions about the mechanisms underlying the calcium oscillations. In particular, we show how recently developed canard theory for singularly perturbed systems with three or more slow variables [M. Wechselberger, "A propos de canards (Apropos canards)," Preprint, 2010] applies to these calcium models and how the presence of a curve of folded singularities and corresponding canards can result in anomalous delays in the response of these models to a pulse of IP3.

  8. Intracellular free calcium and mitosis in mammalian cells: anaphase onset is calcium modulated, but is not triggered by a brief transient

    PubMed Central

    1989-01-01

    Swiss 3T3 fibroblasts and LLC-PK epithelial cells in prometaphase or metaphase were either injected with fura-2 or loaded with the acetoxymethyl ester derivative of fura-2 (fura-2 AM) and monitored by microspectrofluorimetry. With both methods of loading, we observed two aspects of intracellular free calcium (Cai) metabolism. (a) Most fibroblasts and epithelial cells exhibited a gradual rise from 75 nM in metaphase to 185 nM during cleavage, returning to baseline by early G1. (b) Mitotic Swiss 3T3 cells exhibited rapid transient Cai changes, similar to those previously reported [Poenie, M., J. Alderton, R. Y. Tsien, R. A. Steinhardt. 1985. Nature (Lond.). 315:147-149; Poenie, M., J. Alderton, R. Steinhardt, and R. Tsien. 1986. Science (Wash. DC). 233:886-889; Ratan, R., and M. L. Shelanski. 1988. J. Cell Biol. 107:993]. These Cai transients occurred repetitively, often beginning in metaphase and continuing long after daughter cell formation. Eliminating serum or calcium from the medium abolished the transients, but delayed neither the gradual Cai elevation nor anaphase onset. Co- injection of EGTA or 1,2-bis-(2-aminophenoxy)-ethane-N,N,N',N'- tetraacetic acid (BAPTA) with fura-2 in calcium-free medium, but not in calcium containing medium, blocked both anaphase and the sustained Cai elevation in almost all cases. Blocked cells were rescued by returning calcium to the medium, whereupon Cai slowly but steadily rose as the cell entered anaphase. Spindle microtubules persisted through the EGTA block. Depolymerization of spindle microtubules by nocodazole also reversibly blocked anaphase onset and the sustained Cai elevation, but did not block transients. This study has revealed the following: (a) anaphase in mammalian fibroblasts and epithelial cells is not triggered by brief calcium transients; (b) anaphase is a calcium-modulated event, usually accompanied by a sustained elevation of Cai above 50 nM; (c) the elevation of Cai is dependent upon an intact spindle; and (d

  9. Simultaneous recording of calcium transients in skeletal muscle using high- and low-affinity calcium indicators.

    PubMed Central

    Klein, M G; Simon, B J; Szucs, G; Schneider, M F

    1988-01-01

    To monitor cytosolic [Ca2+] over a wide range of concentrations in functioning skeletal muscle cells, we have used simultaneously the rapid but relatively low affinity calcium indicator antipyrylazo III (AP III) and the slower but higher affinity indicator fura-2 in single frog twitch fibers cut at both ends and voltage clamped with a double vaseline gap system. When both dyes were added to the end pool solution the cytosolic fura-2 concentration reached a steady level equal to the end pool concentration within approximately 2.5 h, a time when the AP III concentration was still increasing. For depolarizing pulses of increasing amplitude, the fura-2 fluorescence signal approached saturation when the simultaneously recorded AP III absorbance change was far from saturation. Comparison of simultaneously recorded fura-2 and AP III signals indicated that the mean values of the on and off rate constants for calcium binding to fura-2 in 18 muscle fibers were 1.49 x 10(8) M-1 s-1 and 11.9 s-1, respectively (mean KD = 89 nM), if all AP III in the fiber is assumed to behave as in calibrating solution and to be in instantaneous equilibrium with [Ca2+]. [Ca2+] transients calculated from the fura-2 signals using these rate constants were consistent with the [Ca2+] transients calculated from the AP III signals. Resting [Ca2+] or small changes in [Ca2+] which could not be reliably monitored with AP III could be monitored with fura-2 with little or no interference from changes in [Mg2+] or from intrinsic signals. The fura-2 signal was also less sensitive to movement artifacts than the AP III signal. After a [Ca2+] transient the fura-2 signal demonstrated a relatively small elevation of [Ca2+] that was maintained for many seconds. PMID:3395664

  10. Super-transient scaling in time-delay autonomous Boolean network motifs

    NASA Astrophysics Data System (ADS)

    D'Huys, Otti; Lohmann, Johannes; Haynes, Nicholas D.; Gauthier, Daniel J.

    2016-09-01

    Autonomous Boolean networks are commonly used to model the dynamics of gene regulatory networks and allow for the prediction of stable dynamical attractors. However, most models do not account for time delays along the network links and noise, which are crucial features of real biological systems. Concentrating on two paradigmatic motifs, the toggle switch and the repressilator, we develop an experimental testbed that explicitly includes both inter-node time delays and noise using digital logic elements on field-programmable gate arrays. We observe transients that last millions to billions of characteristic time scales and scale exponentially with the amount of time delays between nodes, a phenomenon known as super-transient scaling. We develop a hybrid model that includes time delays along network links and allows for stochastic variation in the delays. Using this model, we explain the observed super-transient scaling of both motifs and recreate the experimentally measured transient distributions.

  11. Quantum shutter transient solutions and the delay time for the {delta} potential

    SciTech Connect

    Hernandez, Alberto; Garcia-Calderon, Gaston

    2003-07-01

    The analytical solution to the time-dependent Schroedinger equation for tunneling using cutoff plane-wave initial conditions is in general given by the sum of two types of terms that exhibit a transient behavior. The time evolution of the probability density for the {delta} potential is compared with the free case to investigate in this case the role of these transient terms for the delay time. We find, by a dynamical calculation, that the delay time arises from the interference between these transient terms and we show that at very long times it goes into the phase delay time, given by the energy derivative of the phase of the transmission amplitude.

  12. Multi-Gigahertz True-Time-Delay with Optical Coherent Transients

    NASA Astrophysics Data System (ADS)

    Tian, Mingzhen; Reibel, Randy; Babbitt, Wm. Randall

    2001-03-01

    Operation of mutli-element phased array antenna systems with broadband (multi-gigahertz) signals without beam squint requires novel true time-delay devices. Optical coherent transient technology could provide thousands of delays in a compact volume by exploiting the space and frequency dimensions of inhomogeneously broadened absorbers. We have demonstrated broadband true-time-delay using optical coherent transient techniques in a Tm3+:YAG crystal at 4K, which offers delays up to a microsecond on signals having several tens of GHz bandwidth with sub-picosecond delay resolution. The desired delay was programmed in the crystal as a spatial-spectral grating by repeated application of two 30 picosecond pulses. The demonstrated bandwidth was over 3 GHz and the retrieved data showed good fidelity. Delay accuracy of 1 picosecond and delay resolution of 7 picoseconds (measurement limit) were achieved. The bandwidth achieved is 1000 times greater than previous demonstrations of optical coherent transient true-time-delay. We thank the Office of Naval Research and the University of Colorado for supporting this work.

  13. Transient hypothyroxinaemia associated with developmental delay in very preterm infants.

    PubMed Central

    Meijer, W J; Verloove-Vanhorick, S P; Brand, R; van den Brande, J L

    1992-01-01

    In 563 surviving very preterm (less than 32 weeks gestational age) and/or very low birthweight (less than 1500 g) infants the relationship between neonatal thyroxine concentration and psychomotor development at 2 years of age (corrected for preterm birth) was studied. A significant association was found between low neonatal thyroxine concentration and a negative score on the three milestones of development. These findings do not support the view that transient hypothyroxinaemia in preterm infants is harmless. PMID:1381573

  14. Calcium rich transients: tidal detonations of white dwarfs?

    NASA Astrophysics Data System (ADS)

    Maccarone, Thomas

    2013-09-01

    We propose for a 40 kilosecond TOO observation of a new Ca-rich gap transient. These enigmatic objects, with properties intermediate between those of classical novae and Type Ia supernovae, can be well-explained by tidal detonations of low mass white dwarfs by intermediate mass black holes. In such a case, fall-back accretion of the tidal debris would power an X-ray source for which we propose to search. Because supermassive black holes will swallow white dwarfs whole, a successful outcome to this proposal would both explain the Ca-rich gap transients *and* establish the existence of intermediate mass black holes.

  15. [Transient delayed paraplegia after repair of thoracic and thoracoabdominal aneurysms].

    PubMed

    Martín Torrijos, M; Aguilar Lloret, C; Ariño Irujo, J J; Serrano Hernando, F J; López Timoneda, F

    2013-11-01

    Thoracoabdominal aneurysm requires multidisciplinary management due to its complexity both in surgical technique and anesthetic considerations. One of the most feared postoperative complication is spinal cord ischemia. It can be presented as different clinical patterns, and its recovery may be partial or complete. The postoperative management of spinal cord ischemia is mainly based on techniques to increase spinal cord perfusion, above all, hemodynamic stability and cerebrospinal fluid drainage. We present two cases of delayed paraplegia after an open repair of a thoracoabdominal aneurysm and a descending thoracic aortic aneurysm repair using an endovascular stent graft. They both had a complete neurological recovery after cerebrospinal fluid drainage.

  16. Diffuse dispersive delay and the time convolution/attenuation of transients

    NASA Technical Reports Server (NTRS)

    Bittner, Burt J.

    1991-01-01

    Test data and analytic evaluations are presented to show that relatively poor 100 KHz shielding of 12 Db can effectively provide an electromagnetic pulse transient reduction of 100 Db. More importantly, several techniques are shown for lightning surge attenuation as an alternative to crowbar, spark gap, or power zener type clipping which simply reflects the surge. A time delay test method is shown which allows CW testing, along with a convolution program to define transient shielding effectivity where the Fourier phase characteristics of the transient are known or can be broadly estimated.

  17. Effects of photoreleased cADP-ribose on calcium transients and calcium sparks in myocytes isolated from guinea-pig and rat ventricle.

    PubMed Central

    Cui, Y; Galione, A; Terrar, D A

    1999-01-01

    Actions of photoreleased cADP-ribose (cADPR), a novel regulator of calcium-induced calcium release (CICR) from ryanodine-sensitive stores, were investigated in cardiac myocytes. Photoreleased cADPR caused an increase in the magnitude of whole-cell calcium transients studied in mammalian cardiac ventricular myocytes (both guinea-pig and rat) using confocal microscopy). Approx. 15 s was required following photorelease of cADPR for the development of its maximal effect. Photoreleased cADPR also increased the frequency of calcium 'sparks', which are thought to be elementary events which make up the whole-cell calcium transient, and were studied in rat myocytes, but had little or no effect on spark characteristics (amplitude, rise time, decay time and distance to half amplitude). The potentiating effects of photoreleased cADPR on both whole-cell transients and the frequency of calcium sparks were prevented by cytosolic application of the antagonist 8-amino-cADPR (5 microM). These experiments, therefore, provide the first evidence in any cell type for an effect of cADPR on calcium sparks, and are the first to show the actions of photoreleased cADPR on whole-cell calcium transients in mammalian cells. The observations are consistent with the effects of cADPR in enhancing the calcium sensitivity of CICR from the sarcoplasmic reticulum in cardiac ventricular myocytes, leading to an increase in the probability of occurrence of calcium sparks and to an increase in whole-cell calcium transients. The slow time-course for development of the full effect on whole-cell calcium transients might be taken to indicate that the influence of cADPR on CICR may involve complex molecular interactions rather than a simple direct action of cADPR on the ryanodine-receptor channels. PMID:10455010

  18. Computational reconstitution of spine calcium transients from individual proteins

    PubMed Central

    Bartol, Thomas M.; Keller, Daniel X.; Kinney, Justin P.; Bajaj, Chandrajit L.; Harris, Kristen M.; Sejnowski, Terrence J.; Kennedy, Mary B.

    2015-01-01

    We have built a stochastic model in the program MCell that simulates Ca2+ transients in spines from the principal molecular components believed to control Ca2+ entry and exit. Proteins, with their kinetic models, are located within two segments of dendrites containing 88 intact spines, centered in a fully reconstructed 6 × 6 × 5 μm3 cube of hippocampal neuropil. Protein components include AMPA- and NMDA-type glutamate receptors, L- and R-type voltage-dependent Ca2+ channels, Na+/Ca2+ exchangers, plasma membrane Ca2+ ATPases, smooth endoplasmic reticulum Ca2+ ATPases, immobile Ca2+ buffers, and calbindin. Kinetic models for each protein were taken from published studies of the isolated proteins in vitro. For simulation of electrical stimuli, the time course of voltage changes in the dendritic spine was generated with the desired stimulus in the program NEURON. Voltage-dependent parameters were then continuously re-adjusted during simulations in MCell to reproduce the effects of the stimulus. Nine parameters of the model were optimized within realistic experimental limits by a process that compared results of simulations to published data. We find that simulations in the optimized model reproduce the timing and amplitude of Ca2+ transients measured experimentally in intact neurons. Thus, we demonstrate that the characteristics of individual isolated proteins determined in vitro can accurately reproduce the dynamics of experimentally measured Ca2+ transients in spines. The model will provide a test bed for exploring the roles of additional proteins that regulate Ca2+ influx into spines and for studying the behavior of protein targets in the spine that are regulated by Ca2+ influx. PMID:26500546

  19. Microscopic heat pulses induce contraction of cardiomyocytes without calcium transients

    SciTech Connect

    Oyama, Kotaro; Mizuno, Akari; Shintani, Seine A.; Itoh, Hideki; Serizawa, Takahiro; Fukuda, Norio; Suzuki, Madoka

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Infra-red laser beam generates microscopic heat pulses. Black-Right-Pointing-Pointer Heat pulses induce contraction of cardiomyocytes. Black-Right-Pointing-Pointer Ca{sup 2+} transients during the contraction were not detected. Black-Right-Pointing-Pointer Skinned cardiomyocytes in free Ca{sup 2+} solution also contracted. Black-Right-Pointing-Pointer Heat pulses regulated the contractions without Ca{sup 2+} dynamics. -- Abstract: It was recently demonstrated that laser irradiation can control the beating of cardiomyocytes and hearts, however, the precise mechanism remains to be clarified. Among the effects induced by laser irradiation on biological tissues, temperature change is one possible effect which can alter physiological functions. Therefore, we investigated the mechanism by which heat pulses, produced by infra-red laser light under an optical microscope, induce contractions of cardiomyocytes. Here we show that microscopic heat pulses induce contraction of rat adult cardiomyocytes. The temperature increase, {Delta}T, required for inducing contraction of cardiomyocytes was dependent upon the ambient temperature; that is, {Delta}T at physiological temperature was lower than that at room temperature. Ca{sup 2+} transients, which are usually coupled to contraction, were not detected. We confirmed that the contractions of skinned cardiomyocytes were induced by the heat pulses even in free Ca{sup 2+} solution. This heat pulse-induced Ca{sup 2+}-decoupled contraction technique has the potential to stimulate heart and skeletal muscles in a manner different from the conventional electrical stimulations.

  20. Prostaglandin F2 alpha-induced calcium transient in ovine large luteal cells: II. Modulation of the transient and resting cytosolic free calcium alters progesterone secretion.

    PubMed

    Wegner, J A; Martinez-Zaguilan, R; Gillies, R J; Hoyer, P B

    1991-02-01

    A previous study demonstrated that prostaglandin F2 alpha (PGF2 alpha) stimulates a transient increase in cytosolic free Ca2+ levels [( Ca2+]i) in ovine large luteal cells. In the present study, the magnitude of the PGF2 alpha (0.5 microM)-induced calcium transient in Hanks' medium (87 +/- 2 nM increase above resting levels) was reduced (P less than 0.05) but not completely eliminated in fura-2 loaded large luteal cells incubated in Ca2(+)-free or phosphate- and carbonate-free medium (10 +/- 1 nM, 32 +/- 6 nM, above resting levels; respectively). Preincubation for 2 min with 1 mM LaCl3 (calcium antagonist) eliminated the PGF2 alpha-induced calcium transient. The inhibitory effect of PGF2 alpha on secretion of progesterone was reduced in Ca2(+)-free medium or medium plus LaCl3. Resting [Ca2+]i levels and basal secretion of progesterone were both reduced (P less than 0.05) in large cells incubated in Ca2(+)-free medium (27 +/- 4 nM; 70 +/- 6% control, respectively) or with 5 microM 5,5'-dimethyl bis-(O-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (40 +/- 2 nM; 49 +/- 1% control; respectively). In addition, secretion of progesterone was inhibited (P less than 0.05) by conditions that increased (P less than 0.05) [Ca2+]i; that is LaCl3 ([Ca2+]i, 120 +/- 17 nM; progesterone, 82 +/- 8% control) and PGF2 alpha ([Ca2+]i, 102 +/- 10 nM; progesterone, 82 +/- 3% control). In small luteal cells, resting [Ca2+]i levels and secretion of progesterone were reduced by incubation in Ca2(+)-free Hanks ([Ca2+]i, 28 +/- 2 nM; progesterone, 71 +/- 6% control), however, neither LaCl3 nor PGF2 alpha increased [Ca2+]i levels or inhibited secretion of progesterone. The findings presented here provide evidence that extracellular as well as intracellular calcium contribute to the PGF2 alpha-induced [Ca2+]i transient in large cells. Furthermore, whereas an adequate level of [Ca2+]i is required to support progesterone production in both small and large cells, optimal progesterone production in

  1. Signal analysis and classification methods for the calcium transient data of stem cell-derived cardiomyocytes.

    PubMed

    Juhola, Martti; Penttinen, Kirsi; Joutsijoki, Henry; Varpa, Kirsi; Saarikoski, Jyri; Rasku, Jyrki; Siirtola, Harri; Iltanen, Kati; Laurikkala, Jorma; Hyyrö, Heikki; Hyttinen, Jari; Aalto-Setälä, Katriina

    2015-06-01

    Calcium cycling is crucial in the excitation-contraction coupling of cardiomyocytes, and therefore has a key role in cardiac functionality. Cardiac disorders and different drugs alter the calcium transients of cardiomyocytes and can cause serious dysfunction of the heart. New insights into this biochemical phenomena can be achieved by studying and analyzing calcium transients. Calcium transients of spontaneously beating human induced pluripotent stem cell-derived cardiomyocytes were recorded for a data set of 280 signals. Our objective was to develop and program procedures: (1) to automatically detect cycling peaks from signals and to classify the peaks of signals as either normal or abnormal, and (2) on the basis of the preceding peak detection results, to classify the entire signals into either a normal class or an abnormal class. We obtained a classification accuracy of approximately 80% compared to class decisions made separately by an experienced researcher, which is promising for the further development of an automatic classification approach. Automated classification software would be beneficial in the future for analyzing cardiomyocyte functionality on a large scale when screening for the adverse cardiac effects of new potential compounds, and also in future clinical applications.

  2. Calcium transients in asymmetrically activated skeletal muscle fibers.

    PubMed Central

    Trube, G; Lopez, J R; Taylor, S R

    1981-01-01

    Skeletal muscle fibers of the frog Rana temporaria were held just taut and stimulated transversely by unidirectional electrical fields. We observed the reversible effects of stimulus duration (0.1-100 ms) and strength on action potentials, intracellular Ca2+ transients (monitored by aequorin), and contractile force during fixed-end contractions. Long duration stimuli (e.g., 10 ms) induced a maintained depolarization on the cathodal side of a cell and a maintained hyperpolarization on its anodal side. The hyperpolarization of the side facing the anode prevented the action potential from reaching mechanical threshold during strong stimuli. Variation of the duration or strength of a stimulus changed the luminescent response from a fiber injected with aequorin. Thus, the intracellular Ca2+ released during excitation-contraction coupling could be changed by the stimulus parameters. Prolongation of a stimulus at field strengths above 1.1 x rheobase decreased the amplitude of aequorin signals and the force of contractions. The decreases in aequorin and force signals from a given fiber paralleled one another and depended on the stimulus strength, but not on the stimulus polarity. These changes were completely reversible for stimulus strengths up to at least 4.2 x rheobase. The graded decreases in membrane depolarization, aequorin signals, and contractile force were correlated with the previously described folding of myofibrils in fibers allowed to shorten in response to the application of a long duration stimulus. The changes in aequorin signals and force suggest an absence of myofilament activation by Ca2+ in the section of the fiber closest to the anode. The results imply that injected aequorin distributes circumferentially in frog muscle with a coefficient of at least 10(-7) cm2/s, which is not remarkably different from the previously measured coefficient of 5 x 10(-8) cm2/s for its diffusion lengthwise. PMID:6976801

  3. The negative inotropic action of canrenone is mediated by L-type calcium current blockade and reduced intracellular calcium transients

    PubMed Central

    Costa, AR; Torres, LB; Medei, E; Ricardo, RA; França, JP; Smaili, S; Nascimento, JHM; Oshiro, MEM; Bassani, JWM; Ferreira, AT; Tucci, PJF

    2009-01-01

    Background and purpose: Adding spironolactone to standard therapy in heart failure reduces morbidity and mortality, but the underlying mechanisms are not fully understood. We analysed the effect of canrenone, the major active metabolite of spironolactone, on myocardial contractility and intracellular calcium homeostasis. Experimental approach: Left ventricular papillary muscles and cardiomyocytes were isolated from male Wistar rats. Contractility of papillary muscles was assessed with force transducers, Ca2+ transients by fluorescence and Ca2+ fluxes by electrophysiological techniques. Key results: Canrenone (300–600 µmol·L−1) reduced developed tension, maximum rate of tension increase and maximum rate of tension decay of papillary muscles. In cardiomyocytes, canrenone (50 µmol·L−1) reduced cell shortening and L-type Ca2+ channel current, whereas steady-state activation and inactivation, and reactivation curves were unchanged. Canrenone also decreased the Ca2+ content of the sarcoplasmic reticulum, intracellular Ca2+ transient amplitude and intracellular diastolic Ca2+ concentration. However, the time course of [Ca2+]i decline during transients evoked by caffeine was not affected by canrenone. Conclusion and implications: Canrenone reduced L-type Ca2+ channel current, amplitude of intracellular Ca2+ transients and Ca2+ content of sarcoplasmic reticulum in cardiomyocytes. These changes are likely to underlie the negative inotropic effect of canrenone. PMID:19663883

  4. Label-Free Imaging of Dynamic and Transient Calcium Signaling in Single Cells.

    PubMed

    Lu, Jin; Li, Jinghong

    2015-11-01

    Cell signaling consists of diverse events that occur at various temporal and spatial scales, ranging from milliseconds to hours and from single biomolecules to cell populations. The pathway complexities require the development of new techniques that detect the overall signaling activities and are not limited to quantifying a single event. A plasmonic-based electrochemical impedance microscope (P-EIM) that can provide such data with excellent temporal and spatial resolution and does not require the addition of any labels for detection has now been developed. The highly dynamic and transient calcium signaling activities at the early stage of G-protein-coupled receptor (GPCR) stimulation were thus studied. It could be shown that a subpopulation of cells is more responsive towards agonist stimulation, and the heterogeneity of the local distributions and the transient activities of the ion channels during agonist-activated calcium flux in single HeLa cells were investigated.

  5. Calcium-channel blockers and other factors influencing delayed function in renal allografts.

    PubMed

    Ferguson, C J; Hillis, A N; Williams, J D; Griffin, P J; Salaman, J R

    1990-01-01

    A retrospective analysis was undertaken to examine the influence of calcium-channel blocking drugs on early renal allograft function. Delayed function was defined as the need for dialysis or a reduction in serum creatinine of less than 15% within 4 days of transplantation. The drug histories of 172 patients were examined. After exclusions, the data from 138 patients were analysed. No patient was taking any calcium-channel blocking drug other than nifedipine. Thirty-one patients were taking nifedipine at the time of transplantation and these had a delayed function rate of 16% compared with 40% for 107 patients not taking nifedipine (chi 2, P less than 0.05). Delayed function occurred in 61% of cases when the donor age was over 50 years compared with 29% with younger donors (chi 2, P less than 0.05). A total ischaemic time of longer than 24 h and administration of inotropic support to the donor were associated with delayed function (chi 2, P less than 0.05). Administration to the donor of mannitol, steroids, phenoxybenzamine and heparin had no effect on the rate of delayed function. Recipients treated with low-dose dopamine in the perioperative period had no advantage. Elevated trough whole blood concentrations of cyclosporin in the first week after transplant were associated with delayed function (Mann-Whitney U, P less than 0.05).

  6. Role of tissue plasminogen activator/plasmin cascade in delayed neuronal death after transient forebrain ischemia.

    PubMed

    Takahashi, Hiroshi; Nagai, Nobuo; Urano, Tetsumei

    We studied the possible involvement of the tissue plasminogen activator (t-PA)/plasmin system on both delayed neuronal death in the hippocampus and the associated enhancement of locomotor activity in rats, after transient forebrain ischemia induced by a four-vessel occlusion (FVO). Seven days after FVO, locomotor activity was abnormally increased and, after 10 days, pyramidal cells were degraded in the CA1 region of the hippocampus. FVO increased the t-PA antigen level and its activity in the hippocampus, which peaked at 4 h. Both the enhanced locomotor activity and the degradation of pyramidal cells were significantly suppressed by intracerebroventricular injection of aprotinin, a plasmin inhibitor, at 4 h but not during FVO. These results suggest the importance of the t-PA/plasmin cascade during the early pathological stages of delayed neuronal death in the hippocampus following transient forebrain ischemia.

  7. Transient calcium release induced by successive increments of inositol 1,4,5-trisphosphate.

    PubMed Central

    Meyer, T; Stryer, L

    1990-01-01

    Many hormonal, neurotransmitter, and sensory stimuli trigger the formation of inositol 1,4,5-trisphosphate, which in turn releases calcium from intracellular stores. We report here that inositol 1,4,5-trisphosphate-induced calcium release from saponin-permeabilized rat basophilic leukemia cells at 37 degrees C is markedly biphasic, in contrast with nearly monophasic release kinetics at 11 degrees C. Hepatoma, PC-12 neuronal cells, and several other cell types exhibit similar biphasic release at 37 degrees C. The biphasic kinetics are not due to degradation of inositol 1,4,5-trisphosphate or to increased Ca2(+)-ATPase pump activity. Biphasic calcium release was also seen when ATP was quenched to less than 0.4 microM by adding hexokinase and glucose, suggesting that phosphorylation is not involved. External calcium (100 nM-600 nM) range had little influence on the biphasic kinetics. Rapid-mixing experiments revealed that rapid efflux of calcium is followed in approximately 0.5 s by a 30-fold slower efflux. Most striking, successive additions of the same amount of inositol 1,4,5-trisphosphate induced short bursts of calcium release of similar size. This retention of responsiveness, which we term increment detection, may be a distinct mode of signal transduction. Like inactivation and adaptation, increment detection gives rise to transient responses to sustained stimuli. Systems exhibiting inactivation, adaptation, and increment detection differ in their responsiveness (none, partial, and full, respectively) to stepwise increases in stimulus intensity. Increment detection could be advantageous in generating receptor-triggered calcium oscillations. Images PMID:2339124

  8. NOTE: Total body-calcium measurements: comparison of two delayed-gamma neutron activation facilities

    NASA Astrophysics Data System (ADS)

    Ma, R.; Ellis, K. J.; Yasumura, S.; Shypailo, R. J.; Pierson, R. N., Jr.

    1999-06-01

    This study compares two independently calibrated delayed-gamma neutron activation (DGNA) facilities, one at the Brookhaven National Laboratory (BNL), Upton, New York, and the other at the Children's Nutrition Research Center (CNRC), Houston, Texas that measure total body calcium (TBCa). A set of BNL phantoms was sent to CNRC for neutron activation analysis, and a set of CNRC phantoms was measured at BNL. Both facilities showed high precision (<2%), and the results were in good agreement, within 5%.

  9. ATP Released by Electrical Stimuli Elicits Calcium Transients and Gene Expression in Skeletal Muscle*

    PubMed Central

    Buvinic, Sonja; Almarza, Gonzalo; Bustamante, Mario; Casas, Mariana; López, Javiera; Riquelme, Manuel; Sáez, Juan Carlos; Huidobro-Toro, Juan Pablo; Jaimovich, Enrique

    2009-01-01

    ATP released from cells is known to activate plasma membrane P2X (ionotropic) or P2Y (metabotropic) receptors. In skeletal muscle cells, depolarizing stimuli induce both a fast calcium signal associated with contraction and a slow signal that regulates gene expression. Here we show that nucleotides released to the extracellular medium by electrical stimulation are partly involved in the fast component and are largely responsible for the slow signals. In rat skeletal myotubes, a tetanic stimulus (45 Hz, 400 1-ms pulses) rapidly increased extracellular levels of ATP, ADP, and AMP after 15 s to 3 min. Exogenous ATP induced an increase in intracellular free Ca2+ concentration, with an EC50 value of 7.8 ± 3.1 μm. Exogenous ADP, UTP, and UDP also promoted calcium transients. Both fast and slow calcium signals evoked by tetanic stimulation were inhibited by either 100 μm suramin or 2 units/ml apyrase. Apyrase also reduced fast and slow calcium signals evoked by tetanus (45 Hz, 400 0.3-ms pulses) in isolated mouse adult skeletal fibers. A likely candidate for the ATP release pathway is the pannexin-1 hemichannel; its blockers inhibited both calcium transients and ATP release. The dihydropyridine receptor co-precipitated with both the P2Y2 receptor and pannexin-1. As reported previously for electrical stimulation, 500 μm ATP significantly increased mRNA expression for both c-fos and interleukin 6. Our results suggest that nucleotides released during skeletal muscle activity through pannexin-1 hemichannels act through P2X and P2Y receptors to modulate both Ca2+ homeostasis and muscle physiology. PMID:19822518

  10. ATP released by electrical stimuli elicits calcium transients and gene expression in skeletal muscle.

    PubMed

    Buvinic, Sonja; Almarza, Gonzalo; Bustamante, Mario; Casas, Mariana; López, Javiera; Riquelme, Manuel; Sáez, Juan Carlos; Huidobro-Toro, Juan Pablo; Jaimovich, Enrique

    2009-12-11

    ATP released from cells is known to activate plasma membrane P2X (ionotropic) or P2Y (metabotropic) receptors. In skeletal muscle cells, depolarizing stimuli induce both a fast calcium signal associated with contraction and a slow signal that regulates gene expression. Here we show that nucleotides released to the extracellular medium by electrical stimulation are partly involved in the fast component and are largely responsible for the slow signals. In rat skeletal myotubes, a tetanic stimulus (45 Hz, 400 1-ms pulses) rapidly increased extracellular levels of ATP, ADP, and AMP after 15 s to 3 min. Exogenous ATP induced an increase in intracellular free Ca(2+) concentration, with an EC(50) value of 7.8 +/- 3.1 microm. Exogenous ADP, UTP, and UDP also promoted calcium transients. Both fast and slow calcium signals evoked by tetanic stimulation were inhibited by either 100 mum suramin or 2 units/ml apyrase. Apyrase also reduced fast and slow calcium signals evoked by tetanus (45 Hz, 400 0.3-ms pulses) in isolated mouse adult skeletal fibers. A likely candidate for the ATP release pathway is the pannexin-1 hemichannel; its blockers inhibited both calcium transients and ATP release. The dihydropyridine receptor co-precipitated with both the P2Y(2) receptor and pannexin-1. As reported previously for electrical stimulation, 500 mum ATP significantly increased mRNA expression for both c-fos and interleukin 6. Our results suggest that nucleotides released during skeletal muscle activity through pannexin-1 hemichannels act through P2X and P2Y receptors to modulate both Ca(2+) homeostasis and muscle physiology. PMID:19822518

  11. Calcium currents and transients in co-cultured contracting normal and Duchenne muscular dystrophy human myotubes

    PubMed Central

    Imbert, Nathalie; Vandebrouck, Clarisse; Duport, Gérard; Raymond, Guy; Hassoni, Abdul A; Constantin, Bruno; Cullen, Michael J; Cognard, Christian

    2001-01-01

    The goal of the present study was to investigate differences in calcium movements between normal and Duchenne muscular dystrophy (DMD) human contracting myotubes co-cultured with explants of rat spinal cord with attached dorsal root ganglia. Membrane potential, variations of intracellular calcium concentration and T- and L-type calcium currents were recorded. Further, a descriptive and quantitative study by electron microscopy of the ultrastructure of the co-cultures was carried out. The resting membrane potential was slightly less negative in DMD (−61.4 ± 1.1 mV) than in normal myotubes (−65.5 ± 0.9 mV). Both types of myotube displayed spontaneous action potentials (mean firing frequency, 0.42 and 0.16 Hz, respectively), which triggered spontaneous calcium transients measured with Indo-1. The time integral under the spontaneous Ca2+ transients was significantly greater in DMD myotubes (97 ± 8 nm s) than in normal myotubes (67 ± 13 nm s). The L- and T-type current densities estimated from patch-clamp recordings were smaller in DMD cells (2.0 ± 0.5 and 0.90 ± 0.19 pA pF−1, respectively) than in normal cells (3.9 ± 0.7 and 1.39 ± 0.30 pA pF−1, respectively). The voltage-dependent inactivation relationships revealed a shift in the conditioning potential at which inactivation is half-maximal (Vh,0.5) of the T- and L-type currents towards less negative potentials, from −72.1 ± 0.7 and −53.7 ± 1.5 mV in normal cells to −61.9 ± 1.4 and −29.2 ± 1.4 mV in DMD cells, respectively. Both descriptive and quantitative studies by electron microscopy suggested a more advanced development of DMD myotubes as compared to normal ones. This conclusion was supported by the significantly larger capacitance of the DMD myotubes (408 ± 45 pF) than of the normal myotubes (299 ± 34 pF) of the same apparent size. Taken together, these results show that differences in T- and L-type calcium currents between normal and DMD myotubes cannot simply explain all observed

  12. IP(3)-dependent, post-tetanic calcium transients induced by electrostimulation of adult skeletal muscle fibers.

    PubMed

    Casas, Mariana; Figueroa, Reinaldo; Jorquera, Gonzalo; Escobar, Matías; Molgó, Jordi; Jaimovich, Enrique

    2010-10-01

    Tetanic electrical stimulation induces two separate calcium signals in rat skeletal myotubes, a fast one, dependent on Cav 1.1 or dihydropyridine receptors (DHPRs) and ryanodine receptors and related to contraction, and a slow signal, dependent on DHPR and inositol trisphosphate receptors (IP(3)Rs) and related to transcriptional events. We searched for slow calcium signals in adult muscle fibers using isolated adult flexor digitorum brevis fibers from 5-7-wk-old mice, loaded with fluo-3. When stimulated with trains of 0.3-ms pulses at various frequencies, cells responded with a fast calcium signal associated with muscle contraction, followed by a slower signal similar to one previously described in cultured myotubes. Nifedipine inhibited the slow signal more effectively than the fast one, suggesting a role for DHPR in its onset. The IP(3)R inhibitors Xestospongin B or C (5 µM) also inhibited it. The amplitude of post-tetanic calcium transients depends on both tetanus frequency and duration, having a maximum at 10-20 Hz. At this stimulation frequency, an increase of the slow isoform of troponin I mRNA was detected, while the fast isoform of this gene was inhibited. All three IP(3)R isoforms were present in adult muscle. IP(3)R-1 was differentially expressed in different types of muscle fibers, being higher in a subset of fast-type fibers. Interestingly, isolated fibers from the slow soleus muscle did not reveal the slow calcium signal induced by electrical stimulus. These results support the idea that IP(3)R-dependent slow calcium signals may be characteristic of distinct types of muscle fibers and may participate in the activation of specific transcriptional programs of slow and fast phenotype. PMID:20837675

  13. IP3-dependent, post-tetanic calcium transients induced by electrostimulation of adult skeletal muscle fibers

    PubMed Central

    Casas, Mariana; Figueroa, Reinaldo; Jorquera, Gonzalo; Escobar, Matías; Molgó, Jordi

    2010-01-01

    Tetanic electrical stimulation induces two separate calcium signals in rat skeletal myotubes, a fast one, dependent on Cav 1.1 or dihydropyridine receptors (DHPRs) and ryanodine receptors and related to contraction, and a slow signal, dependent on DHPR and inositol trisphosphate receptors (IP3Rs) and related to transcriptional events. We searched for slow calcium signals in adult muscle fibers using isolated adult flexor digitorum brevis fibers from 5–7-wk-old mice, loaded with fluo-3. When stimulated with trains of 0.3-ms pulses at various frequencies, cells responded with a fast calcium signal associated with muscle contraction, followed by a slower signal similar to one previously described in cultured myotubes. Nifedipine inhibited the slow signal more effectively than the fast one, suggesting a role for DHPR in its onset. The IP3R inhibitors Xestospongin B or C (5 µM) also inhibited it. The amplitude of post-tetanic calcium transients depends on both tetanus frequency and duration, having a maximum at 10–20 Hz. At this stimulation frequency, an increase of the slow isoform of troponin I mRNA was detected, while the fast isoform of this gene was inhibited. All three IP3R isoforms were present in adult muscle. IP3R-1 was differentially expressed in different types of muscle fibers, being higher in a subset of fast-type fibers. Interestingly, isolated fibers from the slow soleus muscle did not reveal the slow calcium signal induced by electrical stimulus. These results support the idea that IP3R-dependent slow calcium signals may be characteristic of distinct types of muscle fibers and may participate in the activation of specific transcriptional programs of slow and fast phenotype. PMID:20837675

  14. Transient electrical coupling delays the onset of chemical neurotransmission at developing synapses.

    PubMed

    Szabo, Theresa M; Faber, Donald S; Zoran, Mark J

    2004-01-01

    The formation and subsequent elimination of electrical coupling between neurons has been demonstrated in many developing vertebrate and invertebrate nervous systems. The relationship between the disappearance of electrical synaptic connectivity and the appearance of chemical neurotransmission is not well understood. We report here that identified motoneurons from the snail Helisoma formed transient electrical and chemical connections during regeneration both in vivo and in vitro. Electrical connections that formed in vivo were strongest by day 2 and no longer detectable by day 7. During elimination of this electrical connection, an inhibitory chemical connection from 110 onto 19 formed. This sequence of synaptic development was recapitulated in cell culture with a similar time course. The relationship between the appearance of transient electrical coupling and its possible effects on the subsequent chemical synaptogenesis were examined by reducing transient intercellular coupling. Trophic factor-deprived medium resulted in a 66% reduction in coupling coefficient. In these conditions, the unidirectional chemical connection formed readily; in contrast, chemical synaptogenesis was delayed in cell pairs exposed to trophic factors where transient electrical coupling was strong. Dye coupling and synaptic vesicle cycling studies supported electrophysiological results. Exposure to cholinergic antagonists, curare and hexamethonium bromide, which block chemical neurotransmission in these synapses, resulted in prolonged maintenance of the electrical connection. These studies demonstrated an inverse relationship between chemical and electrical connectivity at early stages of synaptic development and suggest a dynamic interaction between these forms of neuronal communication as adult neural networks are constructed or regenerated. PMID:14715944

  15. Transient exposure to calcium ionophore enables in vitro fertilization in sterile mouse models

    PubMed Central

    Navarrete, Felipe A.; Alvau, Antonio; Lee, Hoi Chang; Levin, Lonny R.; Buck, Jochen; Leon, Patricia Martin-De; Santi, Celia M.; Krapf, Dario; Mager, Jesse; Fissore, Rafael A.; Salicioni, Ana M.; Darszon, Alberto; Visconti, Pablo E.

    2016-01-01

    Mammalian sperm acquire fertilizing capacity in the female tract in a process called capacitation. At the molecular level, capacitation requires protein kinase A activation, changes in membrane potential and an increase in intracellular calcium. Inhibition of these pathways results in loss of fertilizing ability in vivo and in vitro. We demonstrated that transient incubation of mouse sperm with Ca2+ ionophore accelerated capacitation and rescued fertilizing capacity in sperm with inactivated PKA function. We now show that a pulse of Ca2+ ionophore induces fertilizing capacity in sperm from infertile CatSper1 (Ca2+ channel), Adcy10 (soluble adenylyl cyclase) and Slo3 (K+ channel) KO mice. In contrast, sperm from infertile mice lacking the Ca2+ efflux pump PMACA4 were not rescued. These results indicate that a transient increase in intracellular Ca2+ can overcome genetic infertility in mice and suggest this approach may prove adaptable to rescue sperm function in certain cases of human male infertility. PMID:27627854

  16. Transient exposure to calcium ionophore enables in vitro fertilization in sterile mouse models.

    PubMed

    Navarrete, Felipe A; Alvau, Antonio; Lee, Hoi Chang; Levin, Lonny R; Buck, Jochen; Leon, Patricia Martin-De; Santi, Celia M; Krapf, Dario; Mager, Jesse; Fissore, Rafael A; Salicioni, Ana M; Darszon, Alberto; Visconti, Pablo E

    2016-01-01

    Mammalian sperm acquire fertilizing capacity in the female tract in a process called capacitation. At the molecular level, capacitation requires protein kinase A activation, changes in membrane potential and an increase in intracellular calcium. Inhibition of these pathways results in loss of fertilizing ability in vivo and in vitro. We demonstrated that transient incubation of mouse sperm with Ca(2+) ionophore accelerated capacitation and rescued fertilizing capacity in sperm with inactivated PKA function. We now show that a pulse of Ca(2+) ionophore induces fertilizing capacity in sperm from infertile CatSper1 (Ca(2+) channel), Adcy10 (soluble adenylyl cyclase) and Slo3 (K(+) channel) KO mice. In contrast, sperm from infertile mice lacking the Ca(2+) efflux pump PMACA4 were not rescued. These results indicate that a transient increase in intracellular Ca(2+) can overcome genetic infertility in mice and suggest this approach may prove adaptable to rescue sperm function in certain cases of human male infertility. PMID:27627854

  17. Transient absorption spectroscopy detection of sensitized delayed fluorescence in chiral benzophenone/naphthalene systems

    NASA Astrophysics Data System (ADS)

    Bonancía, Paula; Jiménez, M. Consuelo; Miranda, Miguel A.

    2011-10-01

    Transient absorption spectroscopy has proven to be a powerful tool to investigate the formation and decay of excited singlet states upon triplet-triplet annihilation, following T-T energy transfer from a selectively excited sensitizer. Thus, upon selective excitation of benzophenone (BZP) by laser flash photolysis (LFP) at λ = 355 nm in the presence of naphthalene (NPT), a negative band centered at 340 nm has been detected, with growth and decay in the microsecond timescale. It has been assigned to the P-type NPT delayed-fluorescence. In the case of chiral BZP/NPT systems, stereodifferentiation has been observed in the kinetics of the involved photophysical processes.

  18. Microsecond Molecular Simulations Reveal a Transient Proton Pathway in the Calcium Pump.

    PubMed

    Espinoza-Fonseca, L Michel; Ramírez-Salinas, G Lizbeth

    2015-06-10

    The calcium pump sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) counter-transports Ca(2+) and H(+) at the expense of ATP hydrolysis. SERCA uses separate proton and metal ion pathways during active transport to neutralize the highly charged transport site, thus preserving SERCA's structural stability during active Ca(2+) transport. Although separate metal ion and proton pathways have been identified during slow (millisecond) structural transitions of SERCA, the existence of simultaneous metal and proton pathways during fast (microsecond) structural transitions remains unknown. We have analyzed microsecond-long trajectories of E1·H(+)771, a protonated intermediate of the pump populated during SERCA regulation. We found a transiently established hydrophobic pore in the luminal side of the transmembrane helices 6, 8, and 9. This narrow (0.5-0.6 nm) pore connects the transport sites to the sarcoplasmic reticulum lumen through a chain of water molecules. Protein pKa calculations of the transport site residues and structural analysis of the water molecules showed that this pore is suitable for proton transport. This transient proton pathway ensures neutralization of the transport sites during the rapid structural transitions associated with regulation of the pump. We conclude that this transient proton pathway plays a central role in optimizing active Ca(2+) transport by SERCA. Our discovery provides insight into ion-exchange mechanisms through transient hydrophobic pores in P-type ATPases.

  19. Cav3-type α1T calcium channels mediate transient calcium currents that regulate repetitive firing in Drosophila antennal lobe PNs

    PubMed Central

    Iniguez, Jorge; Schutte, Soleil S.

    2013-01-01

    Projection neurons (PNs), located in the antennal lobe region of the insect brain, play a key role in processing olfactory information. To explore how activity is regulated at the level of single PNs within this central circuit we have recorded from these neurons in adult Drosophila melanogaster brains. Our previous study demonstrated that PNs express voltage-gated calcium currents with a transient and sustained component. We found that the sustained component is mediated by cac gene-encoded Cav2-type channels involved in regulating action potential-independent release of neurotransmitter at excitatory cholinergic synapses. The function of the transient calcium current and the gene encoding the underlying channels, however, were unknown. Here we report that the transient current blocked by prepulse inactivation is sensitive to amiloride, a vertebrate Cav3-type channel blocker. In addition PN-specific RNAi knockdown of α1T, the Drosophila Cav3-type gene, caused a dramatic reduction in the transient current without altering the sustained component. These data demonstrate that the α1T gene encodes voltage-gated calcium channels underlying the amiloride-sensitive transient current. Alterations in evoked firing and spontaneous burst firing in the α1T knockdowns demonstrate that the Cav3-type calcium channels are important in regulating excitability in adult PNs. PMID:23864373

  20. On the origin of rhythmic calcium transients in the ICC-MP of the mouse small intestine.

    PubMed

    Lowie, Bobbi-Jo; Wang, Xuan-Yu; White, Elizabeth J; Huizinga, Jan D

    2011-11-01

    Interstitial cells of Cajal associated with the myenteric plexus (ICC-MP) are pacemaker cells of the small intestine, producing the characteristic omnipresent electrical slow waves, which orchestrate peristaltic motor activity and are associated with rhythmic intracellular calcium oscillations. Our objective was to elucidate the origins of the calcium transients. We hypothesized that calcium oscillations in the ICC-MP are primarily regulated by the sarcoplasmic reticulum (SR) calcium release system. With the use of calcium imaging, study of the effect of T-type calcium channel blocker mibefradil revealed that T-type channels did not play a major role in generating the calcium transients. 2-Aminoethoxydiphenyl borate, an inositol 1,4,5 trisphosphate receptor (IP(3)R) inhibitor, and U73122, a phospholipase C inhibitor, both drastically decreased the frequency of calcium oscillations, suggesting a major role of IP(3) and IP(3)-induced calcium release from the SR. Immunohistochemistry proved the expression of IP(3)R type I (IP(3)R-I), but not type II (IP(3)R-II) and type III (IP(3)R-III) in ICC-MP, indicating the involvement of the IP(3)R-I subtype in calcium release from the SR. Cyclopiazonic acid, a SR/endoplasmic reticulum calcium ATPase pump inhibitor, strongly reduced or abolished calcium oscillations. The Na-Ca exchanger (NCX) in reverse mode is likely involved in refilling the SR because the NCX inhibitor KB-R7943 markedly reduced the frequency of calcium oscillations. Immunohistochemistry revealed 100% colocalization of NCX and c-Kit in ICC-MP. Testing a mitochondrial NCX inhibitor, we were unable to show an essential role for mitochondria in regulating calcium oscillations in the ICC-MP. In summary, ongoing IP(3) synthesis and IP(3)-induced calcium release from the SR, via the IP(3)R-I, are the major drivers of the calcium transients associated with ICC pacemaker activity. This suggests that a biochemical clock intrinsic to ICC determines the pacemaker

  1. Demonstration of negative signal delay with short-duration transient pulse

    NASA Astrophysics Data System (ADS)

    Ravelo, B.

    2011-07-01

    This paper introduces theoretic and experimental analyses of short-duration pulse propagation through a negative group delay (NGD) circuit. The basic analysis method of this electronic circuit operating in baseband and microwave frequencies is investigated. Then, its electrical fundamental characteristics vis-à-vis transient signals are developed. To validate the theoretic concept, planar hybrid devices with one- and two-stage NGD cells were designed, simulated, fabricated and tested. Transient analyses with ultra-wide band (UWB) pulse signals with different widths are realized. Then, experimental results in good agreement with the theoretical predictions were observed. Consequently, group delay going down under -2.5 ns is evidenced in baseband frequency up to 63 MHz with one-stage NGD cell. In time-domain, a Gaussian pulse in advance of about t0 = -1.5 ns or 20% of its half-height time-width was measured. This corresponds to a negative group velocity of about vg = L/t0 = -0.13c (L is the physical length of the tested device and c is light speed in the vacuum). More significant NGD value over 100-MHz bandwidth is stated with two-stage NGD cells. This results in a Gaussian pulse peak advance of about -5 ns (raising a group velocity of about vg = -0.12c) or 31% of its half-height time-width. Finally, some potential applications based on the NGD function are discussed.

  2. Calmodulin modulates the delay period between release of calcium from internal stores and activation of calcium influx via endogenous TRP1 channels.

    PubMed

    Vaca, Luis; Sampieri, Alicia

    2002-11-01

    In the present study we have explored the role of calmodulin (CaM) and inositol 1,4,5-trisphosphate receptor (IP(3)R) in the communication process activated after the release of calcium from the endoplasmic reticulum (ER) and the activation of calcium influx via endogenous TRP1 channels from Chinese hamster ovary cells. Experiments using combined rapid confocal calcium and electrophysiology measurements uncovered a consistent delay of around 900 ms between the first detectable calcium released from the ER and the activation of the calcium current. This delay was evident with two different methods used to release calcium from the ER: either the blockade of the microsomal calcium ATPase with thapsigargin or activation of bradykinin receptors linked to the IP(3) cascade. Direct application of IP(3) or a peptide from the NH(2)-terminal region of the IP(3)R activated store operated calcium, reducing the delay period. Introduction of CaM into the cell via the patch pipette increased the delay period from 900 +/- 100 ms to 10 +/- 2.1 s (n = 18). Furthermore, the use of selective CaM antagonists W7 and trifluoperazine maleate resulted in a substantial reduction of the delay period to 200 +/- 100 ms with 5 microm trifluoperazine maleate (n = 16) and 150 +/- 50 ms with 500 nm W7 (n = 22). CaM reduced also the current density activated by thapsigargin or brandykinin to about 60% from control. The CaM antagonists did not affect significantly the current density. The results presented here are consistent with an antagonistic effect of IP(3)R and CaM for the activation of store operated calcium after depletion of the ER. The functional competition between the activating effect of IP(3)R and the inhibiting effect of CaM may modulate the delay period between the release of calcium from the ER and the activation of calcium influx observed in different cells, as well as the amount of current activated after depletion of the ER.

  3. 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

  4. Transient elevations of cytosolic free calcium retard subsequent apoptosis in neutrophils in vitro.

    PubMed Central

    Whyte, M K; Hardwick, S J; Meagher, L C; Savill, J S; Haslett, C

    1993-01-01

    Elevation of cytosolic calcium ([Ca2+]i) has been reported to induce apoptosis in a number of cell types. However, in the neutrophil, which undergoes apoptosis constitutively during aging in vitro, activation by inflammatory mediators elevates [Ca2+]i and prolongs lifespan via inhibition of apoptosis. To examine this paradox, we investigated the effects of modulation of [Ca2+]i upon apoptosis of neutrophils in vitro. Calcium ionophores (A23187, ionomycin) retarded apoptosis in neutrophil populations after 20 h (P < 0.001). Conversely, intracellular Ca(2+)-chelation, using bis-(o-aminophenoxy)-N,N,N'N'-tetraacetic acid (BAPTA) acetoxymethyl ester (AM) promoted apoptosis (P < 0.02). W-7 (an inhibitor of calmodulin) also promoted apoptosis (P < 0.05). Measurements of [Ca2+]i, using fura-2, showed (a) increased apoptosis in neutrophil populations was not associated with elevated [Ca2+]i, (b) neutrophils cultured with ionophore at concentrations inhibiting apoptosis exhibited transient (< 1 h) elevations of [Ca2+]i, to levels previously reported with receptor-mediated stimuli, and (c) BAPTA was able to prevent the elevation of [Ca2+]i and the inhibition of apoptosis produced by ionophore. Modulation of apoptosis occurred without alterations in intracellular pH. Thus, in the neutrophil, unlike lymphoid cells, elevation of [Ca2+]i exerts an inhibitory effect upon apoptosis. Furthermore, these data suggest that transient elevation of [Ca2+]i elicits signaling events leading to prolonged inhibition of apoptosis. Images PMID:8392090

  5. Transient Gain Adjustment in the Inferior Colliculus is Serotonin- and Calcium-dependent

    PubMed Central

    Miko, Ilona J.; Sanes, Dan H.

    2009-01-01

    In the inferior colliculus (IC), a brief period of acoustic conditioning can transiently enhance evoked discharge rate. The cellular basis of this phenomenon was assessed with whole cell current-clamp recordings in a gerbil IC brain slice preparation. The current needed to elicit a single action potential was first established for each neuron. A 5s synaptic stimulus train was delivered to the lateral lemniscus (LL), and followed immediately by the initial current pulse to assess a change in postsynaptic gain. The majority of IC neurons (66%) displayed an increase in current-evoked action potentials (positive gain). Despite the blockade of ionotropic glutamate receptors, this effect was correlated with membrane depolarization that occurred during the synaptic train. The postsynaptic mechanism for positive gain was examined by selective blockade of specific neurotransmitter receptors. Gain in action potentials was enhanced by antagonists of metabotropic glutamate, acetylcholine, GABAA and glycine receptors. In contrast, the gain was blocked or reduced by an antagonist to ionotropic serotonin receptors (5-HT3R). Blocking voltage-activated calcium channels with verapamil also reduced the effect. These results suggest that 5-HT3R activation, coupled with increased intracellular calcium, can transiently alter postsynaptic excitability in IC neurons. PMID:19232535

  6. Dissociation of Calcium Transients and Force Development following a Change in Stimulation Frequency in Isolated Rabbit Myocardium

    PubMed Central

    Haizlip, Kaylan M.; Milani-Nejad, Nima; Varian, Kenneth D.; Slabaugh, Jessica L.; Walton, Shane D.; Gyorke, Sandor; Davis, Jonathan P.; Biesiadecki, Brandon J.; Janssen, Paul M. L.

    2015-01-01

    As the heart transitions from one exercise intensity to another, changes in cardiac output occur, which are modulated by alterations in force development and calcium handling. Although the steady-state force-calcium relationship at various heart rates is well investigated, regulation of these processes during transitions in heart rate is poorly understood. In isolated right ventricular muscle preparations from the rabbit, we investigated the beat-to-beat alterations in force and calcium during the transition from one stimulation frequency to another, using contractile assessments and confocal microscopy. We show that a change in steady-state conditions occurs in multiple phases: a rapid phase, which is characterized by a fast change in force production mirrored by a change in calcium transient amplitude, and a slow phase, which follows the rapid phase and occurs as the muscle proceeds to stabilize at the new frequency. This second/late phase is characterized by a quantitative dissociation between the calcium transient amplitude and developed force. Twitch timing kinetics, such as time to peak tension and 50% relaxation rate, reached steady-state well before force development and calcium transient amplitude. The dynamic relationship between force and calcium upon a switch in stimulation frequency unveils the dynamic involvement of myofilament-based properties in frequency-dependent activation. PMID:25961020

  7. Continuous angiotensin-(1-7) infusion improves myocardial calcium transient and calcium transient alternans in ischemia-induced cardiac dysfunction rats.

    PubMed

    Luo, Duan; Zhuang, Xiaodong; Luo, Chufan; Long, Ming; Deng, Chunyu; Liao, Xinxue; Wang, Lichun

    2015-11-27

    The aim of this study was to evaluate the impact of Ang-(1-7) on calcium transient (CaT) in cardiomyocytes during the pathogenesis of heart failure. Cardiac dysfunction was induced by ligation of left anterior descending coronary artery in adult SD rats. Randomly selected rats were ligated and continuously infused with Ang-(1-7) [HF + Ang-(1-7) group] or saline (HF + saline group) via osmotic minipumps. After 28 days, hemodynamic parameters, the CaT, and the heart rate threshold of CaT alternans (CaT-Alt) were measured. Continuous Ang-(1-7) treatment could attenuate the impairment of cardiac function following LAD ligation. The amplitudes (F/F0) and 50%/90% recovery time of CaT were significantly different among HF + saline, HF + Ang-(1-7) and Sham-operated group. Compared to the Sham-operated group, the HF + saline group showed decreased CaT amplitude, and a prolonged 50%/90% CaT recovery time; Ang-(1-7) significantly improved these abnormalities. Compared with Sham-operated group, heart rate thresholds of CaT-Alt significantly reduced in HF + saline group, and Ang-(1-7) partly restored it. These findings indicate that Ang-(1-7) attenuates the CaT disturbance and increases the heart rate threshold of CaT-Alt during the pathogenesis of ischemic heart failure.

  8. Neuronal damage and calcium accumulation following transient cerebral ischemia in the rat

    SciTech Connect

    Araki, T.; Inoue, T.; Kato, H.; Kogure, K.; Murakami, M. )

    1990-06-01

    The purpose of this study was to examine the distribution of neuronal damage following transient cerebral ischemia in the rat model of four-vessel occlusion utilizing light microscopy as well as {sup 45}Ca-autoradiography. Transient ischemia was induced for 30 min. The animals were allowed to survive for 7 d after ischemia. In the animals subjected to ischemia, the most frequently and seriously damaged areas were the paramedian region of hippocampus, the hippocampal CA1 sector, and the dorsolateral part of striatum, followed by the inferior colliculus, the substantia nigra, the frontal cortex, and the thalamus, which were moderate damaged. Furthermore, the cerebellar Purkinje neurons, the hippocampal CA4 sector, the medial geniculate body, and the hippocampal CA3 sector were slightly affected. {sup 45}Ca-autoradiographyic study also revealed calcium accumulation in the identical sites of ischemic neuronal damage, except for the frontal cortex. Regional cerebral blood flow during 10 min of ischemia was severely decreased in selectively vulnerable areas. The blood flow in the medial geniculate body, the substantia nigra, the inferior colliculus, and the cerebellum was less pronounced than that in the selectively vulnerable areas. The present study demonstrates that transient cerebral ischemia can produce significant neuronal damage not only in the selectively vulnerable regions, but also in the brainstem.

  9. The effects of digitalis on intracellular calcium transients in mammalian working myocardium as detected with aequorin.

    PubMed

    Morgan, J P

    1985-11-01

    The effects of positive inotropic agents on the amplitude and time course of the light signal and corresponding tension response were studied in cat and human working myocardium microinjected with the bioluminescent Ca2+ indicator aequorin. Distinctive patterns of light and tension responses were identified that are consistent with known actions of the various agents on the release of Ca2+ from intracellular stores, rate of uptake of Ca2+ by the sarcoplasmic reticulum and sensitivity of the myofilaments to Ca2+. In common with most other inotropic drugs, the cardiotonic steroid, acetylstrophanthidin, in doses of 4 X 10(-7) to 2 X 10(-6)M increases the amount of Ca2+ available for excitation-contraction coupling in the heart. However, in contrast to most other agents, acetylstrophanthidin does not affect the time course of the calcium transient. In common with changes in [Ca2+]o, acetylstrophanthidin does not alter the relationship between the amplitude of the aequorin light signal and developed tension, which, in contrast to caffeine and isoproterenol, indicates that the increase in tension is fully accounted for by the increase in systolic free calcium. These findings suggest that the cardiotonic steroids increase loading of intracellular calcium stores without affecting the kinetics of subcellular handling of Ca2+. In doses of 8 X 10(-7) to 2 X 10(-6)M, acetylstrophanthidin produces a calcium-overload state characterized by 'after-contractions' and 'after-glimmers' that are associated with the development of automatic and triggerable dysrhythmias. These studies provide direct evidence that the inotropic and toxic effects of digitalis on animal and human working myocardium are produced by changes in intracellular Ca2+.

  10. 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

  11. Seronegative Maternal Ocular Myasthenia Gravis and Delayed Transient Neonatal Myasthenia Gravis.

    PubMed

    Townsel, Courtney; Keller, Rebecca; Johnson, Kendall; Hussain, Naveed; Campbell, Winston A

    2016-03-01

    Background Myasthenia gravis (MG) is an autoimmune disorder with fluctuating muscle weakness, divided into generalized and localized (ocular) forms. Maternal antibodies to acetylcholine receptors cross the placenta and may cause transient neonatal myasthenia gravis (TNMG). We present a case of seronegative maternal ocular MG and delayed TNMG. Case A 29-year-old G3P1011 underwent cesarean birth of a male infant who developed oxygen desaturation requiring supplemental oxygen on day of life (DOL) 3. Based on the clinical course and after exclusion of other diagnoses, the infant was diagnosed with TNMG. Infant's condition improved spontaneously and he was weaned off supplemental oxygen and discharged home on DOL 12. Conclusion Infants born to mothers with seronegative localized (ocular) MG are also susceptible to TNMG which may be late in onset.

  12. Seronegative Maternal Ocular Myasthenia Gravis and Delayed Transient Neonatal Myasthenia Gravis

    PubMed Central

    Townsel, Courtney; Keller, Rebecca; Johnson, Kendall; Hussain, Naveed; Campbell, Winston A.

    2016-01-01

    Background Myasthenia gravis (MG) is an autoimmune disorder with fluctuating muscle weakness, divided into generalized and localized (ocular) forms. Maternal antibodies to acetylcholine receptors cross the placenta and may cause transient neonatal myasthenia gravis (TNMG). We present a case of seronegative maternal ocular MG and delayed TNMG. Case A 29-year-old G3P1011 underwent cesarean birth of a male infant who developed oxygen desaturation requiring supplemental oxygen on day of life (DOL) 3. Based on the clinical course and after exclusion of other diagnoses, the infant was diagnosed with TNMG. Infant's condition improved spontaneously and he was weaned off supplemental oxygen and discharged home on DOL 12. Conclusion Infants born to mothers with seronegative localized (ocular) MG are also susceptible to TNMG which may be late in onset. PMID:26989568

  13. Small-signal transient response and turn-on delay of polariton laser diodes

    NASA Astrophysics Data System (ADS)

    Butté, Raphaël

    2016-03-01

    We present a theoretical description of the small-signal transient response of polariton laser diodes (pol-LDs) based on simplified coupled rate equations describing the exciton reservoir and the ground-state polariton populations. The analytic expressions derived for two pumping geometries, which are valid for all inorganic semiconductors suitable for the realization of pol-LDs, are compared to exact numerical calculations performed for the specific case of GaN-based devices. The two approaches show excellent agreement provided the current step transient remains within the small-signal limit. We report that the temporal attenuation of the envelopes of the oscillations matches half the value of the damping factor ({γ }{{d}}) of the pol-LDs, which is proportional to the square of the oscillation relaxation resonance frequency. An explicit expression for the dependence of {γ }{{d}} on both the exciton-photon detuning and the driving current (equivalently the optical pump power) is also obtained. In a further step, we derive the expression for the turn-on delay (t d) associated with the build-up of the exciton reservoir population up to its threshold value before coherent light emission occurs. We show that t d has the same functional form for the two pumping geometries. It is equal to the effective exciton lifetime ({τ }{x{eff}}) weighted by a logarithmic dependence on the initial and final driving currents. In addition, {τ }{x{eff}} is shown to be approximately equal to the exciton lifetime, which proves to be the main parameter governing the build-up of polariton lasing/condensation. Beyond electrically driven polariton lasers, we highlight that the temporal shape of the transients could also be easily tested by monitoring the time dependence of the output power of optically pumped polariton lasers subjected to a sudden increase in the continuous wave pump power within the small-signal limit.

  14. Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers

    PubMed Central

    Johnson, Matthew W.; Sewell, R. Andrew; Griffiths, Roland R.

    2011-01-01

    Background Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache. Methods This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30 mg/70 kg) on headache in 18 healthy participants. Results Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration. Conclusions Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research. PMID:22129843

  15. Superiority of Biphasic Over Monophasic Defibrillation Shocks is Attributable to Less Intracellular Calcium Transient Heterogeneity

    PubMed Central

    Hwang, Gyo-Seung; Tang, Liang; Joung, Boyoung; Morita, Norishige; Hayashi, Hideki; Karagueuzian, Hrayr S.; Weiss, James N.; Lin, Shien-Fong; Chen, Peng-Sheng

    2008-01-01

    Objectives To test the hypothesis that superiority of biphasic waveform (BW) over monophasic waveform (MW) defibrillation shocks is attributable to less intracellular calcium (Cai) transient heterogeneity. Background The mechanism by which BW shocks have a higher defibrillation efficacy than MW shocks remains unclear. Methods We simultaneously mapped epicardial membrane potential (Vm) and Cai during 6 ms MW and 3/3 ms BW shocks in 19 Langendorff-perfused rabbit ventricles. After shock, the percentage of depolarized area was plotted over time. The maximum (peak) postshock values (VmP and CaiP, respectively) were used to measure heterogeneity. Higher VmP and CaiP imply less heterogeneity. Results The defibrillation threshold was for BW and MW shocks were 288±99 V and 399±155 V, respectively (p=0.0005). Successful BW shocks had higher VmP (88±9 %) and CaiP (70±13 %) than unsuccessful MW shocks (VmP 76 %±10, p<0.001; CaiP, 57±8 %, p<0.001) of the same shock strength. In contrast, for unsuccessful BW and MW shocks of the same shock strengths, the VmP and CaiP were not significantly different. MW shocks more frequently created regions of low Cai surrounded by regions of high Cai (postshock Cai sinkholes). The defibrillation threshold for MW and BW shocks became similar after disabling the sarcoplasmic reticulum with thapsigargin and ryanodine. Conclusions The greater efficacy of BW shocks is directly related to their less heterogeneous effects on shock-induced sarcoplasmic reticulum Ca release and Cai transients. Less heterogeneous Cai transients reduces the probability of Cai sinkhole formation, thereby preventing the postshock reinitiation of VF. PMID:18755345

  16. PMCA4 (ATP2B4) mutation in familial spastic paraplegia causes delay in intracellular calcium extrusion

    PubMed Central

    Ho, Philip Wing-Lok; Pang, Shirley Yin-Yu; Li, Miaoxin; Tse, Zero Ho-Man; Kung, Michelle Hiu-Wai; Sham, Pak-Chung; Ho, Shu-Leong

    2015-01-01

    Background Familial spastic paraplegia (FSP) is a heterogeneous group of disorders characterized primarily by progressive lower limb spasticity and weakness. More than 50 disease loci have been described with different modes of inheritance. Recently, we described a novel missense mutation (c.803G>A, p.R268Q) in the plasma membrane calcium ATPase (PMCA4, or ATP2B4) gene in a Chinese family with autosomal dominant FSP. Further to this finding, here we describe the functional effect of this mutation. Methods As PMCA4 removes cytosolic calcium, we measured transient changes and the time-dependent decay of cytosolic calcium level as visualized by using fura-2 fluorescent dye with confocal microscopy in human SH-SY5Y neuroblastoma cells overexpressing either wild-type or R268Q mutant PMCA4. Results Overexpressing both wild-type and R268Q PMCA4 significantly reduced maximum calcium surge after KCl-induced depolarization as compared with vector control cells. However, cells overexpressing mutant PMCA4 protein demonstrated significantly higher level of calcium surge when compared with wild-type. Furthermore, the steady-state cytosolic calcium concentration in these mutant cells remained markedly higher than the wild-type after SERCA inhibition by thapsigargin. Conclusion Our result showed that p.R268Q mutation in PMCA4 resulted in functional changes in calcium homeostasis in human neuronal cells. This suggests that calcium dysregulation may be associated with the pathogenesis of FSP. PMID:25798335

  17. The Transient Role for Calcium and Vitamin D during the Developmental Hair Follicle Cycle.

    PubMed

    Mady, Leila J; Ajibade, Dare V; Hsaio, Connie; Teichert, Arnaud; Fong, Chak; Wang, Yongmei; Christakos, Sylvia; Bikle, Daniel D

    2016-07-01

    The role for 1,25-dihydroxyvitamin D3 and/or calcium in hair follicle cycling is not clear despite their impact on keratinocyte differentiation. We found that calbindin-D9k null (knockout) pups generated from calbindin-D9k knockout females fed a vitamin D-deficient, low-calcium (0.47%) diet develop transient alopecia. The pups appear phenotypically normal until 13 days of age, after which the hair progressively sheds in a caudocephalic direction, resulting in truncal alopecia totalis by 20-23 days, with spontaneous recovery by 28 days. Histological studies showed markedly dystrophic hair follicles, loss of hair shafts with increased apoptosis, and hyperplastic epidermis during this time. Ha1 expression is lost during catagen in all mice but recovers more slowly in the knockout pups on the vitamin D-deficient, low-calcium diet. Keratin 1 expression is reduced throughout days 19-28. The expressions of involucrin, loricrin, and cathepsin L is initially increased by day 19 but subsequently falls below those of controls by day 23, as does that of desmoglein 3. Feeding the mothers a high-vitamin D/high-calcium (2%)/lactose (20%) diet lessens the phenotype, and knockout pups fostered to mothers fed a normal diet do not develop alopecia. Our results show that in calbindin-D9k knockout pups, a maternal vitamin D-deficient/low-calcium diet leads to transient noncicatricial alopecia. PMID:26994969

  18. Measurement and modification of free calcium transients in frog skeletal muscle fibres by a metallochromic indicator dye.

    PubMed Central

    Kovacs, L; Rios, E; Schneider, M F

    1983-01-01

    Myoplasmic free calcium transients were monitored with the metallochromic indicator dye Antipyrylazo III (AP III) in single frog skeletal muscle fibres cut at both ends, stretched so as to minimize or eliminate contractile filament overlap and voltage clamped using a double-Vaseline-gap system (approximately 6 degrees C). The dye entered the central fibre segment by diffusion from the solution applied to the two cut ends. The diffusion coefficient of AP III was about 20 times lower in the fibre than in solution. This very slow diffusion was not due to binding of dye since the ratio of bound to free dye obtained from analysis of the diffusion was only about 0.45. For a given depolarizing pulse, the ratio of dye-related absorbance changes delta A at 720 and 550 nm was the same as that produced on adding calcium to dye in calibrating solution, indicating that these signals were due to changes in myoplasmic calcium. The delta A signals at 700 or 720 nm were used to monitor transient changes in concentration of calcium-dye complex [CaD2] and of free calcium [Ca] in the myofilament space. By applying the same pulse at different times during dye entry, it was observed that increasing dye concentrations [D]T produced the following effects: (a) [CaD2] was increased; (b) [Ca] was decreased at early times during a pulse; (c) a declining phase of [Ca] observed at late times during pulses was decreased and finally reversed to a slow rising phase at high [D]T; (d) the decay of [Ca] after the pulse was slowed. Analyses of the effects of [D]T on (a) the magnitude of [CaD2] at a given early time during the calcium release produced by pulses to a given voltage and on (b) the time constant for [Ca] decay after a pulse were both consistent with a calcium: dye stoichiometry of 1:2 in the fibre as found in calibrating solution. Analysis of the effect of [D]T on the [Ca] decay time constants also revealed the presence of intrinsic rapidly equilibrating myoplasmic calcium binding sites

  19. Calcium-dependent expression of transient receptor potential canonical type 3 channels in patients with chronic kidney disease.

    PubMed

    Liu, Ying; Krueger, Katharina; Hovsepian, Anahit; Tepel, Martin; Thilo, Florian

    2011-10-01

    It is unknown whether extracellular calcium may regulate the expression of transient receptor potential canonical type 3 (TRPC3) channels in patients with chronic kidney disease. Using quantitative in-cell Western assay we compared the expression of TRPC3 channel protein in monocytes from 20 patients with chronic kidney disease and 19 age- and sex-matched healthy control subjects. TRPC3 channels were identified by immunoblotting using specific antibodies and TRPC3 protein was further confirmed by mass spectrometry. We observed a significant increase of TRPC3 channel protein expression in patients with chronic kidney disease compared to healthy control subjects (normalized expression, 0.42±0.06 vs. 0.19±0.03; p<0.01). Expression of TRPC3 was significantly inversely correlated with estimated glomerular filtration rates (Spearman r=-0.41) or serum calcium concentration (Spearman r=-0.34). During a hemodialysis session serum calcium concentrations significantly increased, whereas the expression of TRPC3 channels and calcium influx significantly decreased. In vitro studies confirmed that higher calcium concentrations but not magnesium, barium nor sodium concentrations significantly decreased TRPC3 expression in human monocytes. This study indicates that reduced extracellular calcium concentrations up-regulate TRPC3 channel protein expression in patients with chronic kidney disease.

  20. Long-term transients and complex dynamics of a stage-structured population with time delay and the Allee effect.

    PubMed

    Morozov, A Yu; Banerjee, M; Petrovskii, S V

    2016-05-01

    Traditionally, mathematical modeling in population ecology is mainly focused on asymptotic behavior of the model, i.e. as given by the system attractors. Recently, however, transient regimes and especially long-term transients have been recognized as playing a crucial role in the dynamics of ecosystems. In particular, long-term transients are a potential explanation of ecological regime shifts, when an apparently healthy population suddenly collapses and goes extinct. In this paper, we show that the interplay between delay in maturation and a strong Allee effect can result in long-term transients in a single species system. We first derive a simple 'conceptual' model of the population dynamics that incorporates both a strong Allee effect and maturation delay. Unlike much of the previous work, our approach is not empirical since our model is derived from basic principles. We show that the model exhibits a high complexity in its asymptotic dynamics including multi-periodic and chaotic attractors. We then show the existence of long-term transient dynamics in the system, when the population size oscillates for a long time between locally stable stationary states before it eventually settles either at the persistence equilibrium or goes extinct. The parametric space of the model is found to have a complex structure with the basins of attraction corresponding to the persistence and extinction states being of a complicated shape. This impedes the prediction of the eventual fate of the population, as a small variation in the maturation delay or the initial population size can either bring the population to extinction or ensure its persistence.

  1. Delay in Seeking Medical Help following Transient Ischemic Attack (TIA) or “Mini-Stroke”: A Qualitative Study

    PubMed Central

    Mc Sharry, Jennifer; Baxter, Alison; Wallace, Louise M.; Kenton, Anthony; Turner, Andrew; French, David P.

    2014-01-01

    Background Prompt treatment following Transient Ischemic Attack (TIA) can reduce the risk of subsequent stroke and disability. However, many patients delay in making contact with medical services. This study aimed to explore TIA patients' accounts of delay between symptom onset and contacting medical services including how decisions to contact services were made and the factors discussed in relation to delay. Methods Twenty interviews were conducted with TIA patients in England. Using a previous systematic review as an initial framework, interview data were organised into categories of symptom recognition, presence of others and type of care sought. A thematic analysis was then conducted to explore descriptions of care-seeking relevant to each category. Results Delay in contacting medical services varied from less than an hour to eight days. Awareness of typical stroke symptoms could lead to urgent action when more severe TIA symptoms were present but could lead to delay when experienced symptoms were less severe. The role of friends and family varied widely from deciding on and enacting care-seeking decisions to simply providing transport to the GP practice. When family or friends played a greater role, and both made and enacted care-seeking decisions, delays were often shorter, even when patients themselves failed to identify symptoms. Healthcare professionals also impacted on patients' care-seeking with greater delays in seeking further care for the same episode described when patients perceived a lack of urgency during initial healthcare interactions. Conclusions This study provides new information on patients' decisions to contact medical services following TIA and identifies overlapping factors that can lead to delay in receiving appropriate treatment. While recognition of symptoms may contribute to delay in contacting medical services, additional factors, including full responsibility being taken by others and initial healthcare interactions, can over

  2. Transient effect of weak electromagnetic fields on calcium ion concentration in Arabidopsis thaliana

    PubMed Central

    Pazur, Alexander; Rassadina, Valentina

    2009-01-01

    Background Weak magnetic and electromagnetic fields can influence physiological processes in animals, plants and microorganisms, but the underlying way of perception is poorly understood. The ion cyclotron resonance is one of the discussed mechanisms, predicting biological effects for definite frequencies and intensities of electromagnetic fields possibly by affecting the physiological availability of small ions. Above all an influence on Calcium, which is crucial for many life processes, is in the focus of interest. We show that in Arabidopsis thaliana, changes in Ca2+-concentrations can be induced by combinations of magnetic and electromagnetic fields that match Ca2+-ion cyclotron resonance conditions. Results An aequorin expressing Arabidopsis thaliana mutant (Col0-1 Aeq Cy+) was subjected to a magnetic field around 65 microtesla (0.65 Gauss) and an electromagnetic field with the corresponding Ca2+ cyclotron frequency of 50 Hz. The resulting changes in free Ca2+ were monitored by aequorin bioluminescence, using a high sensitive photomultiplier unit. The experiments were referenced by the additional use of wild type plants. Transient increases of cytosolic Ca2+ were observed both after switching the electromagnetic field on and off, with the latter effect decreasing with increasing duration of the electromagnetic impact. Compared with this the uninfluenced long-term loss of bioluminescence activity without any exogenic impact was negligible. The magnetic field effect rapidly decreased if ion cyclotron resonance conditions were mismatched by varying the magnetic fieldstrength, also a dependence on the amplitude of the electromagnetic component was seen. Conclusion Considering the various functions of Ca2+ as a second messenger in plants, this mechanism may be relevant for perception of these combined fields. The applicability of recently hypothesized mechanisms for the ion cyclotron resonance effect in biological systems is discussed considering it's operating at

  3. Delay-Induced Transient Increase and Heterogeneity in Gene Expression in Negatively Auto-Regulated Gene Circuits

    PubMed Central

    Maithreye, R.; Sarkar, Ram Rup; Parnaik, Veena K.; Sinha, Somdatta

    2008-01-01

    A generic feature in all intracellular biochemical processes is the time required to complete the whole sequence of reactions to yield any observable quantity-from gene expression to circadian rhythms. This widespread phenomenon points towards the importance of time delay in biological functions. Theoretically time delay is known to be the source of instability, and has been attributed to lead to oscillations or transient dynamics in several biological functions. Negative feedback loops, common in biochemical pathways, have been shown to provide stability and withstand considerable variations and random perturbations of biochemical parameters. The interaction of these two opposing factors-of instability and homeostasis-are features that are widespread in intracellular processes. To test the effect of these divergent forces in the dynamics of gene expression, we have designed and constructed simple negatively auto-regulated gene circuits consisting of a basic regulator and transcriptional repressor module, and compared it with one, which has delayed repression. We show, both theoretically and experimentally, that delayed repression induces transient increase and heterogeneity in gene expression before the gain of stability effected by the negative feedback. This design, therefore, seems to be suitable for conferring both stability and variability in cells required for adaptive response to a noisy environment. PMID:18698420

  4. Cardiac contraction, calcium transients, and myofilament calcium sensitivity fluctuate with the estrous cycle in young adult female mice.

    PubMed

    MacDonald, Jennifer K; Pyle, W Glen; Reitz, Cristine J; Howlett, Susan E

    2014-04-01

    This study established conditions to induce regular estrous cycles in female C57BL/6J mice and investigated the impact of the estrous cycle on contractions, Ca2+ transients, and underlying cardiac excitation-contraction (EC)-coupling mechanisms. Daily vaginal smears from group-housed virgin female mice were stained to distinguish estrous stage (proestrus, estrus, metestrus, diestrus). Ventricular myocytes were isolated from anesthetized mice. Contractions and Ca2+ transients were measured simultaneously (4 Hz, 37 °C). Interestingly, mice did not exhibit regular cycles unless they were exposed to male pheromones in bedding added to their cages. Field-stimulated myocytes from mice in estrus had larger contractions (∼2-fold increase), larger Ca2+ transients (∼1.11-fold increase), and longer action potentials (>2-fold increase) compared with other stages. Larger contractions and Ca2+ transients were not observed in estrus myocytes voltage-clamped with shorter action potentials. Voltage-clamp experiments also demonstrated that estrous stage had no effect on Ca2+ current, EC-coupling gain, diastolic Ca2+, sarcoplasmic reticulum (SR) Ca2+ content, or fractional release. Although contractions were largest in estrus, myofilament Ca2+ sensitivity was lowest (EC50 values ∼1.15-fold higher) in conjunction with increased phosphorylation of myosin binding protein C in estrus. Contractions were enhanced in ventricular myocytes from mice in estrus because action potential prolongation increased SR Ca2+ release. These findings demonstrate that cyclical changes in reproductive hormones associated with the estrous cycle can influence myocardial electrical and contractile function and modify Ca2+ homeostasis. However, such changes are unlikely to occur in female mice housed in groups under conventional conditions, since these mice do not exhibit regular estrous cycles.

  5. Microcephaly, short stature, and developmental delay associated with a chemotactic defect and transient hypogammaglobulinaemia in two brothers.

    PubMed Central

    Say, B; Barber, N; Miller, G C; Grogg, S E

    1986-01-01

    Two brothers presented with unusual facial features, microcephaly, developmental delay, and severe postnatal growth retardation. They both developed eczema in infancy and have had recurrent infections. Additional physical findings in both boys included hypogonadism, flexion contractures, hypoplastic patellae, and scoliosis. Their facial similarity was striking with sloping foreheads, beaked noses, large, protruding ears, and micrognathia. Low levels of serum gammaglobulins and defective chemotaxis were present in both boys in infancy. The hypogammaglobulinaemia was transient and improved, reaching normal levels by 3 1/2 years and 15 months, respectively. Defective chemotaxis and recurrent infections have persisted to the present. Both parents were normal. The mode of inheritance was not clear, as both X linked and autosomal recessive patterns were possible. Although patients with congenital malformations who also had immunodeficiency have previously been reported, immune system abnormalities, especially those of a transient nature, may frequently go unrecognised. Images PMID:3746838

  6. Spike-triggered dendritic calcium transients depend on synaptic activity in the cricket giant interneurons.

    PubMed

    Ogawa, Hiroto; Baba, Yoshichika; Oka, Kotaro

    2002-02-15

    The relationship between electrical activity and spike-induced Ca2+ increases in dendrites was investigated in the identified wind-sensitive giant interneurons in the cricket. We applied a high-speed Ca2+ imaging technique to the giant interneurons, and succeeded in recording the transient Ca2+ increases (Ca2+ transients) induced by a single action potential, which was evoked by presynaptic stimulus to the sensory neurons. The dendritic Ca2+ transients evoked by a pair of action potentials accumulated when spike intervals were shorter than 100 ms. The amplitude of the Ca2+ transients induced by a train of spikes depended on the number of action potentials. When stimulation pulses evoking the same numbers of action potentials were separately applied to the ipsi- or contra-lateral cercal sensory nerves, the dendritic Ca2+ transients induced by these presynaptic stimuli were different in their amplitude. Furthermore, the side of presynaptic stimulation that evoked larger Ca2+ transients depended on the location of the recorded dendritic regions. This result means that the spike-triggered Ca2+ transients in dendrites depend on postsynaptic activity. It is proposed that Ca2+ entry through voltage-dependent Ca2+ channels activated by the action potentials will be enhanced by excitatory synaptic inputs at the dendrites in the cricket giant interneurons.

  7. Phorbol-ester-induced alterations of free calcium ion transients in single rat hepatocytes.

    PubMed Central

    Woods, N M; Cuthbertson, K S; Cobbold, P H

    1987-01-01

    The effect of the phorbol esters phorbol 12-myristate 13-acetate (TPA) and phorbol 12,13-dibutyrate (PDB) on changes in free Ca2+ concentration ([Ca2+]i) in single rat hepatocytes, microinjected with the photoprotein aequorin, were investigated. [Arg8]vasopressin and phenylephrine induced a series of repetitive [Ca2+]i transients. Phorbol esters inhibited the alpha 1-adrenoceptor-induced response; sub-nanomolar concentrations decreased the transient frequency, and higher concentrations abolished the transients. The inhibitory effect of PDB was readily reversible. Phorbol esters were less effective in decreasing the frequency of [Arg8]-vasopressin-induced transients, and the inhibition could be overcome by high [Arg8]vasopressin concentrations. PMID:3479980

  8. Transient receptor potential vanilloid-1-mediated calcium responses are inhibited by the alkylamine antihistamines dexbrompheniramine and chlorpheniramine.

    PubMed

    Sadofsky, Laura R; Campi, Barbara; Trevisani, Marcello; Compton, Steven J; Morice, Alyn H

    2008-12-01

    American guidelines, unlike European guidelines, support the use of antihistamines as a first line of treatment for some causes of chronic cough. Transient receptor potential vanilloid-1 (TRPV1) is an ion channel activated by the tussive agents capsaicin, resiniferatoxin, and protons. It is predominantly expressed by C-fiber and some Adelta -fiber sensory neurons and is thought to be a cough receptor. By measuring increases in intracellular calcium as an indicator of TRPV1 activation, the authors sought to determine whether antihistamines could antagonise TRPV1 permanently expressed in HEK and Pro5 cells and TRPV1 endogenously expressed in rat dorsal root ganglia neurons. In human TRPV1-expressing HEK cells (hTRPV1-HEK), diphenhydramine and fexofenadine failed to inhibit capsaicin-triggered calcium responses. However, both dexbrompheniramine and chlorpheniramine significantly inhibited capsaicin-evoked responses in hTRPV1-HEK. Dexbrompheniramine also inhibited activation of rat TRPV1 expressed in HEK and Pro5 cells, without interfering with TRPA1 and proteinase-activated receptor-2 (PAR(2)) activation. Finally, in rat dorsal root ganglia neuron preparations, dexbrompheniramine dose-dependently inhibited capsaicin-evoked calcium responses. Thus, the inhibition of TRPV1 activation by dexbrompheniramine may provide one potential mechanism whereby this antihistamine exerts its therapeutic effect in chronic cough.

  9. Calcium transients and the effect of a photolytically released calcium chelator during electrically induced contractions in rabbit rectococcygeus smooth muscle.

    PubMed Central

    Arner, A; Malmqvist, U; Rigler, R

    1998-01-01

    Intracellular Ca2+ was determined with the fura-2 technique during electrically induced contractions in the rabbit rectococcygeus smooth muscle at 22 degreesC. The muscles were electrically activated to give short, reproducible contractions. Intracellular [Ca2+] increased during activation; the increase in [Ca2+] preceded force development by approximately 2 s. After cessation of stimulation Ca2+ fell, preceding the fall in force by approximately 4 s. The fluorescence properties of fura-2 were determined with time-resolved spectroscopy using synchrotron light at the MAX-storage ring, Lund, Sweden. The fluorescence decay of free fura-2 was best described by two exponential decays (time constants approximately 0.5 and 1.5 ns) at low Ca2+ (pCa 9). At high Ca2+ (pCa 4.5), fluorescence decay became slower and could be fitted by one exponential decay (1.9 ns). Time-resolved anisotropy of free fura-2 was characteristic of free rotational motion (correlation time 0.3 ns). Motion of fura-2 could be markedly inhibited by high concentrations of creatine kinase. Time-resolved spectroscopy measurements of muscle fibers loaded with fura-2 showed that the fluorescence lifetime of the probe was longer, suggesting an influence of the chemical environment. Anisotropy measurements revealed, however, that the probe was mobile in the cells. The Ca2+-dependence of contraction and relaxation was studied using a photolabile calcium chelator, diazo-2, which could be loaded into the muscle cells in a similar manner as fura-2. Photolysis of diazo-2 leads to an increase in its Ca2+-affinity and a fall in free Ca2+. When muscles that had been loaded with diazo-2 were illuminated with UV light flashes during the rising phase of contraction, the rate of contraction became slower, suggesting a close relation between intracellular Ca2+ and the cross-bridge interaction. In contrast, photolysis during relaxation did not influence the rate of force decay, suggesting that relaxation of these

  10. Regenerative and non-regenerative calcium transients in hamster eggs triggered by inositol 1,4,5-trisphosphate.

    PubMed Central

    Galione, A; Swann, K; Georgiou, P; Whitaker, M

    1994-01-01

    1. Inositol 1,4,5-trisphosphate (InsP3) injected into unfertilized golden hamster eggs elicits a hyperpolarizing response (HR) that is due to stimulation of calcium-activated potassium channels in the egg plasma membrane. 2. A single injection of InsP3 gave a single HR above a threshold value of 0.3 nM. At 5 nM and above, InsP3 induced HRs with no detectable latency. At concentrations between these two values a latency was observed. The amplitude of the HR was independent of InsP3 concentration. 3. A second HR could be elicited by injection of InsP3, but five times more InsP3 was required to trigger a second HR, and 10-100 times more to give an HR of similar magnitude to the first, and there was no latency. 4. The increase in [Ca2+]i in response to an initial injection of 1 nM InsP3 could be resolved into two distinct components: a slow, early rise immediately after InsP3 injection (phase I) followed by a larger and more rapid increase (phase II). The initiation of an HR coincided with the second component of the [Ca2+]i increase. 5. Further injection of InsP3 resulted only in slow, smaller increases in [Ca2+]i that resembled phase I and often did not cause an HR. Phase II appeared to be absent. However, 100-fold greater InsP3 concentrations gave slow, larger Ca2+ transients (and HRs) with no detectable latency. 6. If large amounts of InsP3 were allowed to leak into the eggs constantly from a pipette, repetitive calcium transients were seen. Unlike the sustained repetitive responses seen at fertilization, they were often smaller than the initial transient and less well sustained. However, a subsequent transient could still be elicited on injection of very large concentrations of InsP3. 7. InsP3 can induce regenerative, all-or-none [Ca2+]i increase (CICR) in hamster eggs, often with a long latency, as well as non-regenerative increases. InsP3 injections desensitize CICR and cannot mimic all the features of Ca2+ signalling at fertilization in the hamster egg, in

  11. Calcium regulation by temperature-sensitive transient receptor potential channels in human uveal melanoma cells.

    PubMed

    Mergler, Stefan; Derckx, Raissa; Reinach, Peter S; Garreis, Fabian; Böhm, Arina; Schmelzer, Lisa; Skosyrski, Sergej; Ramesh, Niraja; Abdelmessih, Suzette; Polat, Onur Kerem; Khajavi, Noushafarin; Riechardt, Aline Isabel

    2014-01-01

    Uveal melanoma (UM) is both the most common and fatal intraocular cancer among adults worldwide. As with all types of neoplasia, changes in Ca(2+) channel regulation can contribute to the onset and progression of this pathological condition. Transient receptor potential channels (TRPs) and cannabinoid receptor type 1 (CB1) are two different types of Ca(2+) permeation pathways that can be dysregulated during neoplasia. We determined in malignant human UM and healthy uvea and four different UM cell lines whether there is gene and functional expression of TRP subtypes and CB1 since they could serve as drug targets to either prevent or inhibit initiation and progression of UM. RT-PCR, Ca(2+) transients, immunohistochemistry and planar patch-clamp analysis probed for their gene expression and functional activity, respectively. In UM cells, TRPV1 and TRPM8 gene expression was identified. Capsaicin (CAP), menthol or icilin induced Ca(2+) transients as well as changes in ion current behavior characteristic of TRPV1 and TRPM8 expression. Such effects were blocked with either La(3+), capsazepine (CPZ) or BCTC. TRPA1 and CB1 are highly expressed in human uvea, but TRPA1 is not expressed in all UM cell lines. In UM cells, the CB1 agonist, WIN 55,212-2, induced Ca(2+) transients, which were suppressed by La(3+) and CPZ whereas CAP-induced Ca(2+) transients could also be suppressed by CB1 activation. Identification of functional TRPV1, TRPM8, TRPA1 and CB1 expression in these tissues may provide novel drug targets for treatment of this aggressive neoplastic disease.

  12. Calcium

    MedlinePlus

    ... milligrams) of calcium each day. Get it from: Dairy products. Low-fat milk, yogurt, cheese, and cottage ... lactase that helps digest the sugar (lactose) in dairy products, and may have gas, bloating, cramps, or ...

  13. Calcium

    MedlinePlus

    ... supplements and fortified foods include gluconate, lactate, and phosphate. Calcium absorption is best when a person consumes ... also interfere with the body's ability to absorb iron and zinc, but this effect is not well ...

  14. Controlling pulse delay by light and low magnetic fields: slow light in emerald induced by transient spectral hole-burning.

    PubMed

    Rajan, Rajitha Papukutty; Riesen, Hans; Rebane, Aleksander

    2013-11-15

    Slow light based on transient spectral hole-burning is reported for emerald, Be(3)Al(2)Si(6)O(18):Cr(3+). Experiments were conducted in π polarization on the R(1)(± 3/2) line (E2 ← A(2)4) at 2.2 K in zero field and low magnetic fields B||c. The hole width was strongly dependent on B||c, and this allowed us to smoothly tune the pulse delay from 40 to 154 ns between zero field and B||c = 15.2 mT. The latter corresponds to a group velocity of 16 km/s. Slow light in conjunction with a linear filter theory can be used as a powerful and accurate technique in time-resolved spectroscopy, e.g., to determine spectral hole-widths as a function of time. PMID:24322070

  15. Suppression of aberrant transient receptor potential cation channel, subfamily V, member 6 expression in hyperproliferative colonic crypts by dietary calcium.

    PubMed

    Peleg, Sara; Sellin, Joseph H; Wang, Yu; Freeman, Michael R; Umar, Shahid

    2010-09-01

    Dietary calcium is believed to reduce colon cancer risk, but the mechanism by which this occurs is poorly understood. Employing the Citrobacter rodentium-induced transmissible murine colonic hyperplasia (TMCH) model, we previously showed that a high-calcium diet (hCa) significantly abrogated hyperplasia in the distal colons of NIH-Swiss mice. Here, we explored the mechanism of dietary protection by hCa by analyzing the expression of genes involved in the regulation of Ca uptake/flux in the intestinal epithelium, including the Ca-sensing receptor, vitamin D receptor, Ca binding protein, and transient receptor potential cation channels, subfamily V, members 5 and 6 (TRPV5/6). Interestingly, while TRPV6 expression increased significantly during TMCH, the expression of the other gene products was unchanged. This elevated TRPV6 expression was significantly abrogated by a hCa diet. Immunofluorescence revealed apical membrane localization of TRPV6 in the normal colon, whereas during TMCH we observed intense apical pole and cytoplasmic staining along the entire longitudinal crypt axis, including the expanded proliferating zone. The hCa diet reversed this effect. In humans, overexpression of TRPV6 was associated with early-stage colon cancer, and in colon carcinoma cells, inhibition of TRPV6 expression by small interfering RNA inhibited their proliferation and induced apoptosis. TRPV6 small interfering RNA also diminished the transcriptional activity of the calcium-dependent nuclear factors in activated T cells. Thus the aberrant overexpression of TRPV6 contributes to colonic crypt hyperplasia in mice and to colon cancer cell proliferation in humans. Therefore, it is likely that suppression of TRPV6 by a hCa diet is required for its protective effects in the colon.

  16. Transient CD4+ T Cell Depletion Results in Delayed Development of Functional Vaccine-Elicited Antibody Responses

    PubMed Central

    Provine, Nicholas M.; Badamchi-Zadeh, Alexander; Bricault, Christine A.; Penaloza-MacMaster, Pablo; Larocca, Rafael A.; Borducchi, Erica N.; Seaman, Michael S.

    2016-01-01

    ABSTRACT We have recently demonstrated that CD4+ T cell help is required at the time of adenovirus (Ad) vector immunization for the development of functional CD8+ T cell responses, but the temporal requirement for CD4+ T cell help for the induction of antibody responses remains unclear. Here we demonstrate that induction of antibody responses in C57BL/6 mice can occur at a time displaced from the time of Ad vector immunization by depletion of CD4+ T cells. Transient depletion of CD4+ T cells at the time of immunization delays the development of antigen-specific antibody responses but does not permanently impair their development or induce tolerance against the transgene. Upon CD4+ T cell recovery, transgene-specific serum IgG antibody titers develop and reach a concentration equivalent to that in undepleted control animals. These delayed antibody responses exhibit no functional defects with regard to isotype, functional avidity, expansion after boosting immunization, or the capacity to neutralize a simian immunodeficiency virus (SIV) Env-expressing pseudovirus. The development of this delayed transgene-specific antibody response is temporally linked to the expansion of de novo antigen-specific CD4+ T cell responses, which develop after transient depletion of CD4+ T cells. These data demonstrate that functional vaccine-elicited antibody responses can be induced even if CD4+ T cell help is provided at a time markedly separated from the time of vaccination. IMPORTANCE CD4+ T cells have a critical role in providing positive help signals to B cells, which promote robust antibody responses. The paradigm is that helper signals must be provided immediately upon antigen exposure, and their absence results in tolerance against the antigen. Here we demonstrate that, in contrast to the current model that the absence of CD4+ T cell help at priming results in long-term antibody nonresponsiveness, antibody responses can be induced by adenovirus vector immunization or alum

  17. Novel features on the regulation by mitochondria of calcium and secretion transients in chromaffin cells challenged with acetylcholine at 37°C

    PubMed Central

    Caricati‐Neto, Afonso; Padín, Juan‐Fernando; Silva‐Junior, Edilson‐Dantas; Fernández‐Morales, José‐Carlos; de Diego, Antonio‐Miguel G.; Jurkiewicz, Aron; García, Antonio G.

    2013-01-01

    Abstract From experiments performed at room temperature, we know that the buffering of Ca2+ by mitochondria contributes to the shaping of the bulk cytosolic calcium transient ([Ca2+]c) and secretion transients of chromaffin cells stimulated with depolarizing pulses. We also know that the mitochondrial Ca2+ transporters and the release of catecholamine are faster at 37°C with respect to room temperature. Therefore, we planned this investigation to gain further insight into the contribution of mitochondrial Ca2+ buffering to the shaping of [Ca2+]c and catecholamine release transients, using some novel experimental conditions that have not been yet explored namely: (1) perifusion of bovine chromaffin cells (BCCs) with saline at 37°C and their repeated challenging with the physiological neurotransmitter acetylcholine (ACh); (2) separate blockade of mitochondrial Ca2+ uniporter (mCUP) with Ru360 or the mitochondrial Na+/Ca2+ exchanger (mNCX) with CGP37157; (3) full blockade of the mitochondrial Ca2+ cycling (mCC) by the simultaneous inhibition of the mCUP and the mNCX. Ru360 caused a pronounced delay of [Ca2+]c clearance and augmented secretion. In contrast, CGP37157 only caused a tiny delay of [Ca2+]c clearance and a mild decrease in secretion. The mCC resulting in continued Ca2+ uptake and its release back into the cytosol was interrupted by combined Ru360 + CGP37157 (Ru/CGP), the protonophore carbonyl cyanide‐p‐trifluoromethoxyphenylhydrazone, or combined oligomycin + rotenone (O/R); these three treatments caused a mild but sustained elevation of basal [Ca2+]c that, however, was not accompanied by a parallel increase in basal secretion. Nevertheless, all treatments caused a pronounced augmentation of ACh‐induced secretion, with minor changes of the ACh‐induced [Ca2+]c transients. Combined Ru/CGP did not alter the resting membrane potential in current‐clamped cells. Additionally, Ru/CGP did not increase basal [Ca2+]c near subplasmalemmal sites and caused a

  18. Detection of calcium transients in embryonic stem cells and their differentiated progeny.

    PubMed

    Meyer, Jason S; Tullis, Gregory; Pierret, Christopher; Spears, Kathleen M; Morrison, Jason A; Kirk, Mark D

    2009-12-01

    A central issue in stem cell biology is the determination of function and activity of differentiated stem cells, features that define the true phenotype of mature cell types. Commonly, physiological mechanisms are used to determine the functionality of mature cell types, including those of the nervous system. Calcium imaging provides an indirect method of determining the physiological activities of a mature cell. Camgaroos are variants of yellow fluorescent protein that act as intracellular calcium sensors in transfected cells. We expressed one version of the camgaroos, Camgaroo-2, in mouse embryonic stem (ES) cells under the control of the CAG promoter system. Under the control of this promoter, Camgaroo-2 fluorescence was ubiquitously expressed in all cell types derived from the ES cells that were tested. In response to pharmacological stimulation, the fluorescence levels in transfected cells correlated with cellular depolarization and hyperpolarization. These changes were observed in both undifferentiated ES cells as well as ES cells that had been neurally induced, including putative neurons that were differentiated from transfected ES cells. The results presented here indicate that Camgaroo-2 may be used like traditional fluorescent proteins to track cells as well as to study the functionality of stem cells and their progeny.

  19. Detection of Calcium Transients in Embryonic Stem Cells and Their Differentiated Progeny

    PubMed Central

    Tullis, Gregory; Pierret, Christopher; Spears, Kathleen M.; Morrison, Jason A.; Kirk, Mark D.

    2012-01-01

    A central issue in stem cell biology is the determination of function and activity of differentiated stem cells, features that define the true phenotype of mature cell types. Commonly, physiological mechanisms are used to determine the functionality of mature cell types, including those of the nervous system. Calcium imaging provides an indirect method of determining the physiological activities of a mature cell. Camgaroos are variants of yellow fluorescent protein that act as intracellular calcium sensors in transfected cells. We expressed one version of the camgaroos, Camgaroo-2, in mouse embryonic stem (ES) cells under the control of the CAG promoter system. Under the control of this promoter, Camgaroo-2 fluorescence was ubiquitously expressed in all cell types derived from the ES cells that were tested. In response to pharmacological stimulation, the fluorescence levels in transfected cells correlated with cellular depolarization and hyperpolarization. These changes were observed in both undifferentiated ES cells as well as ES cells that had been neurally induced, including putative neurons that were differentiated from transfected ES cells. The results presented here indicate that Camgaroo-2 may be used like traditional fluorescent proteins to track cells as well as to study the functionality of stem cells and their progeny. PMID:19475505

  20. Calcium.

    PubMed

    Williams, Robert J P

    2002-01-01

    This chapter describes the chemical and biological value of the calcium ion. In calcium chemistry, our main interest is in equilibria within static, nonflowing systems. Hence, we examined the way calcium formed precipitates and complex ions in solution. We observed thereafter its uses by humankind in a vast number of materials such as minerals, e.g., marble, concrete, mortars, which parallel the biological use in shells and bones. In complex formation, we noted that many combinations were of anion interaction with calcium for example in the uses of detergents and medicines. The rates of exchange of calcium from bound states were noted but they had little application. Calcium ions do not act as catalysts of organic reactions. In biological systems, interest is in the above chemistry, but extends to the fact that Ca2+ ions can carry information by flowing in one solution or from one solution to another through membranes. Hence, we became interested in the details of rates of calcium exchange. The fast exchange of this divalent ion from most organic binding sites has allowed it to develop as the dominant second messenger. Now the flow can be examined in vitro as calcium binds particular isolated proteins, which it activates as seen in physical mechanical changes or chemical changes and this piece-by-piece study of cells is common. Here, however, we have chosen to stress the whole circuit of Ca2+ action indicating that the cell is organized both at a basal and an activated state kinetic level by the steady state flow of the ion (see Fig. 11). Different time constants of exchange utilizing very similar binding constants lead to: 1) fast responses as in the muscle of an animal; or 2) slower change as in differentiation of an egg or seed. Many other changes of state may relate to Ca2+ steady-state levels of flow in the circuitry and here we point to two: 1) dormancy in reptiles and animals; and 2) sporulation in both bacteria and lower plants. In the other chapters of

  1. Nimodipine, a calcium channel blocker, delays the spontaneous LH surge in women with regular menstrual cycles: a prospective pilot study

    PubMed Central

    2013-01-01

    Background Currently GnRH analogue injections are used to prevent premature LH surges in women undergoing assisted reproductive technology. This was a pilot study to determine the safety and effectiveness of nimodipine, an oral calcium channel blocker, to delay the mid-cycle spontaneous LH surge in women with regular menstrual cycles. Methods Eight women with regular menstrual cycles self-monitored three consecutive cycles for the day of an LH surge by daily urine assay. The first and third cycles were observatory. In the second cycle, subjects took nimodipine 60 mg by mouth three times daily for four days, starting two days prior to the expected LH surge day based on cycle one. Results The LH surge day in cycle 2 (nimodipine) was significantly delayed in comparison to both observatory cycle 1 (15.5+/−3.4 vs 14.0+/−2.8 days; p = 0.033) and cycle 3 (15.1+/−3.5 vs 13.1+/−2.4 days; p = 0.044). There was no difference in the LH surge day between the two observatory cycles (13.4+/−2.4 vs 13.1+/−2.4 days; p = 0.457). Three patients experienced a mild headache. Conclusions There was a statistically significant delay in the spontaneous LH surge day in the treatment cycle in comparison to both observatory cycles. Nimopidine should be further investigated as an oral alternative to delay a spontaneous LH surge. PMID:23391256

  2. AMPA receptor-mediated miniature synaptic calcium transients in GluR2 null mice.

    PubMed

    Wang, Sabrina; Jia, Zhengping; Roder, John; Murphy, Timothy H

    2002-07-01

    AMPA-type glutamate receptors are normally Ca(2+) impermeable due to the expression of the GluR2 receptor subunit. By using GluR2 null mice we were able to detect miniature synaptic Ca(2+) transients (MSCTs) associated with AMPA-type receptor-mediated miniature synaptic currents at single synapses in primary cortical cultures. MSCTs and associated Ca(2+) transients were monitored under conditions that isolated responses mediated by AMPA or N-methyl-D-aspartate (NMDA) receptors. As expected, addition of the antagonist 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX, 3 microM) blocked the AMPA receptor-mediated MSCTs. Voltage-gated Ca(2+) channels did not contribute to AMPA MSCTs because CdCl(2) (0.1-0.2 mM) did not significantly alter the frequency or the amplitude of the MSCTs. The amplitude of AMPA MSCTs appeared to be regulated independently from event frequency since the two measures were not correlated (R = 0.023). Synapses were identified that only expressed MSCTs attributed to either NMDA or AMPA receptors. At synapses with only NMDA responses, MSCT amplitude was significantly lower (by 40%) than synapses expressing both NMDA and AMPA responses. At synapses that showed MSCTs mediated by both AMPA and NMDA receptors, the amplitude of the transients in each condition was positively correlated (R = 0.94). Our results suggest that when AMPA and NMDA receptors are co-expressed at synapses, mechanisms exist to ensure proportional scaling of each receptor type that are distinct from the presynaptic factors controlling the frequency of miniature release. PMID:12091530

  3. TRPV channel-mediated calcium transients in nociceptor neurons are dispensable for avoidance behaviour

    PubMed Central

    Lindy, Amanda S.; Parekh, Puja K.; Zhu, Richard; Kanju, Patrick; Chintapalli, Sree V.; Tsvilovskyy, Volodymyr; Patterson, Randen L.; Anishkin, Andriy; van Rossum, Damian B.; Liedtke, Wolfgang B.

    2014-01-01

    Animals need to sense and react to potentially dangerous environments. TRP ion channels participate in nociception, presumably via Ca2+ influx, in most animal species. However, the relationship between ion permeation and animals’ nocifensive behaviour is unknown. Here we use an invertebrate animal model with relevance for mammalian pain. We analyse the putative selectivity filter of OSM-9, a TRPV channel, in osmotic avoidance behaviour of Caenorhabditis elegans. Using mutagenized OSM-9 expressed in the head nociceptor neuron, ASH, we study nocifensive behaviour and Ca2+ influx. Within the selectivity filter, M601-F609, Y604G strongly reduces avoidance behaviour and eliminates Ca2+ transients. Y604F also abolishes Ca2+ transients in ASH, while sustaining avoidance behaviour, yet it disrupts behavioral plasticity. Homology modelling of the OSM-9 pore suggests that Y604 may assume a scaffolding role. Thus, aromatic residues in the OSM-9 selectivity filter are critical for pain behaviour and ion permeation. These findings have relevance for understanding evolutionary roots of mammalian nociception. PMID:25178952

  4. Total-body calcium estimated by delayed gamma neutron activation analysis and dual-energy X-ray absorptiometry.

    PubMed

    Aloia, J F; Ma, R; Vaswani, A; Feuerman, M

    1999-01-01

    Total body calcium (TBCa) in 270 black and white women age 21-79 years was measured concurrently by delayed gamma neutron activation analysis (DGNA) and dual-energy X-ray absorptiometry (DXA). The mean value for TBCa calculated from DXA was 933 g compared with 730 g for DGNA. By regression, TBCa(DXA(g)) = 1.35 x TBCa(DGNA(g)) -54 (r = 0. 90, r(2) = 81.4%, SEE = 66.9 g). This remarkable difference of 203 g suggests that one or both these methods is not accurate. Adjustment of the regression of DXA versus DGNA for body mass index or trunk thickness explained 8.5-10% of the variability between methods. The unadjusted slope for the DXA values regressed against the DGNA values was 1.35, indicating significant discordance between the methods. There is greater agreement between the two DGNA facilities (Brookhaven National Laboratory and Baylor College of Medicine) and between the various DXA instruments. Either DGNA underestimates TBCa or DXA overestimates total-body bone mineral content. Resolution of these disparate results may possibly be achieved by concurrent measurement of whole human cadavers of different sizes with chemical determination of the calcium content of the ash. In the interim, cross-calibration equations between DGNA and standardized values for DXA for total-body bone mineral content may be used, which will permit reporting of consistent values for TBCa from the two technologies. PMID:10663353

  5. Seventy per cent hydrofluoric acid burns: delayed decontamination with hexafluorine® and treatment with calcium gluconate.

    PubMed

    Yoshimura, Carlos Alberto; Mathieu, Laurence; Hall, Alan H; Monteiro, Mário G Kool; de Almeida, Décio Moreira

    2011-01-01

    This is a case report of decontamination and treatment of a 70% hydrofluoric acid (HF) dermal splash injury. A worker was splashed with 70% HF, sustaining approximately 10% TBSA first- to third-degree chemical skin burns of the face, trunk, and left thigh and leg. Initial decontamination involved water rinsing, removal of contaminated clothing, more water rinsing, topical application of magnesium oxide, and administration of intravenous narcotics for management of severe pain. After a delay of approximately 3 hours, active skin washing with Hexafluorine®, 5 L, was performed, followed by intravenous, intradermal perilesional, and topical inunction administration of calcium gluconate. Pain relief and a cooling sensation were quite prompt after Hexafluorine® decontamination. Surgical debridement and skin grafting of the more severe burns were required. No significant systemic toxicity developed, although this has occurred in previously reported similar concentrated HF dermal splash exposure cases, some of which resulted in fatality. While burns did develop, the patient was released from the intensive care service after 2 days and, after skin grafting, had a good outcome at 90-day follow-up. Even after a long delay, decontamination with Hexafluorine® appeared to be beneficial in this case.

  6. GFP Facilitates Native Purification of Recombinant Perlucin Derivatives and Delays the Precipitation of Calcium Carbonate

    PubMed Central

    Weber, Eva; Guth, Christina; Weiss, Ingrid M.

    2012-01-01

    Insolubility is one of the possible functions of proteins involved in biomineralization, which often limits their native purification. This becomes a major problem especially when recombinant expression systems are required to obtain larger amounts. For example, the mollusc shell provides a rich source of unconventional proteins, which can interfere in manifold ways with different mineral phases and interfaces. Therefore, the relevance of such proteins for biotechnological processes is still in its infancy. Here we report a simple and reproducible purification procedure for a GFP-tagged lectin involved in biomineralization, originally isolated from mother-of-pearl in abalone shells. An optimization of E. coli host cell culture conditions was the key to obtain reasonable yields and high degrees of purity by using simple one-step affinity chromatography. We identified a dual functional role for the GFP domain when it became part of a mineralizing system in vitro. First, the GFP domain improved the solubility of an otherwise insoluble protein, in this case recombinant perlucin derivatives. Second, GFP inhibited calcium carbonate precipitation in a concentration dependent manner. This was demonstrated here using a simple bulk assay over a time period of 400 seconds. At concentrations of 2 µg/ml and higher, the inhibitory effect was observed predominantly for HCO3− as the first ionic interaction partner, but not necessarily for Ca2+. The interference of GFP-tagged perlucin derivatives with the precipitation of calcium carbonate generated different types of GFP-fluorescent composite calcite crystals. GFP-tagging offers therefore a genetically tunable tool to gently modify mechanical and optical properties of synthetic biocomposite minerals. PMID:23056388

  7. Single event transient modeling and mitigation techniques for mixed-signal delay locked loop (DLL) and clock circuits

    NASA Astrophysics Data System (ADS)

    Maillard, Pierre

    The purpose of this PhD work has been to investigate, model, test, develop and provide hardening techniques and guidelines for the mitigation of single event transients (SETs) in analog mixed-signal (AMS) delay locked loops (DLLs) for radiation-hardened applications. Delay-locked-loops (DLLs) are circuit substructures that are present in complex ASIC and system-on-a-chip designs. These circuits are widely used in on-chip clock distribution systems to reduce clock skew, to reduce jitter noise, and to recover clock signals at regional points within a global clock distribution system. DLLs are critical to the performance of many clock distribution systems, and in turn, the overall performance of the associated integrated system; as such, complex systems often employ multiple DLLs for clock deskew and distribution tasks. In radiation environments such as on-orbit, these critical circuits represent at-risk points of malfunction for large sections of integrated circuits due to vulnerabilities to radiation-generated transients (i.e. single event transients) that fan out across the system. The analysis of single event effects in analog DLLs has shown that each DLL sub-circuit primitive is vulnerable to single event transients. However, we have identified the voltage controlled delay line (VCDL) sub-circuit as the most sensitive to radiation-induced single event effects generating missing clock pulses that increase with the operating frequency of the circuit. This vulnerability increases with multiple instantiation of DLLs as clock distribution nodes throughout an integrated system on a chip. To our knowledge, no complete work in the rad-hard community regarding the hardening of mixed-signal DLLs against single event effects (missing pulses) has been developed. Most of the work present in the literature applies the "brute force" and well-established digital technique of triple modular redundancy (TMR) to the digital subcomponents. We have developed two novel design

  8. Calibration of the Brookhaven National Laboratory delayed gamma neutron activation facility to measure total body calcium.

    PubMed

    Ma, R; Stamatelatos, I E; Yasumura, S

    2000-05-01

    Differences in body size and shape can cause large variances in the in vivo results of neutron activation analysis. To introduce corrections for body size for the delayed gamma neutron activation facility at Brookhaven National Laboratory, "reference man"-sized and "reference woman"-sized phantoms were constructed. Simulation results using the Monte Carlo Neutron and Photon Transport code also provided correction factors for people of different sizes. For individuals with a body mass index (BMI = weight (kg)/height (m)2) between 20 and 30, no correction was required. At BMIs greater than 30, the effects of neutron attenuation were significant and a correction factor of CF = -0.0192 x BMI + 1.5635 can be applied. PMID:10865727

  9. Myofilament calcium sensitization delays decompensated hypertrophy differently between the sexes following myocardial infarction

    PubMed Central

    Shioura, Krystyna M.; Farjah, Mariam; Geenen, David L.; Solaro, R. John

    2011-01-01

    Contractile dysfunction is common to many forms of cardiovascular disease. Approaches directed at enhancing cardiac contractility at the level of the myofilaments during heart failure (HF) may provide a means to improve overall cardiovascular function. We are interested in gender-based differences in cardiac function and the effect of sarcomere activation agents that increase contractility. Thus, we studied the effect of gender and time on integrated arterial-ventricular function (A-V relationship) following myocardial infarction (MI). In addition, transgenic mice that overexpress the slow skeletal troponin I isoform were used to determine the impact of increased myofilament Ca2+ sensitivity following MI. Based on pressure-volume (P-V) loop measurements, we used derived parameters of cardiovascular function to reveal the effects of sex, time, and increased myofilament Ca2+ sensitivity among groups of post-MI mice. Analysis of the A-V relationship revealed that the initial increase was similar between the sexes, but the vascular unloading of the heart served to delay the decompensated stage in females. Conversely, the vascular response at 6 and 10 wk post-MI in males contributed to the continuous decline in cardiovascular function. Increasing the myofilament Ca2+ sensitivity appeared to provide sufficient contractile support to improve contractile function in both male and female transgenic mice. However, the improved contractile function was more beneficial in males as the concurrent vascular response contributed to a delayed decompensated stage in female transgenic mice post-MI. This study represents a quantitative approach to integrating the vascular-ventricular relationship to provide meaningful and diagnostic value following MI. Consequently, the data provide a basis for understanding how the A-V relationship is coupled between males and females and the enhanced ability of the cardiovascular system to tolerate pathophysiological stresses associated with HF in

  10. Forced-exercise delays neuropathic pain in experimental diabetes: effects on voltage-activated calcium channels.

    PubMed

    Shankarappa, Sahadev A; Piedras-Rentería, Erika S; Stubbs, Evan B

    2011-07-01

    Physical exercise produces a variety of psychophysical effects, including altered pain perception. Elevated levels of centrally produced endorphins or endocannabinoids are implicated as mediators of exercise-induced analgesia. The effect of exercise on the development and persistence of disease-associated acute/chronic pain remains unclear. In this study, we quantified the physiological consequence of forced-exercise on the development of diabetes-associated neuropathic pain. Euglycemic control or streptozotocin (STZ)-induced diabetic adult male rats were subdivided into sedentary or forced-exercised (2-10 weeks, treadmill) subgroups and assessed for changes in tactile responsiveness. Two weeks following STZ-treatment, sedentary rats developed a marked and sustained hypersensitivity to von Frey tactile stimulation. By comparison, STZ-treated diabetic rats undergoing forced-exercise exhibited a 4-week delay in the onset of tactile hypersensitivity that was independent of glucose control. Exercise-facilitated analgesia in diabetic rats was reversed, in a dose-dependent manner, by naloxone. Small-diameter (< 30 μm) DRG neurons harvested from STZ-treated tactile hypersensitive diabetic rats exhibited an enhanced (2.5-fold) rightward (depolarizing) shift in peak high-voltage activated (HVA) Ca(2+) current density with a concomitant appearance of a low-voltage activated (LVA) Ca(2+) current component. LVA Ca(2+) currents present in DRG neurons from hypersensitive diabetic rats exhibited a marked depolarizing shift in steady-state inactivation. Forced-exercise attenuated diabetes-associated changes in HVA Ca(2+) current density while preventing the depolarizing shift in steady-state inactivation of LVA Ca(2+) currents. Forced-exercise markedly delays the onset of diabetes-associated neuropathic pain, in part, by attenuating associated changes in HVA and LVA Ca(2+) channel function within small-diameter DRG neurons possibly by altering opioidergic tone. PMID:21554321

  11. Transient activation and delayed inhibition of Na+,K+,Cl- cotransport in ATP-treated C11-MDCK cells involve distinct P2Y receptor subtypes and signaling mechanisms.

    PubMed

    Akimova, Olga A; Grygorczyk, Alexandra; Bundey, Richard A; Bourcier, Nathalie; Gekle, Michael; Insel, Paul A; Orlov, Sergei N

    2006-10-20

    In C11-MDCK cells, which resemble intercalated cells from collecting ducts of the canine kidney, P2Y agonists promote transient activation of the Na+,K+,Cl- cotransporter (NKCC), followed by its sustained inhibition. We designed this study to identify P2Y receptor subtypes involved in dual regulation of this carrier. Real time polymerase chain reaction analysis demonstrated that C11-MDCK cells express abundant P2Y1 and P2Y2 mRNA compared with that of other P2Y receptor subtypes. The rank order of potency of agents (ATP approximately UTP > 2-(methylthio)-ATP (2MeSATP); adenosine 5'-[beta-thio]diphosphate (ADPbetaS) inactive) indicated that P2Y2 rather than P2Y1 receptors mediate a 3-4-fold activation of NKCC within the first 5-10 min of nucleotide addition. NKCC activation in ATP-treated cells was abolished by the intracellular calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, calmodulin (CaM) antagonists trifluoroperazine and W-7, and KN-62, an inhibitor of Ca2+/CaM-dependent protein kinase II. By contrast with the transient activation, 30-min incubation with nucleotides produced up to 4-5-fold inhibition of NKCC, and this inhibition exhibited a rank order of potency (2MeSATP > ADPbetaS > ATP > UTP) typical of P2Y1 receptors. Unlike the early response, delayed inhibition of NKCC occurred in 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-loaded cells and was completely abolished by the P2Y1 antagonists MRS2179 and MRS2500. Transient activation and delayed inhibition of NKCC in C11 cell monolayers were observed after the addition of ATP to mucosal and serosal solutions, respectively. NKCC inhibition triggered by basolateral application of ADPbetaS was abolished by MRS2500. Our results thus show that transient activation and delayed inhibition of NKCC in ATP-treated C11-MDCK cells is mediated by Ca2+/CaM-dependent protein kinase II- and Ca2+-independent signaling triggered by apical P2Y2 and basolateral P2Y1 receptors, respectively

  12. The atrazine metabolite diaminochlorotriazine suppresses LH release from murine LβT2 cells by suppressing GnRH-induced intracellular calcium transients.

    PubMed

    Dooley, Gregory P; Tjalkens, Ronald B; Hanneman, William H

    2013-05-01

    The primary metabolite of the herbicide atrazine (ATRA), diaminochlorotriazine (DACT), has been suggested to cause disruption in the hypothalamic-pituitary-gonadal axis leading to inhibition of luteinizing hormone (LH) release. DACT is a reactive electrophile known to form covalent protein adducts both in vitro and in vivo following ATRA exposure and maybe targeting proteins involved in GnRH-induced calcium signaling and subsequent LH release. To test this hypothesis, LβT2 pituitary cells were exposed to 300 μM DACT for 24 hrs and examined by fluorescence microscopy for GnRH-induced changes in intracellular calcium and LH release. LβT2 cells exposed to DACT had markedly diminished GnRH-induced intracellular calcium transients and a significant decreased LH release in response to GnRH. DACT appeared to cause a selective decrease in caffeine-sensitive ryanodine receptor-operated calcium stores in LβT2 cells, rather than in thapsigargin-sensitive ER calcium stores. This sensitivity correlated with the formation of covalent protein adducts by DACT, as determined by mass spectrometry. ERp57 was identified by mass spectrometry as a target of DACT adduction in the ER that could potentially mediate the effects of DACT on inhibition of GnRH-induced calcium signaling and inhibition of LH release. Intracellular calcium responses to GnRH and release of LH were restored in DACT-treated cells with the addition of a calcium ionophore (A23187). These data suggest that DACT forms adducts on proteins involved in calcium handling within the ER and that dysfunction in this critical signaling system is associated with loss of normal sensitivity to GnRH and subsequent decreased release of LH.

  13. The atrazine metabolite diaminochlorotriazine suppresses LH release from murine LβT2 cells by suppressing GnRH-induced intracellular calcium transients

    PubMed Central

    Dooley, Gregory P.; Tjalkens, Ronald B.; Hanneman, William H.

    2013-01-01

    The primary metabolite of the herbicide atrazine (ATRA), diaminochlorotriazine (DACT), has been suggested to cause disruption in the hypothalamic-pituitary-gonadal axis leading to inhibition of luteinizing hormone (LH) release. DACT is a reactive electrophile known to form covalent protein adducts both in vitro and in vivo following ATRA exposure and maybe targeting proteins involved in GnRH-induced calcium signaling and subsequent LH release. To test this hypothesis, LβT2 pituitary cells were exposed to 300 μM DACT for 24 hrs and examined by fluorescence microscopy for GnRH-induced changes in intracellular calcium and LH release. LβT2 cells exposed to DACT had markedly diminished GnRH-induced intracellular calcium transients and a significant decreased LH release in response to GnRH. DACT appeared to cause a selective decrease in caffeine-sensitive ryanodine receptor-operated calcium stores in LβT2 cells, rather than in thapsigargin-sensitive ER calcium stores. This sensitivity correlated with the formation of covalent protein adducts by DACT, as determined by mass spectrometry. ERp57 was identified by mass spectrometry as a target of DACT adduction in the ER that could potentially mediate the effects of DACT on inhibition of GnRH-induced calcium signaling and inhibition of LH release. Intracellular calcium responses to GnRH and release of LH were restored in DACT-treated cells with the addition of a calcium ionophore (A23187). These data suggest that DACT forms adducts on proteins involved in calcium handling within the ER and that dysfunction in this critical signaling system is associated with loss of normal sensitivity to GnRH and subsequent decreased release of LH. PMID:24052811

  14. Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis

    NASA Technical Reports Server (NTRS)

    Beers, D. R.; Ho, B. K.; Siklos, L.; Alexianu, M. E.; Mosier, D. R.; Mohamed, A. H.; Otsuka, Y.; Kozovska, M. E.; McAlhany, R. E.; Smith, R. G.; Appel, S. H.

    2001-01-01

    Intracellular calcium is increased in vulnerable spinal motoneurons in immune-mediated as well as transgenic models of amyotrophic lateral sclerosis (ALS). To determine whether intracellular calcium levels are influenced by the calcium-binding protein parvalbumin, we developed transgenic mice overexpressing parvalbumin in spinal motoneurons. ALS immunoglobulins increased intracellular calcium and spontaneous transmitter release at motoneuron terminals in control animals, but not in parvalbumin overexpressing transgenic mice. Parvalbumin transgenic mice interbred with mutant SOD1 (mSOD1) transgenic mice, an animal model of familial ALS, had significantly reduced motoneuron loss, and had delayed disease onset (17%) and prolonged survival (11%) when compared with mice with only the mSOD1 transgene. These results affirm the importance of the calcium binding protein parvalbumin in altering calcium homeostasis in motoneurons. The increased motoneuron parvalbumin can significantly attenuate the immune-mediated increases in calcium and to a lesser extent compensate for the mSOD1-mediated 'toxic-gain-of-function' in transgenic mice.

  15. Opposite effects of phosphatase inhibitors on L-type calcium and delayed rectifier currents in frog cardiac myocytes.

    PubMed Central

    Frace, A M; Hartzell, H C

    1993-01-01

    1. Application of the phosphatase inhibitors okadaic acid (OA) and microcystin (MC) to frog cardiomyocytes caused large increases in L-type calcium current (ICa) in the absence of beta-adrenergic agonists. The increase occurred without effects on the peak current-voltage relation or voltage-dependent inactivation. OA and MC caused a decrease in amplitude of delayed rectifier current (IK), which is opposite to the increase produced by cAMP-dependent phosphorylation. The decrease occurred without effects on voltage-dependent activation or reversal potential. 2. Analysis of the dose-response relations for OA and MC on ventricular cell ICa were best fitted with a single-site relationship with a K1/2 of 1.58 microM and 0.81 microM, respectively. These data suggest the predominant form of phosphatase active on ICa in this cell type is produced by protein phosphatase 1. Inhibition of phosphatase 2B (calcineurin) was without appreciable effect. 3. Reducing intracellular ATP levels was without effect on basal ICa suggesting that calcium channels may not need to be phosphorylated to open. ATP depletion was able to block completely the ICa increase induced by OA or MC. This demonstrates that the effects of OA and MC on ICa are mediated by a phosphorylation reaction. In contrast, ATP depletion totally abolished IK, suggesting either a requirement for ATP or phosphorylation for basal function of the delayed rectifier channel. 4. Internal perfusion of a peptide inhibitor (PKI(5-22)) of protein kinase A (PK-A) was without effect on basal current levels of ICa or IK, suggesting that this kinase is not phosphorylating these channels under basal conditions. Furthermore, although PKI is capable of completely blocking the response of ICa to isoprenaline or forskolin, PKI does not affect the increase in ICa induced by MC or OA. Inhibition of adenylate cyclase with acetylcholine or inhibition of PK-A with adenosine cyclic 3',5'-(Rp)-phosphothioate (Rp-cAMPS) also had no effect on the

  16. Transient receptor potential vanilloid 4-dependent calcium influx and ATP release in mouse and rat gastric epithelia

    PubMed Central

    Mihara, Hiroshi; Suzuki, Nobuhiro; Boudaka, Ammar Abdullkader; Muhammad, Jibran Sualeh; Tominaga, Makoto; Tabuchi, Yoshiaki; Sugiyama, Toshiro

    2016-01-01

    AIM: To explore the expression of transient receptor potential vanilloid 4 (TRPV4) and its physiological meaning in mouse and rat gastric epithelia. METHODS: RT-PCR and immunochemistry were used to detect TRPV4 mRNA and protein expression in mouse stomach and a rat normal gastric epithelial cell line (RGE1-01), while Ca2+-imaging and electrophysiology were used to evaluate TRPV4 channel activity. ATP release was measured by a luciferin-luciferase assay. Gastric emptying was also compared between WT and TRPV4 knockout mice. RESULTS: TRPV4 mRNA and protein were detected in mouse tissues and RGE1-01 cells. A TRPV4-specific agonist (GSK1016790A) increased intracellular Ca2+ concentrations and/or evoked TRPV4-like current activities in WT mouse gastric epithelial cells and RGE1-01 cells, but not TRPV4KO cells. GSK1016790A or mechanical stimuli induced ATP release from RGE1-01 cells while TRPV4 knockout mice displayed delayed gastric emptying in vivo. CONCLUSION: TRPV4 is expressed in mouse and rat gastric epithelium and contributes to ATP release and gastric emptying. PMID:27350729

  17. A functional tandem between transient receptor potential canonical channels 6 and calcium-dependent chloride channels in human epithelial cells.

    PubMed

    Bertrand, Johanna; Dannhoffer, Luc; Antigny, Fabrice; Vachel, Laura; Jayle, Christophe; Vandebrouck, Clarisse; Becq, Frédéric; Norez, Caroline

    2015-10-15

    TRPC6 plays important human physiological functions, notably in artery and arterioles constriction, in regulation of vascular volume and in bronchial muscle constriction. It is implicated in pulmonary hypertension, cardiovascular disease, and focal segmental glomerulosclerosis and seems to play a role in cancer development. Previously, we identified Guanabenz, an α2-adrenergic agonist used for hypertension treatment (Wytensin®), as an activator of calcium-dependent chloride channels (CaCC) in human Cystic Fibrosis (CF) nasal epithelial cells by transiently increasing [Ca2+]i via an influx of extracellular Ca2+. In this study, using assays to measure chloride channel activity, we show that guanabenz is an activator of CaCC in freshly dissociated human bronchial epithelial cells from three CF patients with various genotypes (F508del/F508del, F508del/R1066C, F508del/H1085R). We further characterised the effect of guanabenz and show that it is independent of α-adrenergic receptors, is inhibited by the TRPC family inhibitor SKF-96365 but not by the TRPV family inhibitor ruthenium red. Using western-blotting, Ca2+ measurements and iodide efflux assay, we found that TRPC1 siRNA has no effect on guanabenz induced responses whereas TRPC6 siRNA prevented the guanabenz-dependent Ca2+ influx and the CaCC-dependent activity stimulated by guanabenz. In conclusion, we show that TRPC6 channel is pivotal for the activation of CaCC by guanabenz through a α2-adrenergic-independent pathway in human airway epithelial cells. We suggest propose a functional coupling between TRPC6 and CaCC and guanabenz as a potential TRPC6 activator for exploring TRPC6 and CaCC channel functions and corresponding channelopathies.

  18. The calcium-independent transient outward potassium current in isolated ferret right ventricular myocytes. I. Basic characterization and kinetic analysis

    PubMed Central

    1993-01-01

    Enzymatically isolated myocytes from ferret right ventricles (12-16 wk, male) were studied using the whole cell patch clamp technique. The macroscopic properties of a transient outward K+ current I(to) were quantified. I(to) is selective for K+, with a PNa/PK of 0.082. Activation of I(to) is a voltage-dependent process, with both activation and inactivation being independent of Na+ or Ca2+ influx. Steady-state inactivation is well described by a single Boltzmann relationship (V1/2 = -13.5 mV; k = 5.6 mV). Substantial inactivation can occur during a subthreshold depolarization without any measurable macroscopic current. Both development of and recovery from inactivation are well described by single exponential processes. Ensemble averages of single I(to) channel currents recorded in cell-attached patches reproduce macroscopic I(to) and indicate that inactivation is complete at depolarized potentials. The overall inactivation/recovery time constant curve has a bell-shaped potential dependence that peaks between -10 and -20 mV, with time constants (22 degrees C) ranging from 23 ms (-90 mV) to 304 ms (-10 mV). Steady-state activation displays a sigmoidal dependence on membrane potential, with a net aggregate half- activation potential of +22.5 mV. Activation kinetics (0 to +70 mV, 22 degrees C) are rapid, with I(to) peaking in approximately 5-15 ms at +50 mV. Experiments conducted at reduced temperatures (12 degrees C) demonstrate that activation occurs with a time delay. A nonlinear least- squares analysis indicates that three closed kinetic states are necessary and sufficient to model activation. Derived time constants of activation (22 degrees C) ranged from 10 ms (+10 mV) to 2 ms (+70 mV). Within the framework of Hodgkin-Huxley formalism, Ito gating can be described using an a3i formulation. PMID:8505627

  19. Transient Growth Theory Prediction of Optimal Placing of Passive and Active Flow Control Devices for Separation Delay in LPT Airfoils

    NASA Technical Reports Server (NTRS)

    Tumin, Anatoli; Ashpis, David E.

    2003-01-01

    An analysis of the non-modal growth of perturbations in a boundary layer in the presence of a streamwise pressure gradient is presented. The analysis is based on PSE equations for an incompressible fluid. Examples with Falkner-Skan profiles indicate that a favorable pressure gradient decreases the non-modal growth while an unfavorable pressure gradient leads to an increase of the amplification. It is suggested that the transient growth mechanism be utilized to choose optimal parameters of tripping elements on a low-pressure turbine (LPT) airfoil. As an example, a boundary layer flow with a streamwise pressure gradient corresponding to the pressure distribution over a LPT airfoil is considered. It is shown that there is an optimal spacing of the tripping elements and that the transient growth effect depends on the starting point. At very low Reynolds numbers, there is a possibility to enhance the transient energy growth by means of wall cooling.

  20. Down-regulation of ASICs current and the calcium transients by disrupting PICK1 protects primary cultured mouse cortical neurons from OGD-Rep insults.

    PubMed

    Cheng, Jin; Chen, Yu; Xing, Hui; Jiang, Hua; Ye, Xihong

    2015-01-01

    Acid sensing ion channels (ASICs), activated by lowering extracellular pH, play an important role in normal synaptic transmission in brain and in the pathology of brain ischemia. ASICs activation involving in glutamate receptor-independent ischemic brain injury has been generally accepted, and PICK1 is recently shown to be one of partner proteins interacting with ASICs through its PDZ domain. Here we showed that ASICs and PICK1 played key roles in OGD-Rep process. In wild-type cultured cortical neurons, not only the amplitude of ASICs current and the calcium transients induced by acidosis were both increased after OGD-Rep, but also the total protein levels of ASIC1 and ASIC2a were up-regulated progressively after ischemia insults, indicating that ASICs play a vital role in neuronal ischemia. However, these activities were reversed with PICK1-knockout after OGD-Rep, accompanied with the dramatically down-regulating the protein abundances of ASIC1 and ASIC2a, which suggested the neuroprotection activity in brain ischemia by PICK1-knockout. These results indicate that knocking-out PICK1 gene casts the neuroprotection effect by reducing ASICs current and the calcium transients in OGD-Rep neuronal cells, which will offer a promising strategy in the therapy of brain ischemia.

  1. Stimulus-response coupling in monocytes infected with Leishmania. Attenuation of calcium transients is related to defective agonist-induced accumulation of inositol phosphates.

    PubMed

    Olivier, M; Baimbridge, K G; Reiner, N E

    1992-02-15

    Mononuclear phagocytes infected with Leishmania have been shown to have defective responses to extracellular stimuli. To investigate the potential relationship of these findings to alterations in calcium-dependent signaling pathways, the regulation of [Ca2+]i concentrations was examined in human peripheral blood monocytes infected with amastigotes of Leishmania donovani. Measurements of [Ca2+]i in fura-2-loaded monocytes were made at the single cell level by microfluorimetry. In normal monocytes, resting [Ca2+]i was 56 +/- 2 nM (mean +/- SEM). In contrast, in monocytes infected with Leishmania there was an approximately twofold increase in basal [Ca2+]i (122 +/- 5 nM, p less than 0.01 vs control). Treatment of cells with pertussis toxin before infection did not abrogate infection-induced increases in basal [Ca2+]i, suggesting that this effect was not mediated via the activation of a G protein coupled to phospholipase C. However, elevated resting [Ca2+]i did correlate with increased rates of 45Ca2+ uptake by infected monocytes. As expected, in response to treatment with 10(-7) M FMLP, control monocytes showed rapid net increases in [Ca2+]i of 303 +/- 19 nM. In contrast, net transients of [Ca2+]i in infected monocytes in response to FMLP were attenuated to only 137 +/- 9 nM (p less than 0.01 vs control). This result was not related to excess buffering of [Ca2+]i in infected cells as both control and infected monocytes showed equivalent transients of [Ca2+]i in response to the calcium ionophore A23187. Rather, inhibition of agonist-induced calcium release in infected cells appeared related to defective generation of second messenger because compared to control cells labeled with myo-[2-3H]inositol, little accumulation of inositol 1,4,5-trisphosphate was detected in infected monocytes. Attenuation of inositol phosphate accumulation and calcium release in response to chemotactic peptide correlated with decreased FMLP-induced superoxide and hydrogen peroxide production

  2. Left ventricular dysfunction following transient ischaemia induced by transluminal coronary angioplasty. Beneficial effects of calcium antagonists against post-ischaemic myocardial stunning.

    PubMed

    Sheiban, I; Tonni, S; Benussi, P; Marini, A; Trevi, G P

    1993-07-01

    Acute and severe ischaemia is followed by depression of myocardial contractility during reperfusion; return to full recovery might take a long time. This phenomenon, termed myocardial stunning, has been extensively demonstrated in experimental studies and in different clinical settings. The beneficial effects of calcium antagonists in preventing post-ischaemic myocardial stunning have been tested in experimental studies, showing that when administered before or during ischaemia, they inhibit post-ischaemic myocardial dysfunction. The present study was undertaken to verify the possible occurrence of myocardial stunning following transient ischaemia induced by coronary angioplasty. The aim was also to evaluate the possible protective effects of calcium antagonists (nisoldipine) and nitrates against myocardial stunning in patients with coronary artery disease undergoing routine coronary angioplasty (PCTA) with prolonged inflation. The study included 25 patients, aged between 40 and 69 years, with exercise-induced angina and single vessel disease. The stenosis was severe (80% to subtotal occlusion), localized on the left anterior descending artery, but without collaterals at coronary angiogram. All patients had normal left ventricular (LV) overall function and normal systolic thickening of the anterior wall supplied by the diseased artery. Our data suggest that post-ischaemic myocardial stunning is not only an experimental curiosity, but that it does occur in different clinical settings. Calcium antagonists (i.e. nisoldipine), when added before or during ischaemia, seem to prevent myocardial stunning. These findings confer a potential role to these agents in the treatment of post-ischaemic myocardial dysfunction.

  3. Impaired growth, delayed ossification, and reduced osteoclastic activity in the growth plate of calcium-supplemented rats with renal failure.

    PubMed

    Sanchez, C P; Kuizon, B D; Abdella, P A; Jüppner, H; Salusky, I B; Goodman, W G

    2000-04-01

    Linear growth is reduced in prepubertal children with adynamic renal osteodystrophy, suggesting that the proliferation and/or differentiation of epiphyseal growth plate chondrocytes is abnormal in this disorder. To examine this issue, in situ hybridization and histochemistry were used to measure selected markers of endochondral bone formation and bone resorption in the proximal tibia of subtotally nephrectomized rats fed a high calcium diet to induce biochemical changes consistent with adynamic osteodystrophy. Blood ionized calcium concentrations were higher and serum PTH levels were lower in nephrectomized, calcium-supplemented rats than in either intact or nephrectomized control animals. Linear growth and tibial length were reduced, but messenger RNA levels for type II collagen, type X collagen, and the PTH/PTHrP receptor did not differ from control values in nephrectomized rats given supplemental calcium. In contrast, both the width of epiphyseal cartilage and the height of the zone of hypertrophic chondrocytes were greater in calcium-supplemented nephrectomized rats. These morphological changes were associated with decreases in histochemical staining for tartrate-resistant acid phosphatase and lower levels of messenger RNA expression for the matrix metalloproteinase MMP-9/gelatinase B immediately adjacent to the epiphyseal growth plate. Diminished chondroclastic/osteoclastic activity alters growth plate morphology and adversely affects linear bone growth in calcium-supplemented, nephrectomized rats.

  4. Cardiac effects of the extract and active components of Radix stephaniae tetrandrae. I. Electrically-induced intracellular calcium transient and protein release during the calcium paradox.

    PubMed

    Wu, S; Yu, X C; Shan, J; Wong, T M; Chen, C F; Pang, K T

    2001-05-11

    The present study was designed to compare the cardiac actions of the extract and individual components, tetrandrine (Tet) and fangchinoline (Fan), of Radix stephaniae tetrandrae (RST). We measured the electrically induced [Ca2+]i transient in single rat ventricular myocytes and protein release following perfusion with a Ca2+ free solution (the Ca2+ paradox) from the isolated perfused rat heart, both of which are known to relate to Ca2+ influx. We found that Tet inhibited both electrically induced [Ca2+]i transient and protein release during the Ca2+ paradox, while Fan had no significant effects. The RST extract containing 9% Tet and 6% Fan by weight also affected the [Ca2+]i transient, and was only slightly, though significantly, less effective/potent than Tet alone. On the other hand, RST extract had a significantly greater inhibitory effect on protein release during the Ca2+ paradox than Tet alone. The observations suggest that the RST extract, which contains a mixture of components, may have more potent effects in the heart than its main active component. PMID:11432451

  5. JTT-305, an orally active calcium-sensing receptor antagonist, stimulates transient parathyroid hormone release and bone formation in ovariectomized rats.

    PubMed

    Kimura, Shuichi; Nakagawa, Takashi; Matsuo, Yushi; Ishida, Yuji; Okamoto, Yoshihisa; Hayashi, Mikio

    2011-10-01

    Intermittent administration of parathyroid hormone (PTH) has a potent anabolic effect on bone in humans and animals. Calcium-sensing receptor (CaSR) antagonists stimulate endogenous PTH secretion through CaSR on the surface of parathyroid cells and thereby may be anabolic agents for osteoporosis. JTT-305 is a potent oral short-acting CaSR antagonist and transiently stimulates endogenous PTH secretion. The objective of the present study was to investigate the effects of JTT-305 on PTH secretion and bone in ovariectomized rats. Female rats, immediately after ovariectomy (OVX), were orally administered vehicle or JTT-305 (0.3, 1, or 3 mg/kg) for 12 weeks. The serum PTH concentrations were transiently elevated with increasing doses of JTT-305. In the proximal tibia, JTT-305 prevented OVX-induced decreases in both the cancellous and total bone mineral density (BMD) except for the 0.3mg/kg dose. At the 3mg/kg dose, JTT-305 increased the mineralizing surface and bone formation rate in histomorphometry. The efficacy of JTT-305 at the 3mg/kg dose on the BMD corresponded to that of exogenous rat PTH1-84 injection at doses between 3 and 10 μg/kg. In conclusion, JTT-305 stimulated endogenous transient PTH secretion and bone formation, and consequently prevented bone loss in OVX rats. These results suggest that JTT-305 is orally active and has the potential to be an anabolic agent for the treatment of osteoporosis.

  6. N- and L-Type Voltage-Gated Calcium Channels Mediate Fast Calcium Transients in Axonal Shafts of Mouse Peripheral Nerve.

    PubMed

    Barzan, Ruxandra; Pfeiffer, Friederike; Kukley, Maria

    2016-01-01

    In the peripheral nervous system (PNS) a vast number of axons are accommodated within fiber bundles that constitute peripheral nerves. A major function of peripheral axons is to propagate action potentials along their length, and hence they are equipped with Na(+) and K(+) channels, which ensure successful generation, conduction and termination of each action potential. However little is known about Ca(2+) ion channels expressed along peripheral axons and their possible functional significance. The goal of the present study was to test whether voltage-gated Ca(2+) channels (VGCCs) are present along peripheral nerve axons in situ and mediate rapid activity-dependent Ca(2+) elevations under physiological circumstances. To address this question we used mouse sciatic nerve slices, Ca(2+) indicator Oregon Green BAPTA-1, and 2-photon Ca(2+) imaging in fast line scan mode (500 Hz). We report that transient increases in intra-axonal Ca(2+) concentration take place along peripheral nerve axons in situ when axons are stimulated electrically with single pulses. Furthermore, we show for the first time that Ca(2+) transients in peripheral nerves are fast, i.e., occur in a millisecond time-domain. Combining Ca(2+) imaging and pharmacology with specific blockers of different VGCCs subtypes we demonstrate that Ca(2+) transients in peripheral nerves are mediated mainly by N-type and L-type VGCCs. Discovery of fast Ca(2+) entry into the axonal shafts through VGCCs in peripheral nerves suggests that Ca(2+) may be involved in regulation of action potential propagation and/or properties in this system, or mediate neurotransmitter release along peripheral axons as it occurs in the optic nerve and white matter of the central nervous system (CNS).

  7. N- and L-Type Voltage-Gated Calcium Channels Mediate Fast Calcium Transients in Axonal Shafts of Mouse Peripheral Nerve

    PubMed Central

    Barzan, Ruxandra; Pfeiffer, Friederike; Kukley, Maria

    2016-01-01

    In the peripheral nervous system (PNS) a vast number of axons are accommodated within fiber bundles that constitute peripheral nerves. A major function of peripheral axons is to propagate action potentials along their length, and hence they are equipped with Na+ and K+ channels, which ensure successful generation, conduction and termination of each action potential. However little is known about Ca2+ ion channels expressed along peripheral axons and their possible functional significance. The goal of the present study was to test whether voltage-gated Ca2+ channels (VGCCs) are present along peripheral nerve axons in situ and mediate rapid activity-dependent Ca2+ elevations under physiological circumstances. To address this question we used mouse sciatic nerve slices, Ca2+ indicator Oregon Green BAPTA-1, and 2-photon Ca2+ imaging in fast line scan mode (500 Hz). We report that transient increases in intra-axonal Ca2+ concentration take place along peripheral nerve axons in situ when axons are stimulated electrically with single pulses. Furthermore, we show for the first time that Ca2+ transients in peripheral nerves are fast, i.e., occur in a millisecond time-domain. Combining Ca2+ imaging and pharmacology with specific blockers of different VGCCs subtypes we demonstrate that Ca2+ transients in peripheral nerves are mediated mainly by N-type and L-type VGCCs. Discovery of fast Ca2+ entry into the axonal shafts through VGCCs in peripheral nerves suggests that Ca2+ may be involved in regulation of action potential propagation and/or properties in this system, or mediate neurotransmitter release along peripheral axons as it occurs in the optic nerve and white matter of the central nervous system (CNS). PMID:27313508

  8. Comparison of dendritic calcium transients in juvenile wild type and SOD1(G93A) mouse lumbar motoneurons.

    PubMed

    Quinlan, Katharina A; Lamano, Jonathan B; Samuels, Julienne; Heckman, C J

    2015-01-01

    Previous studies of spinal motoneurons in the SOD1 mouse model of amyotrophic lateral sclerosis have shown alterations long before disease onset, including increased dendritic branching, increased persistent Na(+) and Ca(2+) currents, and impaired axonal transport. In this study dendritic Ca(2+) entry was investigated using two photon excitation fluorescence microscopy and whole-cell patch-clamp of juvenile (P4-11) motoneurons. Neurons were filled with both Ca(2+) Green-1 and Texas Red dextrans, and line scans performed throughout. Steps were taken to account for different sources of variability, including (1) dye filling and laser penetration, (2) dendritic anatomy, and (3) the time elapsed from the start of recording. First, Ca(2+) Green-1 fluorescence was normalized by Texas Red; next, neurons were reconstructed so anatomy could be evaluated; finally, time was recorded. Customized software detected the largest Ca(2+) transients (area under the curve) from each line scan and matched it with parameters above. Overall, larger dendritic diameter and shorter path distance from the soma were significant predictors of larger transients, while time was not significant up to 2 h (data thereafter was dropped). However, Ca(2+) transients showed additional variability. Controlling for previous factors, significant variation was found between Ca(2+) signals from different processes of the same neuron in 3/7 neurons. This could reflect differential expression of Ca(2+) channels, local neuromodulation or other variations. Finally, Ca(2+) transients in SOD1(G93A) motoneurons were significantly smaller than in non-transgenic motoneurons. In conclusion, motoneuron processes show highly variable Ca(2+) transients, but these transients are smaller overall in SOD1(G93A) motoneurons. PMID:25914627

  9. New tuning rules of PI-like controllers with transient performances for monotonic time-delay systems.

    PubMed

    Mnif, Faïçal

    2008-10-01

    In this note, new tuning methods for Proportional-Integral (PI) are proposed for monotonic time delay systems. Like the Ziegler-Nichols method, the proposed technique requires only parameters obtained from the plant step response. Unlike conventional techniques, the resultant tuning parameters offer the advantage of obtaining stable response with prescribed dynamic behavior with relation to the maximum overshoot. The idea of the design is simple and relies on basics learned in an introductory control course.

  10. Role of inositol-1,4,5-trisphosphate receptor in the regulation of calcium transients in neonatal rat ventricular myocytes.

    PubMed

    Zeng, Zheng; Zhang, Heping; Lin, Na; Kang, Man; Zheng, Yuanyuan; Li, Chen; Xu, Pingxiang; Wu, Yongquan; Luo, Dali

    2014-01-01

    This study determined the regulatory effect of inositol 1,4,5-trisphosphate receptors (IP3Rs) on the basal Ca(2+) transients in cardiomyocytes. In cultured neonatal rat ventricular myocytes (NRVMs) at different densities, we used confocal microscopy to assess the effect of IP3Rs on the endogenous spontaneous Ca(2+) oscillations through specific activation of IP3Rs with myo-IP3 hexakis (butyryloxymethyl) ester (IP3BM), a membrane permeable IP3, and interference of IP3R expression with shRNA. We found that NRVMs at the monolayer state displayed coordinated Ca(2+) transients with less rate, shorter duration, and higher amplitude compared to single NRVMs. In addition, monolayer NRVMs exhibited 4 or 10 times more increased Ca(2+) transients in response to phenylephrine, an α-adrenergic receptor agonist, or IP3BM than single NRVMs did, while the transient pattern remained unaltered, suggesting that the sensitivity of intracellular Ca(2+) response to IP3R activation is different between single and monolayer NRVMs. However, interference of IP3R expression with shRNA reduced the frequency and amplitude of the spontaneous Ca(2+) fluctuates similarly in both densities of NRVMs, resembling the effects of ryanodine receptor inhibition by ryanodine or tetracaine. Our findings suggest that IP3Rs are involved, in part, in the regulation of native Ca(2+) transients, in profiles of their initiation and Ca(2+) release extent, in developing cardiomyocytes. In addition, caution should be paid in evaluating the behavior of Ca(2+) signaling in primary cultured cardiomyocytes at different densities. PMID:25242084

  11. Free-calcium and force transients during depolarization and pharmacomechanical coupling in guinea-pig smooth muscle.

    PubMed Central

    Himpens, B; Somlyo, A P

    1988-01-01

    1. Fura2 was loaded by permeation and hydrolysis of the acetoxymethyl ester into smooth muscle cells of intact thin sheets of the longitudinal layer of the small intestine of the guinea-pig, to record Ca2+ transients during contraction. 2. Cytoplasmic Ca2+ ([Ca2+]i) was monitored by computing the ratio of the fluorescence signal excited at 340 and 380 nm wavelengths. The dye loading and the exposure to UV light required for the experiments had no significant effect on the contractile parameters observed. 3. Spontaneous, rhythmic increases in [Ca2+]i were often observed, preceding the onset of force. Removal of extracellular Ca2+ caused a very transient increase in [Ca2+]i accompanied by a phasic force transient; this was followed by a decline in [Ca2+]i and tension below control levels. Elevated Ca2+ from 1.2 to 15 mM also caused a fall in [Ca2+]i and a relaxation of basal tension. 4. Elevation of [K+]o increased [Ca2+]i. Graded concentrations of K+ caused graded changes in both fluorescence ratio and tension. 5. Carbachol evoked a transient increase in [Ca2+]i and contraction. Thereafter, in spite of the continued presence of the drug, both signals declined, presumably as the result of cholinergic desensitization. The initial phasic force response to carbachol was usually followed by an 'after-contraction', that was only occasionally accompanied by a similar (small) secondary rise in the fluorescence signal. 6. In depolarized smooth muscle, both in the presence and in the absence of extracellular Ca2+, carbachol induced a transient increase in [Ca2+]i, indicating that Ca2+ release from intracellular stores is a major mechanism of pharmacomechanical coupling. 7. In some preparations an applied stretch caused, after a few seconds, a rise in [Ca2+]i and force development. PMID:3137325

  12. Effects of total flavones from Acanthopanax senticosus on L-type calcium channels, calcium transient and contractility in rat ventricular myocytes.

    PubMed

    Guan, Shengjiang; Ma, Juanjuan; Chu, Xi; Gao, Yonggang; Zhang, Ying; Zhang, Xuan; Zhang, Fenghua; Liu, Zhenyi; Zhang, Jianping; Chu, Li

    2015-04-01

    Acanthopanax senticosus (Rupr. et Maxim.) Harms (AS), a traditional herbal medicine, has been widely used to treat ischemic heart disease. However, the underlying cellular mechanisms of its benefits to cardiac function remain unclear. The present study examined the effects of total flavones from AS (TFAS) on L-type Ca(2+) channel currents (ICa-L ) using the whole cell patch-clamp technique and on intracellular calcium ([Ca(2+) ]i ) handling and cell contractility in rat ventricular myocytes with the aid of a video-based edge-detection system. Exposure to TFAS resulted in a concentration- and voltage-dependent blockade of ICa-L , with the half-maximal inhibitory concentration (IC50 ) of 283.12 µg/mL and the maximal inhibitory effect of 36.49 ± 1.95%. Moreover, TFAS not only increased the maximum current in the current-voltage relationship but also shifted the activation and inactivation curves of ICa-L toward the hyperpolarizing direction. Meanwhile, TFAS significantly reduced amplitudes of myocyte shortening and [Ca(2+) ]i with an increase in the time to 10% of the peak (Tp) and a decrease in the time to 10% of the baseline (Tr). Thus, the cardioprotective effects of TFAS may be attributed mainly to the attenuation of [Ca(2+) ]i through the direct inhibition of ICa-L in rat ventricular myocytes and consequent negative effect on myocardial contractility. PMID:25586009

  13. Peripheral μ-opioid receptor mediated inhibition of calcium signaling and action potential-evoked calcium fluorescent transients in primary afferent CGRP nociceptive terminals.

    PubMed

    Baillie, Landon D; Schmidhammer, Helmut; Mulligan, Sean J

    2015-06-01

    While μ-opioid receptor (MOR) agonists remain the most powerful analgesics for the treatment of severe pain, serious adverse side effects that are secondary to their central nervous system actions pose substantial barriers to therapeutic use. Preclinical and clinical evidence suggest that peripheral MORs play an important role in opioid analgesia, particularly under inflammatory conditions. However, the mechanisms of peripheral MOR signaling in primary afferent pain fibres remain to be established. We have recently introduced a novel ex vivo optical imaging approach that, for the first time, allows the study of physiological functioning within individual peripheral nociceptive fibre free nerve endings in mice. In the present study, we found that MOR activation in selectively identified, primary afferent CGRP nociceptive terminals caused inhibition of N-type Ca(2+) channel signaling and suppression of action potential-evoked Ca(2+) fluorescent transients mediated by 'big conductance' Ca(2+)-activated K(+) channels (BKCa). In the live animal, we showed that the peripherally acting MOR agonist HS-731 produced analgesia and that BKCa channels were the major effectors of the peripheral MOR signaling. We have identified two key molecular transducers of MOR activation that mediate significant inhibition of nociceptive signaling in primary afferent terminals. Understanding the mechanisms of peripheral MOR signaling may promote the development of pathway selective μ-opioid drugs that offer improved therapeutic profiles for achieving potent analgesia while avoiding serious adverse central side effects. PMID:25721395

  14. New Findings on the Effects of Tannic Acid: Inhibition of L-Type Calcium Channels, Calcium Transient and Contractility in Rat Ventricular Myocytes.

    PubMed

    Zhu, Fengli; Chu, Xi; Wang, Hua; Zhang, Xuan; Zhang, Yuanyuan; Liu, Zhenyi; Guo, Hui; Liu, Hongying; Liu, Yang; Chu, Li; Zhang, Jianping

    2016-03-01

    Tannic acid (TA) is a group of water-soluble polyphenolic compounds that occur mainly in plant-derived feeds, food grains and fruits. Many studies have explored its biomedical properties, such as anticancer, antibacterial, antimutagenic, antioxidant, antidiabetic, antiinflammatory and antihypertensive activities. However, the effects of TA on the L-type Ca(2+) current (ICa-L) of cardiomyocytes remain undefined. The present study examined the effects of TA on ICa-L using the whole-cell patch-clamp technique and on intracellular Ca(2+) handling and cell contractility in rat ventricular myocytes with the aid of a video-based edge detection system. Exposure to TA resulted in a concentration- and voltage-dependent blockade of ICa-L, with the half maximal inhibitory concentration of 1.69 μM and the maximal inhibitory effect of 46.15%. Moreover, TA significantly inhibited the amplitude of myocyte shortening and peak value of Ca(2+) transient and increased the time to 10% of the peak. These findings provide new experimental evidence for the cellular mechanism of action of TA and may help to expand clinical treatments for cardiovascular disease. PMID:26762248

  15. Inhibition of presynaptic calcium transients in cortical inputs to the dorsolateral striatum by metabotropic GABAB and mGlu2/3 receptors

    PubMed Central

    Kupferschmidt, David A; Lovinger, David M

    2015-01-01

    Cortical inputs to the dorsolateral striatum (DLS) are dynamically regulated during skill learning and habit formation, and are dysregulated in disorders characterized by impaired action control. Therefore, a mechanistic investigation of the processes regulating corticostriatal transmission is key to understanding DLS-associated circuit function, behaviour and pathology. Presynaptic GABAB and group II metabotropic glutamate (mGlu2/3) receptors exert marked inhibitory control over corticostriatal glutamate release in the DLS, yet the signalling pathways through which they do so are unclear. We developed a novel approach using the genetically encoded calcium (Ca2+) indicator GCaMP6 to assess presynaptic Ca2+ in corticostriatal projections to the DLS. Using simultaneous photometric presynaptic Ca2+ and striatal field potential recordings, we report that relative to P/Q-type Ca2+ channels, N-type channels preferentially contributed to evoked presynaptic Ca2+ influx in motor cortex projections to, and excitatory transmission in, the DLS. Activation of GABAB or mGlu2/3 receptors inhibited both evoked presynaptic Ca2+ transients and striatal field potentials. mGlu2/3 receptor-mediated depression did not require functional N-type Ca2+ channels, but was attenuated by blockade of P/Q-type channels. These findings reveal presynaptic mechanisms of inhibitory modulation of corticostriatal function that probably contribute to the selection and shaping of behavioural repertoires. Key points Plastic changes at cortical inputs to the dorsolateral striatum (DLS) underlie skill learning and habit formation, so characterizing the mechanisms by which these inputs are regulated is important for understanding the neural basis of action control. We developed a novel approach using the genetically encoded calcium (Ca2+) indicator GCaMP6 and brain slice photometry to assess evoked presynaptic Ca2+ transients in cortical inputs to the DLS and study their regulation by GABAB and mGlu2

  16. A transient increase in lipid peroxidation primes preadipocytes for delayed mitochondrial inner membrane permeabilization and ATP depletion during prolonged exposure to fatty acids

    PubMed Central

    Rogers, Carlyle; Davis, Barbara; Neufer, P. Darrell; Murphy, Michael P.; Anderson, Ethan J; Robidoux, Jacques

    2014-01-01

    Preadipocytes are periodically subjected to fatty acid (FA) concentrations that are potentially cytotoxic. We tested the hypothesis that prolonged exposure of preadipocytes of human origin to a physiologically relevant mix of FAs leads to mitochondrial inner membrane (MIM) permeabilization and ultimately to mitochondrial crisis. We found that exposure of preadipocytes to FAs led to progressive cyclosporin A-sensitive MIM permeabilization, which in turn caused reduction in MIM potential (ΔΨM), oxygen consumption, ATP synthetic capacity, and ultimately death. Additionally, we showed that FAs induce a transient increase in intramitochondrial ROS and lipid peroxide production lasting roughly 30 and 120 minutes for the ROS and lipid peroxides, respectively. MIM permeabilization and its deleterious consequences including mitochondrial crisis and cell death were prevented by treating the cells with the mitochondrial FA uptake inhibitor, Etomoxir; the mitochondrion selective superoxide and lipid peroxide antioxidants, MitoTempo and MitoQ; or the lipid peroxide and reactive carbonyl scavenger, L-carnosine. FAs also promoted a delayed oxidative stress phase. However, since the beneficial effects of Etomoxir, MitoTempo and L-carnosine were lost by delaying the treatment by 2 hours, it suggested that the initial phase was sufficient to prime the cells for the delayed MIM permeabilization and mitochondrial crisis. It also suggested that the second ROS production phase is a consequence of this loss in mitochondrial health. Altogether, our data suggest that approaches designed to diminish intramitochondrial ROS or lipid peroxide accumulation as well as MIM permeabilization, are valid mechanism-based therapeutic avenues to prevent the loss in preadipocyte metabolic fitness associated with prolonged exposure to elevated FA levels. PMID:24269897

  17. Cytosolic calcium transients are a determinant of contraction-induced HSP72 transcription in single skeletal muscle fibers.

    PubMed

    Stary, Creed M; Hogan, Michael C

    2016-05-15

    The intrinsic activating factors that induce transcription of heat shock protein 72 (HSP72) in skeletal muscle following exercise remain unclear. We hypothesized that the cytosolic Ca(2+) transient that occurs with depolarization is a determinant. We utilized intact, single skeletal muscle fibers from Xenopus laevis to test the role of the cytosolic Ca(2+) transient and several other exercise-related factors (fatigue, hypoxia, AMP kinase, and cross-bridge cycling) on the activation of HSP72 transcription. HSP72 and HSP60 mRNA levels were assessed with real-time quantitative PCR; cytosolic Ca(2+) concentration ([Ca(2+)]cyt) was assessed with fura-2. Both fatiguing and nonfatiguing contractions resulted in a significant increase in HSP72 mRNA. As expected, peak [Ca(2+)]cyt remained tightly coupled with peak developed tension in contracting fibers. Pretreatment with N-benzyl-p-toluene sulfonamide (BTS) resulted in depressed peak developed tension with stimulation, while peak [Ca(2+)]cyt remained largely unchanged from control values. Despite excitation-contraction uncoupling, BTS-treated fibers displayed a significant increase in HSP72 mRNA. Treatment of fibers with hypoxia (Po2: <3 mmHg) or AMP kinase activation had no effect on HSP72 mRNA levels. These results suggest that the intermittent cytosolic Ca(2+) transient that occurs with skeletal muscle depolarization provides a sufficient activating stimulus for HSP72 transcription. Metabolic or mechanical factors associated with fatigue development and cross-bridge cycling likely play a more limited role. PMID:26869714

  18. Neuroplasticity of A-type potassium channel complexes induced by chronic alcohol exposure enhances dendritic calcium transients in hippocampus

    PubMed Central

    Mulholland, Patrick J.; Spencer, Kathryn B.; Hu, Wei; Kroener, Sven; Chandler, L. Judson

    2014-01-01

    Rationale Chronic alcohol-induced cognitive impairments and maladaptive plasticity of glutamatergic synapses are well-documented. However, it is unknown if prolonged alcohol exposure affects dendritic signaling that may underlie hippocampal dysfunction in alcoholics. Back-propagation of action potentials (bAPs) into apical dendrites of hippocampal neurons provides distance-dependent signals that modulate dendritic and synaptic plasticity. The amplitude of bAPs decreases with distance from the soma that is thought to reflect an increase in the density of Kv4.2 channels toward distal dendrites. Objective The aim of this study was to quantify changes in hippocampal Kv4.2 channel function and expression using electrophysiology, Ca2+ imaging, and western blot analyses in a well-characterized in-vitro model of chronic alcohol exposure. Results Chronic alcohol exposure significantly decreased expression of Kv4.2 channels and KChIP3 in hippocampus. This reduction was associated with an attenuation of macroscopic A-type K+ currents in CA1 neurons. Chronic alcohol exposure increased bAP-evoked Ca2+ transients in the distal apical dendrites of CA1 pyramidal neurons. The enhanced bAP-evoked Ca2+ transients induced by chronic alcohol exposure were not related to alteration of synaptic targeting of NMDA receptors or morphological adaptations in apical dendritic arborization. Conclusions These data suggest that chronic alcohol-induced decreases in Kv4.2 channel function possibly mediated by a down-regulation of KChIP3, drive the elevated bAP-associated Ca2+ transients in distal apical dendrites. Alcohol-induced enhancement of bAPs may affect metaplasticity and signal integration in apical dendrites of hippocampal neurons leading to alterations in hippocampal function. PMID:25510858

  19. Ca analysis: an Excel based program for the analysis of intracellular calcium transients including multiple, simultaneous regression analysis.

    PubMed

    Greensmith, David J

    2014-01-01

    Here I present an Excel based program for the analysis of intracellular Ca transients recorded using fluorescent indicators. The program can perform all the necessary steps which convert recorded raw voltage changes into meaningful physiological information. The program performs two fundamental processes. (1) It can prepare the raw signal by several methods. (2) It can then be used to analyze the prepared data to provide information such as absolute intracellular Ca levels. Also, the rates of change of Ca can be measured using multiple, simultaneous regression analysis. I demonstrate that this program performs equally well as commercially available software, but has numerous advantages, namely creating a simplified, self-contained analysis workflow.

  20. Early and delayed long-term transcriptional changes and short-term transient responses during cold acclimation in olive leaves

    PubMed Central

    Leyva-Pérez, María de la O; Valverde-Corredor, Antonio; Valderrama, Raquel; Jiménez-Ruiz, Jaime; Muñoz-Merida, Antonio; Trelles, Oswaldo; Barroso, Juan Bautista; Mercado-Blanco, Jesús; Luque, Francisco

    2015-01-01

    Low temperature severely affects plant growth and development. To overcome this constraint, several plant species from regions having a cool season have evolved an adaptive response, called cold acclimation. We have studied this response in olive tree (Olea europaea L.) cv. Picual. Biochemical stress markers and cold-stress symptoms were detected after the first 24 h as sagging leaves. After 5 days, the plants were found to have completely recovered. Control and cold-stressed plants were sequenced by Illumina HiSeq 1000 paired-end technique. We also assembled a new olive transcriptome comprising 157,799 unigenes and found 6,309 unigenes differentially expressed in response to cold. Three types of response that led to cold acclimation were found: short-term transient response, early long-term response, and late long-term response. These subsets of unigenes were related to different biological processes. Early responses involved many cold-stress-responsive genes coding for, among many other things, C-repeat binding factor transcription factors, fatty acid desaturases, wax synthesis, and oligosaccharide metabolism. After long-term exposure to cold, a large proportion of gene down-regulation was found, including photosynthesis and plant growth genes. Up-regulated genes after long-term cold exposure were related to organelle fusion, nucleus organization, and DNA integration, including retrotransposons. PMID:25324298

  1. Early and delayed long-term transcriptional changes and short-term transient responses during cold acclimation in olive leaves.

    PubMed

    Leyva-Pérez, María de la O; Valverde-Corredor, Antonio; Valderrama, Raquel; Jiménez-Ruiz, Jaime; Muñoz-Merida, Antonio; Trelles, Oswaldo; Barroso, Juan Bautista; Mercado-Blanco, Jesús; Luque, Francisco

    2015-02-01

    Low temperature severely affects plant growth and development. To overcome this constraint, several plant species from regions having a cool season have evolved an adaptive response, called cold acclimation. We have studied this response in olive tree (Olea europaea L.) cv. Picual. Biochemical stress markers and cold-stress symptoms were detected after the first 24 h as sagging leaves. After 5 days, the plants were found to have completely recovered. Control and cold-stressed plants were sequenced by Illumina HiSeq 1000 paired-end technique. We also assembled a new olive transcriptome comprising 157,799 unigenes and found 6,309 unigenes differentially expressed in response to cold. Three types of response that led to cold acclimation were found: short-term transient response, early long-term response, and late long-term response. These subsets of unigenes were related to different biological processes. Early responses involved many cold-stress-responsive genes coding for, among many other things, C-repeat binding factor transcription factors, fatty acid desaturases, wax synthesis, and oligosaccharide metabolism. After long-term exposure to cold, a large proportion of gene down-regulation was found, including photosynthesis and plant growth genes. Up-regulated genes after long-term cold exposure were related to organelle fusion, nucleus organization, and DNA integration, including retrotransposons.

  2. Early and delayed long-term transcriptional changes and short-term transient responses during cold acclimation in olive leaves.

    PubMed

    Leyva-Pérez, María de la O; Valverde-Corredor, Antonio; Valderrama, Raquel; Jiménez-Ruiz, Jaime; Muñoz-Merida, Antonio; Trelles, Oswaldo; Barroso, Juan Bautista; Mercado-Blanco, Jesús; Luque, Francisco

    2015-02-01

    Low temperature severely affects plant growth and development. To overcome this constraint, several plant species from regions having a cool season have evolved an adaptive response, called cold acclimation. We have studied this response in olive tree (Olea europaea L.) cv. Picual. Biochemical stress markers and cold-stress symptoms were detected after the first 24 h as sagging leaves. After 5 days, the plants were found to have completely recovered. Control and cold-stressed plants were sequenced by Illumina HiSeq 1000 paired-end technique. We also assembled a new olive transcriptome comprising 157,799 unigenes and found 6,309 unigenes differentially expressed in response to cold. Three types of response that led to cold acclimation were found: short-term transient response, early long-term response, and late long-term response. These subsets of unigenes were related to different biological processes. Early responses involved many cold-stress-responsive genes coding for, among many other things, C-repeat binding factor transcription factors, fatty acid desaturases, wax synthesis, and oligosaccharide metabolism. After long-term exposure to cold, a large proportion of gene down-regulation was found, including photosynthesis and plant growth genes. Up-regulated genes after long-term cold exposure were related to organelle fusion, nucleus organization, and DNA integration, including retrotransposons. PMID:25324298

  3. Time-delayed behaviors of transient four-wave mixing signal intensity in inverted semiconductor with carrier-injection pumping

    NASA Astrophysics Data System (ADS)

    Hu, Zhenhua; Gao, Shen; Xiang, Bowen

    2016-01-01

    An analytical expression of transient four-wave mixing (TFWM) in inverted semiconductor with carrier-injection pumping was derived from both the density matrix equation and the complex stochastic stationary statistical method of incoherent light. Numerical analysis showed that the TFWM decayed decay is towards the limit of extreme homogeneous and inhomogeneous broadenings in atoms and the decaying time is inversely proportional to half the power of the net carrier densities for a low carrier-density injection and other high carrier-density injection, while it obeys an usual exponential decay with other decaying time that is inversely proportional to half the power of the net carrier density or it obeys an unusual exponential decay with the decaying time that is inversely proportional to a third power of the net carrier density for a moderate carrier-density injection. The results can be applied to studying ultrafast carrier dephasing in the inverted semiconductors such as semiconductor laser amplifier and semiconductor optical amplifier.

  4. Transient Increased Calcium and Calcitriol Requirements After Discontinuation of Human Synthetic Parathyroid Hormone 1-34 (hPTH 1-34) Replacement Therapy in Hypoparathyroidism.

    PubMed

    Gafni, Rachel I; Guthrie, Lori C; Kelly, Marilyn H; Brillante, Beth A; Christie, C Michele; Reynolds, James C; Yovetich, Nancy A; James, Robert; Collins, Michael T

    2015-11-01

    Synthetic human PTH 1-34 (hPTH 1-34) replacement therapy in hypoparathyroidism maintains eucalcemia and converts quiescent bone to high-turnover bone. However, the skeletal and metabolic effects of drug discontinuation have not been reported. Nine subjects with hypoparathyroidism received subcutaneous injections of hPTH 1-34 two to three times daily for 19.8 to 61.3 months and then transitioned back to calcium and calcitriol. Biochemistries and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) were assessed at baseline, while on treatment, and at follow-up 3 to 12 months after drug discontinuation. Two subjects developed hypocalcemia when hPTH 1-34 was abruptly discontinued. Thus, to avoid hypocalcemia, subjects were slowly weaned from hPTH 1-34 over several weeks. When hPTH 1-34 was stopped, subjects were requiring two to three times pretreatment doses of calcitriol and calcium to maintain blood calcium levels. Doses were gradually reduced over many weeks until calcium levels were stable on doses similar to baseline. Bone-specific alkaline phosphatase (BSAP), N-telopeptide (NTX), and osteocalcin (OC) increased significantly with hPTH 1-34; at follow-up, BSAP and NTX had returned to baseline while OC was still slightly elevated. During treatment, BMD was unchanged at the hip and lateral spine but declined at the anterior-posterior (AP) spine, radius, and total body. During weaning, BMD increased, with the hip and lateral spine exceeding pre-hPTH 1-34 values and the whole body returning to baseline. AP spine was increased non-significantly compared to baseline at follow-up. hPTH 1-34 must be gradually weaned in hypoparathyroid patients with high doses of oral medications given to avoid hypocalcemia. The transient increased requirements accompanied by increased BMD after long-term hPTH 1-34 therapy suggest a reversal of the expanded remodeling space favoring bone formation as the skeleton returns to a low-turnover state, reminiscent of the hungry

  5. Profound regulation of Na/K pump activity by transient elevations of cytoplasmic calcium in murine cardiac myocytes

    PubMed Central

    Lu, Fang-Min; Deisl, Christine; Hilgemann, Donald W

    2016-01-01

    Small changes of Na/K pump activity regulate internal Ca release in cardiac myocytes via Na/Ca exchange. We now show conversely that transient elevations of cytoplasmic Ca strongly regulate cardiac Na/K pumps. When cytoplasmic Na is submaximal, Na/K pump currents decay rapidly during extracellular K application and multiple results suggest that an inactivation mechanism is involved. Brief activation of Ca influx by reverse Na/Ca exchange enhances pump currents and attenuates current decay, while repeated Ca elevations suppress pump currents. Pump current enhancement reverses over 3 min, and results are similar in myocytes lacking the regulatory protein, phospholemman. Classical signaling mechanisms, including Ca-activated protein kinases and reactive oxygen, are evidently not involved. Electrogenic signals mediated by intramembrane movement of hydrophobic ions, such as hexyltriphenylphosphonium (C6TPP), increase and decrease in parallel with pump currents. Thus, transient Ca elevation and Na/K pump inactivation cause opposing sarcolemma changes that may affect diverse membrane processes. DOI: http://dx.doi.org/10.7554/eLife.19267.001 PMID:27627745

  6. SKF-96365 activates cytoprotective autophagy to delay apoptosis in colorectal cancer cells through inhibition of the calcium/CaMKIIγ/AKT-mediated pathway.

    PubMed

    Jing, Zhao; Sui, Xinbing; Yao, Junlin; Xie, Jiansheng; Jiang, Liming; Zhou, Yubin; Pan, Hongming; Han, Weidong

    2016-03-28

    Store-operated Ca(2+) entry (SOCE) inhibitors are emerging as an attractive new generation of anti-cancer drugs. Here, we report that SKF-96365, an SOCE inhibitor, exhibits potent anti-neoplastic activity by inducing cell-cycle arrest and apoptosis in colorectal cancer cells. In the meantime, SKF-96365 also induces cytoprotective autophagy to delay apoptosis by preventing the release of cytochrome c (cyt c) from the mitochondria into the cytoplasm. Mechanistically, SKF-96365 treatment inhibited the calcium/calmodulin-dependent protein kinase IIγ (CaMKIIγ)/AKT signaling cascade in vitro and in vivo. Overexpression of CaMKIIγ or AKT abolished the effects of SKF-96365 on cancer cells, suggesting a critical role of the CaMKIIγ/AKT signaling pathway in SFK-96365-induced biological effects. Moreover, Hydroxychloroquine (HCQ), an FDA-approved drug used to inhibit autophagy, could significantly augment the anti-cancer effect of SFK-96365 in a mouse xenograft model. To our best knowledge, this is the first report to demonstrate that calcium/CaMKIIγ/AKT signaling can regulate apoptosis and autophagy simultaneously in cancer cells, and the combination of the SOCE inhibitor SKF-96365 with autophagy inhibitors represents a promising strategy for treating patients with colorectal cancer. PMID:26803057

  7. SKF-96365 activates cytoprotective autophagy to delay apoptosis in colorectal cancer cells through inhibition of the calcium/CaMKIIγ/AKT-mediated pathway.

    PubMed

    Jing, Zhao; Sui, Xinbing; Yao, Junlin; Xie, Jiansheng; Jiang, Liming; Zhou, Yubin; Pan, Hongming; Han, Weidong

    2016-03-28

    Store-operated Ca(2+) entry (SOCE) inhibitors are emerging as an attractive new generation of anti-cancer drugs. Here, we report that SKF-96365, an SOCE inhibitor, exhibits potent anti-neoplastic activity by inducing cell-cycle arrest and apoptosis in colorectal cancer cells. In the meantime, SKF-96365 also induces cytoprotective autophagy to delay apoptosis by preventing the release of cytochrome c (cyt c) from the mitochondria into the cytoplasm. Mechanistically, SKF-96365 treatment inhibited the calcium/calmodulin-dependent protein kinase IIγ (CaMKIIγ)/AKT signaling cascade in vitro and in vivo. Overexpression of CaMKIIγ or AKT abolished the effects of SKF-96365 on cancer cells, suggesting a critical role of the CaMKIIγ/AKT signaling pathway in SFK-96365-induced biological effects. Moreover, Hydroxychloroquine (HCQ), an FDA-approved drug used to inhibit autophagy, could significantly augment the anti-cancer effect of SFK-96365 in a mouse xenograft model. To our best knowledge, this is the first report to demonstrate that calcium/CaMKIIγ/AKT signaling can regulate apoptosis and autophagy simultaneously in cancer cells, and the combination of the SOCE inhibitor SKF-96365 with autophagy inhibitors represents a promising strategy for treating patients with colorectal cancer.

  8. Blast Overpressure Waves Induce Transient Anxiety and Regional Changes in Cerebral Glucose Metabolism and Delayed Hyperarousal in Rats.

    PubMed

    Awwad, Hibah O; Gonzalez, Larry P; Tompkins, Paul; Lerner, Megan; Brackett, Daniel J; Awasthi, Vibhudutta; Standifer, Kelly M

    2015-01-01

    Physiological alterations, anxiety, and cognitive disorders are strongly associated with blast-induced traumatic brain injury (blast TBI), and are common symptoms in service personnel exposed to blasts. Since 2006, 25,000-30,000 new TBI cases are diagnosed annually in U.S. Service members; increasing evidence confirms that primary blast exposure causes diffuse axonal injury and is often accompanied by altered behavioral outcomes. Behavioral and acute metabolic effects resulting from blast to the head in the absence of thoracic contributions from the periphery were examined, following a single blast wave directed to the head of male Sprague-Dawley rats protected by a lead shield over the torso. An 80 psi head blast produced cognitive deficits that were detected in working memory. Blast TBI rats displayed increased anxiety as determined by elevated plus maze at day 9 post-blast compared to sham rats; blast TBI rats spent significantly more time than the sham controls in the closed arms (p < 0.05; n = 8-11). Interestingly, anxiety symptoms were absent at days 22 and 48 post-blast. Instead, blast TBI rats displayed increased rearing behavior at day 48 post-blast compared to sham rats. Blast TBI rats also exhibited suppressed acoustic startle responses, but similar pre-pulse inhibition at day 15 post-blast compared to sham rats. Acute physiological alterations in cerebral glucose metabolism were determined by positron emission tomography 1 and 9 days post-blast using (18)F-fluorodeoxyglucose ((18)F-FDG). Global glucose uptake in blast TBI rat brains increased at day 1 post-blast (p < 0.05; n = 4-6) and returned to sham levels by day 9. Our results indicate a transient increase in cerebral metabolism following a blast injury. Markers for reactive astrogliosis and neuronal damage were noted by immunoblotting motor cortex tissue from day 10 post-blast in blast TBI rats compared to sham controls (p < 0.05; n = 5-6). PMID:26136722

  9. Blast Overpressure Waves Induce Transient Anxiety and Regional Changes in Cerebral Glucose Metabolism and Delayed Hyperarousal in Rats

    PubMed Central

    Awwad, Hibah O.; Gonzalez, Larry P.; Tompkins, Paul; Lerner, Megan; Brackett, Daniel J.; Awasthi, Vibhudutta; Standifer, Kelly M.

    2015-01-01

    Physiological alterations, anxiety, and cognitive disorders are strongly associated with blast-induced traumatic brain injury (blast TBI), and are common symptoms in service personnel exposed to blasts. Since 2006, 25,000–30,000 new TBI cases are diagnosed annually in U.S. Service members; increasing evidence confirms that primary blast exposure causes diffuse axonal injury and is often accompanied by altered behavioral outcomes. Behavioral and acute metabolic effects resulting from blast to the head in the absence of thoracic contributions from the periphery were examined, following a single blast wave directed to the head of male Sprague-Dawley rats protected by a lead shield over the torso. An 80 psi head blast produced cognitive deficits that were detected in working memory. Blast TBI rats displayed increased anxiety as determined by elevated plus maze at day 9 post-blast compared to sham rats; blast TBI rats spent significantly more time than the sham controls in the closed arms (p < 0.05; n = 8–11). Interestingly, anxiety symptoms were absent at days 22 and 48 post-blast. Instead, blast TBI rats displayed increased rearing behavior at day 48 post-blast compared to sham rats. Blast TBI rats also exhibited suppressed acoustic startle responses, but similar pre-pulse inhibition at day 15 post-blast compared to sham rats. Acute physiological alterations in cerebral glucose metabolism were determined by positron emission tomography 1 and 9 days post-blast using 18F-fluorodeoxyglucose (18F-FDG). Global glucose uptake in blast TBI rat brains increased at day 1 post-blast (p < 0.05; n = 4–6) and returned to sham levels by day 9. Our results indicate a transient increase in cerebral metabolism following a blast injury. Markers for reactive astrogliosis and neuronal damage were noted by immunoblotting motor cortex tissue from day 10 post-blast in blast TBI rats compared to sham controls (p < 0.05; n = 5–6). PMID:26136722

  10. Delayed hippocampal neuronal death in young gerbil following transient global cerebral ischemia is related to higher and longer-term expression of p63 in the ischemic hippocampus.

    PubMed

    Bae, Eun Joo; Chen, Bai Hui; Yan, Bing Chun; Shin, Bich Na; Cho, Jeong Hwi; Kim, In Hye; Ahn, Ji Hyeon; Lee, Jae Chul; Tae, Hyun-Jin; Hong, Seongkweon; Kim, Dong Won; Cho, Jun Hwi; Lee, Yun Lyul; Won, Moo-Ho; Park, Joon Ha

    2015-06-01

    The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions (CA1-3) between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia. p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group. p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults. PMID:26199612

  11. Delayed hippocampal neuronal death in young gerbil following transient global cerebral ischemia is related to higher and longer-term expression of p63 in the ischemic hippocampus

    PubMed Central

    Bae, Eun Joo; Chen, Bai Hui; Yan, Bing Chun; Shin, Bich Na; Cho, Jeong Hwi; Kim, In Hye; Ahn, Ji Hyeon; Lee, Jae Chul; Tae, Hyun-Jin; Hong, Seongkweon; Kim, Dong Won; Cho, Jun Hwi; Lee, Yun Lyul; Won, Moo-Ho; Park, Joon Ha

    2015-01-01

    The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions (CA1–3) between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia. p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group. p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults. PMID:26199612

  12. Actions of a hydrogen sulfide donor (NaHS) on transient sodium, persistent sodium, and voltage-gated calcium currents in neurons of the subfornical organ

    PubMed Central

    Kuksis, Markus

    2015-01-01

    Hydrogen sulfide (H2S) is an endogenously found gasotransmitter that has been implicated in a variety of beneficial physiological functions. This study was performed to investigate the cellular mechanisms underlying actions of H2S previously observed in subfornical organ (SFO), where H2S acts to regulate blood pressure through a depolarization of the membrane and an overall increase in the excitability of SFO neurons. We used whole cell patch-clamp electrophysiology in the voltage-clamp configuration to analyze the effect of 1 mM NaHS, an H2S donor, on voltage-gated potassium, sodium, and calcium currents. We observed no effect of NaHS on potassium currents; however, both voltage-gated sodium currents (persistent and transient) and the N-type calcium current had a depolarized activation curve and an enhanced peak-induced current in response to a series of voltage-step and ramp protocols run in the control and NaHS conditions. These effects were not responsible for the previously observed depolarization of the membrane potential, as depolarizing effects of H2S were still observed following block of these conductances with tetrodotoxin (5 μM) and ω-conotoxin-GVIA (100 nM). Our studies are the first to investigate the effect of H2S on a variety of voltage-gated conductances in a single brain area, and although they do not explain mechanisms underlying the depolarizing actions of H2S on SFO neurons, they provide evidence of potential mechanisms through which this gasotransmitter influences the excitability of neurons in this important brain area as a consequence of the modulation of multiple ion channels. PMID:26180118

  13. Differential expression of the calcium-sensing receptor in the ischemic and border zones after transient focal cerebral ischemia in rats.

    PubMed

    Noh, Jeong Sook; Pak, Ha-Jin; Shin, Yoo-Jin; Riew, Tae-Ryong; Park, Joo-Hee; Moon, Young Wha; Lee, Mun-Yong

    2015-01-01

    G-protein-coupled calcium-sensing receptor (CaSR) has been recently recognized as an important modulator of diverse cellular functions, beyond the regulation of systemic calcium homeostasis. To identify whether CaSR is involved in the pathophysiology of stroke, we studied the spatiotemporal regulation of CaSR protein expression in rats undergoing transient focal cerebral ischemia, which was induced by middle cerebral artery occlusion. We observed very weak or negligible immunoreactivity for CaSR in the striatum of sham-operated rats, as well as in the contralateral striatum of ischemic rats after reperfusion. However, CaSR expression was induced in the ischemic and border zones of the lesion in ischemic rats. Six hours post-reperfusion there was an upregulation of CaSR in the ischemic zone, which seemed to decrease after seven days. This upregulation preferentially affected some neurons and cells associated with blood vessels, particularly endothelial cells and pericytes. In contrast, CaSR expression in the peri-infarct region was prominent three days after reperfusion, and with the exception of some neurons, it was mostly located in reactive astrocytes, up to day 14 after ischemia. On the other hand, activated microglia/macrophages in both the ischemic and border zones were devoid of specific labeling for CaSR at any time point after reperfusion, despite their massive infiltration in both regions. Our results show heterogeneity in CaSR-positive cells within the ischemic and border zones, suggesting that CaSR expression is regulated in response to the altered extracellular ionic environment caused by ischemic injury. Thus, CaSR may have a multifunctional role in the pathophysiology of ischemic stroke, possibly in vascular remodeling and astrogliosis. PMID:26013410

  14. Differential expression of the calcium-sensing receptor in the ischemic and border zones after transient focal cerebral ischemia in rats.

    PubMed

    Noh, Jeong Sook; Pak, Ha-Jin; Shin, Yoo-Jin; Riew, Tae-Ryong; Park, Joo-Hee; Moon, Young Wha; Lee, Mun-Yong

    2015-01-01

    G-protein-coupled calcium-sensing receptor (CaSR) has been recently recognized as an important modulator of diverse cellular functions, beyond the regulation of systemic calcium homeostasis. To identify whether CaSR is involved in the pathophysiology of stroke, we studied the spatiotemporal regulation of CaSR protein expression in rats undergoing transient focal cerebral ischemia, which was induced by middle cerebral artery occlusion. We observed very weak or negligible immunoreactivity for CaSR in the striatum of sham-operated rats, as well as in the contralateral striatum of ischemic rats after reperfusion. However, CaSR expression was induced in the ischemic and border zones of the lesion in ischemic rats. Six hours post-reperfusion there was an upregulation of CaSR in the ischemic zone, which seemed to decrease after seven days. This upregulation preferentially affected some neurons and cells associated with blood vessels, particularly endothelial cells and pericytes. In contrast, CaSR expression in the peri-infarct region was prominent three days after reperfusion, and with the exception of some neurons, it was mostly located in reactive astrocytes, up to day 14 after ischemia. On the other hand, activated microglia/macrophages in both the ischemic and border zones were devoid of specific labeling for CaSR at any time point after reperfusion, despite their massive infiltration in both regions. Our results show heterogeneity in CaSR-positive cells within the ischemic and border zones, suggesting that CaSR expression is regulated in response to the altered extracellular ionic environment caused by ischemic injury. Thus, CaSR may have a multifunctional role in the pathophysiology of ischemic stroke, possibly in vascular remodeling and astrogliosis.

  15. Critical consideration on the relationship between auxin transport and calcium transients in gravity perception of Arabidopsis seedlings

    PubMed Central

    Toyota, Masatsugu; Furuichi, Takuya; Tatsumi, Hitoshi

    2008-01-01

    Plants regulate their growth and morphogenesis in response to gravity field, known as gravitropism. In the early process of gravitropism, changes in the gravity vector (gravistimulation) are transduced into certain intracellular signals, termed gravity perception. The plant hormone auxin is not only a crucial factor to represent gravitropism but also a potential signaling molecule for gravity perception. Another strong candidate for the signaling molecule is calcium ion of which cytoplasmic concentration ([Ca2+]c) is known to increase in response to gravistimulation. However, relationship between these two factors, say which is in the first place, has been controversial. This issue is addressed here mainly based on recent progress including our latest studies. Gravistimulation by turning plants 180° induced a two-peaked [Ca2+]c-increase lasting for several minutes in Arabidopsis seedlings expressing apoaequorin; only the second peak was sensitive to the gravistimulation. Peak amplitudes of the [Ca2+]c-increase were attenuated by the 10 µM auxin transport inhibitor (TIBA) and vesicle trafficking inhibitor (BFA), whereas the onset time and rate of rise of the second peak were not significantly altered. This result indicates that polar auxin transport is not involved in the initial phase of the second [Ca2+]c-increase. It is likely that the gravi-induced [Ca2+]c-increase constitutes an upstream event of the auxin transport, but may positively be modulated by auxin since its peak amplitude is attenuated by the inhibition of auxin transport. PMID:19513245

  16. Calcium homeostasis in human melanocytes: role of transient receptor potential melastatin 1 (TRPM1) and its regulation by ultraviolet light

    PubMed Central

    Devi, Sulochana; Kedlaya, Rajendra; Maddodi, Nityanand; Bhat, Kumar M. R.; Weber, Craig S.; Valdivia, Hector

    2009-01-01

    Transient receptor potential melastatin (TRPM) is a subfamily of ion channels that are involved in sensing taste, ambient temperature, low pH, osmolarity, and chemical ligands. Melastatin 1/TRPM1, the founding member, was originally identified as melanoma metastasis suppressor based on its expression in normal pigment cells in the skin and the eye but not in aggressive, metastasis-competent melanomas. The role of TRPM1 and its regulation in normal melanocytes and in melanoma progression is not understood. Here, we studied the relationship of TRPM1 expression to growth and differentiation of human epidermal melanocytes. TRPM1 expression and intracellular Ca2+ levels are significantly lower in rapidly proliferating melanocytes compared to the slow growing, differentiated melanocytes. We show that lentiviral short hairpin RNA (shRNA)-mediated knockdown of TRPM1 results in reduced intracellular Ca2+ and decreased Ca2+ uptake suggesting a role for TRPM1 in Ca2+ homeostasis in melanocytes. TRPM1 knockdown also resulted in a decrease in tyrosinase activity and intracellular melanin pigment. Expression of the tumor suppressor p53 by transfection or induction of endogenous p53 by ultraviolet B radiation caused repression of TRPM1 expression accompanied by decrease in mobilization of intracellular Ca2+ and uptake of extracellular Ca2+. These data suggest a role for TRPM1-mediated Ca2+ homeostasis, which is also regulated by ultraviolet B, in melanogenesis. PMID:19587221

  17. Modeling the effects of vorinostat in vivo reveals both transient and delayed HIV transcriptional activation and minimal killing of latently infected cells

    SciTech Connect

    Ke, Ruian; Lewin, Sharon R.; Elliott, Julian H.; Perelson, Alan S.; Chakraborty, Arup K.

    2015-10-23

    Recent efforts to cure human immunodeficiency virus type-1 (HIV-1) infection have focused on developing latency reversing agents as a first step to eradicate the latent reservoir. The histone deacetylase inhibitor, vorinostat, has been shown to activate HIV RNA transcription in CD4+ T-cells and alter host cell gene transcription in HIV-infected individuals on antiretroviral therapy. In order to understand how latently infected cells respond dynamically to vorinostat treatment and determine the impact of vorinostat on reservoir size in vivo, we have constructed viral dynamic models of latency that incorporate vorinostat treatment. We fitted these models to data collected from a recent clinical trial in which vorinostat was administered daily for 14 days to HIV-infected individuals on suppressive ART. The results show that HIV transcription is increased transiently during the first few hours or days of treatment and that there is a delay before a sustained increase of HIV transcription, whose duration varies among study participants and may depend on the long term impact of vorinostat on host gene expression. Parameter estimation suggests that in latently infected cells, HIV transcription induced by vorinostat occurs at lower levels than in productively infected cells. Lastly, the estimated loss rate of transcriptionally induced cells remains close to baseline in most study participants, suggesting vorinostat treatment does not induce latently infected cell killing and thus reduce the latent reservoir in vivo.

  18. Modeling the effects of vorinostat in vivo reveals both transient and delayed HIV transcriptional activation and minimal killing of latently infected cells

    DOE PAGESBeta

    Ke, Ruian; Lewin, Sharon R.; Elliott, Julian H.; Perelson, Alan S.; Chakraborty, Arup K.

    2015-10-23

    Recent efforts to cure human immunodeficiency virus type-1 (HIV-1) infection have focused on developing latency reversing agents as a first step to eradicate the latent reservoir. The histone deacetylase inhibitor, vorinostat, has been shown to activate HIV RNA transcription in CD4+ T-cells and alter host cell gene transcription in HIV-infected individuals on antiretroviral therapy. In order to understand how latently infected cells respond dynamically to vorinostat treatment and determine the impact of vorinostat on reservoir size in vivo, we have constructed viral dynamic models of latency that incorporate vorinostat treatment. We fitted these models to data collected from a recentmore » clinical trial in which vorinostat was administered daily for 14 days to HIV-infected individuals on suppressive ART. The results show that HIV transcription is increased transiently during the first few hours or days of treatment and that there is a delay before a sustained increase of HIV transcription, whose duration varies among study participants and may depend on the long term impact of vorinostat on host gene expression. Parameter estimation suggests that in latently infected cells, HIV transcription induced by vorinostat occurs at lower levels than in productively infected cells. Lastly, the estimated loss rate of transcriptionally induced cells remains close to baseline in most study participants, suggesting vorinostat treatment does not induce latently infected cell killing and thus reduce the latent reservoir in vivo.« less

  19. Modeling the Effects of Vorinostat In Vivo Reveals both Transient and Delayed HIV Transcriptional Activation and Minimal Killing of Latently Infected Cells.

    PubMed

    Ke, Ruian; Lewin, Sharon R; Elliott, Julian H; Perelson, Alan S

    2015-10-01

    Recent efforts to cure human immunodeficiency virus type-1 (HIV-1) infection have focused on developing latency reversing agents as a first step to eradicate the latent reservoir. The histone deacetylase inhibitor, vorinostat, has been shown to activate HIV RNA transcription in CD4+ T-cells and alter host cell gene transcription in HIV-infected individuals on antiretroviral therapy. In order to understand how latently infected cells respond dynamically to vorinostat treatment and determine the impact of vorinostat on reservoir size in vivo, we have constructed viral dynamic models of latency that incorporate vorinostat treatment. We fitted these models to data collected from a recent clinical trial in which vorinostat was administered daily for 14 days to HIV-infected individuals on suppressive ART. The results show that HIV transcription is increased transiently during the first few hours or days of treatment and that there is a delay before a sustained increase of HIV transcription, whose duration varies among study participants and may depend on the long term impact of vorinostat on host gene expression. Parameter estimation suggests that in latently infected cells, HIV transcription induced by vorinostat occurs at lower levels than in productively infected cells. Furthermore, the estimated loss rate of transcriptionally induced cells remains close to baseline in most study participants, suggesting vorinostat treatment does not induce latently infected cell killing and thus reduce the latent reservoir in vivo.

  20. Modeling the Effects of Vorinostat In Vivo Reveals both Transient and Delayed HIV Transcriptional Activation and Minimal Killing of Latently Infected Cells

    PubMed Central

    Ke, Ruian; Lewin, Sharon R.; Elliott, Julian H; Perelson, Alan S.

    2015-01-01

    Recent efforts to cure human immunodeficiency virus type-1 (HIV-1) infection have focused on developing latency reversing agents as a first step to eradicate the latent reservoir. The histone deacetylase inhibitor, vorinostat, has been shown to activate HIV RNA transcription in CD4+ T-cells and alter host cell gene transcription in HIV-infected individuals on antiretroviral therapy. In order to understand how latently infected cells respond dynamically to vorinostat treatment and determine the impact of vorinostat on reservoir size in vivo, we have constructed viral dynamic models of latency that incorporate vorinostat treatment. We fitted these models to data collected from a recent clinical trial in which vorinostat was administered daily for 14 days to HIV-infected individuals on suppressive ART. The results show that HIV transcription is increased transiently during the first few hours or days of treatment and that there is a delay before a sustained increase of HIV transcription, whose duration varies among study participants and may depend on the long term impact of vorinostat on host gene expression. Parameter estimation suggests that in latently infected cells, HIV transcription induced by vorinostat occurs at lower levels than in productively infected cells. Furthermore, the estimated loss rate of transcriptionally induced cells remains close to baseline in most study participants, suggesting vorinostat treatment does not induce latently infected cell killing and thus reduce the latent reservoir in vivo. PMID:26496627

  1. No advantage to delaying the introduction of calcium soaps of palm oil fatty acids to early lactation dairy rations.

    PubMed

    Holter, J B; Hayes, H H

    1994-03-01

    Holstein cows (n = 105, 39 primiparous) were blocked by parity (1 vs. > 1) and assigned randomly at calving to receive supplemental Ca soaps of palm oil (2.9% fatty acids in dietary DM), commencing on DIM 1, 29, or 57 and ending on DIM 112. Effects on DMI, BW and condition score, and milk yield and composition were studied during 1 to 140 DIM. Control TMR contained 4.4% ether extract (mainly from corn meal and dried distillers grains with solubles), was fed using four grain to forage ratios, and, in early lactation, averaged 60% concentrate, 25% corn silage, and 15% wilted grass silage DM. Delayed supplementation of soaps did not promote higher dietary DMI, resulted in reduced milk fat percentage and yield, tended to decrease 4% FCM yield, and did not significantly influence milk protein content. Supplementation of soaps in wk 1 to 8 did not spare postpartum BW loss, hasten BW regain, or affect the normal change in body condition score. Ad libitum DMI and 4% FCM yield were significantly and negatively correlated (r = -.3) with the proportion of dietary CP that was ruminally undegradable.

  2. Transient coupling of Ng-CAM expression to NgCAM-dependent calcium signaling during migration of new neurons in the adult songbird brain.

    PubMed

    Goldman, S A; Williams, S; Barami, K; Lemmon, V; Nedergaard, M

    1996-01-01

    The adult avian forebrain continues to generate neurons from subependymal zone (SZ) precursor cells, whose neuronal progeny migrate into the brain upon radial guide fibers. These neurons express the immunoglobulin-family adhesion molecule NgCAM, and their migration in culture is disrupted by anti-NgCAM Fab. Confocal imaging of adult zebra finch SZ loaded with the calcium indicator fluo-3, as well as ratio imaging with the indicator fura-2, revealed that migrating new neurons responded to microgram amounts of NgCAM with reversible increments in cytosolic calcium. The calcium response to NgCAM antigen was developmentally restricted, in that it was only manifested by neurons for roughly the 3- to 4-day period between 6 and 9 DIV, even though NgCAM expression persisted tonically thereafter. The period during which NgCAM elicited a calcium signal corresponded to the postmitotic age at which new, bipolar neurons leave the adult SZ to enter the brain parenchyma in vivo. Accordingly, the calcium response to NgCAM was largely limited to morphologically bipolar cells. Anti-NgCAM IgG also evoked a neuronal calcium signal over the same restricted period that NgCAM protein exerted its effect. These findings suggest a dynamic coupling and uncoupling of calcium-dependent signal transduction pathways to a stably expressed surface adhesion molecule, whose function in a given neuron may therefore evolve with cellular maturation.

  3. Z944, a Novel Selective T-Type Calcium Channel Antagonist Delays the Progression of Seizures in the Amygdala Kindling Model.

    PubMed

    Casillas-Espinosa, Pablo Miguel; Hicks, Ashleigh; Jeffreys, Amy; Snutch, Terrance P; O'Brien, Terence J; Powell, Kim L

    2015-01-01

    Temporal lobe epilepsy (TLE) is the most common form of drug resistant epilepsy. Current treatment is symptomatic, suppressing seizures, but has no disease modifying effect on epileptogenesis. We examined the effects of Z944, a potent T-type calcium channel antagonist, as an anti-seizure agent and against the progression of kindling in the amygdala kindling model of TLE. The anti-seizure efficacy of Z944 (5mg/kg, 10mg/kg, 30mg/kg and 100mg/kg) was assessed in fully kindled rats (5 class V seizures) as compared to vehicle, ethosuximide (ETX, 100mg/kg) and carbamazepine (30mg/kg). Each animal received the seven treatments in a randomised manner. Seizure class and duration elicited by six post-drug stimulations was determined. To investigate for effects in delaying the progression of kindling, naive animals received Z944 (30mg/kg), ETX (100mg/kg) or vehicle 30-minutes prior to each kindling stimulation up to a maximum of 30 stimulations, with seizure class and duration recorded after each stimulation. At the completion of drug treatment, CaV3.1, CaV3.2 and CaV3.3 mRNA expression levels were assessed in the hippocampus and amygdala using qPCR. Z944 was not effective at suppressing seizures in fully kindled rats compared to vehicle. Animals receiving Z944 required significantly more stimulations to evoke a class III (p<0.05), IV (p<0.01) or V (p<0.0001) seizure, and to reach a fully kindled state (p<0.01), than animals receiving vehicle. There was no significant difference in the mRNA expression of the T-type Ca2+ channels in the hippocampus or amygdala. Our results show that selectively targeting T-type Ca2+ channels with Z944 inhibits the progression of amygdala kindling. This could be a potential for a new therapeutic intervention to mitigate the development and progression of epilepsy.

  4. Z944, a Novel Selective T-Type Calcium Channel Antagonist Delays the Progression of Seizures in the Amygdala Kindling Model

    PubMed Central

    Casillas-Espinosa, Pablo Miguel; Hicks, Ashleigh; Jeffreys, Amy; Snutch, Terrance P.; O’Brien, Terence J.; Powell, Kim L.

    2015-01-01

    Temporal lobe epilepsy (TLE) is the most common form of drug resistant epilepsy. Current treatment is symptomatic, suppressing seizures, but has no disease modifying effect on epileptogenesis. We examined the effects of Z944, a potent T-type calcium channel antagonist, as an anti-seizure agent and against the progression of kindling in the amygdala kindling model of TLE. The anti-seizure efficacy of Z944 (5mg/kg, 10mg/kg, 30mg/kg and 100mg/kg) was assessed in fully kindled rats (5 class V seizures) as compared to vehicle, ethosuximide (ETX, 100mg/kg) and carbamazepine (30mg/kg). Each animal received the seven treatments in a randomised manner. Seizure class and duration elicited by six post-drug stimulations was determined. To investigate for effects in delaying the progression of kindling, naive animals received Z944 (30mg/kg), ETX (100mg/kg) or vehicle 30-minutes prior to each kindling stimulation up to a maximum of 30 stimulations, with seizure class and duration recorded after each stimulation. At the completion of drug treatment, CaV3.1, CaV3.2 and CaV3.3 mRNA expression levels were assessed in the hippocampus and amygdala using qPCR. Z944 was not effective at suppressing seizures in fully kindled rats compared to vehicle. Animals receiving Z944 required significantly more stimulations to evoke a class III (p<0.05), IV (p<0.01) or V (p<0.0001) seizure, and to reach a fully kindled state (p<0.01), than animals receiving vehicle. There was no significant difference in the mRNA expression of the T-type Ca2+ channels in the hippocampus or amygdala. Our results show that selectively targeting T-type Ca2+ channels with Z944 inhibits the progression of amygdala kindling. This could be a potential for a new therapeutic intervention to mitigate the development and progression of epilepsy. PMID:26274319

  5. Detection, Properties, and Frequency of Local Calcium Release from the Sarcoplasmic Reticulum in Teleost Cardiomyocytes

    PubMed Central

    Alvarez-Lacalle, Enrique; Tort, Lluis; Benítez, Raul; Hove-Madsen, Leif

    2011-01-01

    Calcium release from the sarcoplasmic reticulum (SR) plays a central role in the regulation of cardiac contraction and rhythm in mammals and humans but its role is controversial in teleosts. Since the zebrafish is an emerging model for studies of cardiovascular function and regeneration we here sought to determine if basic features of SR calcium release are phylogenetically conserved. Confocal calcium imaging was used to detect spontaneous calcium release (calcium sparks and waves) from the SR. Calcium sparks were detected in 16 of 38 trout atrial myocytes and 6 of 15 ventricular cells. The spark amplitude was 1.45±0.03 times the baseline fluorescence and the time to half maximal decay of sparks was 27±3 ms. Spark frequency was 0.88 sparks µm−1 min−1 while calcium waves were 8.5 times less frequent. Inhibition of SR calcium uptake reduced the calcium transient (F/F0) from 1.77±0.17 to 1.12±0.18 (p = 0.002) and abolished calcium sparks and waves. Moreover, elevation of extracellular calcium from 2 to 10 mM promoted early and delayed afterdepolarizations (from 0.6±0.3 min−1 to 8.1±2.0 min−1, p = 0.001), demonstrating the ability of SR calcium release to induce afterdepolarizations in the trout heart. Calcium sparks of similar width and duration were also observed in zebrafish ventricular myocytes. In conclusion, this is the first study to consistently report calcium sparks in teleosts and demonstrate that the basic features of calcium release through the ryanodine receptor are conserved, suggesting that teleost cardiac myocytes is a relevant model to study the functional impact of abnormal SR function. PMID:21897853

  6. Source of nuclear calcium signals.

    PubMed Central

    Allbritton, N L; Oancea, E; Kuhn, M A; Meyer, T

    1994-01-01

    Transient increases of Ca2+ concentration in the nucleus regulate gene expression and other nuclear processes. We investigated whether nuclear Ca2+ signals could be regulated independently of the cytoplasm or were controlled by cytoplasmic Ca2+ signals. A fluorescent Ca2+ indicator that is targeted to the nucleus was synthesized by coupling a nuclear localization peptide to Calcium Green dextran, a 70-kDa Ca2+ indicator. Stimulation of rat basophilic leukemia cells by antigen or by photolytic uncaging of inositol 1,4,5-trisphosphate induced transient increases in nuclear and cytosolic Ca2+ concentrations. Elevations in the nuclear Ca2+ concentration followed those in the nearby perinuclear cytosol within 200 ms. Heparin-dextran, an inhibitor of the inositol 1,4,5-trisphosphate receptor that is excluded from the nucleus, was synthesized to specifically block the release of Ca2+ from cytosolic stores. Addition of this inhibitor suppressed Ca2+ transients in the nucleus and the cytosol. We conclude that the Ca2+ level in the nucleus is not independently controlled. Rather, nuclear Ca2+ increases follow cytosolic Ca2+ increases with a short delay most likely due to Ca2+ diffusion from the cytosol through the nuclear pores. Images Fig. 1 Fig. 3 Fig. 4 PMID:7809059

  7. PRECISION TIME-DELAY CIRCUIT

    DOEpatents

    Creveling, R.

    1959-03-17

    A tine-delay circuit which produces a delay time in d. The circuit a capacitor, an te back resistance, connected serially with the anode of the diode going to ground. At the start of the time delay a negative stepfunction is applied to the series circuit and initiates a half-cycle transient oscillatory voltage terminated by a transient oscillatory voltage of substantially higher frequency. The output of the delay circuit is taken at the junction of the inductor and diode where a sudden voltage rise appears after the initiation of the higher frequency transient oscillations.

  8. Calcium signaling and epilepsy.

    PubMed

    Steinlein, Ortrud K

    2014-08-01

    Calcium signaling is involved in a multitude of physiological and pathophysiological mechanisms. Over the last decade, it has been increasingly recognized as an important factor in epileptogenesis, and it is becoming obvious that the excess synchronization of neurons that is characteristic for seizures can be linked to various calcium signaling pathways. These include immediate effects on membrane excitability by calcium influx through ion channels as well as delayed mechanisms that act through G-protein coupled pathways. Calcium signaling is able to cause hyperexcitability either by direct modulation of neuronal activity or indirectly through calcium-dependent gliotransmission. Furthermore, feedback mechanisms between mitochondrial calcium signaling and reactive oxygen species are able to cause neuronal cell death and seizures. Unravelling the complexity of calcium signaling in epileptogenesis is a daunting task, but it includes the promise to uncover formerly unknown targets for the development of new antiepileptic drugs.

  9. Combined use of UV-labile calcium chelators and calcium-sensitive dyes in a microscope with two light sources influencing different regions in a group of coordinated contracting cardiac myocytes

    NASA Astrophysics Data System (ADS)

    Pilarczyk, Goetz; Greulich, Karl-Otto

    1997-12-01

    The coordination of excitation in a biological system of cells such as cardiac myocytes in heart tissue has crucial influence on the function of the entire organ. This coordinated behavior can be visualized in a small group of embryonic cardiac myocytes derived from the hearts of unborn chicken. Loaded with a calcium sensitive dye the excitation can be imaged via the occurring transient rise in cytosolic calcium concentration. It can be shown that in regions with physiological or morphological restrictions the transient rise in cytosolic calcium occurs with a temporal delay compared to the ordinary array of coupled myocytes. The height of the transient rise of cytosolic calcium is related to the ability of the individual cell to participate in the coordinated contraction. The free cytosolic calcium concentration is decreased with the UV-labile calcium, chelator diazo-2. Our setup allows to decrease the free cytosolic calcium in a single cell of the contracting array of cells. This allows us to introduce mismatches in selected regions of the coordinated contraction and to visualize the effects simultaneously.

  10. Calcium supplements

    MedlinePlus

    ... TYPES OF CALCIUM SUPPLEMENTS Forms of calcium include: Calcium carbonate: Over-the-counter (OTC) antacid products, such as Tums and Rolaids, contain calcium carbonate. These sources of calcium do not cost much. ...

  11. Glutamate Receptor-Like Channel3.3 Is Involved in Mediating Glutathione-Triggered Cytosolic Calcium Transients, Transcriptional Changes, and Innate Immunity Responses in Arabidopsis1[W][OA

    PubMed Central

    Li, Feng; Wang, Jing; Ma, Chunli; Zhao, Yongxiu; Wang, Yingchun; Hasi, Agula; Qi, Zhi

    2013-01-01

    The tripeptide reduced glutathione (GSH; γ-glutamate [Glu]-cysteine [Cys]-glycine) is a major endogenous antioxidant in both animal and plant cells. It also functions as a neurotransmitter mediating communication among neurons in the central nervous system of animals through modulating specific ionotropic Glu receptors (GLRs) in the membrane. Little is known about such signaling roles in plant cells. Here, we report that transient rises in cytosolic calcium triggered by exogenous GSH in Arabidopsis (Arabidopsis thaliana) leaves were sensitive to GLR antagonists and abolished in loss-of-function atglr3.3 mutants. Like the GSH biosynthesis-defective mutant PHYTOALEXIN DEFICIENT2, atglr3.3 showed enhanced susceptibility to the bacterial pathogen Pseudomonas syringae pv tomato DC3000. Pathogen-induced defense marker gene expression was also decreased in atglr3.3 mutants. Twenty-seven percent of genes that were rapidly responsive to GSH treatment of seedlings were defense genes, most of which were dependent on functional AtGLR3.3, while GSH suppressed pathogen propagation through the AtGLR3.3-dependent pathway. Eight previously identified putative AtGLR3.3 ligands, GSH, oxidized glutathione, alanine, asparagine, Cys, Glu, glycine, and serine, all elicited the AtGLR3.3-dependent cytosolic calcium transients, but only GSH and Cys induced the defense response, with the Glu-induced AtGLR3.3-dependent transcription response being much less apparent than that triggered by GSH. Together, these observations suggest that AtGLR3.3 is required for several signaling effects mediated by extracellular GSH, even though these effects may not be causally related. PMID:23656893

  12. Effects of serum immunoglobulins from patients with complex regional pain syndrome (CRPS) on depolarisation-induced calcium transients in isolated dorsal root ganglion (DRG) neurons.

    PubMed

    Reilly, Joanne M; Dharmalingam, Backialakshmi; Marsh, Stephen J; Thompson, Victoria; Goebel, Andreas; Brown, David A

    2016-03-01

    Complex regional pain syndrome (CRPS) is thought to have an auto-immune component. One such target recently proposed from the effects of auto-immune IgGs on Ca(2+) transients in cardiac myocytes and cell lines is the α1-adrenoceptor. We have tested whether such IgGs exerted comparable effects on nociceptive sensory neurons isolated from rat dorsal root ganglia. Depolarisation-induced [Ca(2+)]i transients were generated by applying 30 mM KCl for 2 min and monitored by Fura-2 fluorescence imaging. No IgGs tested (including 3 from CRPS patients) had any significant effect on these [Ca(2+)]i transients. However, IgG from one CRPS patient consistently and significantly reduced the K(+)-induced response of cells that had been pre-incubated for 24h with a mixture of inflammatory mediators (1 μM histamine, 5-hydroxytryptamine, bradykinin and PGE2). Since this pre-incubation also appeared to induce a comparable inhibitory response to the α1-agonist phenylephrine, this is compatible with the α1-adrenoceptor as a target for CRPS auto-immunity. A mechanism whereby this might enhance pain is suggested.

  13. Endotoxin-induced vascular endothelial cell migration is dependent on TLR4/NF-κB pathway, NAD(P)H oxidase activation, and transient receptor potential melastatin 7 calcium channel activity.

    PubMed

    Sarmiento, Daniela; Montorfano, Ignacio; Cáceres, Mónica; Echeverría, César; Fernández, Ricardo; Cabello-Verrugio, Claudio; Cerda, Oscar; Tapia, Pablo; Simon, Felipe

    2014-10-01

    Endothelial dysfunction is decisive and leads to the development of several inflammatory diseases. Endotoxemia-derived sepsis syndrome exhibits a broad inflammation-induced endothelial dysfunction. We reported previously that the endotoxin, lipopolysaccharide (LPS), induces the conversion of endothelial cells (ECs) into activated fibroblasts, showing a myofibroblast-like protein expression profile. Enhanced migration is a hallmark of myofibroblast function. However, the mechanism involved in LPS-induced EC migration is no totally understood. Some studies have shown that the transient receptor potential melastatin 7 (TRPM7) ion channel is involved in fibroblast and tumor cell migration through the regulation of calcium influx. Furthermore, LPS modulates TRPM7 expression. However, whether TRPM7 is involved in LPS-induced EC migration remains unknown. Here, we study the participation of LPS as an inducer of EC migration and study the mechanism underlying evaluating the participation of the TRPM7 ion channel. Our results demonstrate that LPS induced EC migration in a dose-dependent manner. Furthermore, this migratory process was mediated by the TLR-4/NF-κB pathway and the generation of ROS through the PKC-activated NAD(P)H oxidase. In addition, LPS increased the intracellular calcium level and the number of focal adhesion kinase (FAK)-positive focal adhesions in EC. Finally, we demonstrate that using TRPM7 blockers or suppressing TRPM7 expression through siRNA successfully inhibits the calcium influx and the LPS-induced EC migration. These results point out TRPM7 as a new target in the drug design for several inflammatory diseases that impair vascular endothelium function.

  14. Transient increases in cytosolic free calcium appear to be required for the migration of adherent human neutrophils [published erratum appears in J Cell Biol 1990 Mar;110(3):861

    PubMed Central

    1990-01-01

    Human neutrophils exhibit multiple increases in cytosolic free calcium concentration [( Ca2+]i) spontaneously and in response to the chemoattractant N-formyl-L-methionyl-L-leucyl-L-phenylalanine (Jaconi, M. E. E., R. W. Rivest, W. Schlegel, C. B. Wollheim, D. Pittet, and P. D. Lew. 1988. J. Biol. Chem. 263:10557-10560). The function of these repetitive increases in [Ca2+]i, as well as the role of Ca2+ in human neutrophil migration, remain unresolved. We have used microspectrofluorometry to measure [Ca2+]i in single fura-2-loaded human neutrophils as they moved on poly-D-lysine-coated glass in the presence of serum. To investigate the role of Ca2+ in human neutrophil migration, we examined cells in the presence and absence of extracellular Ca2+, as well as intracellular Ca2(+)-buffered and Ca2(+)- depleted cells. In the presence of extracellular Ca2+, multiple increases and decreases in [Ca2+]i were frequently observed, and at least one such transient increase in [Ca2+]i occurred in every moving cell during chemokinesis, chemotaxis, and phagocytosis. In addition, neutrophils that extended pseudopodia and assumed a polarized morphology after plating onto a surface were always observed to exhibit [Ca2+]i transients even in the absence of chemoattractant. In contrast, a [Ca2+]i transient was observed in only one of the nonpolarized stationary cells that were examined (n = 15). Although some cells exhibited relatively periodic increases and decreases in [Ca2+]i, resembling the regular oscillations that have been observed in some cell types, many others exhibited increases and decreases in [Ca2+]i that varied in their timing, magnitude, and duration. Buffering of [Ca2+]i or removal of extracellular Ca2+ damped out or blocked transient increases in [Ca2+]i and reduced or inhibited the migration of neutrophils. Under these conditions, polarized cells were often observed to make repeated attempts at migration, but they remained anchored at their rear. These data suggest

  15. Activation of Akt/FoxO and inactivation of MEK/ERK pathways contribute to induction of neuroprotection against transient global cerebral ischemia by delayed hypoxic postconditioning in adult rats.

    PubMed

    Zhan, Lixuan; Li, Danfang; Liang, Donghai; Wu, Baoxing; Zhu, Pingping; Wang, Yanmei; Sun, Weiwen; Xu, En

    2012-10-01

    Ischemic postconditioning, a series of mechanical interruptions of blood flow immediately after reperfusion, has been described in brain studies. However, hypoxic postconditioning (HPC) has never been reported in transient global cerebral ischemia (tGCI) adult rat model. The purpose of this study is to explore the effects of neuroprotection by delayed HPC against tGCI in adult rats and investigate underlying mechanisms involving the Akt/Forkhead transcription factor, class O (FoxO) and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways. Postconditioning with 60-120 min hypoxia significantly reduced cell death in hippocampal CA1 subregion after 10 min of tGCI. Postconditioning was effective only when applied 1-2 days after tGCI. Nevertheless, the combination of hypoxic preconditioning and postconditioning provided no additive protection. Additionally, postconditioning increased phosphorylation of Akt and FoxOs after tGCI. Inhibiting phosphorylation of Akt and FoxOs with LY294002 suppressed the postconditioning-induced neuroprotection. In addition, postconditioning blocked the increase of MEK and ERK phosphorylation after tGCI. Inhibiting phosphorylation of MEK and ERK with U0126 attenuated neuronal damage after tGCI. These results suggest that delayed HPC exerts neuroprotection against tGCI-induced injury in adult rats. The activation of Akt/FoxO and inactivation of MEK/ERK pathways by postconditioning contributed to the induction of neuroprotection against tGCI.

  16. Intracellular calcium puffs in osteoclasts.

    PubMed

    Radding, W; Jordan, S E; Hester, R B; Blair, H C

    1999-12-15

    We studied intracellular calcium ([Ca(2+)](i)) in acid-secreting bone-attached osteoclasts, which produce a high-calcium acidic extracellular compartment. Acid secretion and [Ca(2+)](i) were followed using H(+)-restricted dyes and fura-2 or fluo-3. Whole cell calcium of acid-secreting osteoclasts was approximately 100 nM, similar to cells on inert substrate that do not secrete acid. However, measurements in restricted areas of the cell showed [Ca(2+)](i) transients to 500-1000 nM consistent with calcium puffs, transient (millisecond) localized calcium elevations reported in other cells. Spot measurements at 50-ms intervals indicated that puffs were typically less than 400 ms. Transients did not propagate in waves across the cell in scanning confocal measurements. Calcium puffs occurred mainly over regions of acid secretion as determined using lysotracker red DND99 and occurred at irregular periods averaging 5-15 s in acid secreting cells, but were rare in lysotracker-negative nonsecretory cells. The calmodulin antagonist trifluoperazine, cell-surface calcium transport inhibitors lanthanum or barium, and the endoplasmic reticulum ATPase inhibitor thapsigargin had variable acute effects on the mean [Ca(2+)](i) and puff frequency. However, none of these agents prevented calcium puff activity, suggesting that the mechanism producing the puffs is independent of these processes. We conclude that [Ca(2+)](i) transients in osteoclasts are increased in acid-secreting osteoclasts, and that the puffs occur mainly near the acid-transporting membrane. Cell membrane acid transport requires calcium, suggesting that calcium puffs function to maintain acid secretion. However, membrane H(+)-ATPase activity was insensitive to calcium in the 100 nM-1 microM range. Thus, any effects of calcium puffs on osteoclastic acid transport must be indirect.

  17. Folic acid deficiency increases delayed neuronal death, DNA damage, platelet endothelial cell adhesion molecule-1 immunoreactivity, and gliosis in the hippocampus after transient cerebral ischemia.

    PubMed

    Hwang, In Koo; Yoo, Ki-Yeon; Suh, Hong-Won; Kim, Young Sup; Kwon, Dae Young; Kwon, Young-Guen; Yoo, Jun-Hyun; Won, Moo-Ho

    2008-07-01

    Folic acid deficiency increases stroke risk. In the present study, we examined whether folic acid deficiency enhances neuronal damage and gliosis via oxidative stress in the gerbil hippocampus after transient forebrain ischemia. Animals were exposed to a folic acid-deficient diet (FAD) for 3 months and then subjected to occlusion of both common carotid arteries for 5 min. Exposure to an FAD increased plasma homocysteine levels by five- to eightfold compared with those of animals fed with a control diet (CD). In CD-treated animals, most neurons were dead in the hippocampal CA1 region 4 days after ischemia/reperfusion, whereas, in FAD-treated animals, this occurred 3 days after ischemia/reperfusion. Immunostaining for 8-hydroxy-2'-deoxyguanosine (8-OHdG) was performed to examine DNA damage in CA1 neurons in both groups after ischemia, and it was found that 8-OHdG immunoreactivity in both FAD and CD groups peaked at 12 hr after reperfusion, although the immunoreactivity in the FAD group was much greater than that in the CD group. Platelet endothelial cell adhesion molecule-1 (PECAM-1; a final mediator of neutrophil transendothelial migration) immunoreactivity in both groups increased with time after ischemia/reperfusion: Its immunoreactivity in the FAD group was much higher than that in the CD group 3 days after ischemia/reperfusion. In addition, reactive gliosis in the ischemic CA1 region increased with time after ischemia in both groups, but astrocytosis and microgliosis in the FAD group were more severe than in the CD group at all times after ischemia. Our results suggest that folic acid deficiency enhances neuronal damage induced by ischemia.

  18. Role of Ca2+-dependent Cl- current on delayed afterdepolarizations. A simulation study.

    PubMed

    Gomis-Tena, Julio; Saiz, Javier

    2008-05-01

    Calcium-dependent chloride current (I (Cl,Ca)) is the second component (I (to2)) of the transient outward current (I (to)) that provokes the action potential (AP) phase 1 repolarization. This current contributes to the transient inward current (I (ti)) that generates delayed afterdepolarizations (DAD) in several pathological conditions. The present work uses a computer AP model of rabbit atrial myocyte and a one-dimensional (1D) tissue model of 400 cells to study the role of I (Cl,Ca) on the generation of DAD and triggered activity under calcium-overload conditions. A mathematical model describing the dependence of I (Cl,Ca) on intracellular Ca(2+) is proposed. This model takes into account the experimentally recorded characteristics of I (Cl,Ca): (1) calcium dependence, (2) voltage-dependent inactivation, and (3) I-V field-diffusion relation. Our results support the hypothesis that I (Cl,Ca) plays an important role in action potential repolarization, mainly at high frequencies. In the calcium-overload conditions tested in this work, I (Cl,Ca) represents between 28% and 44% of the total I (ti) that provokes DADs. Our simulations also show that the blockage of I (Cl,Ca) reduces the calcium overload range in which DADs provoke triggered activity.

  19. Calcium Carbonate

    MedlinePlus

    Calcium carbonate is a dietary supplement used when the amount of calcium taken in the diet is not ... for healthy bones, muscles, nervous system, and heart. Calcium carbonate also is used as an antacid to relieve ...

  20. Calcium - urine

    MedlinePlus

    High levels of urine calcium (above 300 mg/day) may be due to: Chronic kidney disease High vitamin D levels Leaking of calcium from the kidneys into the urine, which causes calcium kidney stones Sarcoidosis Taking ...

  1. Calcium Efflux from Internally Dialyzed Squid Giant Axons

    PubMed Central

    Dipolo, Reinaldo

    1973-01-01

    Calcium efflux has been studied in squid giant axons under conditions in which the internal composition was controlled by means of a dialysis perfusion technique. The mean calcium efflux from axons dialyzed with 0.3 µM calcium and 5 mM ATP was 0.26 pmol/cm2·s at 22°C. The curve relating the Ca efflux with the internal Ca concentration had a slope of about one for [Ca]i lower than 0.3µM and a slope smaller than one for higher concentrations. Under the above conditions replacement of [Na]o and [Ca]o by Tris and Mg causes an 80% fall in the calcium efflux. When the axons were dialyzed with a medium free of ATP and containing 2 mM cyanide plus 5µg/ml oligomycin, analysis of the perfusion effluent gave values of 1–4 µM ATP. Under this low ATP condition, replacement of external sodium and calcium causes the same drop in the calcium efflux. The same effect was observed at higher [Ca]i, (80 µM). These results suggest that the Na-Ca exchange component of the calcium efflux is apparently not dependent on the amounts of ATP in the axoplasm. Axons previously depleted of ATP show a significant transient drop in the calcium efflux when ATP is added to the dialysis medium. This effect probably represents the sequestering of calcium by the mitochondrial system. The consumption of calcium by the mitochondria of the axoplasm in dialyzed axons was determined to be of the order of 6.0 x 10-7 mol Ca++/mg of protein with an initial rate of 2.6 x 10-8 mol Ca++/min·mg of protein. Axons dialyzed with 2 mM cyanide after 8–10-min delays show a rise in the calcium efflux in the presence of "normal" amounts of exogenous ATP. This effect seems to indicate that cyanide, per se, can release calcium ions from internal sources. PMID:4751386

  2. Delayed-rectifier (KV2.1) regulation of pancreatic beta-cell calcium responses to glucose: inhibitor specificity and modeling.

    PubMed

    Tamarina, Natalia A; Kuznetsov, Andrey; Fridlyand, Leonid E; Philipson, Louis H

    2005-10-01

    The delayed-rectifier (voltage-activated) K(+) conductance (K(V)) in pancreatic islet beta-cells has been proposed to regulate plasma membrane repolarization during responses to glucose, thereby determining bursting and Ca(2+) oscillations. Here, we verified the expression of K(V)2.1 channel protein in mouse and human islets of Langerhans. We then probed the function of K(V)2.1 channels in islet glucose responses by comparing the effect of hanatoxin (HaTx), a specific blocker of K(V)2.1 channels, with a nonspecific K(+) channel blocker, tetraethylammonium (TEA). Application of HaTx (1 microM) blocked delayed-rectifier currents in mouse beta-cells, resulting in a 40-mV rightward shift in threshold of activation of the voltage-dependent outward current. In the presence of HaTx, there was negligible voltage-activated outward current below 0 mV, suggesting that K(V)2.1 channels form the predominant part of this current in the physiologically relevant range. We then employed HaTx to study the role of K(V)2.1 in the beta-cell Ca(2+) responses to elevated glucose in comparison with TEA. Only HaTx was able to induce slow intracellular Ca(2+) concentration ([Ca(2+)](i)) oscillations in cells stimulated with 20 mM glucose, whereas TEA induced an immediate rise in [Ca(2+)](i) followed by rapid oscillations. In human islets, HaTx acted in a similar fashion. The data were analyzed using a detailed mathematical model of ionic flux and Ca(2+) regulation in beta-cells. The results can be explained by a specific HaTx effect on the K(V) current, whereas TEA affects multiple K(+) conductances. The results underscore the importance of K(V)2.1 channel in repolarization of the pancreatic beta-cell plasma membrane and its role in regulating insulin secretion. PMID:16014354

  3. Voltage-gated calcium and Ca2+-activated chloride channels and Ca2+ transients: voltage-clamp studies of perfused and intact cells of Chara.

    PubMed

    Berestovsky, Genrikh N; Kataev, Anatoly A

    2005-11-01

    The voltage-clamp technique was used to study Ca(2+) and Cl(-) transient currents in the plasmalemma of tonoplast-free and intact Chara corallina cells. In tonoplast-free cells [perfused medium with ethylene glycol bis(2-aminoethyl ether)tetraacetic acid] long-term inward and outward currents through Ca channels consisted of two components: with and without time-dependent inactivation. The voltage dependence of the Ca channel activation ratio was found to be sigmoid-shaped, with about -140-mV activation threshold, reaching a plateau at V>50 mV. As the voltage increased, the characteristic activation time decreased from approximately 10(3) ms in the threshold region to approximately 10 ms in the positive region. The positive pulse-activated channels can then be completely deactivated, which is recorded by the Ca(2+) tail currents, at below-threshold negative voltages with millisecond-range time constants. This tail current is used for fast and brief Ca(2+) injection into tonoplast-free and intact cells, to activate the chloride channels by Ca(2+) . When cells are perfused with EDTA-containing medium in the presence of excess Mg(2+), this method of injection allows the free submembrane Ca(2+) concentration, [Ca(2+)](c), to be raised rapidly to several tens of micromoles per liter. Then a chloride component is recorded in the inward tail current, with the amplitude proportional to [see text]. When Ca(2+) is thus injected into an intact cell, it induces an inward current in the voltage-clamped plasmalemma, having activation-inactivation kinetics qualitatively resembling that in EDTA-perfused cells, but a considerably higher amplitude and duration (approximately 10 A m(-2) and tau(inact)~0.5 s at -200 mV). Analysis of our data and theoretical considerations indicate that the [Ca(2+)](c) rise during cell excitation is caused mainly by Ca(2+) entry through plasmalemma Ca channels rather than by Ca(2+) release from intracellular stores.

  4. Delayed ejaculation

    MedlinePlus

    Ejaculatory incompetence; Sex - delayed ejaculation; Retarded ejaculation; Anejaculation; Infertility - delayed ejaculation ... include: Religious background that makes the person view sex as sinful Lack of attraction for a partner ...

  5. Roles of calcium-activated and voltage-gated delayed rectifier potassium channels in endothelium-dependent vasorelaxation of the rabbit middle cerebral artery

    PubMed Central

    Dong, Hui; Waldron, Gareth J; Cole, William C; Triggle, Christopher R

    1998-01-01

    The cellular mechanism(s) of action of endothelium-derived vasodilator substances in the rabbit middle cerebral artery (RMCA) were investigated. Specifically, the subtypes of potassium channels involved in the effects of endothelium-derived relaxing factors (EDRFs) in acetylcholine (ACh)-induced endothelium-dependent vasorelaxation in this vessel were systematically compared. In the endothelium-intact RMCA precontracted with histamine (3 μM), ACh induced a concentration-dependent vasorelaxation, which was sensitive to indomethacin (10 μM) or NG-nitro-L-arginine (L-NOARG; 100 μM); pD2 values 8.36 vs 7.40 and 6.38, P<0.01 for both, n=6 and abolished by a combination of both agents. ACh caused relaxation in the presence of high K+ PSS (40 mM KCl), which was not affected by indomethacin, but abolished by L-NOARG and a combination of indomethacin and L-NOARG. In the presence of indomethacin, relaxation to ACh in the endothelium-intact RMCA precontracted with histamine was unaffected by either glibenclamide (10 μM), an ATP-sensitive K+ channel (KATP) blocker, 4-aminopyridine (4-AP, 1 mM) or dendrotoxin (DTX, 0.1 μM), delayed rectifier K+ channel (KV) blockers. However, relaxation responses to ACh were significantly inhibited by either LY83583 (10 μM) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 10 μM), guanylyl cyclase inhibitors, or charybdotoxin (CTX; 0.1 μM), iberiotoxin (ITX, 0.1 μM) and apamin (APA, 0.1 μM), large conductance Ca2+ -activated K+ channels (BKCa) blocker and small conductance Ca2+ -activated K+ channel (SKCa) blocker, respectively. In the presence of L-NOARG, relaxation to ACh was unaffected by glibenclamide or the cytochrome P450 mono-oxygenase inhibitor, clotrimazole (1 μM), but was significantly inhibited by either 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ  22,536, 10 μM) and 2′,3′-dideoxyadenosine (2′,3′-DDA, 30 μM), adenylyl cyclase inhibitors, or 4-AP, DTX, CTX, ITX and APA. In

  6. Store-operated calcium entry compensates fast ER calcium loss in resting hippocampal neurons.

    PubMed

    Samtleben, Samira; Wachter, Britta; Blum, Robert

    2015-08-01

    The endoplasmic reticulum (ER) acts as a dynamic calcium store and is involved in the generation of specific patterns of calcium signals in neurons. Calcium is mobilized from the ER store by multiple signaling cascades, and neuronal activity is known to regulate ER calcium levels. We asked how neurons regulate ER calcium levels in the resting state. Direct ER calcium imaging showed that ER calcium was lost quite rapidly from the somatic and dendritic ER when resting neurons were transiently kept under calcium-free conditions. Interestingly, free ER and free cytosolic calcium was lost continuously across the plasma membrane and was not held back in the cytosol, implying the presence of a prominent calcium influx mechanism to maintain ER calcium levels at rest. When neurons were treated acutely with inhibitors of store-operated calcium entry (SOCE), an immediate decline in ER calcium levels was observed. This continuous SOCE-like calcium entry did not require the activation of a signaling cascade, but was rather a steady-state phenomenon. The SOCE-like mechanism maintains medium-high ER calcium levels at rest and is essential for balanced resting calcium levels in the ER and cytosol.

  7. Calcium and osteoporosis.

    PubMed

    Nordin, B E

    1997-01-01

    Calcium is an essential nutrient that is involved in most metabolic processes and the phosphate salts of which provide mechanical rigidity to the bones and teeth, where 99% of the body's calcium resides. The calcium in the skeleton has the additional role of acting as a reserve supply of calcium to meet the body's metabolic needs in states of calcium deficiency. Calcium deficiency is easily induced because of the obligatory losses of calcium via the bowel, kidneys, and skin. In growing animals, it may impair growth, delay consolidation of the skeleton, and in certain circumstances give rise to rickets but the latter is more often due to deficiency of vitamin D. In adult animals, calcium deficiency causes mobilization of bone and leads sooner or later to osteoporosis, i.e., a reduction in the "amount of bone in the bone" or apparent bone density. The effects of calcium deficiency and oophorectomy (ovariectomy) are additive. In humans, osteoporosis is a common feature of aging. Loss of bone starts in women at the time of the menopause and in men at about age 55 and leads to an increase in fracture rates in both sexes. Individual fracture risk is inversely related to bone density, which in turn is determined by the density achieved at maturity (peak bone density) and the subsequent rate of bone loss. At issue is whether either or both of these variables is related to calcium intake. The calcium requirement of adults may be defined as the mean calcium intake needed to preserve calcium balance, i.e., to meet the significant obligatory losses of calcium through the gastrointestinal tract, kidneys, and skin. The calcium allowance is the higher intake recommended for a population to allow for individual variation in the requirement. The mean requirement defined in this way, calculated from balance studies, is about 20 mmol (800 mg) a day on Western diets, implying an allowance of 25 mmol (1000 mg) or more. Corresponding requirements and allowances have been calculated for

  8. Calcium signals and oocyte maturation in marine invertebrates.

    PubMed

    Deguchi, Ryusaku; Takeda, Noriyo; Stricker, Stephen A

    2015-01-01

    In various oocytes and eggs of animals, transient elevations in cytoplasmic calcium ion concentrations are known to regulate key processes during fertilization and the completion of meiosis. However, whether or not calcium transients also help to reinitiate meiotic progression at the onset of oocyte maturation remains controversial. This article summarizes reports of calcium signals playing essential roles during maturation onset (=germinal vesicle breakdown, GVBD) in several kinds of marine invertebrate oocytes. Conversely, other data from the literature, as well as previously unpublished findings for jellyfish oocytes, fail to support the view that calcium signals are required for GVBD. In addition to assessing the effects of calcium transients on GVBD in marine invertebrate oocytes, the ability of maturing oocytes to enhance their calcium-releasing capabilities after GVBD is also reviewed. Furthermore, possible explanations are proposed for the contradictory results that have been obtained regarding calcium signals during oocyte maturation in marine invertebrates. PMID:26679945

  9. Calcium signals and oocyte maturation in marine invertebrates.

    PubMed

    Deguchi, Ryusaku; Takeda, Noriyo; Stricker, Stephen A

    2015-01-01

    In various oocytes and eggs of animals, transient elevations in cytoplasmic calcium ion concentrations are known to regulate key processes during fertilization and the completion of meiosis. However, whether or not calcium transients also help to reinitiate meiotic progression at the onset of oocyte maturation remains controversial. This article summarizes reports of calcium signals playing essential roles during maturation onset (=germinal vesicle breakdown, GVBD) in several kinds of marine invertebrate oocytes. Conversely, other data from the literature, as well as previously unpublished findings for jellyfish oocytes, fail to support the view that calcium signals are required for GVBD. In addition to assessing the effects of calcium transients on GVBD in marine invertebrate oocytes, the ability of maturing oocytes to enhance their calcium-releasing capabilities after GVBD is also reviewed. Furthermore, possible explanations are proposed for the contradictory results that have been obtained regarding calcium signals during oocyte maturation in marine invertebrates.

  10. Delayed stochastic control

    NASA Astrophysics Data System (ADS)

    Hosaka, Tadaaki; Ohira, Toru; Lucian, Christian; Milton, John

    2005-03-01

    Time-delayed feedback control becomes problematic in situations in which the time constant of the system is fast compared to the feedback reaction time. In particular, when perturbations are unpredictable, traditional feedback or feed-forward control schemes can be insufficient. Nonethless a human can balance a stick at their fingertip in the presence of fluctuations that occur on time scales shorter than their neural reaction times. Here we study a simple model of a repulsive delayed random walk and demonstrate that the interplay between noise and delay can transiently stabilize an unstable fixed-point. This observation leads to the concept of ``delayed stochastic control,'' i.e. stabilization of tasks, such as stick balancing at the fingertip, by optimally tuning the noise level with respect to the feedback delay time. References:(1)J.L.Cabrera and J.G.Milton, PRL 89 158702 (2002);(2) T. Ohira and J.G.Milton, PRE 52 3277 (1995);(3)T.Hosaka, T.Ohira, C.Lucian, J.L.Cabrera, and J.G.Milton, Prog. Theor. Phys. (to appear).

  11. Astrocyte calcium signaling: the third wave.

    PubMed

    Bazargani, Narges; Attwell, David

    2016-02-01

    The discovery that transient elevations of calcium concentration occur in astrocytes, and release 'gliotransmitters' which act on neurons and vascular smooth muscle, led to the idea that astrocytes are powerful regulators of neuronal spiking, synaptic plasticity and brain blood flow. These findings were challenged by a second wave of reports that astrocyte calcium transients did not mediate functions attributed to gliotransmitters and were too slow to generate blood flow increases. Remarkably, the tide has now turned again: the most important calcium transients occur in fine astrocyte processes not resolved in earlier studies, and new mechanisms have been discovered by which astrocyte [Ca(2+)]i is raised and exerts its effects. Here we review how this third wave of discoveries has changed our understanding of astrocyte calcium signaling and its consequences for neuronal function.

  12. Calcium-induced calcium release and gap junctions mediate large-scale calcium waves in olfactory ensheathing cells in situ.

    PubMed

    Stavermann, Maren; Meuth, Patrick; Doengi, Michael; Thyssen, Anne; Deitmer, Joachim W; Lohr, Christian

    2015-08-01

    Olfactory ensheathing cells (OECs) are a specialised type of glial cells, supporting axon growth and guidance during development and regeneration of the olfactory nerve and the nerve layer of the olfactory bulb. We measured calcium signalling in OECs in olfactory bulb in-toto preparations using confocal and epifluorescence microscopy and the calcium indicator Fluo-4. We identified two subpopulations of olfactory bulb OECs: OECs in the outer sublamina of the nerve layer responded to purinergic neurotransmitters such as adenosine triphosphate with calcium transients, while OECs in the inner sublamina of the nerve layer did not respond to neurotransmitters. However, the latter generated spontaneous calcium waves that covered hundreds of cells. These calcium waves persisted in the presence of tetrodotoxin and in calcium-free saline, but were abolished after calcium store depletion with cyclopiazonic acid or inositol trisphosphate receptor blockage with 2-APB. Calcium waves could be triggered by laser photolysis of caged inositol trisphosphate. Blocking purinoceptors with PPADS had no effect on calcium wave propagation, whereas blocking gap junctions with carbenoxolone or meclofenamic acid entirely suppressed calcium waves. Increasing calcium buffer capacity in OECs with NP-EGTA ("caged" Ca(2+)) prevented calcium wave generation, and laser photolysis of NP-EGTA in a small group of OECs resulted in a calcium increase in the irradiated cells followed by a calcium wave. We conclude that calcium waves in OECs can be initiated by calcium-induced calcium release via InsP3 receptors and propagate through gap junctions, while purinergic signalling is not involved.

  13. Intracellular sphingosine releases calcium from lysosomes.

    PubMed

    Höglinger, Doris; Haberkant, Per; Aguilera-Romero, Auxiliadora; Riezman, Howard; Porter, Forbes D; Platt, Frances M; Galione, Antony; Schultz, Carsten

    2015-11-27

    To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC.

  14. Calcium currents in a fast-twitch skeletal muscle of the rat

    PubMed Central

    1983-01-01

    Slow ionic currents were measured in the rat omohyoid muscle with the three-microelectrode voltage-clamp technique. Sodium and delayed rectifier potassium currents were blocked pharmacologically. Under these conditions, depolarizing test pulses elicited an early outward current, followed by a transient slow inward current, followed in turn by a late outward current. The early outward current appeared to be a residual delayed rectifier current. The slow inward current was identified as a calcium current on the basis that (a) its magnitude depended on extracellular calcium concentration, (b) it was blocked by the addition of the divalent cations cadmium or nickel, and reduced in magnitude by the addition of manganese or cobalt, and (c) barium was able to replace calcium as an inward current carrier. The threshold potential for inward calcium current was around -20 mV in 10mM extracellular calcium and about -35 mV in 2 mM calcium. Currents were net inward over part of their time course for potentials up to at least +30 mV. At temperatures of 20-26 degrees C, the peak inward current (at approximately 0 mV) was 139 +/- 14 microA/cm2 (mean +/- SD), increasing to 226 +/- 28 microA/cm2 at temperatures of 27-37 degrees C. The late outward current exhibited considerable fiber-to-fiber variability. In some fibers it was primarily a time-independent, nonlinear leakage current. In other fibers it was primarily a time-independent, nonlinear leakage current. In other fibers it appeared to be the sum of both leak and a slowly activated outward current. The rate of activation of inward calcium current was strongly temperature dependent. For example, in a representative fiber, the time-to-peak inward current for a +10-mV test pulse decreased from approximately 250 ms at 20 degrees C to 100 ms at 30 degrees C. At 37 degrees C, the time-to-peak current was typically approximately 25 ms. The earliest phase of activation was difficult to quantify because the ionic current was partially

  15. Control of kidney development by calcium ions.

    PubMed

    Gilbert, Thierry; Leclerc, Catherine; Moreau, Marc

    2011-12-01

    From the formation of a simple kidney in amphibian larvae, the pronephros, to the formation of the more complex mammalian kidney, the metanephros, calcium is present through numerous steps of tubulogenesis and nephron induction. Several calcium-binding proteins such as regucalcin/SMP-30 and calbindin-D28k are commonly used to label pronephric tubules and metanephric ureteral epithelium, respectively. However, the involvement of calcium and calcium signalling at various stages of renal organogenesis was not clearly delineated. In recent years, several studies have pinpointed an unsuspected role of calcium in determination of the pronephric territory and for conversion of metanephric mesenchyme into nephrons. Influx of calcium and calcium transients have been recorded in the pool of renal progenitors to allow tubule formation, highlighting the occurrence of calcium-dependent signalling events during early kidney development. Characterization of nuclear calcium signalling is emerging. Implication of the non-canonical calcium/NFAT Wnt signalling pathway as an essential mechanism to promote nephrogenesis has recently been demonstrated. This review examines the current knowledge of the impact of calcium ions during embryonic development of the kidney. It focuses on Ca(2+) binding proteins and Ca(2+) sensors that are involved in renal organogenesis and briefly examines the link between calcium-dependent signals and polycystins.

  16. [Delayed puberty].

    PubMed

    Antoniazzi, F; Zamboni, G; Tatò, L

    1996-01-01

    Delayed puberty can be defined as the absence of any signs of puberty in subjects that have attained an age at the upper limit (+2DS) for the onset of puberty, that means 13 years in girls and 14 years in boys. The causes of delayed puberty can be classified into three groups, functional temporary impairment in gonadotropin and sex steroid secretion (most frequently constitutional delay of puberty), hypothalamo-pituitary failure with deficiency in gonadotropin secretion, primary gonadal failure with increased gonadotropin levels. The Authors discuss about etiology, diagnostic testing and therapeutic approach in these conditions. The majority of children with delayed puberty are males that have only a constitutional delay of growth and puberty. It is difficult, in teenage years, to distinguish this common and benign condition from true gonadotropin deficiency, in spite of the variety of endocrine tests developed for this purpose. Individuals with constitutional delayed puberty with a bone age greater than 11.5 years, show after triptorelin stimulation an increase in LH capable of distinguishing them from patients with gonadotropin deficiency. In our opinion this could be an important screening test to exclude gonadotropin deficiency in boys with delayed puberty.

  17. Influence of sodium borate on the early age hydration of calcium sulfoaluminate cement

    SciTech Connect

    Champenois, Jean-Baptiste; Dhoury, Mélanie; Cau Dit Coumes, Céline; Mercier, Cyrille; Revel, Bertrand; Le Bescop, Patrick; Damidot, Denis

    2015-04-15

    Calcium sulfoaluminate (CSA) cements are potential candidates for the conditioning of radioactive wastes with high sodium borate concentrations. This work thus investigates early age hydration of two CSA cements with different gypsum contents (0 to 20%) as a function of the mixing solution composition (borate and NaOH concentrations). Gypsum plays a key role in controlling the reactivity of cement. When the mixing solution is pure water, increasing the gypsum concentration accelerates cement hydration. However, the reverse is observed when the mixing solution contains sodium borate. Until gypsum exhaustion, the pore solution pH remains constant at ~ 10.8, and a poorly crystallized borate compound (ulexite) precipitates. A correlation is established between this transient precipitation and the hydration delay. Decreasing the gypsum content in the binder, or increasing the sodium content in the mixing solution, are two ways of reducing the stability of ulexite, thus decreasing the hydration delay.

  18. Yeast respond to hypotonic shock with a calcium pulse

    NASA Technical Reports Server (NTRS)

    Batiza, A. F.; Schulz, T.; Masson, P. H.

    1996-01-01

    We have used the transgenic AEQUORIN calcium reporter system to monitor the cytosolic calcium ([Ca2+]cyt) response of Saccharomyces cerevisiae to hypotonic shock. Such a shock generates an almost immediate and transient rise in [Ca2+]cyt which is eliminated by gadolinium, a blocker of stretch-activated channels. In addition, this transient rise in [Ca2+]cyt is initially insensitive to 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), an extracellular calcium chelator. However, BAPTA abruptly attenuates the maintenance of that transient rise. These data show that hypotonic shock generates a stretch-activated channel-dependent calcium pulse in yeast. They also suggest that the immediate calcium influx is primarily generated from intracellular stores, and that a sustained increase in [Ca2+]cyt depends upon extracellular calcium.

  19. Calcium in diet

    MedlinePlus

    ... of calcium dietary supplements include calcium citrate and calcium carbonate. Calcium citrate is the more expensive form of ... the body on a full or empty stomach. Calcium carbonate is less expensive. It is absorbed better by ...

  20. Calcium Test

    MedlinePlus

    ... as thyroid disease , parathyroid disorder , malabsorption , cancer, or malnutrition An ionized calcium test may be ordered when ... albumin , which can result from liver disease or malnutrition , both of which may result from alcoholism or ...

  1. Calcium Calculator

    MedlinePlus

    ... with Sarcopenia Skeletal Rare Disorders Data & Publications Facts and Statistics Vitamin D map Fracture Risk Map Hip Fracture ... Training Courses Working Groups Regional Audits Reports Facts and Statistics Popular content Calcium content of common foods What ...

  2. Calcium Carbonate.

    PubMed

    Al Omari, M M H; Rashid, I S; Qinna, N A; Jaber, A M; Badwan, A A

    2016-01-01

    Calcium carbonate is a chemical compound with the formula CaCO3 formed by three main elements: carbon, oxygen, and calcium. It is a common substance found in rocks in all parts of the world (most notably as limestone), and is the main component of shells of marine organisms, snails, coal balls, pearls, and eggshells. CaCO3 exists in different polymorphs, each with specific stability that depends on a diversity of variables.

  3. Calcium Carbonate.

    PubMed

    Al Omari, M M H; Rashid, I S; Qinna, N A; Jaber, A M; Badwan, A A

    2016-01-01

    Calcium carbonate is a chemical compound with the formula CaCO3 formed by three main elements: carbon, oxygen, and calcium. It is a common substance found in rocks in all parts of the world (most notably as limestone), and is the main component of shells of marine organisms, snails, coal balls, pearls, and eggshells. CaCO3 exists in different polymorphs, each with specific stability that depends on a diversity of variables. PMID:26940168

  4. Calcium orthophosphates

    PubMed Central

    Dorozhkin, Sergey V.

    2011-01-01

    The present overview is intended to point the readers’ attention to the important subject of calcium orthophosphates. This type of materials is of special significance for human beings, because they represent the inorganic part of major normal (bones, teeth and antlers) and pathological (i.e., those appearing due to various diseases) calcified tissues of mammals. For example, atherosclerosis results in blood vessel blockage caused by a solid composite of cholesterol with calcium orthophosphates, while dental caries and osteoporosis mean a partial decalcification of teeth and bones, respectively, that results in replacement of a less soluble and harder biological apatite by more soluble and softer calcium hydrogenphosphates. Therefore, the processes of both normal and pathological calcifications are just an in vivo crystallization of calcium orthophosphates. Similarly, dental caries and osteoporosis might be considered an in vivo dissolution of calcium orthophosphates. Thus, calcium orthophosphates hold a great significance for humankind, and in this paper, an overview on the current knowledge on this subject is provided. PMID:23507744

  5. Electrical synapse formation disrupts calcium-dependent exocytosis, but not vesicle mobilization.

    PubMed

    Neunuebel, Joshua P; Zoran, Mark J

    2005-06-01

    Electrical coupling exists prior to the onset of chemical connectivity at many developing and regenerating synapses. At cholinergic synapses in vitro, trophic factors facilitated the formation of electrical synapses and interfered with functional neurotransmitter release in response to photolytic elevations of intracellular calcium. In contrast, neurons lacking trophic factor induction and electrical coupling possessed flash-evoked transmitter release. Changes in cytosolic calcium and postsynaptic responsiveness to acetylcholine were not affected by electrical coupling. These data indicate that transient electrical synapse formation delayed chemical synaptic transmission by imposing a functional block between the accumulation of presynaptic calcium and synchronized, vesicular release. Despite the inability to release neurotransmitter, neurons that had possessed strong electrical coupling recruited secretory vesicles to sites of synaptic contact. These results suggest that the mechanism by which neurotransmission is disrupted during electrical synapse formation is downstream of both calcium influx and synaptic vesicle mobilization. Therefore, electrical synaptogenesis may inhibit synaptic vesicles from acquiring a readily releasable state. We hypothesize that gap junctions might negatively interact with exocytotic processes, thereby diminishing chemical neurotransmission. PMID:15765535

  6. Calcium store-mediated signaling in sustentacular cells of the mouse olfactory epithelium.

    PubMed

    Hegg, Colleen Cosgrove; Irwin, Mavis; Lucero, Mary T

    2009-04-15

    Sustentacular cells have structural features that allude to functions of secretion, absorption, phagocytosis, maintenance of extracellular ionic gradients, metabolism of noxious chemicals, and regulation of cell turnover. We present data detailing their dynamic activity. We show, using a mouse olfactory epithelium slice model, that sustentacular cells are capable of generating two types of calcium signals: intercellular calcium waves where elevations in intracellular calcium propagate between neighboring cells, and intracellular calcium oscillations consisting of repetitive elevations in intracellular calcium confined to single cells. Sustentacular cells exhibited rapid, robust increases in intracellular calcium in response to G-protein coupled muscarinic and purinergic receptor stimulation. In a subpopulation of sustentacular cells, oscillatory calcium transients were evoked. We pharmacologically characterized the properties of purinergic-evoked increases in intracellular calcium. Calcium transients were elicited by release from intracellular stores and were not dependent on extracellular calcium. BAPTA-AM, a cytosolic calcium chelator, and cyclopiazonic acid, an endoplasmic reticulum Ca(2+)-ATPase inhibitor irreversibly blocked the purinergic-induced calcium transient. Phospholipase C antagonist U73122 inhibited the purinergic-evoked calcium transient. 2-Aminoethoxydiphenyl borate, an inositol-1,4,5-trisphosphate (IP(3)) receptor antagonist, and the ryanodine receptor (RyR) antagonists tetracaine and ryanodine, inhibited the UTP-induced calcium transients. Collectively, these data suggest that activation of the phospholipase C pathway, IP(3)-mediated calcium release, and subsequent calcium-induced-calcium release is involved in ATP-elicited increases in intracellular calcium. Our findings indicate that sustentacular cells are not static support cells, and, like glia in the central nervous system, have complex calcium signaling.

  7. Spatiotemporal intracellular calcium dynamics during cardiac alternans

    NASA Astrophysics Data System (ADS)

    Restrepo, Juan G.; Karma, Alain

    2009-09-01

    Cellular calcium transient alternans are beat-to-beat alternations in the peak cytosolic calcium concentration exhibited by cardiac cells during rapid electrical stimulation or under pathological conditions. Calcium transient alternans promote action potential duration alternans, which have been linked to the onset of life-threatening ventricular arrhythmias. Here we use a recently developed physiologically detailed mathematical model of ventricular myocytes to investigate both stochastic and deterministic aspects of intracellular calcium dynamics during alternans. The model combines a spatially distributed description of intracellular calcium cycling, where a large number of calcium release units are spatially distributed throughout the cell, with a full set of ionic membrane currents. The results demonstrate that ion channel stochasticity at the level of single calcium release units can influence the whole-cell alternans dynamics by causing phase reversals over many beats during fixed frequency pacing close to the alternans bifurcation. They also demonstrate the existence of a wide range of dynamical states. Depending on the sign and magnitude of calcium-voltage coupling, calcium alternans can be spatially synchronized or desynchronized, in or out of phase with action potential duration alternans, and the node separating out-of-phase regions of calcium alternans can be expelled from or trapped inside the cell. This range of states is found to be larger than previously anticipated by including a robust global attractor where calcium alternans can be spatially synchronized but out of phase with action potential duration alternans. The results are explained by a combined theoretical analysis of alternans stability and node motion using general iterative maps of the beat-to-beat dynamics and amplitude equations.

  8. Transient effects in Herschel/PACS spectroscopy

    NASA Astrophysics Data System (ADS)

    Fadda, Dario; Jacobson, Jeffery D.; Appleton, Philip N.

    2016-10-01

    Context. The Ge:Ga detectors used in the PACS spectrograph onboard the Herschel space telescope react to changes of the incident flux with a certain delay. This generates transient effects on the resulting signal which can be important and last for up to an hour. Aims: The paper presents a study of the effects of transients on the detected signal and proposes methods to mitigate them especially in the case of the unchopped mode. Methods: Since transients can arise from a variety of causes, we classified them in three main categories: transients caused by sudden variations of the continuum due to the observational mode used; transients caused by cosmic ray impacts on the detectors; transients caused by a continuous smooth variation of the continuum during a wavelength scan. We propose a method to disentangle these effects and treat them separately. In particular, we show that a linear combination of three exponential functions is needed to fit the response variation of the detectors during a transient. An algorithm to detect, fit, and correct transient effects is presented. Results: The solution proposed to correct the signal for the effects of transients substantially improves the quality of the final reduction with respect to the standard methods used for archival reduction in the cases where transient effects are most pronounced. Conclusions: The programs developed to implement the corrections are offered through two new interactive data reduction pipelines in the latest releases of the Herschel Interactive Processing Environment.

  9. Get Enough Calcium

    MedlinePlus

    ... Calcium Print This Topic En español Get Enough Calcium Browse Sections The Basics Overview Foods and Vitamins ... 2 of 4 sections Take Action! Take Action: Calcium Sources Protect your bones – get plenty of calcium ...

  10. Calcium carbonate overdose

    MedlinePlus

    Tums overdose; Calcium overdose ... Calcium carbonate can be dangerous in large amounts. ... Some products that contain calcium carbonate are certain: ... and mineral supplements Other products may also contain calcium ...

  11. Characterizing Nanoscale Transient Communication.

    PubMed

    Chen, Yifan; Anwar, Putri Santi; Huang, Limin; Asvial, Muhamad

    2016-04-01

    We consider the novel paradigm of nanoscale transient communication (NTC), where certain components of the small-scale communication link are physically transient. As such, the transmitter and the receiver may change their properties over a prescribed lifespan due to their time-varying structures. The NTC systems may find important applications in the biomedical, environmental, and military fields, where system degradability allows for benign integration into life and environment. In this paper, we analyze the NTC systems from the channel-modeling and capacity-analysis perspectives and focus on the stochastically meaningful slow transience scenario, where the coherence time of degeneration Td is much longer than the coding delay Tc. We first develop novel and parsimonious models to characterize the NTC channels, where three types of physical layers are considered: electromagnetism-based terahertz (THz) communication, diffusion-based molecular communication (DMC), and nanobots-assisted touchable communication (TouchCom). We then revisit the classical performance measure of ϵ-outage channel capacity and take a fresh look at its formulations in the NTC context. Next, we present the notion of capacity degeneration profile (CDP), which describes the reduction of channel capacity with respect to the degeneration time. Finally, we provide numerical examples to demonstrate the features of CDP. To the best of our knowledge, the current work represents a first attempt to systematically evaluate the quality of nanoscale communication systems deteriorating with time.

  12. Calcium cyanide

    Integrated Risk Information System (IRIS)

    Jump to main content . Integrated Risk Information System Recent Additions | Contact Us Search : All EPA IRIS • You are here : EPA Home • Research • Environmental Assessment • IRIS • IRIS Summaries Redirect Page As of September 28 , 2010 , the assessment summary for calcium cyanide is included in th

  13. "Caged calcium" in Aplysia pacemaker neurons. Characterization of calcium-activated potassium and nonspecific cation currents

    PubMed Central

    1989-01-01

    We have studied calcium-activated potassium current, IK(Ca), and calcium-activated nonspecific cation current, INS(Ca), in Aplysia bursting pacemaker neurons, using photolysis of a calcium chelator (nitr-5 or nitr-7) to release "caged calcium" intracellularly. A computer model of nitr photolysis, multiple buffer equilibration, and active calcium extrusion was developed to predict volume-average and front-surface calcium concentration transients. Changes in arsenazo III absorbance were used to measure calcium concentration changes caused by nitr photolysis in microcuvettes. Our model predicted the calcium increments caused by successive flashes, and their dependence on calcium loading, nitr concentration, and light intensity. Flashes also triggered the predicted calcium concentration jumps in neurons filled with nitr-arsenazo III mixtures. In physiological experiments, calcium- activated currents were recorded under voltage clamp in response to flashes of different intensity. Both IK(Ca) and INS(Ca) depended linearly without saturation upon calcium concentration jumps of 0.1-20 microM. Peak membrane currents in neurons exposed to repeated flashes first increased and then declined much like the arsenazo III absorbance changes in vitro, which also indicates a first-order calcium activation. Each flash-evoked current rose rapidly to a peak and decayed to half in 3-12 s. Our model mimicked this behavior when it included diffusion of calcium and nitr perpendicular to the surface of the neuron facing the flashlamp. Na/Ca exchange extruding about 1 pmol of calcium per square centimeter per second per micromolar free calcium appeared to speed the decline of calcium-activated membrane currents. Over a range of different membrane potentials, IK(Ca) and INS(Ca) decayed at similar rates, indicating similar calcium stoichiometries independent of voltage. IK(Ca), but not INS(Ca), relaxes exponentially to a different level when the voltage is suddenly changed. We have estimated

  14. An Attempt to Induce Transient Immunosuppression Pre-erythrocytapheresis in a Girl With Sickle Cell Disease, a History of Severe Delayed Hemolytic Transfusion Reactions and Need for Hip Prosthesis

    PubMed Central

    Cattoni, Alessandro; Cazzaniga, Giovanni; Perseghin, Paolo; Zatti, Giovanni; Gaddi, Diego; Cossio, Andrea; Biondi, Andrea; Corti, Paola; Masera, Nicoletta

    2013-01-01

    Abstract We report on a case of delayed hemolytic transfusion reaction (DHTR) occurred 7 days after an erythrocytapheresis or eritroexchange procedure (EEX) treated with rituximab and glucocorticoids in a 15-years old patient with sickle cell disease. EEX was performed despite a previous diagnosis of alloimmunization, in order to reduce hemoglobin S rate before a major surgery for avascular necrosis of the femoral head. A first dose of rituximab was administered before EEX. However, rituximab couldn’t prevent DHTR that occurred with acute hemolysis, hemoglobinuria and hyperbilirubinemia. A further dose of rituximab and three boli of methylprednisolone were given after the onset of the reaction. It is likely that the combined use of rituximab and steroids managed to gradually improve both patient’s general conditions and hemoglobin levels. Nor early or late side effects were registered in a 33-months follow-up period. This report suggests the potential effectiveness and safety of rituximab in combination with steroids in managing and mitigating the symptoms of delayed post-transfusional hemolytic reactions in alloimmunized patients affected by sickle cell disease with absolute need for erythrocytapheresis. PMID:23888247

  15. An Attempt to Induce Transient Immunosuppression Pre-erythrocytapheresis in a Girl With Sickle Cell Disease, a History of Severe Delayed Hemolytic Transfusion Reactions and Need for Hip Prosthesis.

    PubMed

    Cattoni, Alessandro; Cazzaniga, Giovanni; Perseghin, Paolo; Zatti, Giovanni; Gaddi, Diego; Cossio, Andrea; Biondi, Andrea; Corti, Paola; Masera, Nicoletta

    2013-06-28

    We report on a case of delayed hemolytic transfusion reaction (DHTR) occurred 7 days after an erythrocytapheresis or eritroexchange procedure (EEX) treated with rituximab and glucocorticoids in a 15-years old patient with sickle cell disease. EEX was performed despite a previous diagnosis of alloimmunization, in order to reduce hemoglobin S rate before a major surgery for avascular necrosis of the femoral head. A first dose of rituximab was administered before EEX. However, rituximab couldn't prevent DHTR that occurred with acute hemolysis, hemoglobinuria and hyperbilirubinemia. A further dose of rituximab and three boli of methylprednisolone were given after the onset of the reaction. It is likely that the combined use of rituximab and steroids managed to gradually improve both patient's general conditions and hemoglobin levels. Nor early or late side effects were registered in a 33-months follow-up period. This report suggests the potential effectiveness and safety of rituximab in combination with steroids in managing and mitigating the symptoms of delayed post-transfusional hemolytic reactions in alloimmunized patients affected by sickle cell disease with absolute need for erythrocytapheresis.

  16. Redox control of brain calcium in health and disease.

    PubMed

    Hidalgo, Cecilia; Carrasco, M Angélica

    2011-04-01

    Calcium ion is a highly versatile cellular messenger. Calcium signals-defined as transient increments in intracellular-free calcium concentration-elicit a multiplicity of responses that depend on cell type and signal properties such as their intensity, duration, cellular localization, and frequency. The vast literature available on the role of calcium signals in brain cells, chiefly centered on neuronal cells, indicates that calcium signals regulate essential neuronal functions, including synaptic transmission, gene expression, synaptic plasticity processes underlying learning and memory, and survival or death. The eight articles comprising this forum issue address different and novel aspects of calcium signaling in normal neuronal function, including how calcium signals interact with the generation of reactive species of oxygen/nitrogen with various functional consequences, and focus also on how abnormal calcium homeostasis and signaling, plus oxidative stress, affect overall brain physiology during aging and in neurodegenerative conditions such as Alzheimer's or Parkinson's disease. PMID:21050143

  17. An immediate hemolytic transfusion reaction due to anti-C and a delayed hemolytic transfusion reaction due to anti-Ce+e: hemoglobinemia, hemoglobinuria and transient impaired renal function.

    PubMed

    Molthan, L; Matulewicz, T J; Bansal-Carver, B; Benz, E J

    1984-01-01

    A patient with phenotype R2r and anti-C has a hemolytic transfusion reaction (HTR) with hemoglobinemia and hemoglobinuria which occurred within 2 h of receiving an R1r transfusion. Transient impaired renal function ensued. A patient with phenotype R2R2 and anti-Ce+e had the same experience on day 4 after receiving three R1r and one rr units. 2 other patients, 1 R2r with anti-C who received one R1r unit and the other R2R2 with anti-Ce+e who received two R1r units, showed no clinical evidence of HTR. Both anti-C antibodies were entirely IgG while both anti-Ce+e antibodies initially were predominantly IgM. IgG subclassing was unsuccessful and red blood cell-mononuclear phagocyte assays were normal. These cases occurred from 1979 to 1981.

  18. An immediate hemolytic transfusion reaction due to anti-C and a delayed hemolytic transfusion reaction due to anti-Ce+e: hemoglobinemia, hemoglobinuria and transient impaired renal function.

    PubMed

    Molthan, L; Matulewicz, T J; Bansal-Carver, B; Benz, E J

    1984-01-01

    A patient with phenotype R2r and anti-C has a hemolytic transfusion reaction (HTR) with hemoglobinemia and hemoglobinuria which occurred within 2 h of receiving an R1r transfusion. Transient impaired renal function ensued. A patient with phenotype R2R2 and anti-Ce+e had the same experience on day 4 after receiving three R1r and one rr units. 2 other patients, 1 R2r with anti-C who received one R1r unit and the other R2R2 with anti-Ce+e who received two R1r units, showed no clinical evidence of HTR. Both anti-C antibodies were entirely IgG while both anti-Ce+e antibodies initially were predominantly IgM. IgG subclassing was unsuccessful and red blood cell-mononuclear phagocyte assays were normal. These cases occurred from 1979 to 1981. PMID:6438912

  19. The spatial pattern of atrial cardiomyocyte calcium signalling modulates contraction.

    PubMed

    Mackenzie, Lauren; Roderick, H Llewelyn; Berridge, Michael J; Conway, Stuart J; Bootman, Martin D

    2004-12-15

    We examined the regulation of calcium signalling in atrial cardiomyocytes during excitation-contraction coupling, and how changes in the distribution of calcium impacts on contractility. Under control conditions, calcium transients originated in subsarcolemmal locations and showed local regeneration through activation of calcium-induced calcium release from ryanodine receptors. Despite functional ryanodine receptors being expressed at regular (approximately 2 microm) intervals throughout atrial myocytes, the subsarcolemmal calcium signal did not spread in a fully regenerative manner through the interior of a cell. Rather, there was a diminishing centripetal propagation of calcium. The lack of regeneration was due to mitochondria and SERCA pumps preventing the inward movement of calcium. Inhibiting these calcium buffering mechanisms allowed the globalisation of action potential-evoked responses. In addition, physiological positive inotropic agents, such as endothelin-1 and beta-adrenergic agonists, as well as enhanced calcium current, calcium store loading and inositol 1,4,5-trisphosphate infusion also led to regenerative global responses. The consequence of globalising calcium signals was a significant increase in cellular contraction. These data indicate how calcium signals and their consequences are determined by the interplay of multiple subcellular calcium management systems.

  20. Measurement of calcium release due to inositol trisphosphate receptors in skeletal muscle.

    PubMed

    Casas, Mariana; Altamirano, Francisco; Jaimovich, Enrique

    2012-01-01

    Calcium transients elicited by IP(3) receptors upon electrical stimulation of skeletal muscle cells (slow calcium signals) are often hard to visualize due to their relatively small amplitude compared to the large transient originated from ryanodine receptors associated to excitation-contraction coupling. The study of slow calcium transients, however, is relevant due to their function in regulation of muscle gene expression and in the process of excitation-transcription coupling. Discussed here are the procedures used to record slow calcium signals from both cultured mouse myotubes and from cultured adult skeletal muscle fibers. PMID:22130849

  1. Calcium flux assay in Xenopus oocytes.

    PubMed

    Murphy, P M

    2001-05-01

    Many G protein-coupled receptors of interest to neuroscientists induce transient increases in [Ca(2+)](i), which can be used as a convenient measure of receptor activation in a variety of applications. This unit describes a simple calcium flux assay applied to Xenopus oocytes. PMID:18428482

  2. Delaying obsolescence.

    PubMed

    Lawlor, Rob

    2015-04-01

    This paper argues that those who emphasise that designers and engineers need to plan for obsolescence are too conservative. Rather, in addition to planning for obsolescence, designers and engineers should also think carefully about what they could do in order delay obsolescence. They should so this by thinking about the design itself, thinking of ways in which products could be useful and appealing for longer before becoming obsolete, as well thinking about the wider context in terms of the marketing of products, and also the social and legal. The paper also considers objections that these suggestions are unrealistically idealistic, failing to recognise the economic realities. I respond to these objections appealing to research in advertising, psychology, cognitive linguistics, philosophy, history, and economics, as well as drawing on the Statement of Ethical Principles developed by the Royal Academy of Engineering and the Engineering Council. PMID:24792878

  3. Deoxynivalenol (Vomitoxin)-Induced Cholecystokinin and Glucagon-Like Peptide-1 Release in the STC-1 Enteroendocrine Cell Model Is Mediated by Calcium-Sensing Receptor and Transient Receptor Potential Ankyrin-1 Channel.

    PubMed

    Zhou, Hui-Ren; Pestka, James J

    2015-06-01

    Food refusal is a hallmark of exposure of experimental animals to the trichothecene mycotoxin deoxynivalenol (DON), a common foodborne contaminant. Although studies in the mouse suggest that DON suppresses food intake by aberrantly inducing the release of satiety hormones from enteroendocrine cells (EECs) found in the gut epithelium, the underlying mechanisms for this effect are not understood. To address this gap, we employed the murine neuroendocrine tumor STC-1 cell line, a widely used EEC model, to test the hypothesis that DON-induced hormone exocytosis is mediated by G protein-coupled receptor (GPCR)-mediated Ca(2+) signaling. The results indicate for the first time that DON elicits Ca(2)-dependent secretion of cholecystokinin (CCK) and glucagon-like peptide-1(7-36) amide (GLP-1), hormones that regulate food intake and energy homeostasis and that are products of 2 critical EEC populations--I cells of the small intestine and L cells of the large intestine, respectively. Furthermore, these effects were mediated by the GPCR Ca(2+)-sensing receptor (CaSR) and involved the following serial events: (1)PLC-mediated activation of the IP3 receptor and mobilization of intracellular Ca(2+) stores, (2) activation of transient receptor potential melastatin-5 ion channel and resultant L-type voltage-sensitive Ca(2+) channel-facilitated extracellular Ca(2+) entry, (3) amplification of extracellular Ca(2+) entry by transient receptor potential ankyrin-1 channel activation, and finally (4) Ca(2+)-driven CCK and GLP-1 excytosis. These in vitro findings provide a foundation for future investigation of mechanisms by which DON and other trichothecenes modulate EEC function in ex vivo and in vivo models. PMID:25787141

  4. Deoxynivalenol (Vomitoxin)-Induced Cholecystokinin and Glucagon-Like Peptide-1 Release in the STC-1 Enteroendocrine Cell Model Is Mediated by Calcium-Sensing Receptor and Transient Receptor Potential Ankyrin-1 Channel.

    PubMed

    Zhou, Hui-Ren; Pestka, James J

    2015-06-01

    Food refusal is a hallmark of exposure of experimental animals to the trichothecene mycotoxin deoxynivalenol (DON), a common foodborne contaminant. Although studies in the mouse suggest that DON suppresses food intake by aberrantly inducing the release of satiety hormones from enteroendocrine cells (EECs) found in the gut epithelium, the underlying mechanisms for this effect are not understood. To address this gap, we employed the murine neuroendocrine tumor STC-1 cell line, a widely used EEC model, to test the hypothesis that DON-induced hormone exocytosis is mediated by G protein-coupled receptor (GPCR)-mediated Ca(2+) signaling. The results indicate for the first time that DON elicits Ca(2)-dependent secretion of cholecystokinin (CCK) and glucagon-like peptide-1(7-36) amide (GLP-1), hormones that regulate food intake and energy homeostasis and that are products of 2 critical EEC populations--I cells of the small intestine and L cells of the large intestine, respectively. Furthermore, these effects were mediated by the GPCR Ca(2+)-sensing receptor (CaSR) and involved the following serial events: (1)PLC-mediated activation of the IP3 receptor and mobilization of intracellular Ca(2+) stores, (2) activation of transient receptor potential melastatin-5 ion channel and resultant L-type voltage-sensitive Ca(2+) channel-facilitated extracellular Ca(2+) entry, (3) amplification of extracellular Ca(2+) entry by transient receptor potential ankyrin-1 channel activation, and finally (4) Ca(2+)-driven CCK and GLP-1 excytosis. These in vitro findings provide a foundation for future investigation of mechanisms by which DON and other trichothecenes modulate EEC function in ex vivo and in vivo models.

  5. Cell-type-specific modelling of intracellular calcium signalling: a urothelial cell model.

    PubMed

    Appleby, Peter A; Shabir, Saqib; Southgate, Jennifer; Walker, Dawn

    2013-09-01

    Calcium signalling plays a central role in regulating a wide variety of cell processes. A number of calcium signalling models exist in the literature that are capable of reproducing a variety of experimentally observed calcium transients. These models have been used to examine in more detail the mechanisms underlying calcium transients, but very rarely has a model been directly linked to a particular cell type and experimentally verified. It is important to show that this can be achieved within the general theoretical framework adopted by these models. Here, we develop a framework designed specifically for modelling cytosolic calcium transients in urothelial cells. Where possible, we draw upon existing calcium signalling models, integrating descriptions of components known to be important in this cell type from a number of studies in the literature. We then add descriptions of several additional pathways that play a specific role in urothelial cell signalling, including an explicit ionic influx term and an active pumping mechanism that drives the cytosolic calcium concentration to a target equilibrium. The resulting one-pool model of endoplasmic reticulum (ER)-dependent calcium signalling relates the cytosolic, extracellular and ER calcium concentrations and can generate a wide range of calcium transients, including spikes, bursts, oscillations and sustained elevations in the cytosolic calcium concentration. Using single-variate robustness and multivariate sensitivity analyses, we quantify how varying each of the parameters of the model leads to changes in key features of the calcium transient, such as initial peak amplitude and the frequency of bursting or spiking, and in the transitions between bursting- and plateau-dominated modes. We also show that, novel to our urothelial cell model, the ionic and purinergic P2Y pathways make distinct contributions to the calcium transient. We then validate the model using human bladder epithelial cells grown in monolayer cell

  6. Effect of insulin on renal calcium transport

    SciTech Connect

    Gollaher, C.J.

    1985-01-01

    The author has investigated both the indirect effect of insulin parathyroid hormone (PTH) activity, and the direct effect of insulin on renal calcium transport. The indirect study was performed by comparing calcium excretion in sham-operated and parathyroidectomized rats infused with the insulin secretagogue, arginine. Arginine infusion increased urinary calcium excretion in both groups. Therefore, it is concluded that neither PTH activity nor secretion is involved in this response. The direct effects of insulin were investigated by exposing rat kidney slices in vitro to varying concentrations of insulin and performing a kinetic analysis to interpret insulin's effect on calcium transport through cellular compartments. Steady state calcium transport through the plasma membrane, cytosol and mitochondria were compared in the presence and absence of insulin. Insulin had no effect on any calcium pool size or exchange rate. The direct effect of insulin was also studied in an acute experiment, which simulates conditions where insulin levels are raised rapidly as in the case with protein or glucose consumption. Under these conditions insulin treatment caused a rapid, but transient increase in /sup 45/Ca efflux from rat kidney slices. This pattern is usually indicative of a stimulation of calcium efflux across the plasma membrane. Finally, insulin caused a slight decrease in slice chemical calcium concentration.

  7. Transient simulation of absorption machines

    NASA Astrophysics Data System (ADS)

    Anand, D. K.; Allen, R. W.; Kumar, B.

    A model for a water-cooled Lithium-Bromide/water absorption chiller is presented. Its transient response both during the start-up phase and during the shut-off period is predicted. The simulation model incorporates such influencing factors as the thermodynamic properties of the working fluid, the absorbent, the heat-transfer configuration of different components of the chiller and related physical data. The time constants of different components are controlled by a set of key parameters that have been identified. The results show a variable but at times significant amount of time delay before the chiller capacity gets close to its steady-state value. The model is intended to provide an insight into the mechanism of build-up to steady-state performance. By recognizing the significant factors contributing to transient degradation, steps can be taken to reduce such degradation.

  8. Calcium and Vitamin D

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Calcium is required for the bone formation phase of bone remodeling. Typically about 5 nmol (200 mg) of calcium is removed from the adult skeleton and replaced each day. To supply this amount, one would need to consume about 600 mg of calcium, since calcium is not very efficiently absorbed. Calcium ...

  9. Intracellular Calcium Release at Fertilization in the Sea Urchin Egg

    PubMed Central

    Steinhardt, R.; Zucker, R.; Schattenand, G.

    2015-01-01

    Fertilization or ionophore activation of Lytechinus pictus eggs can be monitored after injection with the Ca-sensitive photoprotein aequorin to estimate calcium release during activation. We estimate the peak calcium transient to reach concentrations of 2.5–4.5 μM free calcium 45–60 sec after activation and to last 2–3 min, assuming equal Ca2+ release throughout the cytoplasm. Calcium is released from an intracellular store, since similar responses are obtained during fertilization at a wide range of external calcium concentrations or in zero-calcium seawater in ionophore activations. In another effort to estimate free calcium at fertilization, we isolated egg cortices, added back calcium quantitatively, and fixed for observation with a scanning electron microscope. In this way, we determined that the threshold for discharge of the cortical granules is between 9 and 18 μM Ca2+. Therefore, the threshold for the in vitro cortical reaction is about five times the amount of free calcium, assuming equal distribution in the egg. This result suggests that transient calcium release is confined to the inner subsurface of the egg. PMID:326602

  10. Calcium signals and calcium channels in osteoblastic cells

    NASA Technical Reports Server (NTRS)

    Duncan, R. L.; Akanbi, K. A.; Farach-Carson, M. C.

    1998-01-01

    Calcium (Ca2+) channels are present in non-excitable as well as in excitable cells. In bone cells of the osteoblast lineage, Ca2+ channels play fundamental roles in cellular responses to external stimuli including both mechanical forces and hormonal signals. They are also proposed to modulate paracrine signaling between bone-forming osteoblasts and bone-resorbing osteoclasts at local sites of bone remodeling. Calcium signals are characterized by transient increases in intracellular Ca2+ levels that are associated with activation of intracellular signaling pathways that control cell behavior and phenotype, including patterns of gene expression. Development of Ca2+ signals is a tightly regulated cellular process that involves the concerted actions of plasma membrane and intracellular Ca2+ channels, along with Ca2+ pumps and exchangers. This review summarizes the current state of knowledge concerning the structure, function, and role of Ca2+ channels and Ca2+ signals in bone cells, focusing on the osteoblast.

  11. Excitability in a stochastic differential equation model for calcium puffs

    NASA Astrophysics Data System (ADS)

    Rüdiger, S.

    2014-06-01

    Calcium dynamics are essential to a multitude of cellular processes. For many cell types, localized discharges of calcium through small clusters of intracellular channels are building blocks for all spatially extended calcium signals. Because of the large noise amplitude, the validity of noise-approximating model equations for this system has been questioned. Here we revisit the master equations for local calcium release, examine the multiple scales of calcium concentrations in the cluster domain, and derive adapted stochastic differential equations. We show by comparison of discrete and continuous trajectories that the Langevin equations can be made consistent with the master equations even for very small channel numbers. In its deterministic limit, the model reveals that excitability, a dynamical phenomenon observed in many natural systems, is at the core of calcium puffs. The model also predicts a bifurcation from transient to sustained release which may link local and global calcium signals in cells.

  12. Hamlet's delay.

    PubMed

    Dendy, E B

    2001-01-01

    This paper raises a question about Freud's understanding of Hamlet and offers a fresh psychoanalytic perspective on the play, emphasizing the psychological use made of Hamlet by the audience. It suggests Hamlet and Claudius both serve as sacrificial objects, scapegoats, for the audience, embodying, through a mechanism of both identification and disidentification, the fulfillment, punishment, and renunciation of the audience's forbidden (i.e. Oedipal) wishes. The play is thus seen to represent unconsciously a rite of sacrifice in which both Claudius and Hamlet, both the father and the son, are led, albeit circuitously, to the slaughter. The need for delay on the part of Hamlet is thus seen to arise not merely from Hamlet's psychology, whatever the audience may project onto it, but ultimately from the function (both sadistic and defensive) that the sacrificial spectacle, the play as a whole, serves for the audience. The paper also speculates somewhat on the role of tragic heroes and heroines in general, and points to the unconscious collusion that permits author and audience to make use of them. Finally, in an addendum, the paper discusses the work of René Girard, a nonpsychoanalytic thinker whose ideas nonetheless are somewhat similar to those presented here. PMID:12102022

  13. Computational modeling of cardiac dual calcium-voltage optical mapping.

    PubMed

    Walton, Richard D; Bernus, Olivier

    2009-01-01

    Optical imaging allows mapping the complex spatiotemporal dynamics of transmembrane potential and intracellular calcium in cardiac tissue. Several studies have shown that the epi-fluorescent optical action potential contains contributions from the sub-epicardium, owing to scattering of photons in tissue. Hybrid electro-optical models have allowed careful quantification of these scattering effects and have lead to a better interpretation of the optical action potential. However, until now, these effects have not been investigated for optically recorded calcium transients. Here, we develop a hybrid model of cardiac dual calcium-voltage epi-fluorescence mapping. This model allows simulating both optical action potentials and optical calcium transients and investigating the effects of photon scattering on their synthesis. We find that optical calcium transients contain contributions from sub-epicardial layers up to 0.8 mm below the epicardium. These lead to significant differences in rise time and activation times between the optically acquired calcium signal and the epicardial intracellular calcium concentration. As has been the case with optically recording action potentials, these results should be taken into account in the interpretation of experimental optical measurements of intracellular calcium.

  14. Biologically formed amorphous calcium carbonate.

    PubMed

    Weiner, Steve; Levi-Kalisman, Yael; Raz, Sefi; Addadi, Lia

    2003-01-01

    Many organisms from a wide variety of taxa produce amorphous calcium carbonate (ACC), despite the fact that it is inherently unstable and relatively soluble in its pure state. These properties also make it difficult to detect and characterize ACC. Raman spectroscopy is a particularly useful method for investigating ACC because the sample can be examined wet, and extended X-ray absorption fine structure (EXAFS) analysis can provide detailed information on the short-range order. Other methods for characterizing ACC include infrared spectroscopy, thermogravimetric analysis and differential thermal analysis (TGA and DTA), transmission electron microscopy (TEM), and electron and X-ray diffraction. Because of the difficulties involved, we suspect that ACC is far more widely distributed than is presently known, and a comparison of EXAFS spectra shows that different biogenic ACC phases have different short-range order structures. We also suspect that ACC fulfils many different functions, including as a transient precursor phase during the formation of crystalline calcium carbonate.

  15. Coronary Calcium Scan

    MedlinePlus

    ... the NHLBI on Twitter. What Is a Coronary Calcium Scan? A coronary calcium scan is a test ... you have calcifications in your coronary arteries. Coronary Calcium Scan Figure A shows the position of the ...

  16. Calcium and bones (image)

    MedlinePlus

    Calcium is one of the most important minerals for the growth, maintenance, and reproduction of the human ... body, are continually being re-formed and incorporate calcium into their structure. Calcium is essential for the ...

  17. Calcium hydroxide poisoning

    MedlinePlus

    Hydrate - calcium; Lime milk; Slaked lime ... Calcium hydroxide ... These products contain calcium hydroxide: Cement Limewater Many industrial solvents and cleaners (hundreds to thousands of construction products, flooring strippers, brick cleaners, cement ...

  18. Calcium source (image)

    MedlinePlus

    Getting enough calcium to keep bones from thinning throughout a person's life may be made more difficult if that person has ... as a tendency toward kidney stones, for avoiding calcium-rich food sources. Calcium deficiency also effects the ...

  19. Intracellular calcium measurements with arsenazo III during cyclic AMP injections into molluscan neurons.

    PubMed

    Hockberger, P; Connor, J A

    1983-02-18

    Injections of cyclic adenosine monophosphate into molluscan neurons often produce a transient membrane depolarization. By using the calcium indicator dye arsenazo III, it was found that cyclic nucleotide injections into neurons of Archidoris montereyensis resulted in elevation of internal calcium concentrations. However, this was demonstrated to be a secondary consequence of an induced increase in membrane sodium permeability, and not due to any direct effect of cyclic adenosine monophosphate on cellular calcium influx or internal calcium regulating processes.

  20. Transient catalytic combustor model

    NASA Technical Reports Server (NTRS)

    Tien, J. S.

    1981-01-01

    A quasi-steady gas phase and thermally thin substrate model is used to analyze the transient behavior of catalytic monolith combustors in fuel lean operation. The combustor response delay is due to the substrate thermal inertia. Fast response is favored by thin substrate, short catalytic bed length, high combustor inlet and final temperatures, and small gas channel diameters. The calculated gas and substrate temperature time history at different axial positions provides an understanding of how the catalytic combustor responds to an upstream condition change. The computed results also suggest that the gas residence times in the catalytic bed in the after bed space are correlatable with the nondimensional combustor response time. The model also performs steady state combustion calculations; and the computed steady state emission characteristics show agreement with available experimental data in the range of parameters covered. A catalytic combustor design for automotive gas turbine engine which has reasonably fast response ( 1 second) and can satisfy the emission goals in an acceptable total combustor length is possible.

  1. Potentiation of fractional sarcoplasmic reticulum calcium release by total and free intra-sarcoplasmic reticulum calcium concentration.

    PubMed Central

    Shannon, T R; Ginsburg, K S; Bers, D M

    2000-01-01

    Our aim was to measure the influence of sarcoplasmic reticulum (SR) calcium content ([Ca](SRT)) and free SR [Ca] ([Ca](SR)) on the fraction of SR calcium released during voltage clamp steps in isolated rabbit ventricular myocytes. [Ca](SRT), as measured by caffeine application, was progressively increased by conditioning pulses. Sodium was absent in both the intracellular and in the extracellular solutions to block sodium/calcium exchange. Total cytosolic calcium flux during the transient was inferred from I(Ca), [Ca](SRT), [Ca](i), and cellular buffering characteristics. Fluxes via the calcium current (I(Ca)), the SR calcium pump, and passive leak from the SR were evaluated to determine SR calcium release flux (J(rel)). Excitation-contraction (EC) coupling was characterized with respect to both gain (integral J(rel)/integral I(Ca)) and fractional SR calcium release. Both parameters were virtually zero for a small, but measurable [Ca](SRT). Gain and fractional SR calcium release increased steeply and nonlinearly with both [Ca](SRT) and [Ca](SR). We conclude that potentiation of EC coupling can be correlated with both [Ca](SRT) and [Ca](SR). While fractional SR calcium release was not linearly dependent upon [Ca](SR), intra-SR calcium may play a crucial role in regulating the SR calcium release process. PMID:10620297

  2. Intracellular sphingosine releases calcium from lysosomes

    PubMed Central

    Höglinger, Doris; Haberkant, Per; Aguilera-Romero, Auxiliadora; Riezman, Howard; Porter, Forbes D; Platt, Frances M; Galione, Antony; Schultz, Carsten

    2015-01-01

    To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC. DOI: http://dx.doi.org/10.7554/eLife.10616.001 PMID:26613410

  3. Intracellular sphingosine releases calcium from lysosomes.

    PubMed

    Höglinger, Doris; Haberkant, Per; Aguilera-Romero, Auxiliadora; Riezman, Howard; Porter, Forbes D; Platt, Frances M; Galione, Antony; Schultz, Carsten

    2015-01-01

    To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC. PMID:26613410

  4. Application of HTSC-thin films in microwave integrated delay lines

    NASA Astrophysics Data System (ADS)

    Jha, A. R.

    This paper reveals unique capabilities of High-Temperature Superconducting Thin Films (HTSTF) for possible application in microwave integrated delay lines. HTSTF can be characterized as Thin Film Microstrip (TFMS) lines operating at superconducting temperatures. Low insertion loss, minimum signal delay, and small power dissipation are possible with HTSTF delay lines. The conductor loss, dielectric loss, signal distortion, signal delay, and instantaneous bandwidth are dependent on the film thickness, superconducting film material, and substrate properties. Thin films of Yttrium Barium Copper Oxide (YBCO), Bismuth Strontium Calcium Copper Oxide (BSCCO), and Thallium Calcium Barium Copper Oxide (TCBCO) appear to be most suitable for microwave integrated delay lines.

  5. Transient triggering of near and distant earthquakes

    USGS Publications Warehouse

    Gomberg, J.; Blanpied, M.L.; Beeler, N.M.

    1997-01-01

    We demonstrate qualitatively that frictional instability theory provides a context for understanding how earthquakes may be triggered by transient loads associated with seismic waves from near and distance earthquakes. We assume that earthquake triggering is a stick-slip process and test two hypotheses about the effect of transients on the timing of instabilities using a simple spring-slider model and a rate- and state-dependent friction constitutive law. A critical triggering threshold is implicit in such a model formulation. Our first hypothesis is that transient loads lead to clock advances; i.e., transients hasten the time of earthquakes that would have happened eventually due to constant background loading alone. Modeling results demonstrate that transient loads do lead to clock advances and that the triggered instabilities may occur after the transient has ceased (i.e., triggering may be delayed). These simple "clock-advance" models predict complex relationships between the triggering delay, the clock advance, and the transient characteristics. The triggering delay and the degree of clock advance both depend nonlinearly on when in the earthquake cycle the transient load is applied. This implies that the stress required to bring about failure does not depend linearly on loading time, even when the fault is loaded at a constant rate. The timing of instability also depends nonlinearly on the transient loading rate, faster rates more rapidly hastening instability. This implies that higher-frequency and/or longer-duration seismic waves should increase the amount of clock advance. These modeling results and simple calculations suggest that near (tens of kilometers) small/moderate earthquakes and remote (thousands of kilometers) earthquakes with magnitudes 2 to 3 units larger may be equally effective at triggering seismicity. Our second hypothesis is that some triggered seismicity represents earthquakes that would not have happened without the transient load (i

  6. Stimulation-dependent myocardial calcium uptake into slowly exchangeable compartments

    SciTech Connect

    Fintel, M.; Langer, G.A.

    1986-03-01

    Myocardial calcium uptake into slowly exchangeable sites was increased in response to beating following a period of prolonged quiescence (> 1 hr). Net calcium uptake was measured in rabbit interventricular septa using the /sup 45/Ca washout technique. The maximal increment of slowly exchangeable calcium induced by beating was 20 +/- 2% of calcium uptake during quiescence. The increment in calcium uptake induced by 282 beats in 10 minutes did not differ from the increment induced by 60 beats but was significantly greater than the increment induced by 35 and 15 beats. The total number of beats rather than the frequency of stimulation appeared to be the most critical factor which determined the increment in calcium uptake. Based on the increment of 0.12 +/- 0.02 mmoles/kg dry weight obtained when 15 beats occurred in 10 minutes, the minimum amount of calcium which entered slowly exchangeable sites per beat was calculated to be 1 ..mu..mol/kg wet weight. The increment in slowly exchangeable calcium induced by beating was not affected by ryanodine but was inhibited by the metabolic inhibitor CCCP. In conclusion, a net increment in slowly exchangeable calcium occurs when beating is resumed following a period of prolonged quiescence. This suggests that calcium influx exceeds efflux transiently, under these conditions, and that slowly exchangeable sites represent an important mechanism by which a fraction of incoming calcium is buffered.

  7. Transient combustion in hybrid rockets

    NASA Astrophysics Data System (ADS)

    Karabeyoglu, Mustafa Arif

    1998-09-01

    Hybrid rockets regained interest recently as an alternative chemical propulsion system due to their advantages over the solid and liquid systems that are currently in use. Development efforts on hybrids revealed two important problem areas: (1) low frequency instabilities and (2) slow transient response. Both of these are closely related to the transient behavior which is a poorly understood aspect of hybrid operation. This thesis is mainly involved with a theoretical study of transient combustion in hybrid rockets. We follow the methodology of identifying and modeling the subsystems of the motor such as the thermal lags in the solid, boundary layer combustion and chamber gasdynamics from a dynamic point of view. We begin with the thermal lag in the solid which yield the regression rate for any given wall heat flux variation. Interesting phenomena such as overshooting during throttling and the amplification and phase lead regions in the frequency domain are discovered. Later we develop a quasi-steady transient hybrid combustion model supported with time delays for the boundary layer processes. This is integrated with the thermal lag system to obtain the thermal combustion (TC) coupled response. The TC coupled system with positive delays generated low frequency instabilities. The scaling of the instabilities are in good agreement with actual motor test data. Finally, we formulate a gasdynamic model for the hybrid chamber which successfully resolves the filling/emptying and longitudinal acoustic behavior of the motor. The TC coupled system is later integrated to the gasdynamic model to obtain the overall response (TCG coupled system) of gaseous oxidizer motors with stiff feed systems. Low frequency instabilities were also encountered for the TCG coupled system. Apart from the transient investigations, the regression rate behavior of liquefying hybrid propellants such as solid cryogenic materials are also studied. The theory is based on the possibility of enhancement

  8. Transient tachypnea - newborn

    MedlinePlus

    TTN; Wet lungs - newborns; Retained fetal lung fluid; Transient RDS; Prolonged transition; Neonatal - transient tachypnea ... As the baby grows in the womb, the lungs make a special fluid. This fluid fills the ...

  9. Transient drainage summary report

    SciTech Connect

    1996-09-01

    This report summarizes the history of transient drainage issues on the Uranium Mill Tailings Remedial Action (UMTRA) Project. It defines and describes the UMTRA Project disposal cell transient drainage process and chronicles UMTRA Project treatment of the transient drainage phenomenon. Section 4.0 includes a conceptual cross section of each UMTRA Project disposal site and summarizes design and construction information, the ground water protection strategy, and the potential for transient drainage.

  10. Transient Ischemic Attack

    MedlinePlus

    Transient Ischemic Attack TIA , or transient ischemic attack, is a "mini stroke" that occurs when a blood clot blocks an artery for a short time. The only ... TIA is that with TIA the blockage is transient (temporary). TIA symptoms occur rapidly and last a ...

  11. Delayed coker fractionator advanced control

    SciTech Connect

    Jaisinghani, R.; Minter, B. ); Tica, A.; Puglesi, A.; Ojeda, R. )

    1993-08-01

    In a delayed coking process, as coke drum switches are made, rapid changes occur in both the fractionator feed rate and composition. With conventional control, it is not unusual to see long transient behavior of large swings in both quality and flowrates of coker gas oils. This can extract a heavy economic toll, not only in coker operation, but in the operation of downstream units as the upset is propagated. An advanced process control application (APC) was recently implemented on the coker fractionator at the Yacimentos Petroliferos Fiscales (YPF), Lujan de Cuyo Refinery, in Mendoza, Argentina. This coker fractionator control design was unique as it handled two different operating objectives: control of product qualities via tower temperature profile during normal operation and control of gas oil product flow ratio during drum switch. This combination of control objectives in one multivariable predictive control program was achieved by including special logic to decouple the individual tuning requirements. Also, additional logic was included to unambiguously detect and identify drum switch and drum steam out as discrete events within 30 seconds of their actual occurrence. These discrete events were then used as disturbance variables to minimize fractionator transient behavior. As a performance measure, the overhead temperature was controlled within 2 C to 2.5 C of its target, gas oil flows were stabilized during drum switches and steam generation via pump around was maximized. Overall, implementing advanced control for the delayed coker fractionator resulted in substantial benefits from product quality control, product flow control and minimized energy consumption.

  12. Cameleon calcium indicator reports cytoplasmic calcium dynamics in Arabidopsis guard cells

    NASA Technical Reports Server (NTRS)

    Allen, G. J.; Kwak, J. M.; Chu, S. P.; Llopis, J.; Tsien, R. Y.; Harper, J. F.; Schroeder, J. I.; Evans, M. L. (Principal Investigator)

    1999-01-01

    Cytoplasmic free calcium ([Ca2+]cyt) acts as a stimulus-induced second messenger in plant cells and multiple signal transduction pathways regulate [Ca2+]cyt in stomatal guard cells. Measuring [Ca2+]cyt in guard cells has previously required loading of calcium-sensitive dyes using invasive and technically difficult micro-injection techniques. To circumvent these problems, we have constitutively expressed the pH-independent, green fluorescent protein-based calcium indicator yellow cameleon 2.1 in Arabidopsis thaliana (Miyawaki et al. 1999; Proc. Natl. Acad. Sci. USA 96, 2135-2140). This yellow cameleon calcium indicator was expressed in guard cells and accumulated predominantly in the cytoplasm. Fluorescence ratio imaging of yellow cameleon 2.1 allowed time-dependent measurements of [Ca2+]cyt in Arabidopsis guard cells. Application of extracellular calcium or the hormone abscisic acid (ABA) induced repetitive [Ca2+]cyt transients in guard cells. [Ca2+]cyt changes could be semi-quantitatively determined following correction of the calibration procedure for chloroplast autofluorescence. Extracellular calcium induced repetitive [Ca2+]cyt transients with peak values of up to approximately 1.5 microM, whereas ABA-induced [Ca2+]cyt transients had peak values up to approximately 0.6 microM. These values are similar to stimulus-induced [Ca2+]cyt changes previously reported in plant cells using ratiometric dyes or aequorin. In some guard cells perfused with low extracellular KCl concentrations, spontaneous calcium transients were observed. As yellow cameleon 2.1 was expressed in all guard cells, [Ca2+]cyt was measured independently in the two guard cells of single stomates for the first time. ABA-induced, calcium-induced or spontaneous [Ca2+]cyt increases were not necessarily synchronized in the two guard cells. Overall, these data demonstrate that that GFP-based cameleon calcium indicators are suitable to measure [Ca2+]cyt changes in guard cells and enable the pattern of [Ca

  13. Dysgraphia in Children: Lasting Psychomotor Deficiency or Transient Developmental Delay?

    ERIC Educational Resources Information Center

    Smits-Engelsman, Bouwien C. M.; Van Galen, Gerard P.

    1997-01-01

    Used writing tasks recorded on a computer-monitored XY tablet to differentiate between normal variations in psychomotor development and dysgraphia in 16 young children. Found that control of spatial accuracy, not allograph retrieval or size control, discriminated dysgraphic children from others. Poor writers were less accurate than proficient…

  14. Functional characterization of linear delay Langevin equations

    NASA Astrophysics Data System (ADS)

    Budini, Adrián A.; Cáceres, Manuel O.

    2004-10-01

    We present an exact functional characterization of linear delay Langevin equations driven by any noise structure defined through its characteristic functional. This method relies on the possibility of finding an explicitly analytical expression for each realization of the delayed stochastic process in terms of those of the driving noise. General properties of the transient dissipative dynamics are analyzed. The corresponding interplay with a color Gaussian noise is presented. As a full application of our functional method we study a model for population growth with non-Gaussian fluctuations: the Gompertz model driven by multiplicative white shot noise.

  15. Calcium waves along the cleavage furrows in cleavage-stage Xenopus embryos and its inhibition by heparin

    PubMed Central

    1996-01-01

    Calcium signaling is known to be associated with cytokinesis; however, the detailed spatio-temporal pattern of calcium dynamics has remained unclear. We have studied changes of intracellular free calcium in cleavage-stage Xenopus embryos using fluorescent calcium indicator dyes, mainly Calcium Green-1. Cleavage formation was followed by calcium transients that localized to cleavage furrows and propagated along the furrows as calcium waves. The calcium transients at the cleavage furrows were observed at each cleavage furrow at least until blastula stage. The velocity of the calcium waves at the first cleavage furrow was approximately 3 microns/s, which was much slower than that associated with fertilization/egg activation. These calcium waves traveled only along the cleavage furrows and not in the direction orthogonal to the furrows. These observations imply that there exists an intracellular calcium-releasing activity specifically associated with cleavage furrows. The calcium waves occurred in the absence of extracellular calcium and were inhibited in embryos injected with heparin an inositol 1,4,5-trisphosphate (InsP3) receptor antagonist. These results suggest that InsP3 receptor-mediated calcium mobilization plays an essential role in calcium wave formation at the cleavage furrows. PMID:8858172

  16. Calcium and calcium isotope changes during carbon cycle perturbations at the end-Permian

    NASA Astrophysics Data System (ADS)

    Komar, N.; Zeebe, R. E.

    2016-01-01

    Negative carbon and calcium isotope excursions, as well as climate shifts, took place during the most severe mass extinction event in Earth's history, the end-Permian (˜252 Ma). Investigating the connection between carbon and calcium cycles during transient carbon cycle perturbation events, such as the end-Permian, may help resolve the intricacies between the coupled calcium-carbon cycles, as well as provide a tool for constraining the causes of mass extinction. Here we identify the deficiencies of a simplified calcium model employed in several previous studies, and we demonstrate the importance of a fully coupled carbon cycle model when investigating the dynamics of carbon and calcium cycling. Simulations with a modified version of the Long-term Ocean-atmosphere-Sediment CArbon cycle Reservoir model, which includes a fully coupled carbon-calcium cycle, indicate that increased weathering rates and ocean acidification (potentially caused by Siberian Trap volcanism) are not capable of producing trends observed in the record, as previously claimed. Our model results suggest that combined effects of carbon input via Siberian Trap volcanism (12,000 Pg C), the cessation of biological carbon export, and variable calcium isotope fractionation (due to a change in the seawater carbonate ion concentration) represents a more plausible scenario. This scenario successfully reconciles δ13C and δ44Ca trends observed in the sediment record, as well as the proposed warming of >6°C.

  17. Calcium and calcium isotope changes during carbon cycle perturbations at the end-Permian

    NASA Astrophysics Data System (ADS)

    Komar, Nemanja; Zeebe, Richard

    2016-04-01

    Negative carbon and calcium isotope excursions, as well as climate shifts, took place during the most severe mass extinction event in Earth's history, the end-Permian (˜252 Ma). Investigating the connection between carbon and calcium cycles during transient carbon cycle perturbation events, such as the end-Permian, may help resolve the intricacies between the coupled calcium-carbon cycles, as well as provide a tool for constraining the causes of mass extinction. Here, we identify the deficiencies of a simplified calcium model employed in several previous studies and we demonstrate the importance of a fully coupled carbon-cycle model when investigating the dynamics of carbon and calcium cycling. Simulations with a modified version of the LOSCAR model, which includes a fully coupled carbon-calcium cycle, indicate that increased weathering rates and ocean acidification (potentially caused by Siberian Trap volcanism) are not capable of producing trends observed in the record, as previously claimed. Our model results suggest that combined effects of carbon input via Siberian Trap volcanism (12,000 Pg C), the cessation of biological carbon export, and variable calcium isotope fractionation (due to a change in the seawater carbonate ion concentration) represents a more plausible scenario. This scenario successfully reconciles δ13C and δ44Ca trends observed in the sediment record, as well as the proposed warming of >6oC.

  18. Reduced calcium-dependent mitochondrial damage underlies the reduced vulnerability of excitotoxicity-tolerant hippocampal neurons.

    PubMed

    Pivovarova, Natalia B; Stanika, Ruslan I; Watts, Charlotte A; Brantner, Christine A; Smith, Carolyn L; Andrews, S Brian

    2008-03-01

    In central neurons, over-stimulation of NMDA receptors leads to excessive mitochondrial calcium accumulation and damage, which is a critical step in excitotoxic death. This raises the possibility that low susceptibility to calcium overload-induced mitochondrial damage might characterize excitotoxicity-resistant neurons. In this study, we have exploited two complementary models of preconditioning-induced excitotoxicity resistance to demonstrate reduced calcium-dependent mitochondrial damage in NMDA-tolerant hippocampal neurons. We have further identified adaptations in mitochondrial calcium handling that account for enhanced mitochondrial integrity. In both models, enhanced tolerance was associated with improved preservation of mitochondrial membrane potential and structure. In the first model, which exhibited modest neuroprotection, mitochondria-dependent calcium deregulation was delayed, even though cytosolic and mitochondrial calcium loads were quantitatively unchanged, indicating that enhanced mitochondrial calcium capacity accounts for reduced injury. In contrast, the second model, which exhibited strong neuroprotection, displayed further delayed calcium deregulation and reduced mitochondrial damage because downregulation of NMDA receptor surface expression depressed calcium loading. Reducing calcium entry also modified the chemical composition of the calcium-buffering precipitates that form in calcium-loaded mitochondria. It thus appears that reduced mitochondrial calcium loading is a major factor underlying the robust neuroprotection seen in highly tolerant cells. PMID:18036152

  19. CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING IN CENTER, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING IN CENTER, CALCIUM CHLORIDE STORAGE BUILDING ON RIGHT WITH SA (SODA ASH) BUILDING IN RIGHT BACKGROUND. - Solvay Process Company, Calcium Chloride Plant, Between Willis & Milton Avenues, Solvay, Onondaga County, NY

  20. Calcium and Vitamin D

    MedlinePlus

    ... to your weekly shopping list. Produce Serving Size Estimated Calcium* Collard greens, frozen 8 oz 360 mg ... Oranges 1 whole 55 mg Seafood Serving Size Estimated Calcium* Sardines, canned with bones 3 oz 325 ...

  1. Fenoprofen calcium overdose

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/002649.htm Fenoprofen calcium overdose To use the sharing features on this page, please enable JavaScript. Fenoprofen calcium is a type of medicine called a nonsteroidal ...

  2. Calcium and bones

    MedlinePlus

    ... only gets the calcium it needs through the food you eat, or from supplements. If you do ... materials it needs to build bones. High-calcium foods include: Milk Cheese Ice cream Leafy green vegetables, ...

  3. Calcium and Mitosis

    NASA Technical Reports Server (NTRS)

    Hepler, P.

    1983-01-01

    Although the mechanism of calcium regulation is not understood, there is evidence that calcium plays a role in mitosis. Experiments conducted show that: (1) the spindle apparatus contains a highly developed membrane system that has many characteristics of sarcoplasmic reticulum of muscle; (2) this membrane system contains calcium; and (3) there are ionic fluxes occurring during mitosis which can be seen by a variety of fluorescence probes. Whether the process of mitosis can be modulated by experimentally modulating calcium is discussed.

  4. Caffeine-induced myocardial injury in calcium-free perfused rat hearts.

    PubMed

    Vander Heide, R S; Ganote, C E

    1985-01-01

    Hearts depleted of extracellular calcium become susceptible to injury caused by repletion of extracellular calcium (calcium paradox). It has been suggested that calcium-free perfusion causes weakening of intercalated disks and that the physical stress of contracture may cause sarcolemmal membrane rupture and creatine kinase (CK) release. To further investigate this hypothesis, the effects of caffeine on contracture, cellular morphology, and CK release were studied in control and calcium-free perfused isolated rat hearts. Control hearts perfused with 2.5 mM calcium retained normal ultrastructure for long periods of perfusion. Calcium-free hearts perfused for 12 minutes developed separations of fascia adherens portions of intercalated disks but retained intact nexus junctions. Hearts subjected to 5-minute calcium-free perfusion, followed by calcium repletion, developed a massive CK release and extensive contraction band necrosis (calcium paradox). Ten millimolar caffeine, which causes rapid calcium release from sarcoplasmic reticulum (SR), produced contracture, but not CK release, from control hearts perfused with medium containing 2.5 mM calcium. In calcium-free perfused hearts, caffeine caused sudden CK release accompanied by contracture, development of contraction bands, wide separations of cells at intercalated disks, and sarcolemmal membrane injury. Caffeine-induced injury occurred despite 3 mM amobarbital inhibition of mitochondrial respiration. Hearts perfused with caffeine in the presence of calcium relaxed when made calcium-free and did not release CK. Addition of caffeine following calcium-free perfusion at 22 C, which protects the heart from the calcium paradox, produced a rapid, transient contracture. These results are compatible with the hypothesis that myocardial cell injury in calcium-free hearts is not dependent on repletion of extracellular calcium or mitochondrial function, but can result from contracture following caffeine-induced release of

  5. Attosecond Electron Wave-Packet Interference Observed by Transient Absorption

    SciTech Connect

    Holler, M.; Schapper, F.; Gallmann, L.; Keller, U.

    2011-03-25

    We perform attosecond time-resolved transient absorption spectroscopy around the first ionization threshold of helium and observe rapid oscillations of the absorption of the individual harmonics as a function of time delay with respect to a superimposed, moderately strong infrared laser field. The phase relation between the absorption modulation of individual harmonics gives direct evidence for the interference of transiently bound electronic wave packets as the mechanism behind the absorption modulation.

  6. Attosecond electron wave-packet interference observed by transient absorption.

    PubMed

    Holler, M; Schapper, F; Gallmann, L; Keller, U

    2011-03-25

    We perform attosecond time-resolved transient absorption spectroscopy around the first ionization threshold of helium and observe rapid oscillations of the absorption of the individual harmonics as a function of time delay with respect to a superimposed, moderately strong infrared laser field. The phase relation between the absorption modulation of individual harmonics gives direct evidence for the interference of transiently bound electronic wave packets as the mechanism behind the absorption modulation.

  7. Visualization of calcium transients controlling orientation of ciliary beat

    PubMed Central

    1994-01-01

    To image changes in intraciliary Ca controlling ciliary motility, we microinjected Ca Green dextran, a visible wavelength fluorescent Ca indicator, into eggs or two cell stages of the ctenophore Mnemiopsis leidyi. The embryos developed normally into free-swimming, approximately 0.5 mm cydippid larvae with cells and ciliary comb plates (approximately 100 microns long) loaded with the dye. Comb plates of larvae, like those of adult ctenophores, undergo spontaneous or electrically stimulated reversal of beat direction, triggered by Ca influx through voltage-sensitive Ca channels. Comb plates of larvae loaded with Ca Green dextran emit spontaneous or electrically stimulated fluorescent flashes along the entire length of their cilia, correlated with ciliary reversal. Fluorescence intensity peaks rapidly (34-50 ms), then slowly falls to resting level in approximately 1 s. Electrically stimulated Ca Green emissions often increase in steps to a maximum value near the end of the stimulus pulse train, and slowly decline in 1-2 s. In both spontaneous and electrically stimulated flashes, measurements at multiple sites along a single comb plate show that Ca Green fluorescence rises within 17 ms (1 video field) and to a similar relative extent above resting level from base to tip of the cilia. The decline of fluorescence intensity also begins simultaneously and proceeds at similar rates along the ciliary length. Ca-free sea water reversibly abolishes spontaneous and electrically stimulated Ca Green ciliary emissions as well as reversed beating. Calculations of Ca diffusion from the ciliary base show that Ca must enter the comb plate along the entire length of the ciliary membranes. The voltage-dependent Ca channels mediating changes in beat direction are therefore distributed over the length of the comb plate cilia. The observed rapid and virtually instantaneous Ca signal throughout the intraciliary space may be necessary for reprogramming the pattern of dynein activity responsible for reorientation of the ciliary beat cycle. PMID:8195294

  8. Transient simulation of absorption machines

    NASA Astrophysics Data System (ADS)

    Anand, D. K.; Allen, R. W.; Kumar, B.

    1982-08-01

    This paper presents a model for a water-cooled Lithium-Bromide/water absorption chiller and predicts its transient response both during the start-up phase and during the shutoff period. The simulation model incorporates such influencing factors as the thermodynamic properties of the working fluid, the absorbent, the heat-transfer configuration of different components of the chiller and related physical data. The time constants of different components are controlled by a set of key parameters that have been identified in this study. The results show a variable but at times significant amount of time delay before the chiller capacity gets close to its steady-state value. The model is intended to provide an insight into the mechanism of build-up to steady-state performance. By recognizing the significant factors contributing to transient degradation, steps can be taken to reduce such degradation. The evaluation of the residual capacity in the shut-off period will yield more realistic estimates of chiller COP for a chiller satisfying dynamic space cooling load.

  9. Speech and Language Delay

    MedlinePlus

    MENU Return to Web version Speech and Language Delay Overview How do I know if my child has speech delay? Every child develops at his or her ... of the same age, the problem may be speech delay. Your doctor may think your child has ...

  10. Delay Discounting and Gambling

    PubMed Central

    Madden, Gregory J.; Francisco, Monica T.; Brewer, Adam T.; Stein, Jeffrey S.

    2011-01-01

    Delay discounting describes the decline in the value of a reinforcer as the delay to that reinforcer increases. A review of the available studies revealed that steep delay discounting is positively correlated with problem or pathological gambling. One hypothesis regarding this correlation derives from the discounting equation proposed by Mazur (1989). According to the equation, steeper discounting renders the difference between fixed-delayed rewards and gambling-like variable-delayed rewards larger; with the latter being more valuable. The present study was designed to test this prediction by first assessing rats’ impulsive choices across four delays to a larger-later reinforcer. A second condition quantified strength of preference for mixed- over fixed-delays, with the duration of the latter adjusted between sessions to achieve indifference. Strength of preference for the mixed-delay alternative is given by the fixed delay at indifference (lower fixed-delay values reflect stronger preferences). Percent impulsive choice was not correlated with the value of the fixed delay at indifference and, therefore, the prediction of the hyperbolic model of gambling was not supported. A follow-up assessment revealed a significant decrease in impulsive choice after the second condition. This shift in impulsive choice could underlie the failure to observe the predicted correlation between impulsive choice and degree of preference for mixed- over fixed delays. PMID:21352902

  11. Cytosolic Calcium Measurements in Renal Epithelial Cells by Flow Cytometry

    PubMed Central

    Lee, Wing-Kee; Dittmar, Thomas

    2014-01-01

    A variety of cellular processes, both physiological and pathophysiological, require or are governed by calcium, including exocytosis, mitochondrial function, cell death, cell metabolism and cell migration to name but a few. Cytosolic calcium is normally maintained at low nanomolar concentrations; rather it is found in high micromolar to millimolar concentrations in the endoplasmic reticulum, mitochondrial matrix and the extracellular compartment. Upon stimulation, a transient increase in cytosolic calcium serves to signal downstream events. Detecting changes in cytosolic calcium is normally performed using a live cell imaging set up with calcium binding dyes that exhibit either an increase in fluorescence intensity or a shift in the emission wavelength upon calcium binding. However, a live cell imaging set up is not freely accessible to all researchers. Alternative detection methods have been optimized for immunological cells with flow cytometry and for non-immunological adherent cells with a fluorescence microplate reader. Here, we describe an optimized, simple method for detecting changes in epithelial cells with flow cytometry using a single wavelength calcium binding dye. Adherent renal proximal tubule epithelial cells, which are normally difficult to load with dyes, were loaded with a fluorescent cell permeable calcium binding dye in the presence of probenecid, brought into suspension and calcium signals were monitored before and after addition of thapsigargin, tunicamycin and ionomycin. PMID:25407650

  12. [The role of gastro-intestinal tract in the calcium absorption].

    PubMed

    Kuwabara, Akiko; Tanaka, Kiyoshi

    2015-11-01

    Calcium is associated with various functions of clinical importance. Its unique distribution;low intracellular and high extracellular concentration, is crucial for the neuro-muscular function. Calcium is also indispensable for the vascular contraction and blood coagulation. Thus, circulating calcium concentration must be strictly maintained within a narrow range, for which parathyroid hormone(PTH), vitamin D, and calcitonin contribute. Food-derived protein-bound calcium must be first released in the acidic condition. Thus, gastric acid is essential for the effective calcium absorption. Intestinal calcium absorption occurs via both active transport and passive transport. For the former, such molecules as transient receptor potential vanilloid type 6(TRPV6), calbindin 9k, and Ca²⁺-ATPase contribute. In the adult, calcium absorption rate is approximately 30% under the ordinary condition. Lower calcium intake is associated with increased calcium absorption and decreased urinary excretion. In the Dietary Reference Intakes for Japanese, calcium requirement is determined based on factorial method. Recommended Dietary Allowance(RDA)for calcium ranges from 600-800 mg/day for adult. However, the average calcium intake is far lower than Estimated Average Requirement(EAR). Thus, an effort to increase the calcium intake, rather than considering the detailed calcium absorption rate, is most essential in Japan.

  13. [The role of gastro-intestinal tract in the calcium absorption].

    PubMed

    Kuwabara, Akiko; Tanaka, Kiyoshi

    2015-11-01

    Calcium is associated with various functions of clinical importance. Its unique distribution;low intracellular and high extracellular concentration, is crucial for the neuro-muscular function. Calcium is also indispensable for the vascular contraction and blood coagulation. Thus, circulating calcium concentration must be strictly maintained within a narrow range, for which parathyroid hormone(PTH), vitamin D, and calcitonin contribute. Food-derived protein-bound calcium must be first released in the acidic condition. Thus, gastric acid is essential for the effective calcium absorption. Intestinal calcium absorption occurs via both active transport and passive transport. For the former, such molecules as transient receptor potential vanilloid type 6(TRPV6), calbindin 9k, and Ca²⁺-ATPase contribute. In the adult, calcium absorption rate is approximately 30% under the ordinary condition. Lower calcium intake is associated with increased calcium absorption and decreased urinary excretion. In the Dietary Reference Intakes for Japanese, calcium requirement is determined based on factorial method. Recommended Dietary Allowance(RDA)for calcium ranges from 600-800 mg/day for adult. However, the average calcium intake is far lower than Estimated Average Requirement(EAR). Thus, an effort to increase the calcium intake, rather than considering the detailed calcium absorption rate, is most essential in Japan. PMID:26503863

  14. Perception of acoustic transients

    NASA Astrophysics Data System (ADS)

    Howard, J. H., Jr.

    1984-01-01

    The research investigates the role of knowledge based or top-down processing in the perception of nonlinguistic, transient signals. The experiments address issues in transient pattern classification, target observation, attentional focusing, auditory induction, and computer based performance aids. The theoretical significance and naval relevance of the research is considered.

  15. Mitochondria: the calcium connection.

    PubMed

    Contreras, Laura; Drago, Ilaria; Zampese, Enrico; Pozzan, Tullio

    2010-01-01

    Calcium handling by mitochondria is a key feature in cell life. It is involved in energy production for cell activity, in buffering and shaping cytosolic calcium rises and also in determining cell fate by triggering or preventing apoptosis. Both mitochondria and the mechanisms involved in the control of calcium homeostasis have been extensively studied, but they still provide researchers with long-standing or even new challenges. Technical improvements in the tools employed for the investigation of calcium dynamics have been-and are still-opening new perspectives in this field, and more prominently for mitochondria. In this review we present a state-of-the-art toolkit for calcium measurements, with major emphasis on the advantages of genetically encoded indicators. These indicators can be efficiently and selectively targeted to specific cellular sub-compartments, allowing previously unavailable high-definition calcium dynamic studies. We also summarize the main features of cellular and, in more detail, mitochondrial calcium handling, especially focusing on the latest breakthroughs in the field, such as the recent direct characterization of the calcium microdomains that occur on the mitochondrial surface upon cellular stimulation. Additionally, we provide a major example of the key role played by calcium in patho-physiology by briefly describing the extensively reported-albeit highly controversial-alterations of calcium homeostasis in Alzheimer's disease, casting lights on the possible alterations in mitochondrial calcium handling in this pathology.

  16. A Novel Calcium Binding Site in the Slow Vacuolar Cation Channel TPC1 Senses Luminal Calcium Levels[W

    PubMed Central

    Dadacz-Narloch, Beata; Beyhl, Diana; Larisch, Christina; López-Sanjurjo, Enrique J.; Reski, Ralf; Kuchitsu, Kazuyuki; Müller, Thomas D.; Becker, Dirk; Schönknecht, Gerald; Hedrich, Rainer

    2011-01-01

    Cytosolic calcium homeostasis is pivotal for intracellular signaling and requires sensing of calcium concentrations in the cytosol and accessible stores. Numerous Ca2+ binding sites have been characterized in cytosolic proteins. However, little is known about Ca2+ binding inside organelles, like the vacuole. The slow vacuolar (SV) channel, encoded by Arabidopsis thaliana TPC1, is regulated by luminal Ca2+. However, the D454/fou2 mutation in TPC1 eliminates vacuolar calcium sensitivity and increases store calcium content. In a search for the luminal calcium binding site, structure modeling indicated a possible coordination site formed by residues Glu-450, Asp-454, Glu-456, and Glu-457 on the luminal side of TPC1. Each Glu residue was replaced by Gln, the modified genes were transiently expressed in loss-of-TPC1-function protoplasts, and SV channel responses to luminal calcium were recorded by patch clamp. SV channels lacking any of the four negatively charged residues appeared altered in calcium sensitivity of channel gating. Our results indicate that Glu-450 and Asp-454 are directly involved in Ca2+ binding, whereas Glu-456 and Glu-457 are probably involved in connecting the luminal Ca2+ binding site to the channel gate. This novel vacuolar calcium binding site represents a potential tool to address calcium storage in plants. PMID:21764990

  17. The yin and yang of calcium effects on synaptic vesicle endocytosis.

    PubMed

    Wu, Xin-Sheng; Wu, Ling-Gang

    2014-02-12

    A large number of studies suggest that calcium triggers and accelerates vesicle endocytosis at many synapses and non-neuronal secretory cells. However, many studies show that prolonging the duration of the stimulation train, which induces more calcium influx, slows down endocytosis; and several studies suggest that instead of triggering endocytosis, calcium actually inhibits endocytosis. Here we addressed this apparent conflict at a large nerve terminal, the calyx of Held in rat brainstem, in which recent studies suggest that transient calcium increase up to tens of micromolar concentration at the micro/nano domain triggers endocytosis. By dialyzing 0-1 μM calcium into the calyx via a whole-cell pipette, we found that slow endocytosis was inhibited by calcium dialysis in a concentration-dependent manner. Thus, prolonged, small, and global calcium increase inhibits endocytosis, whereas transient and large calcium increase at the micro/nano domain triggers endocytosis and facilitates endocytosis. This yin and yang effect of calcium may reconcile apparent conflicts regarding whether calcium accelerates or inhibits endocytosis. Whether endocytosis is fast or slow depends on the net outcome between the yin and yang effect of calcium.

  18. Nonlinear femtosecond pump-probe spectroscopy using a power-encoded soliton delay line.

    PubMed

    Saint-Jalm, Sarah; Andresen, Esben Ravn; Bendahmane, Abdelkrim; Kudlinski, Alexandre; Rigneault, Hervé

    2016-01-01

    We show femtosecond time-resolved nonlinear pump-probe spectroscopy using a fiber soliton as the probe pulse. Furthermore, we exploit soliton dynamics to record an entire transient trace with a power-encoded delay sweep. The power-encoded delay line takes advantage of the dependency of the soliton trajectory in the (λ,z) space upon input power; the difference in accumulated group delay between trajectories converts a fast power sweep into a fast delay sweep. We demonstrate the concept by performing transient absorption spectroscopy in a test sample and validate it against a conventional pump-probe setup.

  19. Inhibitors of calcium buffering depress evoked transmitter release at the squid giant synapse.

    PubMed Central

    Adams, D J; Takeda, K; Umbach, J A

    1985-01-01

    Evoked release of transmitter at the squid giant synapse was examined under conditions where the calcium ion concentration in the presynaptic terminal was manipulated by inhibitors of calcium sequestration. Simultaneous intracellular recordings of presynaptic and post-synaptic resting and action potentials were made during bath application of one of the following metabolic inhibitors: sodium cyanide (NaCN), carbonyl cyanide-p-trifluoromethoxyphenyl hydrazone (FCCP); ruthenium red (RuR) and sodium-free (lithium) sea water. Cyanide and lithium sea water reversibly depressed the post-synaptic potential (p.s.p.) whilst RuR and FCCP blocked the evoked post-synaptic response irreversibly. The progressive reduction of p.s.p. amplitude was accompanied by a reversible increase in synaptic delay. The time course of block of the p.s.p. was similar for different agents and dependent on the rate of presynaptic activity (30-40 min at 0.01 Hz). Recovery of the post-synaptic action potential following block by cyanide and lithium sea water was obtained within 40 min and 5 min respectively. Synaptic depression by the metabolic inhibitors does not result from changes in presynaptic resting or action potentials, nor from a change in post-synaptic receptor sensitivity. The post-synaptic response to the local ionophoresis of L-glutamate was unchanged following inhibition of evoked release of transmitter by cyanide. Injections of EGTA into presynaptic terminals poisoned by cyanide produced transient increases in p.s.p. amplitude, suggesting that cyanide is having its effect through raising intracellular calcium rather than lowering ATP. Control experiments injecting EGTA into unpoisoned nerve terminals showed no apparent effect on evoked transmitter release. PMID:2419546

  20. Recommendations for the Avoidance of Delayed-Onset Muscle Soreness.

    ERIC Educational Resources Information Center

    Szymanski, David J.

    2001-01-01

    Describes the possible causes of delayed-onset muscle soreness (DOMS), which include buildup of lactic acid in muscle, increased intracellular calcium concentration, increased intramuscular inflammation, and muscle fiber and connective tissue damage. Proposed methods to reduce DOMS include warming up before exercise and performing repeated bouts…

  1. Smoking, calcium, calcium antagonists, and aging.

    PubMed

    Nicita-Mauro, V

    1990-01-01

    Aging is characterized, besides other changes, by a progressive increase in calcium content in the arterial wall, which is enhanced by diabetes mellitus, osteoporosis, arterial hypertension, and tabagism. As to tabagism, experiments in animals have shown that nicotine can increase calcium content of the arterial wall, and clinical studies have demonstrated that cigarette smoking induces peripheral vasoconstriction, with consequent increase in blood pressure levels. In order to study the role of calcium ions in the pathogenesis of the vasoconstrictive lesions caused by "acute" smoking, the author has studied the peripheral vascular effects of the calcium-channel antagonist nifedipine, a dihydropyridine derivative, and calcitonin, a hypocalcemizing hormone which possess vasoactive actions on 12 elderly regular smokers (mean age 65.8 years). The results demonstrated that both nifedipine (10 mg sublingually 20 min before smoking) and salmon calcitonin (100 MRC U/daily intramuscularly for three days) are able to prevent peripheral vasoconstriction evaluated by Doppler velocimetry, as well as the increase of blood pressure induced by smoking. On the basis of our results, the author proposes that cigarette smoking-induced vasoconstriction is a calcium-mediated process, which can be hindered by drugs with calcium antagonist action. PMID:2226675

  2. Functional Calcium Imaging in Developing Cortical Networks

    PubMed Central

    Dawitz, Julia; Kroon, Tim; Hjorth, J.J. Johannes; Meredith, Rhiannon M.

    2011-01-01

    , synaptogenesis and plasticity (Rakic & Komuro, 1995; Spitzer et al., 2004) are of critical importance for the correct development and maturation of the cortical circuitry. In this JoVE video, we demonstrate the methods used to image spontaneous activity in developing cortical networks. Calcium-sensitive indicators, such as Fura 2-AM ester diffuse across the cell membrane where intracellular esterase activity cleaves the AM esters to leave the cell-impermeant form of indicator dye. The impermeant form of indicator has carboxylic acid groups which are able to then detect and bind calcium ions intracellularly.. The fluorescence of the calcium-sensitive dye is transiently altered upon binding to calcium. Single or multi-photon imaging techniques are used to measure the change in photons being emitted from the dye, and thus indicate an alteration in intracellular calcium. Furthermore, these calcium-dependent indicators can be combined with other fluorescent markers to investigate cell types within the active network. PMID:22041662

  3. High-energy transients.

    PubMed

    Gehrels, Neil; Cannizzo, John K

    2013-06-13

    We present an overview of high-energy transients in astrophysics, highlighting important advances over the past 50 years. We begin with early discoveries of γ-ray transients, and then delve into physical details associated with a variety of phenomena. We discuss some of the unexpected transients found by Fermi and Swift, many of which are not easily classifiable or in some way challenge conventional wisdom. These objects are important insofar as they underscore the necessity of future, more detailed studies. PMID:23630376

  4. Transient nucleation in glasses

    NASA Technical Reports Server (NTRS)

    Kelton, K. F.

    1991-01-01

    Nucleation rates in condensed systems are frequently not at their steady state values. Such time dependent (or transient) nucleation is most clearly observed in devitrification studies of metallic and silicate glasses. The origin of transient nucleation and its role in the formation and stability of desired phases and microstructures are discussed. Numerical models of nucleation in isothermal and nonisothermal situations, based on the coupled differential equations describing cluster evolution within the classical theory, are presented. The importance of transient nucleation in glass formation and crystallization is discussed.

  5. [Transient epileptic amnesia].

    PubMed

    Muramatsu, Kazuhiro; Yoshizaki, Takahito

    2016-03-01

    Transient amnesia is one of common clinical phenomenon of epilepsy that are encountered by physicians. The amnestic attacks are often associated with persistent memory disturbances. Epilepsy is common among the elderly, with amnesia as a common symptom and convulsions relatively uncommon. Therefore, amnesia due to epilepsy can easily be misdiagnosed as dementia. The term 'transient epileptic amnesia (TEA)' was introduced in the early 1990s by Kapur, who highlighted that amnestic attacks caused by epilepsy can be similar to those occurring in 'transient global amnesia', but are distinguished by features brevity and recurrence. In 1998, Zeman et al. proposed diagnostic criteria for TEA.

  6. CGI delay compensation

    NASA Technical Reports Server (NTRS)

    Mcfarland, Richard E.

    1986-01-01

    Computer-generated graphics in real-time helicopter simulation produces objectionable scene-presentation time delays. In the flight simulation laboratory at Ames Research Center, it has been determined that these delays have an adverse influence on pilot performance during aggressive tasks such as nap-of-the-earth (NOE) maneuvers. Using contemporary equipment, computer-generated image (CGI) time delays are an unavoidable consequence of the operations required for scene generation. However, providing that magnitide distortions at higher frequencies are tolerable, delay compensation is possible over a restricted frequency range. This range, assumed to have an upper limit of perhaps 10 or 15 rad/sec, conforms approximately to the bandwidth associated with helicopter handling qualities research. A compensation algorithm is introduced here and evaluated in terms of tradeoffs in frequency responses. The algorithm has a discrete basis and accommodates both a large, constant transport delay interval and a periodic delay interval, as associated with asynchronous operations.

  7. Structure and functions of plant calcium-dependent protein kinases.

    PubMed

    Klimecka, Maria; Muszyńska, Grazyna

    2007-01-01

    Calcium ions as second messengers play an essential role in many important cellular processes. In plants, transient changes in calcium content in the cytosol (calcium signatures) have been observed during growth, development and under stress conditions. Such diverse functions require many different calcium sensors. One of the largest and most differentiated group of calcium sensors are protein kinases, among them calcium-dependent protein kinases (CDPKs) which were identified only in plants and protists. CDPKs have a regulatory domain which is able to bind calcium ions. For regulation of CDPKs activities not only calcium ions but also specific phospholipids and autophosphorylation are responsible. CDPKs have many different substrates, which reflects the diversity of their functions. Potential protein substrates of CDPK are involved in carbon and nitrogen metabolism, phospholipid synthesis, defense responses, ion and water transport, cytoskeleton organization, transcription and hormone responses. Presently, participation of CDPKs in stress signal transduction pathways (e.g., cold, drought, high salinity, wounding) is intensively studied in many laboratories. An intriguing, but still not fully clarified problem is the cross-talk via CDPKs among different signaling pathways that enables signal integration at different levels and ensure appropriate downstream responses.

  8. Gamma ray transients

    NASA Technical Reports Server (NTRS)

    Cline, Thomas L.

    1987-01-01

    The discovery of cosmic gamma ray bursts was made with systems designed at Los Alamos Laboratory for the detection of nuclear explosions beyond the atmosphere. HELIOS-2 was the first gamma ray burst instrument launched; its initial results in 1976, seemed to deepen the mystery around gamma ray transients. Interplanetary spacecraft data were reviewed in terms of explaining the behavior and source of the transients.

  9. VARIABLE TIME DELAY MEANS

    DOEpatents

    Clemensen, R.E.

    1959-11-01

    An electrically variable time delay line is described which may be readily controlled simuitaneously with variable impedance matching means coupied thereto such that reflections are prevented. Broadly, the delay line includes a signal winding about a magnetic core whose permeability is electrically variable. Inasmuch as the inductance of the line varies directly with the permeability, the time delay and characteristic impedance of the line both vary as the square root of the permeability. Consequently, impedance matching means may be varied similariy and simultaneously w:th the electrically variable permeability to match the line impedance over the entire range of time delay whereby reflections are prevented.

  10. Relationship between intracellular calcium and its muffling measured by calcium iontophoresis in snail neurones.

    PubMed Central

    Schwiening, C J; Thomas, R C

    1996-01-01

    1. We have measured intracellular free calcium ion concentration ([Ca2+]i) with fura-2, and intracellular chloride with chloride-sensitive microelectrodes, in voltage-clamped snail neurones. By making iontophoretic injections of CaCl2 we have investigated calcium muffling, the sum of the processes which minimize the calcium transient, at different values of [Ca2+]i. 2. By injection of calcium into cell-sized droplets of buffer we measured the calcium transport index. It was stable over the range pCa 6-7.4 (0.48 +/- 0.06 measured at pCa 6.70 +/- 0.12, n = 5). 3. Measurement of intracellular chloride activity during a series of fura-2-KCl pressure injections revealed a nearly linear relationship between fura-2 Ca(2+)-insensitive fluorescence and the sum of the increments in intracellular chloride. This allowed us to calculate the intracellular fura-2 concentration ([fura-2]i). 4. The rate of recovery of [Ca2+]i following a depolarization-induced load was increased by low [fura-2]i (10-20 microM) but decreased by higher [fura-2]i (40-80 microM). These effects are consistent with the addition of a mobile buffer to the cytoplasm. 5. Iontophoresis of Ca2+ at various membrane potentials allowed us to calculate the intracellular calcium muffling power (the amount of calcium required to cause a transient tenfold increase in [Ca2+]i per unit volume) and calcium muffling ratio (number of Ca2+ ions injected divided by the maximum increase in [Ca2+]i per unit volume) at different values of [Ca2+]i. 6. Calcium muffling power at resting [Ca2+]i was approximately 40 microM Ca2+ (pCa unit)-1, (about 250 times less than for hydrogen ions). It increased linearly about fivefold with [Ca2+]i over the range 20-120 nM (10 cells, 153 measurements) and therefore exponentially with decreasing pCa. 7. The calcium muffling ratio appeared to be constant (361 +/- 14, n = 10 cells, 130 measurements) over the range 20-120 nM Ca2+. 8. In three experiments we modelled the additional calcium

  11. Localised calcium release events in cells from the muscle of guinea-pig gastric fundus

    PubMed Central

    Parsons, S P; Bolton, T B

    2004-01-01

    After enzymatic dispersion of the muscle of the guinea-pig gastric fundus, single elongated cells were observed which differed from archetypal smooth muscle cells due to their knurled, tuberose or otherwise irregular surface morphology. These, but not archetypal smooth muscle cells, consistently displayed spontaneous localized (i.e. non-propagating) intracellular calcium ([Ca2+]i) release events. Such calcium events were novel in their magnitude and kinetic profiles. They included short transient events, plateau events and events which coalesced spatially or temporally (compound events). Quantitative analysis of the events with an automatic detection programme showed that their spatio-temporal characteristics (full width and full duration at half-maximum amplitude) were approximately exponentially distributed. Their amplitude distribution suggested the presence of two release modes. Carbachol application caused an initial cell-wide calcium transient followed by an increase in localized calcium release events. Pharmacological analysis suggested that localized calcium release was largely dependent on external calcium entry acting on both inositol trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) to release stored calcium. Nominally calcium-free external solution immediately and reversibly abolished all localized calcium release without blocking the initial transient calcium release response to carbachol. This was inhibited by 2-APB (100 μm), ryanodine (10 or 50 μm) or U-73122 (1 μm). 2-APB (100 μm), xestospongin C (XeC, 10 μm) or U-73122 (1 μm) blocked both spontaneous localized calcium release and localized release stimulated by 10 μm carbachol. Ryanodine (50 μm) also inhibited spontaneous release, but enhanced localized release in response to carbachol. This study represents the first characterization of localized calcium release events in cells from the gastric fundus. PMID:14608011

  12. Synaptic plasticity and calcium signaling in Purkinje cells of the central cerebellar lobes of mormyrid fish.

    PubMed

    Han, Victor Z; Zhang, Yueping; Bell, Curtis C; Hansel, Christian

    2007-12-01

    Climbing fiber (CF)-evoked calcium transients play a key role in plasticity at parallel fiber (PF) to Purkinje cell synapses in the mammalian cerebellum. Whereas PF activation alone causes long-term potentiation (LTP), coactivation of the heterosynaptic CF input, which evokes large dendritic calcium transients, induces long-term depression (LTD). This unique type of heterosynaptic interaction is a hallmark feature of synaptic plasticity in mammalian Purkinje cells. Purkinje cells in the cerebellum of mormyrid electric fish are characterized by a different architecture of their dendritic trees and by a more pronounced separation of CF and PF synaptic contact sites. We therefore examined the conditions for bidirectional plasticity at PF synapses onto Purkinje cells in the mormyrid cerebellum in vitro. PF stimulation at elevated frequencies induces LTP, whereas LTD results from PF stimulation at enhanced intensities and depends on dendritic calcium influx and metabotropic glutamate receptor type 1 activation. LTD can also be observed after pairing of low intensity PF stimulation with CF stimulation. Using a combination of whole-cell patch-clamp recordings and fluorometric calcium imaging, we characterized calcium transients in Purkinje cell dendrites. CF activation elicits calcium transients not only within the CF input territory (smooth proximal dendrites) but also within the PF input territory (spiny palisade dendrites). Paired PF and CF activation elicits larger calcium transients than stimulation of either input alone. A major source for dendritic calcium signaling is provided by P/Q-type calcium channels. Our data show that despite the spatial separation between the two inputs CF activity facilitates LTD induction at PF synapses.

  13. Digital time delay

    DOEpatents

    Martin, A.D.

    1986-05-09

    Method and apparatus are provided for generating an output pulse following a trigger pulse at a time delay interval preset with a resolution which is high relative to a low resolution available from supplied clock pulses. A first lumped constant delay provides a first output signal at predetermined interpolation intervals corresponding to the desired high resolution time interval. Latching circuits latch the high resolution data to form a first synchronizing data set. A selected time interval has been preset to internal counters and corrected for circuit propagation delay times having the same order of magnitude as the desired high resolution. Internal system clock pulses count down the counters to generate an internal pulse delayed by an internal which is functionally related to the preset time interval. A second LCD corrects the internal signal with the high resolution time delay. A second internal pulse is then applied to a third LCD to generate a second set of synchronizing data which is complementary with the first set of synchronizing data for presentation to logic circuits. The logic circuits further delay the internal output signal with the internal pulses. The final delayed output signal thereafter enables the output pulse generator to produce the desired output pulse at the preset time delay interval following input of the trigger pulse.

  14. Calcium hydroxyapatite fillers.

    PubMed

    Tansavatdi, Kristina; Mangat, Devinder S

    2011-12-01

    Calcium hydroxyapatite fillers have unique advantages over other fillers in regards to duration of action and volume of product required for augmentation, especially in the midface and lower face. In this article, we describe our experience with calcium hydroxyapatite fillers and compare them with other available filler products.

  15. Steroid hormone 20-hydroxyecdysone promotes higher calcium mobilization to induce apoptosis.

    PubMed

    Wang, Di; Pei, Xu-Yang; Zhao, Wen-Li; Zhao, Xiao-Fan

    2016-07-01

    Calcium ions are essential secondary messengers that regulate diverse cellular processes including gene transcription, cell proliferation, and apoptosis. The steroid hormone 20-hydroxyecdysone (20E) promotes programmed cell death during insect metamorphosis, whereas juvenile hormone (JH) counteracts 20E activity to prevent metamorphosis. Both 20E and JH can induce cellular calcium increase; however, the mechanisms and physiological consequences resulting from calcium increase caused by the two counteracting hormones are unclear. Here, using Helicoverpa armigera epidermal cell line, we show that 20E via a G-protein-coupled receptor induced a major calcium rise in the cells, whereas JH via receptor tyrosine kinase induced a minor calcium increase. The calcium release-activated calcium modulator 1 (Orai1) and transient receptor potential (TRP) channels were necessary for 20E-induced rapid calcium influx. A higher calcium level was maintained in a long time and more genes including Orai1 and TRP channels showed elevated expression after the treatment of 20E than did after JH treatment. Caspase3/7 activation, cell death and pro-apoptotic gene expression were elicited by 20E induction, but not by JH. JH could repress 20E-induced calcium influx, caspase3/7 activation and gene expression. Higher calcium levels induced apoptosis. These results suggest that 20E and JH via different pathways regulate calcium mobilization and homeostasis at different levels, thus inform different gene expression and cellular responses. PMID:27209368

  16. Calcium-dependent regulation of photosynthesis.

    PubMed

    Hochmal, Ana Karina; Schulze, Stefan; Trompelt, Kerstin; Hippler, Michael

    2015-09-01

    The understanding of calcium as a second messenger in plants has been growing intensively over the last decades. Recently, attention has been drawn to the organelles, especially the chloroplast but focused on the stromal Ca2+ transients in response to environmental stresses. Herein we will expand this view and discuss the role of Ca2+ in photosynthesis. Moreover we address of how Ca2+ is delivered to chloroplast stroma and thylakoids. Thereby, new light is shed on the regulation of photosynthetic electron flow and light-dependent metabolism by the interplay of Ca2+, thylakoid acidification and redox status. This article is part of a Special Issue entitled: Chloroplast biogenesis.

  17. The LOFAR Transients Pipeline

    NASA Astrophysics Data System (ADS)

    Swinbank, John D.; Staley, Tim D.; Molenaar, Gijs J.; Rol, Evert; Rowlinson, Antonia; Scheers, Bart; Spreeuw, Hanno; Bell, Martin E.; Broderick, Jess W.; Carbone, Dario; Garsden, Hugh; van der Horst, Alexander J.; Law, Casey J.; Wise, Michael; Breton, Rene P.; Cendes, Yvette; Corbel, Stéphane; Eislöffel, Jochen; Falcke, Heino; Fender, Rob; Grießmeier, Jean-Mathias; Hessels, Jason W. T.; Stappers, Benjamin W.; Stewart, Adam J.; Wijers, Ralph A. M. J.; Wijnands, Rudy; Zarka, Philippe

    2015-06-01

    Current and future astronomical survey facilities provide a remarkably rich opportunity for transient astronomy, combining unprecedented fields of view with high sensitivity and the ability to access previously unexplored wavelength regimes. This is particularly true of LOFAR, a recently-commissioned, low-frequency radio interferometer, based in the Netherlands and with stations across Europe. The identification of and response to transients is one of LOFAR's key science goals. However, the large data volumes which LOFAR produces, combined with the scientific requirement for rapid response, make automation essential. To support this, we have developed the LOFAR Transients Pipeline, or TraP. The TraP ingests multi-frequency image data from LOFAR or other instruments and searches it for transients and variables, providing automatic alerts of significant detections and populating a lightcurve database for further analysis by astronomers. Here, we discuss the scientific goals of the TraP and how it has been designed to meet them. We describe its implementation, including both the algorithms adopted to maximize performance as well as the development methodology used to ensure it is robust and reliable, particularly in the presence of artefacts typical of radio astronomy imaging. Finally, we report on a series of tests of the pipeline carried out using simulated LOFAR observations with a known population of transients.

  18. Voltage transients elicited by sudden step-up of auxin

    NASA Technical Reports Server (NTRS)

    Pickard, B. G.

    1984-01-01

    It is hypothesized (i) that the molecular mechanism for the reception of friction and flexure and the mechanism by which auxin enhances ethylene production have in common a release of free calcium into the cytosol, (ii) that elevated cytosolic calcium initiates vesicle exocytosis, and (iii) that the vesicles release a factor or set of factors which depolarizes the plasmalemma and promotes ethylene synthesis. One consequence of such exocytosis should be small, extracellularly observable voltage transients. Transients, ranging in size up to 600 microvolts and possessing risetimes (10-90%) of approximately 200 ms, are known to be elicited in etiolated stems of Pisum sativum L. by friction and are here shown to be elicited by sudden increase of auxin concentration and also by a Ca2+ ionophore.

  19. Calcium signaling and endoplasmic reticulum dynamics during fertilization in marine protostome worms belonging to the phylum Nemertea.

    PubMed

    Stricker, Stephen A

    2014-08-01

    Metaphase-I-arrested eggs of marine protostome worms in the phylum Nemertea generate a series of point-source calcium waves during fertilization. Such calcium oscillations depend on inositol-1,4,5-trisphosphate-mediated calcium release from endoplasmic reticulum (ER) stores that undergo structural reorganizations prior to and after fertilization. This article reviews fertilization-induced calcium transients and ER dynamics in nemertean eggs and compares these topics to what has been reported for other animals in order to identify unifying characteristics and distinguishing features of calcium responses during fertilization across the animal kingdom.

  20. Mobilization of hepatic calcium pools by platelet activating factor

    SciTech Connect

    Lapointe, D.S.; Hanahan, D.J.; Olson, M.S.

    1987-03-24

    In the perfused rat liver, platelet activating factor, 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC), infusion produces an extensive but transient glycogenolytic response which at low AGEPC concentrations is markedly dependent upon the perfusate calcium levels. The role of calcium in the glycogenolytic response of the liver to AGEPC was investigated by assessing the effect of AGEPC on various calcium pools in the intact liver. Livers from fed rats were equilibrated with /sup 45/Ca/sup 2 +/, and the kinetics of /sup 45/Ca/sup 2 +/ efflux were determined in control, AGEPC-stimulated, and phenylephrine-stimulated livers during steady-state washout of /sup 45/Ca/sup 2 +/. AGEPC treatment had only a slight if any effect on the pattern of steady-state calcium efflux from the liver, as opposed to major perturbations in the pattern of calcium efflux effected by the ..cap alpha..-adrenergic agonist phenylephrine. Infusion of short pulses of AGEPC during the washout of /sup 45/Ca/sup 2 +/ from labeled livers caused a transient release of /sup 45/Ca/sup 2 +/ which was not abolished at low calcium concentrations in the perfusate. Infusion of latex beads, which are removed by the reticuloendothelial cells, caused the release of hepatic /sup 45/Ca/sup 2 +/ in a fashion similar to the case with AGEPC. The findings indicate that AGEPC does not perturb a major pool of calcium within the liver as occurs upon ..cap alpha..-adrenergic stimulation; it is likely that AGEPC mobilizes calcium from a smaller yet very important pool, very possibly from nonparenchymal cells in the liver.

  1. Effects of calcium entry blockers on calcium-dependent contractions of rat portal vein.

    PubMed Central

    Dacquet, C.; Mironneau, C.; Mironneau, J.

    1987-01-01

    1 The effects of six calcium entry blockers belonging to the dihydropyridine (isradipine or PN 200-110, nifedipine, nicardipine), verapamil (D888 or desmethoxyverapamil, D600 or gallopamil) and diltiazem classes were investigated on isometric spontaneous contractions and contractions induced by high-K+ solutions, noradrenaline, acetylcholine and caffeine. 2 The rank order of potency was PN 200-110 greater than nicardipine = nifedipine = D888 greater than D600 greater than diltiazem from experiments on spontaneous contractions and high-K+ induced contractions. With depolarized preparations, the concentration-response curves for nicardipine, PN 200-110, nifedipine and D600 were significantly shifted to the left indicating that the calcium entry blockers show voltage-dependent inhibitory properties. This effect was not significant with D888 and diltiazem. 3 All the calcium entry blockers strongly reduced the noradrenaline (NA)- and acetylcholine (ACh)-induced contractions at concentrations which produced complete inhibition of spontaneous contractions. They had a slight effect on caffeine-induced contractions. 4 In Ca2+-free, EGTA-containing solutions, both ACh, NA and caffeine produced transient contractions, the amplitude of which could be taken as a measurement of the amount of internal calcium present in a drug-sensitive calcium store. The filling of the calcium store was maximal after 10-12 min of calcium loading in 2.1 mM Ca2+, while the depletion was complete after 4-6 min of perfusion in Ca2+-free solution. 5 At concentrations which abolished spontaneous contractions, PN 200-110, nifedipine, D888 and D600 had no appreciable effect on contractions evoked in Ca2+-free solutions by ACh, NA and caffeine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2959345

  2. Calibration of acoustic transients.

    PubMed

    Burkard, Robert

    2006-05-26

    This article reviews the appropriate stimulus parameters (click duration, toneburst envelope) that should be used when eliciting auditory brainstem responses from mice. Equipment specifications required to calibrate these acoustic transients are discussed. Several methods of calibrating the level of acoustic transients are presented, including the measurement of peak equivalent sound pressure level (peSPL) and peak sound pressure level (pSPL). It is hoped that those who collect auditory brainstem response thresholds in mice will begin to use standardized methods of acoustic calibration, so that hearing thresholds across mouse strains obtained in different laboratories can more readily be compared.

  3. The Transient Universe

    NASA Astrophysics Data System (ADS)

    Shappee, Benjamin John

    When one looks at the night sky, one usually gets the impression of a static and constant universe. Quite apart from appearances, the sky is teeming with violent, variable, and transient events that shape our universe. These capricious objects are not only penetrating probes into physical conditions too extreme for earthbound laboratories, but they are also useful tools to measure the universe. In this dissertation, I investigate the observational and theoretical properties of three classes of transient/variable objects: thermonuclear supernovae, Cepheid variable stars, and active galactic nuclei.

  4. Visualization of Calcium Dynamics in Kidney Proximal Tubules.

    PubMed

    Szebényi, Kornélia; Füredi, András; Kolacsek, Orsolya; Csohány, Rózsa; Prókai, Ágnes; Kis-Petik, Katalin; Szabó, Attila; Bősze, Zsuzsanna; Bender, Balázs; Tóvári, József; Enyedi, Ágnes; Orbán, Tamás I; Apáti, Ágota; Sarkadi, Balázs

    2015-11-01

    Intrarenal changes in cytoplasmic calcium levels have a key role in determining pathologic and pharmacologic responses in major kidney diseases. However, cell-specific delivery of calcium-sensitive probes in vivo remains problematic. We generated a transgenic rat stably expressing the green fluorescent protein-calmodulin-based genetically encoded calcium indicator (GCaMP2) predominantly in the kidney proximal tubules. The transposon-based method used allowed the generation of homozygous transgenic rats containing one copy of the transgene per allele with a defined insertion pattern, without genetic or phenotypic alterations. We applied in vitro confocal and in vivo two-photon microscopy to examine basal calcium levels and ligand- and drug-induced alterations in these levels in proximal tubular epithelial cells. Notably, renal ischemia induced a transient increase in cellular calcium, and reperfusion resulted in a secondary calcium load, which was significantly decreased by systemic administration of specific blockers of the angiotensin receptor and the Na-Ca exchanger. The parallel examination of in vivo cellular calcium dynamics and renal circulation by fluorescent probes opens new possibilities for physiologic and pharmacologic investigations.

  5. Chondrocyte death in mechanically injured articular cartilage--the influence of extracellular calcium.

    PubMed

    Amin, Anish K; Huntley, James S; Bush, Peter G; Simpson, A Hamish R W; Hall, Andrew C

    2009-06-01

    Calcium is thought to be an important regulator of chondrocyte death associated with articular cartilage injury. Our objective was to determine the influence of extracellular calcium on chondrocyte death following mechanical injury. Using a surgically relevant model of sharp mechanical injury (with a scalpel) and confocal laser scanning microscopy (CLSM), in situ chondrocyte death was quantified within the full thickness of articular cartilage as a function of medium calcium concentration and time (2.5 h and 7 days). Exposure of articular cartilage to calcium-free media (approximately 0 mM) significantly reduced superficial zone chondrocyte death after mechanical injury compared with exposure to calcium-rich media (2-20 mM, ANOVA at 2.5 h, p = 0.002). In calcium-rich media, although the extent of chondrocyte death increased with increasing medium calcium concentration, cell death remained localized to the superficial zone of articular cartilage over 7 days (ANOVA, p < 0.05). However, in calcium-free media, there was an increase in chondrocyte death within deeper zones of articular cartilage over 7 days. The early (within hours) chondroprotective effect in calcium-free media suggests that the use of joint irrigation solutions without added calcium may decrease chondrocyte death from mechanical injury during articular surgery. The delayed (within days) increase in chondrocyte death in calcium-free media supports the use of calcium supplementation in media used during cartilage culture for tissue engineering or transplantation.

  6. [Calcium and health].

    PubMed

    Ortega Anta, Rosa M; Jiménez Ortega, Ana I; López-Sobaler, Ana M

    2015-04-07

    An adequate intake of calcium is only not limited to avoid the risk of osteoporosis and its benefits in longterm bone health, but also it has been linked to protection against various major diseases, such as hypertension, cancer, kidney stones, insulin resistance, diabetes... and several investigations suggest its importance in preventing and controlling obesity. Studies conducted in Spanish representative samples show that a high percentage of adults and children (> 75%) don't achieve the recommended intake of calcium. Moreover, are growing trends among the population suggesting that calcium intake and dairy consumption (main food source of the mineral) are high, and even excessive, in many individuals. This misconception results in that the calcium intake is increasingly far from the recommended one. The maximum tolerable intake of the mineral is fixed at 2.500 mg/day, but this intake is unusual, and it's more disturbing and frequent, to find intakes below the recommended calcium intakes (1.000 and 1.200 mg/day in adults, men and women, respectively). Data from different studies highlight the risk of an inadequate calcium intake and the damages that may affect the health in a long term. It is not about transmitting indiscriminate guidelines in order to increase the intake of calcium / dairy, but the recommended intakes must be met to achieve both the nutritional and health benefits. Also activities for demystification of misconceptions are need, increasingly frequent, that may impair health population.

  7. A theoretical model of cytosolic calcium elevation following wounding in urothelial cell monolayers

    NASA Astrophysics Data System (ADS)

    Appleby, Peter A.; Shabir, Saqib; Southgate, Jennifer; Walker, Dawn

    2013-02-01

    Scratch wounding of a urothelial cell monolayer triggers a number of events including the release of soluble, diffusible signalling factors and mechanical stimulation of cells at the wound edge. These events cause a sustained elevation in cytosolic calcium concentration in the cells surrounding the wound and a transient rise in those further away. The precise form of this calcium transient is believed to play a central role in determining the subsequent response of individual cells and ultimately leads to a co-ordinated, population-level response that rapidly closes the wound. Here we present a framework for modelling the initial phases of this process. We combine a PDE model of diffusion in the extracellular medium and an ODE model of calcium signalling that has been tailored to represent urothelial cells. The ODE model is capable of generating a wide range of calcium transients, including spikes, bursts, oscillations and sustained elevations in the cytosolic calcium concentration. In multi-cell simulations of scratch wounding in a perfusion flow we find that the spatial position of the cells relative to the wound site leads to distinct classes of calcium response, with cells proximal to the wound exhibiting a sustained elevation and cells distal to the wound exhibiting a more transient elevation. We compare these results to existing experimental data and generate a number of novel predictions that could be used to test the model experimentally.

  8. CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING ON LEFT, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    CALCIUM CHLORIDE PLANT LOOKING EAST. CALCIUM CHLORIDE BUILDING ON LEFT, CALCIUM CHLORIDE STORAGE BUILDING ON RIGHT OF CENTER WITH TOP OF SA (SODA ASH) BUILDING IN RIGHT BACKGROUND. - Solvay Process Company, Calcium Chloride Plant, Between Willis & Milton Avenues, Solvay, Onondaga County, NY

  9. 21 CFR 184.1191 - Calcium carbonate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... soda process”; (2) By precipitation of calcium carbonate from calcium hydroxide in the “Carbonation process”; or (3) By precipitation of calcium carbonate from calcium chloride in the “Calcium...

  10. 21 CFR 184.1191 - Calcium carbonate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... soda process”; (2) By precipitation of calcium carbonate from calcium hydroxide in the “Carbonation process”; or (3) By precipitation of calcium carbonate from calcium chloride in the “Calcium...

  11. 21 CFR 184.1191 - Calcium carbonate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... soda process”; (2) By precipitation of calcium carbonate from calcium hydroxide in the “Carbonation process”; or (3) By precipitation of calcium carbonate from calcium chloride in the “Calcium...

  12. 21 CFR 184.1191 - Calcium carbonate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... soda process”; (2) By precipitation of calcium carbonate from calcium hydroxide in the “Carbonation process”; or (3) By precipitation of calcium carbonate from calcium chloride in the “Calcium...

  13. Delayed emergence after anesthesia.

    PubMed

    Tzabazis, Alexander; Miller, Christopher; Dobrow, Marc F; Zheng, Karl; Brock-Utne, John G

    2015-06-01

    In most instances, delayed emergence from anesthesia is attributed to residual anesthetic or analgesic medications. However, delayed emergence can be secondary to unusual causes and present diagnostic dilemmas. Data from clinical studies is scarce and most available published material is comprised of case reports. In this review, we summarize and discuss less common and difficult to diagnose reasons for delayed emergence and present cases from our own experience or reference published case reports/case series. The goal is to draw attention to less common reasons for delayed emergence, identify patient populations that are potentially at risk and to help anesthesiologists identifying a possible cause why their patient is slow to wake up. PMID:25912729

  14. Time delay spectrum conditioner

    DOEpatents

    Greiner, Norman R.

    1980-01-01

    A device for delaying specified frequencies of a multiple frequency laser beam. The device separates the multiple frequency beam into a series of spatially separated single frequency beams. The propagation distance of the single frequency beam is subsequently altered to provide the desired delay for each specific frequency. Focusing reflectors can be utilized to provide a simple but nonadjustable system or, flat reflectors with collimating and focusing optics can be utilized to provide an adjustable system.

  15. Swept group delay measurement

    NASA Technical Reports Server (NTRS)

    Trowbridge, D. L. (Inventor)

    1978-01-01

    Direct recording of group delay measurements on a system under temperature and stress tests employs modulated carrier frequency sweep over an S or X band. Reference path and test paths to separate detectors utilize a power divider e.g., a directional coupler or a hybrid T junction. An initially balanced phase comparator is swept in frequency by modulated carrier over the band of interest for different conditions of temperature and/or mechanical stress to obtain characteristic group delay curves.

  16. Myoscape controls cardiac calcium cycling and contractility via regulation of L-type calcium channel surface expression.

    PubMed

    Eden, Matthias; Meder, Benjamin; Völkers, Mirko; Poomvanicha, Montatip; Domes, Katrin; Branchereau, M; Marck, P; Will, Rainer; Bernt, Alexander; Rangrez, Ashraf; Busch, Matthias; Hrabě de Angelis, Martin; Heymes, Christophe; Rottbauer, Wolfgang; Most, Patrick; Hofmann, Franz; Frey, Norbert

    2016-01-01

    Calcium signalling plays a critical role in the pathogenesis of heart failure. Here we describe a cardiac protein named Myoscape/FAM40B/STRIP2, which directly interacts with the L-type calcium channel. Knockdown of Myoscape in cardiomyocytes decreases calcium transients associated with smaller Ca(2+) amplitudes and a lower diastolic Ca(2+) content. Likewise, L-type calcium channel currents are significantly diminished on Myoscape ablation, and downregulation of Myoscape significantly reduces contractility of cardiomyocytes. Conversely, overexpression of Myoscape increases global Ca(2+) transients and enhances L-type Ca(2+) channel currents, and is sufficient to restore decreased currents in failing cardiomyocytes. In vivo, both Myoscape-depleted morphant zebrafish and Myoscape knockout (KO) mice display impairment of cardiac function progressing to advanced heart failure. Mechanistically, Myoscape-deficient mice show reduced L-type Ca(2+)currents, cell capacity and calcium current densities as a result of diminished LTCC surface expression. Finally, Myoscape expression is reduced in hearts from patients suffering of terminal heart failure, implying a role in human disease. PMID:27122098

  17. Delayed voice communication

    NASA Astrophysics Data System (ADS)

    Love, Stanley G.; Reagan, Marcum L.

    2013-10-01

    We present results from simulated deep-space exploration missions that investigated voice communication with significant time delays. The simulations identified many challenges: confusion of sequence, blocked calls, wasted crew time, impaired ability to provide relevant information to the other party, losing track of which messages have reached the other party, weakened rapport between crew and ground, slow response to rapidly changing situations, and reduced situational awareness. These challenges were met in part with additional training; greater attention and foresight; longer, less frequent transmissions; meticulous recordkeeping and timekeeping; and specific alerting and acknowledging calls. Several simulations used both delayed voice and text messaging. Text messaging provided a valuable record of transmissions and allowed messages to be targeted to subsets of the flight and ground crew, but it was a poor choice for high-workload operators such as vehicle drivers and spacewalkers. Even with the foregoing countermeasures, delayed voice communication is difficult. Additional aids such as automatic delay timers and voice-to-text transcription would help. Tests comparing delays of 50 and 300 s unexpectedly revealed that communicating with the shorter delay was just as challenging as with the longer one.

  18. CREB modulates calcium signaling in cAMP-induced bone marrow stromal cells (BMSCs).

    PubMed

    Zhang, Linxia; Liu, Li; Thompson, Ryan; Chan, Christina

    2014-10-01

    Calcium signaling has a versatile role in many important cellular functions. Despite its importance, regulation of calcium signaling in bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) has not been explored extensively. Our previous study revealed that cyclic adenosine monophosphate (cAMP) enabled BMSCs to generate calcium signal upon stimulation by dopamine, KCl and glutamate. Concurrently, cAMP transiently activated the transcription factor cAMP response element binding protein (CREB) in BMSCs. Activity of CREB can be modulated by the calcium/calmodulin-dependent kinase signaling pathway, however, whether the calcium signaling observed in cAMP-induced BMSCs requires CREB has not been investigated. In an effort to uncover the role of CREB in the generation of calcium signaling in response to modulators such as dopamine and KCl, we knocked down CREB activity in BMSCs. Our study indicated that BMSCs, but not its close relative fibroblasts, are responsive to dopamine and KCl after cAMP treatment. Calcium signal elicited by dopamine depends, in part, on calcium influx whereas that elicited by KCl depends completely on calcium influx. Knock-down of CREB activity significantly reduced or abolished the cAMP-induced calcium response, and reintroducing a constitutively active CREB partially restored the calcium response.

  19. Acetylcholine and calcium on membrane permeability and contraction of intestinal smooth muscle.

    PubMed

    Hurwitz, L; Von Hagen, S; Joiner, P D

    1967-05-01

    Acetylcholine elicited a sustained contraction and an increase in potassium efflux in longitudinal muscle isolated from the guinea pig ileum. Stepwise increases in the calcium concentration of the bathing medium, from 0.06 to 36 mM generally reduced the increase in potassium efflux, but had a complex effect on the mechanical response. Contractions produced by high levels of acetylcholine became progressively larger or remained at a high magnitude as the calcium concentration was increased. Contractions produced by low levels of acetylcholine also improved initially, but were depressed again by the highest concentration of calcium introduced. Ethanol, in the appropriate concentration, inhibited completely the acetylcholine-induced contraction without reducing the increase in potassium efflux. Calcium reversed this effect. Both extracellular calcium and ethanol depressed the large, transient increase in muscle tone developed by fibers that were preincubated in a high calcium medium and then exposed to a calcium-free medium. These findings suggested that extracellular calcium ions react with two different sites in the membrane, a stabilizing site and a storage site. A muscle contraction is activated by calcium ions which diffuse from the storage site to the myoplasm. Calcium ions reacting with the stabilizing site impede this diffusion process. Part of the stimulatory effect of acetylcholine is derived from its capacity to counteract the action of calcium at the stabilizing site.

  20. CREB modulates calcium signaling in cAMP-induced bone marrow stromal cells (BMSCs)

    PubMed Central

    Zhang, Linxia; Liu, Li; Thompson, Ryan; Chan, Christina

    2014-01-01

    Calcium signaling has a versatile role in many important cellular functions. Despite its importance, regulation of calcium signaling in bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) has not been explored extensively. Our previous study revealed that cyclic adenosine monophosphate (cAMP) enabled BMSCs to generate calcium signal upon stimulation by dopamine, KCl and glutamate. Concurrently, cAMP transiently activated the transcription factor cAMP response element binding protein (CREB) in BMSCs. Activity of CREB can be modulated by the calcium/calmodulin-dependent kinase signaling pathway, however, whether the calcium signaling observed in cAMP-induced BMSCs requires CREB has not been investigated. In an effort to uncover the role of CREB in the generation of calcium signaling in response to modulators such as dopamine and KCl, we knocked down CREB activity in BMSCs. Our study indicated that BMSCs, but not its close relative fibroblasts, are responsive to dopamine and KCl after cAMP treatment. Calcium signal elicited by dopamine depends, in part, on calcium influx whereas that elicited by KCl depends completely on calcium influx. Knock-down of CREB activity significantly reduced or abolished the cAMP-induced calcium response, and reintroducing a constitutively active CREB partially restored the calcium response. PMID:25154887

  1. Calcium-activated conductance in skate electroreceptors: current clamp experiments

    PubMed Central

    1977-01-01

    When current clamped, skate electroreceptor epithelium produces large action potentials in response to stimuli that depolarize the lumenal faces of the receptor cells. With increasing stimulus strength these action potentials become prolonged. When the peak voltage exceeds about 140 mV the repolarizing phase is blocked until the end of the stimulus. Perfusion experiments show that the rising phase of the action potential results from an increase in calcium permeability in the lumenal membranes. Perfusion of the lumen with cobalt or with a zero calcium solution containing EGTA blocks the action potential. Perfusion of the lumen with a solution containing 10 mM Ca and 20 mM EGTA initially slows the repolarizing process at all voltages and lowers the potential at which it is blocked. With prolonged perfusion, repolarization is blocked at all voltages. When excitability is abolished by perfusion with cobalt, or with a zero calcium solution containing EGTA, no delayed rectification occurs. We suggest that repolarization during the action potential depends on an influx of calcium into the cytoplasm, and that the rate of repolarization depends on the magnitude of the inward calcium current. Increasingly large stimuli reduce the rate of repolarization by reducing the driving force for calcium, and then block repolarization by causing the lumenal membrane potential to exceed ECa. Changes in extracellular calcium affect repolarization in a manner consistent with the resulting change in ECa. PMID:190338

  2. Stoichiometry of Calcium Medicines

    ERIC Educational Resources Information Center

    Pinto, Gabriel

    2005-01-01

    The topic of calcium supplement and its effects on human lives is presented in the way of questions to the students. It enables the students to realize the relevance of chemistry outside the classroom surrounding.

  3. Calcium channel blocker overdose

    MedlinePlus

    ... Goldschlager N. Cardiovascular toxicology. In: Shannon MW, Borron SW, Burns MJ, eds. Haddad and Winchester's Clinical Management ... SD. Calcium channel antagonists. In: Shannon MW, Borron SW, Burns MJ, eds. Haddad and Winchester's Clinical Management ...

  4. Calcium blood test

    MedlinePlus

    ... failure Low blood level of albumin Liver disease Magnesium deficiency Pancreatitis Vitamin D deficiency ... PA: Elsevier; 2013:chap 66. Leone KA. Calcium, magnesium, and phosphorus. In: Adams JG, ed. Emergency Medicine: ...

  5. Electron Wavepacket Interference Observed by Attosecond Transient Absorption Spectroscopy

    NASA Astrophysics Data System (ADS)

    Gallmann, L.; Holler, M.; Schapper, F.; Keller, U.

    Attosecond time-resolved transient absorption spectroscopy is performed in a dense helium target by superimposing an attosecond pulse train (APT) with a moderately strong infrared field. We observe rapid oscillations of the absorption of the individual harmonics as a function of time-delay between the APT and IR field even for harmonic energies well below the ionization threshold. The phase dependence of these modulations on atto-chirp and IR intensity yields direct evidence for the interference of transiently bound electronic wavepackets as the underlying mechanism.

  6. Calmidazolium evokes high calcium fluctuations in Plasmodium falciparum.

    PubMed

    Budu, Alexandre; Gomes, Mayrim M; Melo, Pollyana M; El Chamy Maluf, Sarah; Bagnaresi, Piero; Azevedo, Mauro F; Carmona, Adriana K; Gazarini, Marcos L

    2016-03-01

    Calcium and calmodulin (CaM) are important players in eukaryote cell signaling. In the present study, by using a knockin approach, we demonstrated the expression and localization of CaM in all erythrocytic stages of Plasmodium falciparum. Under extracellular Ca(2+)-free conditions, calmidazolium (CZ), a potent CaM inhibitor, promoted a transient cytosolic calcium ([Ca(2+)]cyt) increase in isolated trophozoites, indicating that CZ mobilizes intracellular sources of calcium. In the same extracellular Ca(2+)-free conditions, the [Ca(2+)]cyt rise elicited by CZ treatment was ~3.5 fold higher when the endoplasmic reticulum (ER) calcium store was previously depleted ruling out the mobilization of calcium from the ER by CZ. The effects of the Ca(2+)/H(+) ionophore ionomycin (ION) and the Na(+)/H(+) ionophore monensin (MON) suggest that the [Ca(2+)]cyt-increasing effect of CZ is driven by the removal of Ca(2+) from at least one Ca(2+)-CaM-related (CaMR) protein as well as by the mobilization of Ca(2+) from intracellular acidic calcium stores. Moreover, we showed that the mitochondrion participates in the sequestration of the cytosolic Ca(2+) elicited by CZ. Finally, the modulation of membrane Ca(2+) channels by CZ and thapsigargin (THG) was demonstrated. The opened channels were blocked by the unspecific calcium channel blocker Co(2+) but not by 2-APB (capacitative calcium entry inhibitor) or nifedipine (L-type Ca(2+) channel inhibitor). Taken together, the results suggested that one CaMR protein is an important modulator of calcium signaling and homeostasis during the Plasmodium intraerythrocytic cell cycle, working as a relevant intracellular Ca(2+) reservoir in the parasite.

  7. Intracellular calcium channels in protozoa.

    PubMed

    Docampo, Roberto; Moreno, Silvia N J; Plattner, Helmut

    2014-09-15

    Ca(2+)-signaling pathways and intracellular Ca(2+) channels are present in protozoa. Ancient origin of inositol 1,4,5-trisphosphate receptors (IP3Rs) and other intracellular channels predates the divergence of animals and fungi as evidenced by their presence in the choanoflagellate Monosiga brevicollis, the closest known relative to metazoans. The first protozoan IP3R cloned, from the ciliate Paramecium, displays strong sequence similarity to the rat type 3 IP3R. This ciliate has a large number of IP3- and ryanodine(Ry)-like receptors in six subfamilies suggesting the evolutionary adaptation to local requirements for an expanding diversification of vesicle trafficking. IP3Rs have also been functionally characterized in trypanosomatids, where they are essential for growth, differentiation, and establishment of infection. The presence of the mitochondrial calcium uniporter (MCU) in a number of protozoa indicates that mitochondrial regulation of Ca(2+) signaling is also an early appearance in evolution, and contributed to the discovery of the molecular nature of this channel in mammalian cells. There is only sequence evidence for the occurrence of two-pore channels (TPCs), transient receptor potential Ca(2+) channels (TRPCs) and intracellular mechanosensitive Ca(2+)-channels in Paramecium and in parasitic protozoa.

  8. Intracellular Calcium Channels in Protozoa

    PubMed Central

    Docampo, Roberto; Moreno, Silvia N.J.; Plattner, Helmut

    2014-01-01

    Ca2+-signaling pathways and intracellular Ca2+ channels are present in protozoa. Ancient origin of inositol 1,4,5-trisphosphate receptors (IP3Rs) and other intracellular channels predates the divergence of animals and fungi as evidenced by their presence in the choanoflagellate Monosiga brevicollis, the closest known relative to metazoans. The first protozoan IP3R cloned, from the ciliate Paramecium, displays strong sequence similarity to the rat type 3 IP3R. This ciliate has a large number of IP3- and ryanodine(Ry)-like receptors in 6 subfamilies suggesting the evolutionary adaptation to local requirements for an expanding diversification of vesicle trafficking. IP3Rs have also been functionally characterized in trypanosomatids, where they are essential for growth, differentiation, and establishment of infection. The presence of the mitochondrial calcium uniporter (MCU) in a number of protozoa indicates that mitochondrial regulation of Ca2+ signaling is also an early appearance in evolution, and contributed to the discovery of the molecular nature of this channel in mammalian cells. There is only sequence evidence for the occurrence of two-pore channels (TPCs), transient receptor potential Ca2+ channels (TRPCs) and intracellular mechanosensitive Ca2+-channels in Paramecium and in parasitic protozoa. PMID:24291099

  9. Downhole delay assembly for blasting with series delay

    DOEpatents

    Ricketts, Thomas E.

    1982-01-01

    A downhole delay assembly is provided which can be placed into a blasthole for initiation of explosive in the blasthole. The downhole delay assembly includes at least two detonating time delay devices in series in order to effect a time delay of longer than about 200 milliseconds in a round of explosions. The downhole delay assembly provides a protective housing to prevent detonation of explosive in the blasthole in response to the detonation of the first detonating time delay device. There is further provided a connection between the first and second time delay devices. The connection is responsive to the detonation of the first detonating time delay device and initiates the second detonating time delay device. A plurality of such downhole delay assemblies are placed downhole in unfragmented formation and are initiated simultaneously for providing a round of explosive expansions. The explosive expansions can be used to form an in situ oil shale retort containing a fragmented permeable mass of formation particles.

  10. Transient neonatal zinc deficiency.

    PubMed

    Krieger, I; Alpern, B E; Cunnane, S C

    1986-06-01

    We report an infant who developed clinical manifestations of zinc deficiency during the first month of life although the diet was adequate for zinc and no other causes could be ascertained. The diagnosis was confirmed by low plasma-zinc concentrations and a positive response to zinc treatment. The fatty acid profile of plasma phospholipids was typical of zinc deficiency (ie, arachidonic acid was markedly decreased). The transient nature of this disorder was evident when no relapse occurred after cessation of zinc therapy and plasma-zinc and arachidonic acid concentrations remained normal. Several explanations for the development of transient neonatal zinc deficiency are offered. The observation demonstrates that occasional infants may have requirements for zinc that are beyond the intakes of the conventional RDA. PMID:3717070

  11. Reactor System Transient Code.

    1999-07-14

    RELAP3B describes the behavior of water-cooled nuclear reactors during postulated accidents or power transients, such as large reactivity excursions, coolant losses or pump failures. The program calculates flows, mass and energy inventories, pressures, temperatures, and steam qualities along with variables associated with reactor power, reactor heat transfer, or control systems. Its versatility allows one to describe simple hydraulic systems as well as complex reactor systems.

  12. Bright Transients discovered by PSST

    NASA Astrophysics Data System (ADS)

    Smith, K. W.; Wright, D.; Smartt, S. J.; Huber, M.; Chambers, K. C.; Flewelling, H.; Willman, M.; Primak, N.; Schultz, A.; Gibson, B.; Magnier, E.; Waters, C.; Tonry, J.; Wainscoat, R. J.; Denneau, L.; Stalder, B.; Heinze, A.; Sherstyuk, A.; Foley, R. J.; Jha, S. W.; Rest, A.; Scolnic, D.

    2016-04-01

    Seven bright transients have been discovered as part of the Pan-STARRS Survey for Transients (PSST). Information on all objects discovered by the Pan-STARRS Survey for Transients is available at http://star.pst.qub.ac.uk/ps1threepi/ (see Huber et al. ATel #7153).

  13. Bright Transients discovered by PSST

    NASA Astrophysics Data System (ADS)

    Smith, K. W.; Wright, D.; Smartt, S. J.; Huber, M.; Chambers, K. C.; Flewelling, H.; Willman, M.; Primak, N.; Schultz, A.; Gibson, B.; Magnier, E.; Waters, C.; Tonry, J.; Wainscoat, R. J.; Foley, R. J.; Jha, S. W.; Rest, A.; Scolnic, D.

    2016-03-01

    Seven bright transients have been discovered as part of the Pan-STARRS Survey for Transients (PSST). Information on all objects discovered by the Pan-STARRS Survey for Transients is available at http://star.pst.qub.ac.uk/ps1threepi/ (see Huber et al. ATel #7153).

  14. Bright Transients discovered by PSST

    NASA Astrophysics Data System (ADS)

    Smith, K. W.; Wright, D.; Smartt, S. J.; Young, D. R.; Huber, M.; Chambers, K. C.; Flewelling, H.; Willman, M.; Primak, N.; Schultz, A.; Gibson, B.; Magnier, E.; Waters, C.; Tonry, J.; Wainscoat, R. J.; Foley, R. J.; Jha, S. W.; Rest, A.; Scolnic, D.

    2016-08-01

    Six bright transients have been discovered as part of the Pan-STARRS Survey for Transients (PSST). Information on all objects discovered by the Pan-STARRS Survey for Transients is available at http://star.pst.qub.ac.uk/ps1threepi/ (see Huber et al. ATel #7153).

  15. Two Transients discovered by PSST

    NASA Astrophysics Data System (ADS)

    Smith, K. W.; Wright, D.; Smartt, S. J.; Young, D. R.; Huber, M.; Chambers, K. C.; Flewelling, H.; Willman, M.; Primak, N.; Schultz, A.; Gibson, B.; Magnier, E.; Waters, C.; Tonry, J.; Wainscoat, R. J.; Foley, R. J.; Jha, S. W.; Rest, A.; Scolnic, D.

    2016-08-01

    Two transients have been discovered as part of the Pan-STARRS Survey for Transients (PSST). Information on all objects discovered by the Pan-STARRS Survey for Transients is available at http://star.pst.qub.ac.uk/ps1threepi/ (see Huber et al. ATel #7153).

  16. Delays and Growth Rates of Multiple TEOAE Components

    NASA Astrophysics Data System (ADS)

    Goodman, Shawn S.; Mertes, Ian B.; Scheperle, Rachel A.

    2011-11-01

    Bandpass-filtered transient-evoked otoacoustic emissions (TEOAEs) show multiple energy peaks with time delays that are invariant with level and growth rates that vary with delay and stimulus level, suggesting that multiple generation mechanisms may be involved at moderate and high stimulus levels. We measured delays and magnitude growths of multiple TEOAE energy peaks and compared the results obtained from linear and nonlinear extraction methods. To test the hypothesis that early components are generated at the basal portion of the cochlea, delays and growth rates were also measured in the presence of highpass masking noise for a subset of subjects. No effect of the highpass masking was seen. The results are discussed in terms of potential generation mechanisms of the multiple energy peaks.

  17. [Microbial geochemical calcium cycle].

    PubMed

    Zavarzin, G A

    2002-01-01

    The participation of microorganisms in the geochemical calcium cycle is the most important factor maintaining neutral conditions on the Earth. This cycle has profound influence on the fate of inorganic carbon, and, thereby, on the removal of CO2 from the atmosphere. The major part of calcium deposits was formed in the Precambrian, when prokaryotic biosphere predominated. After that, calcium recycling based on biogenic deposition by skeletal organisms became the main process. Among prokaryotes, only a few representatives, e.g., cyanobacteria, exhibit a special calcium function. The geochemical calcium cycle is made possible by the universal features of bacteria involved in biologically mediated reactions and is determined by the activities of microbial communities. In the prokaryotic system, the calcium cycle begins with the leaching of igneous rock predominantly through the action of the community of organotrophic organisms. The release of carbon dioxide to the soil air by organotrophic aerobes leads to leaching with carbonic acid and soda salinization. Under anoxic conditions, of major importance is the organic acid production by primary anaerobes (fermentative microorganisms). Calcium carbonate is precipitated by secondary anaerobes (sulfate reducers) and to a smaller degree by methanogens. The role of the cyanobacterial community in carbonate deposition is exposed by stromatolites, which are the most common organo-sedimentary Precambrian structures. Deposition of carbonates in cyanobacterial mats as a consequence of photoassimilation of CO2 does not appear to be a significant process. It is argued that carbonates were deposited at the boundary between the "soda continent", which emerged as a result of subaerial leaching with carbonic acid, and the ocean containing Ca2+. Such ecotones provided favorable conditions for the development of the benthic cyanobacterial community, which was a precursor of stromatolites.

  18. Advanced PFBC transient analysis

    SciTech Connect

    White, J.S.; Bonk, D.L.

    1997-05-01

    Transient modeling and analysis of advanced Pressurized Fluidized Bed Combustion (PFBC) systems is a research area that is currently under investigation by the US Department of Energy`s Federal Energy Technology Center (FETC). The object of the effort is to identify key operating parameters that affect plant performance and then quantify the basic response of major sub-systems to changes in operating conditions. PC-TRAX{trademark}, a commercially available dynamic software program, was chosen and applied in this modeling and analysis effort. This paper describes the development of a series of TRAX-based transient models of advanced PFBC power plants. These power plants burn coal or other suitable fuel in a PFBC, and the high temperature flue gas supports low-Btu fuel gas or natural gas combustion in a gas turbine topping combustor. When it is utilized, the low-Btu fuel gas is produced in a bubbling bed carbonizer. High temperature, high pressure combustion products exiting the topping combustor are expanded in a modified gas turbine to generate electrical power. Waste heat from the system is used to raise and superheat steam for a reheat steam turbine bottoming cycle that generates additional electrical power. Basic control/instrumentation models were developed and modeled in PC-TRAX and used to investigate off-design plant performance. System performance for various transient conditions and control philosophies was studied.

  19. ON DETECTING TRANSIENT PHENOMENA

    SciTech Connect

    Belanger, G.

    2013-08-10

    Transient phenomena are interesting and potentially highly revealing of details about the processes under observation and study that could otherwise go unnoticed. It is therefore important to maximize the sensitivity of the method used to identify such events. In this article, we present a general procedure based on the use of the likelihood function for identifying transients which is particularly suited for real-time applications because it requires no grouping or pre-processing of the data. The method makes use of all the information that is available in the data throughout the statistical decision-making process, and is suitable for a wide range of applications. Here we consider those most common in astrophysics, which involve searching for transient sources, events or features in images, time series, energy spectra, and power spectra, and demonstrate the use of the method in the case of a weak X-ray flare in a time series and a short-lived quasi-periodic oscillation in a power spectrum. We derive a fit statistic that is ideal for fitting arbitrarily shaped models to a power density distribution, which is of general interest in all applications involving periodogram analysis.

  20. Wnt-induced calcium signaling mediates axon growth and guidance in the developing corpus callosum.

    PubMed

    Hutchins, B Ian; Li, Li; Kalil, Katherine

    2012-01-10

    Wnt5a gradients guide callosal axons by repulsion through Ryk receptors in vivo. We recently found that Wnt5a repels cortical axons and promotes axon outgrowth through calcium signaling in vitro. Here, using cortical slices, we show that Wnt5a signals through Ryk to guide and promote outgrowth of callosal axons after they cross the midline. Calcium transient frequencies in callosal growth cones positively correlate with axon outgrowth rates in vitro. In cortical slices, calcium release through inositol 1,4,5-trisphosphate (IP(3)) receptors and calcium entry through transient receptor potential channels modulate axon growth and guidance. Knocking down Ryk inhibits calcium signaling in cortical axons, reduces rates of axon outgrowth subsequent to midline crossing, and causes axon guidance defects. Calcium- and calmodulin-dependent protein kinase II (CaMKII) is required downstream of Wnt-induced calcium signaling for postcrossing callosal axon growth and guidance. Taken together, these results suggest that growth and guidance of postcrossing callosal axons by Wnt-Ryk-calcium signaling involves axon repulsion through CaMKII.

  1. Effects of fluoride, calcium, and phosphate administration on mineralization in rats.

    PubMed

    Larsen, M J; Fejerskov, O; Jensen, S J

    1980-01-01

    Seven days before a fluoride injection of 20 mg sodium fluoride per kg body weight, 3-month-old rats grown on a standard pellet diet containing 0.8% calcium and 1.4% phosphate were given a diet of rice with only 0.025% calcium and 0.1% phosphate. Microradiographs of the continuously growing incisors showed a hypermineralized and subsequent hypomineralized zone. Blood analysis demonstrated a decrease and a subsequent reestablishment of plasma calcium concentration. In some experiments calcium and phosphate were administered to compensate the hypocalcemia which prevented the hypomineralized zone from arising. A delay of calcium and phosphate administration led to formation of a mineralized band within the hypomineralized zone. The results are discussed with reference to calcium homeostasis.

  2. Gravimetric Determination of Calcium as Calcium Carbonate Hydrate.

    ERIC Educational Resources Information Center

    Henrickson, Charles H.; Robinson, Paul R.

    1979-01-01

    The gravimetric determination of calcium as calcium carbonate is described. This experiment is suitable for undergraduate quantitative analysis laboratories. It is less expensive than determination of chloride as silver chloride. (BB)

  3. Delayed traumatic diaphragmatic hernia

    PubMed Central

    Lu, Jing; Wang, Bo; Che, Xiangming; Li, Xuqi; Qiu, Guanglin; He, Shicai; Fan, Lin

    2016-01-01

    Abstract Background: Traumatic diaphragmatic hernias (TDHs) are sometimes difficult to identify at an early stage and can consequently result in diagnostic delays with life-threatening outcomes. It is the aim of this case study to highlight the difficulties encountered with the earlier detection of traumatic diaphragmatic hernias. Methods: Clinical data of patients who received treatment for delayed traumatic diaphragmatic hernias in registers of the First Affiliated Hospital of Xi’an Jiaotong University from 1998 to 2014 were analyzed retrospectively. Results: Six patients were included in this study. Left hemidiaphragm was affected in all of them. Most of the patients had a history of traffic accident and 1 a stab-penetrating injury. The interval from injury to developing symptoms ranged from 2 to 11 years (median 5 years). The hernial contents included the stomach, omentum, small intestine, and colon. Diaphragmatic injury was missed in all of them during the initial managements. All patients received operations once the diagnosis of delayed TDH was confirmed, and no postoperative mortality was detected. Conclusions: Delayed TDHs are not common, but can lead to serious consequences once occurred. Early detection of diaphragmatic injuries is crucial. Surgeons should maintain a high suspicion for injuries of the diaphragm in cases with abdominal or lower chest traumas, especially in the initial surgical explorations. We emphasize the need for radiographical follow-up to detect diaphragmatic injuries at an earlier stage. PMID:27512848

  4. Contingencies promote delay tolerance.

    PubMed

    Ghaemmaghami, Mahshid; Hanley, Gregory P; Jessel, Joshua

    2016-09-01

    The effectiveness of functional communication training as treatment for problem behavior depends on the extent to which treatment can be extended to typical environments that include unavoidable and unpredictable reinforcement delays. Time-based progressive delay (TBPD) often results in the loss of acquired communication responses and the resurgence of problem behavior, whereas contingency-based progressive delay (CBPD) appears to be effective for increasing tolerance for delayed reinforcement. No direct comparison of TBPD and CBPD has, however, been conducted. We used single-subject designs to compare the relative efficacy of TBPD and CBPD. Four individuals who engaged in problem behavior (e.g., aggression, vocal and motor disruptions, self-injury) participated. Results were consistent across all participants, and showed lower rates of problem behavior and collateral responses during CBPD than during TBPD. The generality of CBPD treatment effects, including optimal rates of communication and compliance with demands, was demonstrated across a small but heterogeneous group of participants, reinforcement contingencies, and contexts. PMID:27449401

  5. Pharmacology of the calcium sensing receptor

    PubMed Central

    Filopanti, Marcello; Corbetta, Sabrina; Barbieri, Anna Maria; Spada, Anna

    2013-01-01

    Summary Calcium sensing receptor (CASR) is a G-protein couple receptor which plays a key role in calcium homeostasis in vertebrates. Its extracellular domain is sensitive to divalent cations, aminoacids and polyamines. In parathyroid glands, CASR activation causes parathyroid hormone (PTH) reduction and subsequently a decrease in blood calcium concentration. In PTH-dependent disorders, e.g. primary and secondary hyperparathyroidism (HPT), the need for therapeutic options other than surgery led to the synthesis of various allosteric CASR agonists (calcimimetics), such as cinacalcet. Cinacalcet is the only calcimimetic approved for HPT secondary to chronic kidney disease (CDK), parathyroid carcinoma, and, in some countries, primary HPT. Clinical trials showed that cinacalcet reduced PTH and calcemia both in CDK and primary HPT, lowering the risk of bone fractures, surgery, and cardiovascular complications in the former patients. Long-term safety and pharmacoeconomics have to be fully tested yet. Few both in vitro and in vivo studies showed an association between Arg990Gly-CASR polymorphism and cinacalcet sensitivity, though in patients with severe CASR inactivating mutations the drug substantially retained its positive clinical effects. Recently, a new class of allosteric antagonists of CASR, i.e. calcilytics, has been synthesized. Calcilytics are structurally similar to calcimimetics, but exert their effects acting on a different allosteric site. Infusion of calcilytics was followed by transient rise in PTH and calcium. One of these compounds, ronacaleret, was able to increase femur BMD in post menopausal women, but with induction of mild hyperparathyroidism. In the future, calcilytics may contribute to the osteoporosis treatment choice. PMID:24554924

  6. Workshop on Radio Transients

    NASA Astrophysics Data System (ADS)

    Croft, Steve; Gaensler, Bryan

    2012-04-01

    abstract-type="normal">SummaryWe are entering a new era in the study of variable and transient radio sources. This workshop discussed the instruments and the strategies employed to study those sources, how they are identified and classified, how results from different surveys can be compared, and how radio observations tie in with those at other wavelengths. The emphasis was on learning what common ground there is between the plethora of on-going projects, how methods and code can be shared, and how best practices regarding survey strategy could be adopted. The workshop featured the four topics below. Each topic commenced with a fairly brief introductory talk, which then developed into discussion. By way of preparation, participants had been invited to upload and discuss one slide per topic to a wiki ahead of the workshop. 1. Telescopes, instrumentation and survey strategy. New radio facilities and on-going projects (including upgrades) are both studying the variability of the radio sky, and searching for transients. The discussion first centred on the status of those facilities, and on projects with a time-domain focus, both ongoing and planned, before turning to factors driving choices of instrumentation, such as phased array versus single pixel feeds, the field of view, spatial and time resolution, frequency and bandwidth, depth, area, and cadence of the surveys. 2. Detection, pipelines, and classification. The workshop debated (a) the factors that influence decisions to study variability in the (u,v) plane, in images, or in catalogues, (b) whether, and how much, pipeline code could potentially be shared between one project and another, and which software packages are best for different approaches, (c) how data are stored and later accessed, and (d) how transients and variables are defined and classified. 3. Statistics, interpretation, and synthesis. It then discussed how (i) the choice of facility and strategy and (ii) detection and classification schemes

  7. Thermal transient anemometer

    DOEpatents

    Bailey, James L.; Vresk, Josip

    1989-01-01

    A thermal transient anemometer having a thermocouple probe which is utilized to measure the change in temperature over a period of time to provide a measure of fluid flow velocity. The thermocouple probe is located in the fluid flow path and pulsed to heat or cool the probe. The cooling of the heated probe or the heating of the cooled probe from the fluid flow over a period of time is measured to determine the fluid flow velocity. The probe is desired to be locally heated near the tip to increase the efficiency of devices incorporating the probe.

  8. Thermal transient anemometer

    DOEpatents

    Bailey, J.L.; Vresk, J.

    1989-07-18

    A thermal transient anemometer is disclosed having a thermocouple probe which is utilized to measure the change in temperature over a period of time to provide a measure of fluid flow velocity. The thermocouple probe is located in the fluid flow path and pulsed to heat or cool the probe. The cooling of the heated probe or the heating of the cooled probe from the fluid flow over a period of time is measured to determine the fluid flow velocity. The probe is desired to be locally heated near the tip to increase the efficiency of devices incorporating the probe. 12 figs.

  9. Transient neonatal tyrosinaemia.

    PubMed

    Rice, D N; Houston, I B; Lyon, I C; Macarthur, B A; Mullins, P R; Veale, A M; Guthrie, R

    1989-01-01

    Children who had presented with transient neonatal tyrosinaemia (TNT) were compared with a group of unaffected controls at 7-9 years of age. A comprehensive psychometric assessment revealed significant differences between the groups in adaptive behaviour, psycholinguistic abilities, and speed of learning. In nearly all components of the tests used, higher levels of TNT were associated with lower levels of performance. This study demonstrates that TNT, a condition commonly regarded as benign in the short term, has long-term effects which may be detrimental to the child in school.

  10. Transient enthalpy probe development

    NASA Astrophysics Data System (ADS)

    Bennett, Brian K.

    A reliable diagnostic probe has been developed to measure the local enthalpy in high-pressure, arc heated test streams that simulate atmospheric reentry conditions. The probe employs the double sonic-throat technique and is designed for the sweep (transient) mode to survive the severe heating environment. Tests in the high-pressure arc heater facilities show that, under certain conditions, the enthalpy probe measurements are in good agreement with enthalpy profiles inferred from heat flux measurements using the theory of Fay and Riddell (1958).

  11. The Rapid Transient Surveyor

    NASA Astrophysics Data System (ADS)

    Baranec, Christoph; Tonry, John; Wright, Shelley; Tully, R. Brent; Lu, Jessica R.; Takamiya, Marianne Y.; Hunter, Lisa

    2016-01-01

    The next decade of astronomy will be dominated by large area surveys (see the detailed discussion in the Astro-2010 Decadal survey and NRC's recent OIR System Report). Ground-based optical transient surveys, e.g., LSST, ZTF and ATLAS and space-based exoplanet, supernova, and lensing surveys such as TESS and WFIRST will join the Gaia all-sky astrometric survey in producing a flood of data that will enable leaps in our understanding of the universe. There is a critical need for further characterization of these discoveries through high angular resolution images, deeper images, spectra, or observations at different cadences or periods than the main surveys. Such follow-up characterization must be well matched to the particular surveys, and requires sufficient additional observing resources and time to cover the extensive number of targets.We describe plans for the Rapid Transient Surveyor (RTS), a permanently mounted, rapid-response, high-cadence facility for follow-up characterization of transient objects on the U. of Hawai'i 2.2-m telescope on Maunakea. RTS will comprise an improved robotic laser adaptive optics system, based on the prototype Robo-AO system (formerly at the Palomar 1.5-m and now at the Kitt Peak 2.2-m telescope), with simultaneous visible and near-infrared imagers as well as a near-infrared integral field spectrograph (R~100, λ = 850 - 1830 nm, 0.15″ spaxels, 8.7″×6.0″ FoV). RTS will achieve an acuity of ~0.07″ in visible wavelengths and < 0.16″ in the near infrared leading to an increase of the infrared point-source sensitivity against the sky background by a factor of ~9, crucial for efficient near-infrared spectroscopy.RTS will allow us to map the dark matter distribution in the z < 0.1 local universe with ten times better accuracy and precision than previous experiments. ATLAS will discover several thousand SNIae per year, measuring SNIa peak brightness, and decline rates, while RTS will measure reddening by dust, confirm SN type and

  12. Calcium current in isolated neonatal rat ventricular myocytes.

    PubMed Central

    Cohen, N M; Lederer, W J

    1987-01-01

    1. Calcium currents (ICa) from neonatal rat ventricular heart muscle cells grown in primary culture were examined using the 'whole-cell' voltage-clamp technique (Hamill, Marty, Neher, Sakmann & Sigworth, 1981). Examination of ICa was limited to one calcium channel type, 'L' type (Nilius, Hess, Lansman & Tsien, 1985), by appropriate voltage protocols. 2. We measured transient and steady-state components of ICa, and could generally describe ICa in terms of the steady-state activation (d infinity) and inactivation (f infinity) parameters. 3. We observed that the reduction of ICa by the calcium channel antagonist D600 can be explained by both a shift of d infinity to more positive potentials as well as a slight reduction of ICa conductance. D600 did not significantly alter either the rate of inactivation of ICa or the voltage dependence of f infinity. 4. The calcium channel modulator BAY K8644 shifted both d infinity and f infinity to more negative potentials. Additionally, BAY K8644 increased the rate of inactivation at potentials between +5 and +55 mV. Furthermore, BAY K8644 also increased ICa conductance, a change consistent with a promotion of 'mode 2' calcium channel activity (Hess, Lansman & Tsien, 1984). 5. We conclude that, as predicted by d infinity and f infinity, there is a significant steady-state component of ICa ('window current') at plateau potentials in neonatal rat heart cells. Modulation of the steady-state and transient components of ICa by various agents can be attributed both to specific alterations in d infinity and f infinity and to more complicated alterations in the mode of calcium channel activity. PMID:2451004

  13. CALCIUM-INDUCED SUPRAMOLECULAR STRUCTURES IN THE CALCIUM CASEINATE SYSTEM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The molecular details deciphering the spontaneous calcium-induced protein aggregation process in the calcium caseinate system remain obscure. Understanding this complex process could lead to potential new applications of this important food ingredient. In this work, we studied calcium-induced supra...

  14. Calcium-mediated inactivation of calcium current in Paramecium.

    PubMed

    Brehm, P; Eckert, R; Tillotson, D

    1980-09-01

    1. The Ca current seen in response to depolarization was investigated in Paramecium caudatum under voltage clamp. Inactivation of the current was measured with the double pulse method; a fixed test pulse of an amplitude sufficient to evoke maximal inward current was preceded by a conditioning pulse of variable amplitude (0-120 mV).2. The amplitude of the current recorded during the test pulse was related to the potential of the conditioning pulse. Reduction of test pulse current was taken as an index of Ca current inactivation. The current recorded during a test pulse showed a progressive decrease to a minimum as the potential of the conditioning pulse approached +10 to +30 mV. Further increase in conditioning pulse amplitude was accompanied by a progressive restoration of the test pulse current. Conditioning pulses near the calcium equilibrium potential had only a slight inactivating effect on the test pulse current.3. Injection of a mixture of Cs and TEA which blocked late outward current had essentially no effect on the inward current or its inactivation.4. Elevation of external Ca from 0.5 to 5 mM was accompanied by increased inactivation of the test pulse current. The enhanced inactivation of the test pulse current was approximately proportional to the increase in current recorded during the conditioning pulse.5. Following injection of the Ca chelating agent, EGTA, the inactivation of the test pulse current was diminished; in addition, the transient inward current relaxed slightly more slowly, and the transient was followed by a steady net inward current.6. The time course of recovery from inactivation in the double pulse experiment approximated a single exponential having a time constant of 80-110 msec. Injection of EGTA shortened the time constant by as much as 50%.7. It is concluded that interference with the entry of Ca or enhanced removal of intracellular free Ca(2+) interferes with the process of Ca current inactivation, while enhanced entry of Ca

  15. Calcium Content of Common Foods

    MedlinePlus

    ... 130 Waffle 80 g 47 Meat, fish and eggs Food Serving Size Calcium (mg) Egg 50 g 27 Red meat 120 g 7 ... foods Food Serving Size Calcium (mg) Quiche (cheese, eggs) 200 g 212 Omelette with cheese 120 g ...

  16. Children's Bone Health and Calcium

    MedlinePlus

    ... Trials Resources and Publications Children's Bone Health and Calcium: Condition Information Skip sharing on social media links ... straight, walk, run, and lead an active life. Calcium is one of the key dietary building blocks ...

  17. Intestinal Stem Cells: Got Calcium?

    PubMed

    Nászai, Máté; Cordero, Julia B

    2016-02-01

    Calcium ions are well-known intracellular signalling molecules. A new study identifies local cytoplasmic calcium as a central integrator of metabolic and proliferative signals in Drosophila intestinal stem cells. PMID:26859268

  18. Calcium carbonate with magnesium overdose

    MedlinePlus

    The combination of calcium carbonate and magnesium is commonly found in antacids. These medicines provide heartburn relief. Calcium carbonate with magnesium overdose occurs when someone takes more than the ...

  19. Spatially confined diffusion of calcium in dendrites of hippocampal neurons revealed by flash photolysis of caged calcium.

    PubMed

    Korkotian, Eduard; Segal, Menahem

    2006-01-01

    The extent of diffusion of a locally evoked calcium surge in dendrites of cultured hippocampal neurons was studied by flash photolysis of caged EGTA. Cells were transfected with pDsRed for visualization, preincubated with caged NP-EGTA (AM) and Fluo-4 (AM) at room temperature and imaged in a PASCAL confocal microscope. Pulses of UV laser light within an active sphere of about 1 micro m(2) produced a rise of Fluo-4 fluorescence transients in dendrites which peaked at 1 ms and decayed exponentially with a fast (8-10 ms) time constant. A slower decay component was uncovered following incubation with thapsigargin. Lateral diffusion of [Ca(2+)]i did not vary significantly among different size dendrites being symmetric and reaching about 3-3.5 micro mm at a diffusion rate of 0.8 micro mm/ms on both sides of the photolysis center. Fluo-4 was also replaced by the membrane-bound Fluo-NOMO (AM) or by the 'heavy' Calcium Green dextran (CGd) loaded through a patch pipette. Similar rates of diffusion were found in these cases, indicating that the diffusion is not of the dye complexed to calcium but of genuine free calcium ions. Interestingly, presence of a dendritic spine at the focus of photolysis significantly reduced [Ca(2+)]i spread while the focal transient remained unaffected. Finally, [Ca(2+)]i diffused about twice as far from the photolysis sphere in glass tubes of a similar diameter to that of a dendrite, indicating that intrinsic calcium uptake mechanisms in the dendrite determine the diffusion of calcium away from its original site of rise. PMID:17064764

  20. Transient congenital hypothyroidism

    PubMed Central

    Bhavani, Nisha

    2011-01-01

    Transient thyroid function abnormalities in the new born which revert back to normal after varying periods of time are mostly identified in the neonatal screening tests for thyroid and are becoming more common because of the survival of many more premature infants. It can be due to factors primarily affecting the thyroid-like iodine deficiency or excess, maternal thyroid-stimulating hormone receptor (TSHR) antibodies, maternal use of antithyroid drugs, DUOX 2 (dual oxidase 2) mutations, and prematurity or those that affect the pituitary-like untreated maternal hyperthyroidism, prematurity, and drugs. Most of these require only observation, whereas some, such as those due to maternal TSHR antibodies may last for upto three-to-six months and may necessitate treatment. Isolated hyperthyrotropinemia (normal Tetraiodothyronine (T4) and high Thyroid Stimulating hormone (TSH)) may persist as subclinical hypothyroidism in childhood. Transient hypothyroxinemia (low T4 and normal TSH) is very common in premature babies. The recognition of these conditions will obviate the risks associated with unnecessary thyroxine supplementation in childhood and parental concerns of a life long illness in their offspring. PMID:21966647

  1. Calcium and phosphorus fluxes during hemodialysis with low calcium dialysate.

    PubMed

    Hou, S H; Zhao, J; Ellman, C F; Hu, J; Griffin, Z; Spiegel, D M; Bourdeau, J E

    1991-08-01

    We evaluated the acute effects of varying dialysate calcium concentration on plasma concentrations and dialyzer fluxes of calcium and phosphorus in adult hemodialysis patients. Seven individuals with stable end-stage renal failure were dialyzed 4 hours, three times weekly. The effects of dialysates containing 1.75, 1.25, or 0.75 mmol/L (70.1, 50.1, or 30.1 mg/L) of calcium were compared. Each patient was studied once at each bath calcium concentration. Compared with the predialysis mean value of 2.27 mmol/L (9.1 mg/dL), plasma total calcium concentration increased, remained constant, or decreased with the 1.75-, 1.25-, or 0.75-mmol/L calcium dialysates, respectively. The 0.75-mmol/L calcium dialysate did not cause signs or symptoms of hypocalcemia (and the plasma calcium concentration did not fall below 1.80 mmol/L [7.2 mg/dL]). Plasma phosphorus concentrations decreased equally from a predialysis mean value of 2.16 mmol/L (6.7 mg/dL), regardless of the dialysate calcium concentration. After 4 hours of treatment with the three different dialysates, the cumulative calcium fluxes were significantly different. With 1.75 mmol/L calcium, mean bodily calcium accumulation was 21.9 mmol (879 mg). With 1.25 mmol/L, there was no net calcium flux. With 0.75 mmol/L, mean patient calcium loss was 5.8 mmol (231 mg). Mean phosphorus removal after 4 hours was 32.5 mmol (1,006 mg) and was unaffected by dialysate calcium concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1867178

  2. Calcium biofortification of crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    More than half of the world's population is deficient in calcium (Ca), iron (Fe), iodine (I), magnesium (Mg), selenium (Se), or zinc (Zn). The consumption of plants, directly or via livestock, containing inadequate concentrations of particular minerals causes these deficiencies. Agronomic and geneti...

  3. Diet and calcium stones.

    PubMed Central

    Hughes, J; Norman, R W

    1992-01-01

    OBJECTIVE: To review the current literature on the dietary modification of urinary risk factors as a means of reducing the likelihood of recurrent stone formation and to develop practical dietary recommendations that might be useful to this end. DATA SOURCES: MEDLINE was searched for English-language articles published from 1983 to 1990. Additional references were selected from the bibliographies of identified articles. STUDY SELECTION: Nonrandomized trials and retrospective reviews were included because of a paucity of randomized controlled trials. DATA SYNTHESIS: Information on the dietary intake of calcium, oxalate, protein, sodium and fibre and on alcohol and fluid intake was used to develop practical guidelines on dietary modification. CONCLUSION: Dietary modification plays an important role in the reduction of urinary risk factors in patients with calcium stone disease of the urinary tract. As an initial form of prevention attention should be directed toward moderating the intake of calcium, oxalate, protein, sodium and alcohol and increasing the intake of fibre and water. Future research should include an assessment of the long-term reduction of dietary and urinary risk factors and the rates of recurrence of calcium stones. PMID:1310430

  4. Calcium silicate insulation structure

    DOEpatents

    Kollie, Thomas G.; Lauf, Robert J.

    1995-01-01

    An insulative structure including a powder-filled evacuated casing utilizes a quantity of finely divided synthetic calcium silicate having a relatively high surface area. The resultant structure-provides superior thermal insulating characteristics over a broad temperature range and is particularly well-suited as a panel for a refrigerator or freezer or the insulative barrier for a cooler or a insulated bottle.

  5. High Blood Calcium (Hypercalcemia)

    MedlinePlus

    ... as sarcoidosis • Hormone disorders, such as overactive thyroid (hyperthyroidism) • A genetic condition called familial hypocalciuric hypercalcemia • Kidney ... topics: www.hormone.org (search for PHPT, calcium, hyperthyroidism, or osteoporosis) • MedlinePlus (National Institutes of Health-NIH): ...

  6. Calcium aluminate in alumina

    NASA Astrophysics Data System (ADS)

    Altay, Arzu

    The properties of ceramic materials are determined not only by the composition and structure of the phases present, but also by the distribution of impurities, intergranular films and second phases. The phase distribution and microstructure both depend on the fabrication techniques, the raw materials used, the phase-equilibrium relations, grain growth and sintering processes. In this dissertation research, various approaches have been employed to understand fundamental phenomena such as grain growth, impurity segregation, second-phase formation and crystallization. The materials system chosen was alumina intentionally doped with calcium. Atomic-scale structural analyses of grain boundaries in alumina were carried on the processed samples. It was found that above certain calcium concentrations, CA6 precipitated as a second phase at all sintering temperatures. The results also showed that abnormal grain growth can occur after precipitation and it is not only related to the calcium level, but it is also temperature dependent. In order to understand the formation mechanism of CA6 precipitates in calcium doped alumina samples, several studies have been carried out using either bulk materials or thin films The crystallization of CA2 and CA6 powders has been studied. Chemical processing techniques were used to synthesize the powders. It was observed that CA2 powders crystallized directly, however CA6 powders crystallized through gamma-Al 2O3 solid solution. The results of energy-loss near-edge spectrometry confirmed that gamma-Al2O3 can dissolve calcium. Calcium aluminate/alumina reaction couples have also been investigated. All reaction couples were heat treated following deposition. It was found that gamma-Al2O3 was formed at the interface as a result of the interfacial reaction between the film and the substrate. gamma-Al 2O3 at the interface was stable at much higher temperatures compared to the bulk gamma-Al2O3 formed prior to the CA6 crystallization. In order to

  7. The Plasma Membrane Calcium Pump

    NASA Technical Reports Server (NTRS)

    Rasmussen, H.

    1983-01-01

    Three aspect of cellular calcium metabolism in animal cells was discussed including the importance of the plasma membrane in calcium homeostasis, experiments dealing with the actual mechanism of the calcium pump, and the function of the pump in relationship to the mitochondria and to the function of calmodulin in the intact cell.

  8. Impregnating Coal With Calcium Carbonate

    NASA Technical Reports Server (NTRS)

    Sharma, Pramod K.; Voecks, Gerald E.; Gavalas, George R.

    1991-01-01

    Relatively inexpensive process proposed for impregnating coal with calcium carbonate to increase rates of gasification and combustion of coal and to reduce emission of sulfur by trapping sulfur in calcium sulfide. Process involves aqueous-phase reactions between carbon dioxide (contained within pore network of coal) and calcium acetate. Coal impregnated with CO2 by exposing it to CO2 at high pressure.

  9. New reference values for calcium.

    PubMed

    2013-01-01

    The nutrition societies of Germany, Austria and Switzerland are the joint editors of the 'reference values for nutrient intake'. They have revised the reference values for the intake of calcium and published them in June 2013. The reference values for the calcium intake for infants are derived from the calcium content of breast milk. For infants from 4 to <12 months of age, the calcium intake from solid foods is included in addition to the calcium intake from breast milk. Thus, the reference values for infants are estimated values; they are 220 mg/day for infants to <4 months and 330 mg/day for infants from 4 to <12 months of age. As a parameter for determining the calcium requirement in children and adolescents, calcium retention is taken into account. The average requirement is calculated by the factorial method. A balanced calcium metabolism is calculated based upon calcium balance studies and used as a parameter for the determination of the calcium requirement in adults. On the basis of the average requirement, recommended calcium intake levels for children, adolescents and adults are derived. Depending on age, the recommended calcium intake ranges between 600 mg/day for children aged 1 to <4 years and 1,200 mg/day for adolescents aged 13 to <19 years; for adults, it is 1,000 mg/day. PMID:24356454

  10. [Diagnosis of delayed puberty].

    PubMed

    Busiah, K; Belien, V; Dallot, N; Fila, M; Guilbert, J; Harroche, A; Leger, J

    2007-09-01

    Puberty is the phenomenon that conducts once to reproductive maturation. Delayed puberty (DP) is defined by the absence of testicular development in boys beyond 14 years old (or a testicular volume lower than 4 ml) and by the absence of breast development in girls beyond 13 years old. DP occurs in approximatively 3% of cases. Most cases are functional DP, with a large amount of constitutional delay of puberty. Others etiologies are hypogonadotrophic hypogonadism like Kallmann syndrome, or hypergonadotrophic hypogonadism. Turner syndrome is a diagnostic one should not forget by its frequency. Treatment is hormonal replacement therapy and of the etiology. During the last decade, many genes have been identified and elucidated the etiological diagnosis of some hypogonadotrophic hypogonadism syndrome. Further studies are required in collaboration with molecular biologists to better understand the mechanism of hypothalamic pituitary gonadal axis abnormalities and of the neuroendocrine physiology of the onset of puberty.

  11. Delayed coking process

    SciTech Connect

    Dabkowski, M.J.; Malladi, M.

    1987-04-28

    This patent describes a delayed cooking process in which a heavy oil coker feedstock is heated to an elevated coking temperature in a furnace and the heated feedstock is subsequently subjected to delayed coking in a coker drum under superatmospheric pressure and the vaporous coking products are removed from the drum and passed to a coker fractionator from which a bottoms fraction is removed. The improvement comprises coking a feed without the addition of the bottoms fraction from the fractionator and adding to the feed to the coker drum a lower boiling hydrocarbon diluent having an end boiling point of not more than 450/sup 0/C, the lower boiling hydrocarbon diluent being added to the heated feedstock after the feedstock has passed through the furnace.

  12. Delayed skin grafting.

    PubMed

    Ceilley, R I; Bumsted, R M; Panje, W R

    1983-04-01

    The use of skin grafts on granulating wounds is an established practice. Delaying the application of a full- or split-thickness skin graft may be an advantageous alternative method of surgical reconstruction in selected cases. Partial healing by secondary intention is useful for filling in deeper defects and usually produces a wound that is much smaller and of more normal contour than the original defect. Contraction of the graft bed is markedly influenced by location, tissue laxity, surface tension lines, motion, and wound geometry. Proper wound care, correct surgical preparation of the defect, and timing of the graft procedure are all important considerations in maximizing the overall result. Through-and-through defects and wounds produced over areas with little underlying support (eyelids and lip) often need flap reconstruction or immediate grafting to prevent undesirable functional and cosmetic results. By combining delayed healing and conventional reconstructive techniques, major tissue loss can often be restored while minimizing patient morbidity.

  13. [Calcium suppletion for patients who use gastric acid inhibitors: calcium citrate or calcium carbonate?].

    PubMed

    de Jonge, H J M Henk-Marijn; Gans, R O B Rijk; Huls, Gerwin

    2012-01-01

    Various calcium supplements are available for patients who have an indication for calcium suppletion. American guidelines and UpToDate recommend prescribing calcium citrate to patients who use antacids The rationale for this advice is that water-insoluble calcium carbonate needs acid for adequate absorption. No convincing scientific evidence supporting the advice to prescribe calcium citrate instead of calcium carbonate to patients who also take antacids is available, and therefore deserves further investigation. On the contrary, the fact that calcium carbonate does not need acid in order to be absorbed, has also not been proven. In clinical practise, it appears important that calcium is taken with meals in order to improve its absorption. PMID:22914054

  14. [Calcium suppletion for patients who use gastric acid inhibitors: calcium citrate or calcium carbonate?].

    PubMed

    de Jonge, H J M Henk-Marijn; Gans, R O B Rijk; Huls, Gerwin

    2012-01-01

    Various calcium supplements are available for patients who have an indication for calcium suppletion. American guidelines and UpToDate recommend prescribing calcium citrate to patients who use antacids The rationale for this advice is that water-insoluble calcium carbonate needs acid for adequate absorption. No convincing scientific evidence supporting the advice to prescribe calcium citrate instead of calcium carbonate to patients who also take antacids is available, and therefore deserves further investigation. On the contrary, the fact that calcium carbonate does not need acid in order to be absorbed, has also not been proven. In clinical practise, it appears important that calcium is taken with meals in order to improve its absorption.

  15. Preservation of the secretory response of peritoneal mast cells in the absence of extracellular calcium.

    PubMed

    Bronner, C; Gies, J P; Vallé, A; Landry, Y

    1987-12-01

    The transfer of rat peritoneal mast cells from balanced salt solution to calcium-free buffer led to a time-dependent decrease in their response to compound 48/80 and to ionophore A23187. The concomittant absence of potassium from the calcium-free buffer enabled the mast cells to retain their secretory response. The increase in potassium level, with a parallel decrease in sodium to maintain osmolarity, led to a slight potentiation of the response to 48/80 and to a large but transient potentiation of the response to A23187. Mast cells can be considered nonexcitable. The apparent dependency upon extracellular calcium of mast cell secretory responses might be related to the presumed tight equilibrium between endoplasmic reticulum calcium stores and extracellular calcium. The control of this equilibrium by transmembrane gradients of monovalent ions is proposed. PMID:2446099

  16. The joy of transient chaos

    SciTech Connect

    Tél, Tamás

    2015-09-15

    We intend to show that transient chaos is a very appealing, but still not widely appreciated, subfield of nonlinear dynamics. Besides flashing its basic properties and giving a brief overview of the many applications, a few recent transient-chaos-related subjects are introduced in some detail. These include the dynamics of decision making, dispersion, and sedimentation of volcanic ash, doubly transient chaos of undriven autonomous mechanical systems, and a dynamical systems approach to energy absorption or explosion.

  17. The joy of transient chaos

    NASA Astrophysics Data System (ADS)

    Tél, Tamás

    2015-09-01

    We intend to show that transient chaos is a very appealing, but still not widely appreciated, subfield of nonlinear dynamics. Besides flashing its basic properties and giving a brief overview of the many applications, a few recent transient-chaos-related subjects are introduced in some detail. These include the dynamics of decision making, dispersion, and sedimentation of volcanic ash, doubly transient chaos of undriven autonomous mechanical systems, and a dynamical systems approach to energy absorption or explosion.

  18. [Acromegaly: reducing diagnostic delay].

    PubMed

    Giustina, Andrea

    2016-08-01

    Diagnostic delay of acromegaly is still very relevant (6-8 years on average) without substantial changes in last twenty years. Clinical impact of this diagnostic delay is significant: tumor growth (2/3 of the patients at diagnosis bear a pituitary macroadenoma), development of irreversible complications (arthropathy, sleep apnea) and in all increased mortality. Reasons for this delay are related to the disease itself (facial and acral changes are very slow and subtle) but also to medical unawareness. Simple tools based on a few sufficiently sensitive and specific signs and symptoms which can trigger the diagnostic suspect would be useful in clinical practice. Global evaluation during follow-up (tumor volume, signs and symptoms, complications, circulating levels of growth hormone and its peripheral mediator IGF-I) has become crucial for the therapeutic decision making. In this regard, tools like SAGIT are now under validation and are expected to improve management of acromegaly. In fact, in the last 30 years there has been a relevant growth of the medical options to treat acromegaly and in the near future there will be an expansion of the medical options. This will greatly help the needed personalization of treatment which necessarily should consider patient convenience and preference and control of complications such as diabetes mellitus. PMID:27571562

  19. Phagocytosis executes delayed neuronal death after focal brain ischemia.

    PubMed

    Neher, Jonas J; Emmrich, Julius V; Fricker, Michael; Mander, Palwinder K; Théry, Clotilde; Brown, Guy C

    2013-10-22

    Delayed neuronal loss and brain atrophy after cerebral ischemia contribute to stroke and dementia pathology, but the mechanisms are poorly understood. Phagocytic removal of neurons is generally assumed to be beneficial and to occur only after neuronal death. However, we report herein that inhibition of phagocytosis can prevent delayed loss and death of functional neurons after transient brain ischemia. Two phagocytic proteins, Mer receptor tyrosine kinase (MerTK) and Milk fat globule EGF-like factor 8 (MFG-E8), were transiently up-regulated by macrophages/microglia after focal brain ischemia in vivo. Strikingly, deficiency in either protein completely prevented long-term functional motor deficits after cerebral ischemia and strongly reduced brain atrophy as a result of inhibiting phagocytosis of neurons. Correspondingly, in vitro glutamate-stressed neurons reversibly exposed the "eat-me" signal phosphatidylserine, leading to their phagocytosis by microglia; this neuronal loss was prevented in the absence of microglia and reduced if microglia were genetically deficient in MerTK or MFG-E8, both of which mediate phosphatidylserine-recognition. Thus, phagocytosis of viable neurons contributes to brain pathology and, surprisingly, blocking this process is strongly beneficial. Therefore, inhibition of specific phagocytic pathways may present therapeutic targets for preventing delayed neuronal loss after transient cerebral ischemia.

  20. The Zwicky Transient Facility

    NASA Astrophysics Data System (ADS)

    Kulkarni, Shrinivas R.

    2016-01-01

    The Zwicky Transient Facility (ZTF) has been designed with a singular focus: a systematic exploration of the night sky at a magnitude level well suited for spectral classification and follow up with the existing class of 4-m to 10-m class telescopes. ZTF is the successor to the Palomar Transient Factory (PTF). The discovery engine for ZTF is a 47 square degree camera (realized through 16 e2V monolithic CCDs) that fills the entire focal plane of the 48-inch Oschin telescope of the Palomar Observatory. Single 30-s epoch sensitivity is about 20.5 in g and R bands. The Infarared Processing & Analysis Center (IPAC) is the data center for ZTF. ZTF is a public-private partnership with equal contributions from a consortium of world-wide partners and an NSF MSIP grant. Forty percent of ZTF time is set aside for two major community surveys: a 3-day cadence survey of high latitudes (to mimic LSST) and a time domain survey of the entire Northern Galactic plane. We expect first light in February 2017 and begin a 3-year survey starting summer of 2017. The first year will be spent on building up deep reference images of the sky (a must for transient surveys). During the second year IPAC will deliver near archival quality photometric products within 12 hours of observations. By comparison to reference images photometric alerts will be sent out. Year 3 will see the near real-time release of image differencing products. A Community Science Advisory Committee (CSAC), chaired by S. Ridgway (NOAO), has been set up to both advise the PI and to ensure that the US community's interests are well served. Astronomers interested in getting a head start on ZTF may wish to peruse the data releases from PTF. Young people (or young at heart) may wish to attend the annual summer school on PTF/ZTF (August, Caltech campus). The Principal Investigator (PI) for the project is S. Kulkarni and the Project Scientist is Eric Bellm.For further details please consult http://www.ptf.caltech.edu/ztf

  1. Effects of chill stress on prompt and delayed chlorophyll fluorescence from leaves.

    PubMed

    Melcarek, P K; Brown, G N

    1977-12-01

    This paper describes the utilization of a portable solid state device for the simultaneous measurement of prompt and delayed fluorescence transients in leaves from a variety of species subjected to temperature lowering. The induction transients of the two phenomena were not identical as the peak in prompt fluorescence yield always preceded that of delayed fluorescence. Temperature lowering delayed the occurrence of peak fluorescence, increased prompt fluorescence yield, decreased delayed fluorescence yield, and caused the occurrence of a new, more rapid delayed fluorescence transient. Leaves from all species had qualitatively the same type of induction curves although the response to temperature differed between species. The delayed fluorescence yield of chill-sensitive species was reduced to a greater extent than that of chill-insensitive species. Cold hardening leaf material did not greatly change the fluorescence response to temperature lowering. Arrhenius plots showed a linear relationship between delayed fluorescence yield and temperature. There were no breaks that would suggest membrane lipid phase changes. The data indicate that thylakoid membranes of chill-sensitive species are less capable of maintaining a light-induced high energy state at low temperatures than are thylakoid membranes of chill-resistant species. PMID:16660193

  2. Assessing delay discounting in mice

    PubMed Central

    Mitchell, Suzanne H.

    2014-01-01

    Delay discounting (also intertemporal choice or impulsive choice) is the process by which delayed outcomes, such as delayed food delivery, are valued less than the same outcomes delivered immediately or with a shorter delay. This process is of interest because many psychopathologies, including substance dependence, pathological gambling, attention deficit hyperactivity disorder and conduct disorder, are characterized by heightened levels of delay discounting. Some of these disorders are heritable, and data indicate that delay discounting also has a genetic component. To identify the genes underlying the delay discounting decision-making process and genetic correlates of heightened discounting, researchers have used mouse models. This unit describes a protocol for generating delay discounting behavior in mice and discusses analysis techniques for such behavior. PMID:24510779

  3. Delayed Speech or Language Development

    MedlinePlus

    ... to Know About Zika & Pregnancy Delayed Speech or Language Development KidsHealth > For Parents > Delayed Speech or Language ... your child is right on schedule. Normal Speech & Language Development It's important to discuss early speech and ...

  4. Tooth formation - delayed or absent

    MedlinePlus

    Delayed or absent tooth formation; Teeth - delayed or absent formation ... The age at which a tooth comes in varies. Most infants get their first tooth between 6 and 9 months, but it may be earlier or later. ...

  5. Requirement for nuclear calcium signaling in Drosophila long-term memory.

    PubMed

    Weislogel, Jan-Marek; Bengtson, C Peter; Müller, Michaela K; Hörtzsch, Jan N; Bujard, Martina; Schuster, Christoph M; Bading, Hilmar

    2013-05-07

    Calcium is used throughout evolution as an intracellular signal transducer. In the mammalian central nervous system, calcium mediates the dialogue between the synapse and the nucleus that is required for transcription-dependent persistent neuronal adaptations. A role for nuclear calcium signaling in similar processes in the invertebrate brain has yet to be investigated. Here, we show by in vivo calcium imaging of adult brain neurons of the fruit fly Drosophila melanogaster, that electrical foot shocks used in olfactory avoidance conditioning evoked transient increases in cytosolic and nuclear calcium concentrations in neurons. These calcium signals were detected in Kenyon cells of the flies' mushroom bodies, which are sites of learning and memory related to smell. Acute blockade of nuclear calcium signaling during conditioning selectively and reversibly abolished the formation of long-term olfactory avoidance memory, whereas short-term, middle-term, or anesthesia-resistant olfactory memory remained unaffected. Thus, nuclear calcium signaling is required in flies for the progression of memories from labile to transcription-dependent long-lasting forms. These results identify nuclear calcium as an evolutionarily conserved signal needed in both invertebrate and vertebrate brains for transcription-dependent memory consolidation.

  6. Spatiotemporal calcium signaling in a Drosophila melanogaster cell line stably expressing a Drosophila muscarinic acetylcholine receptor.

    PubMed

    Cordova, D; Delpech, V Raymond; Sattelle, D B; Rauh, J J

    2003-11-01

    A muscarinic acetylcholine receptor (mAChR), DM1, expressed in the nervous system of Drosophila melanogaster, has been stably expressed in a Drosophila S2 cell line (S2-DM1) and used to investigate spatiotemporal calcium changes following agonist activation. Carbamylcholine (CCh) and oxotremorine are potent agonists, whereas application of the vertebrate M1 mAChR agonist, McN-A-343, results in a weak response. Activation of S2-DM1 receptors using CCh resulted in an increase in intracellular calcium ([Ca(2+)](i)) that was biphasic. Two distinct calcium sources were found to contribute to calcium signaling: (1) internal stores that are sensitive to both thapsigargin and 2-aminoethoxydiphenyl borate and (2) capacitative calcium entry. Spatiotemporal imaging of individual S2-DM1 cells showed that the CCh-induced [Ca(2+)](i) transient resulted from a homogeneous calcium increase throughout the cell, indicative of calcium release from internal stores. In contrast, ionomycin induced the formation of a "calcium ring" at the cell periphery, consistent with external calcium influx. PMID:12827518

  7. Transient mitochondrial permeability transition mediates excitotoxicity in glutamate-sensitive NSC34D motor neuron-like cells

    PubMed Central

    Liu, Xiaoyun; Xu, Shangcheng; Wang, Pei; Wang, Wang

    2015-01-01

    Excitotoxicity plays a critical role in neurodegenerative disease. Cytosolic calcium overload and mitochondrial dysfunction are among the major mediators of high level glutamate-induced neuron death. Here, we show that the transient opening of mitochondrial permeability transition pore (tMPT) bridges cytosolic calcium signaling and mitochondrial dysfunction and mediates glutamate-induced neuron death. Incubation of the differentiated motor neuron-like NSC34D cells with glutamate (1 mM) acutely induces cytosolic calcium transient (30% increase). Glutamate also stimulates tMPT opening, as reflected by a 2-fold increase in the frequency of superoxide flash, a bursting superoxide production event in individual mitochondria coupled to tMPT opening. The glutamate-induced tMPT opening is attenuated by suppressing cytosolic calcium influx and abolished by inhibiting mitochondrial calcium uniporter (MCU) with Ru360 (100 µM) or MCU shRNA. Further, increased cytosolic calcium is sufficient to induce tMPT in a mitochondrial calcium dependent manner. Finally, chronic glutamate incubation (24 hr) persistently elevates the probability of tMPT opening, promotes oxidative stress and induces neuron death. Attenuating tMPT activity or inhibiting MCU protects NSC34D cells from glutamate-induced cell death. These results indicate that high level glutamate-induced neuron toxicity is mediated by tMPT, which connects increased cytosolic calcium signal to mitochondrial dysfunction. PMID:26024861

  8. Microwave-assisted magnetization reversal using transient precession of magnetization in permalloy hexagons

    NASA Astrophysics Data System (ADS)

    Okano, Genki; Nozaki, Yukio

    2016-06-01

    Microwave-assisted magnetization reversal utilizing a transient precession of magnetization was demonstrated in a permalloy hexagon by applying a 25-ns-wide microwave field and a 500-ps-wide pulsed field with a tunable delay to the microwave field. The switching field in a combination of these two fields becomes smaller than that in only the microwave field, and this additional reduction in switching field oscillates relative to the delay time. From the comparison with the results of micromagnetic simulations, we found that the oscillatory behavior is attributed to the beats in transient precession that occurs in the early stage of microwave-field-induced magnetization excitation.

  9. Transient complex peroxisomal interactions

    PubMed Central

    Bonekamp, Nina A.; Schrader, Michael

    2012-01-01

    Mitochondria and peroxisomes are ubiquitous subcellular organelles that fulfill essential metabolic functions, rendering them indispensable for human development and health. Both are highly dynamic organelles that can undergo remarkable changes in morphology and number to accomplish cellular needs. While mitochondrial dynamics are also regulated by frequent fusion events, the fusion of mature peroxisomes in mammalian cells remained a matter of debate. In our recent study, we clarified systematically that there is no complete fusion of mature peroxisomes analogous to mitochondria. Moreover, in contrast to key division components such as DLP1, Fis1 or Mff, mitochondrial fusion proteins were not localized to peroxisomes. However, we discovered and characterized novel transient, complex interactions between individual peroxisomes which may contribute to the homogenization of the often heterogeneous peroxisomal compartment, e.g., by distribution of metabolites, signals or other “molecular information” via interperoxisomal contact sites. PMID:23336019

  10. Perturbations for transient acceleration

    SciTech Connect

    Vargas, Cristofher Zuñiga; Zimdahl, Winfried; Hipólito-Ricaldi, Wiliam S. E-mail: hipolito@ceunes.ufes.br

    2012-04-01

    According to the standard ΛCDM model, the accelerated expansion of the Universe will go on forever. Motivated by recent observational results, we explore the possibility of a finite phase of acceleration which asymptotically approaches another period of decelerated expansion. Extending an earlier study on a corresponding homogeneous and isotropic dynamics, in which interactions between dark matter and dark energy are crucial, the present paper also investigates the dynamics of the matter perturbations both on the Newtonian and General Relativistic (GR) levels and quantifies the potential relevance of perturbations of the dark-energy component. In the background, the model is tested against the Supernova type Ia (SNIa) data of the Constitution set and on the perturbative level against growth rate data, among them those of the WiggleZ survey, and the data of the 2dFGRS project. Our results indicate that a transient phase of accelerated expansion is not excluded by current observations.

  11. Transient infrared transmission spectroscopy

    SciTech Connect

    Jones, R.W.; McClelland, J.F. )

    1990-10-15

    Transient infrared transmission spectroscopy is a new method that can acquire analytically useful transmission spectra from moving, optically thick solids. No sample preparation is required. The spectra are of sufficient quality for accurate quantitative compositional analysis. The method works by the creation of a thin, short-lived, chilled layer at the sample surface. Blackbody-like thermal emission from the bulk of the sample is selectively absorbed as it passes through the chilled layer, so the transmission spectrum of the layer is superimposed on the observed thermal emission. Spectra of polycarbonate, beeswax, and copolymers of methyl and butyl methacrylate are presented. Compositional analysis of the methacrylate copolymers with a standard error or prediction of only 0.87 mol % is demonstrated.

  12. Transient infrared transmission spectroscopy.

    PubMed

    Jones, R W; McClelland, J F

    1990-10-15

    Transient infrared transmission spectroscopy is a new method that can acquire analytically useful transmission spectra from moving, optically thick solids. No sample preparation is required. The spectra are of sufficient quality for accurate quantitative compositional analysis. The method works by the creation of a thin, short-lived, chilled layer at the sample surface. Blackbody-like thermal emission from the bulk of the sample is selectively absorbed as it passes through the chilled layer, so the transmission spectrum of the layer is superimposed on the observed thermal emission. Spectra of polycarbonate, beeswax, and copolymers of methyl and butyl methacrylate are presented. Compositional analysis of the methacrylate copolymers with a standard error of prediction of only 0.87 mol % is demonstrated.

  13. SLO BK Potassium Channels Couple Gap Junctions to Inhibition of Calcium Signaling in Olfactory Neuron Diversification.

    PubMed

    Alqadah, Amel; Hsieh, Yi-Wen; Schumacher, Jennifer A; Wang, Xiaohong; Merrill, Sean A; Millington, Grethel; Bayne, Brittany; Jorgensen, Erik M; Chuang, Chiou-Fen

    2016-01-01

    The C. elegans AWC olfactory neuron pair communicates to specify asymmetric subtypes AWCOFF and AWCON in a stochastic manner. Intercellular communication between AWC and other neurons in a transient NSY-5 gap junction network antagonizes voltage-activated calcium channels, UNC-2 (CaV2) and EGL-19 (CaV1), in the AWCON cell, but how calcium signaling is downregulated by NSY-5 is only partly understood. Here, we show that voltage- and calcium-activated SLO BK potassium channels mediate gap junction signaling to inhibit calcium pathways for asymmetric AWC differentiation. Activation of vertebrate SLO-1 channels causes transient membrane hyperpolarization, which makes it an important negative feedback system for calcium entry through voltage-activated calcium channels. Consistent with the physiological roles of SLO-1, our genetic results suggest that slo-1 BK channels act downstream of NSY-5 gap junctions to inhibit calcium channel-mediated signaling in the specification of AWCON. We also show for the first time that slo-2 BK channels are important for AWC asymmetry and act redundantly with slo-1 to inhibit calcium signaling. In addition, nsy-5-dependent asymmetric expression of slo-1 and slo-2 in the AWCON neuron is necessary and sufficient for AWC asymmetry. SLO-1 and SLO-2 localize close to UNC-2 and EGL-19 in AWC, suggesting a role of possible functional coupling between SLO BK channels and voltage-activated calcium channels in AWC asymmetry. Furthermore, slo-1 and slo-2 regulate the localization of synaptic markers, UNC-2 and RAB-3, in AWC neurons to control AWC asymmetry. We also identify the requirement of bkip-1, which encodes a previously identified auxiliary subunit of SLO-1, for slo-1 and slo-2 function in AWC asymmetry. Together, these results provide an unprecedented molecular link between gap junctions and calcium pathways for terminal differentiation of olfactory neurons.

  14. SLO BK Potassium Channels Couple Gap Junctions to Inhibition of Calcium Signaling in Olfactory Neuron Diversification

    PubMed Central

    Schumacher, Jennifer A.; Wang, Xiaohong; Merrill, Sean A.; Millington, Grethel; Bayne, Brittany; Jorgensen, Erik M.; Chuang, Chiou-Fen

    2016-01-01

    The C. elegans AWC olfactory neuron pair communicates to specify asymmetric subtypes AWCOFF and AWCON in a stochastic manner. Intercellular communication between AWC and other neurons in a transient NSY-5 gap junction network antagonizes voltage-activated calcium channels, UNC-2 (CaV2) and EGL-19 (CaV1), in the AWCON cell, but how calcium signaling is downregulated by NSY-5 is only partly understood. Here, we show that voltage- and calcium-activated SLO BK potassium channels mediate gap junction signaling to inhibit calcium pathways for asymmetric AWC differentiation. Activation of vertebrate SLO-1 channels causes transient membrane hyperpolarization, which makes it an important negative feedback system for calcium entry through voltage-activated calcium channels. Consistent with the physiological roles of SLO-1, our genetic results suggest that slo-1 BK channels act downstream of NSY-5 gap junctions to inhibit calcium channel-mediated signaling in the specification of AWCON. We also show for the first time that slo-2 BK channels are important for AWC asymmetry and act redundantly with slo-1 to inhibit calcium signaling. In addition, nsy-5-dependent asymmetric expression of slo-1 and slo-2 in the AWCON neuron is necessary and sufficient for AWC asymmetry. SLO-1 and SLO-2 localize close to UNC-2 and EGL-19 in AWC, suggesting a role of possible functional coupling between SLO BK channels and voltage-activated calcium channels in AWC asymmetry. Furthermore, slo-1 and slo-2 regulate the localization of synaptic markers, UNC-2 and RAB-3, in AWC neurons to control AWC asymmetry. We also identify the requirement of bkip-1, which encodes a previously identified auxiliary subunit of SLO-1, for slo-1 and slo-2 function in AWC asymmetry. Together, these results provide an unprecedented molecular link between gap junctions and calcium pathways for terminal differentiation of olfactory neurons. PMID:26771544

  15. Controlled environment life support system: Calcium-related leaf injuries on plants

    NASA Technical Reports Server (NTRS)

    Tibbitts, T. W.

    1986-01-01

    Calcium related injuries to plants grown in controlled environments under conditions which maximize plant growth rates are described. Procedures to encourage movement of calcium into developing leaves of lettuce plants were investigated. The time course and pattern of calcium accumulation was determined to develop effective control procedures for this injury, termed tipburn. Procedures investigated were: (1) increasing the relative humidity to saturation during the dark period and altering root temperatures, (2) maximizing water stress during light and minimizing water stress during dark periods, (3) shortening the light-dark cycle lengths in combination with elevated moisture levels during the dark cycles, (4) reducing nutrient concentrations and (5) vibrating the plants. Saturated humidities at night increased the rate of growth and the large fluctuation in plant water potential encouraged calcium movement to the young leaves and delayed tipburn. Root temperature regulation between 15 and 26 C was not effective in preventing tipburn. Attempts to modulate water stress produced little variation, but no difference in tipburn development. Variations in light-dark cycle lengths also had no effect on calcium concentrations within developing leaves and no variation in tipburn development. Low concentrations of nutrient solution delayed tipburn, presumably because of greater calcium transport in the low concentration plants. Shaking of the plants did not prevent tipburn, but did delay it slightly.

  16. PYK2: A Calcium-sensitive Protein Tyrosine Kinase Activated in Response to Fertilization of the Zebrafish Oocyte

    PubMed Central

    Sharma, Dipika; Kinsey, William H.

    2012-01-01

    Fertilization begins with binding and fusion of a sperm with the oocyte, a process that triggers a high amplitude calcium transient which propagates through the oocyte and stimulates a series of preprogrammed signal transduction events critical for zygote development. Identification of the pathways downstream of this calcium transient remains an important step in understanding the basis of zygote quality. The present study demonstrates that the calcium-calmodulin sensitive protein tyrosine kinase PYK2 is a target of the fertilization-induced calcium transient in the zebrafish oocyte and that it plays an important role in actin-mediated events critical for sperm incorporation. At fertilization, PYK2 was activated initially at the site of sperm-oocyte interaction and was closely associated with actin filaments forming the fertilization cone. Later PYK2 activation was evident throughout the entire oocyte cortex, however activation was most intense over the animal hemisphere. Fertilization-induced PYK2 activation could be blocked by suppressing calcium transients in the ooplasm via injection of BAPTA as a calcium chelator. PYK2 activation could be artificially induced in unfertilized oocytes by injection of IP3 at concentrations sufficient to induce calcium release. Functionally, suppression of PYK2 activity by chemical inhibition or by injection of a dominant-negative construct encoding the N-terminal ERM domain of PKY2 inhibited formation of an organized fertilization cone and reduced the frequency of successful sperm incorporation. Together, the above findings support a model in which PYK2 responds to the fertilization-induced calcium transient by promoting reorganization of the cortical actin cytoskeleton to form the fertilization cone. PMID:23084926

  17. PYK2: a calcium-sensitive protein tyrosine kinase activated in response to fertilization of the zebrafish oocyte.

    PubMed

    Sharma, Dipika; Kinsey, William H

    2013-01-01

    Fertilization begins with binding and fusion of a sperm with the oocyte, a process that triggers a high amplitude calcium transient which propagates through the oocyte and stimulates a series of preprogrammed signal transduction events critical for zygote development. Identification of the pathways downstream of this calcium transient remains an important step in understanding the basis of zygote quality. The present study demonstrates that the calcium-calmodulin sensitive protein tyrosine kinase PYK2 is a target of the fertilization-induced calcium transient in the zebrafish oocyte and that it plays an important role in actin-mediated events critical for sperm incorporation. At fertilization, PYK2 was activated initially at the site of sperm-oocyte interaction and was closely associated with actin filaments forming the fertilization cone. Later PYK2 activation was evident throughout the entire oocyte cortex, however activation was most intense over the animal hemisphere. Fertilization-induced PYK2 activation could be blocked by suppressing calcium transients in the ooplasm via injection of BAPTA as a calcium chelator. PYK2 activation could be artificially induced in unfertilized oocytes by injection of IP3 at concentrations sufficient to induce calcium release. Functionally, suppression of PYK2 activity by chemical inhibition or by injection of a dominant-negative construct encoding the N-terminal ERM domain of PKY2 inhibited formation of an organized fertilization cone and reduced the frequency of successful sperm incorporation. Together, the above findings support a model in which PYK2 responds to the fertilization-induced calcium transient by promoting reorganization of the cortical actin cytoskeleton to form the fertilization cone.

  18. Calcium signal induced by mechanical perturbation of osteoclasts.

    PubMed

    Xia, S L; Ferrier, J

    1995-06-01

    Multinucleated osteoclasts from rabbit long bone, 1-6 days in culture, respond to mechanical perturbation with a transient increase of intracellular calcium concentration ([Ca2+]i), as measured with the fluorescent indicator fluo-3 on a confocal laser scanning microscope. In experiments with different extracellular calcium concentrations (from 11.8 mM to calcium-free), the incidence, the magnitude, and the duration of [Ca2+]i responses decreases with decreasing bathing [Ca2+]. Following mechanical perturbation, a thapsigargin-induced [Ca2+]i response has a lower magnitude than the thapsigargin-induced response without mechanical perturbation. In thapsigargin-pretreated osteoclasts the mechanical perturbation-induced rise in [Ca2+]i is larger and longer than in control cells. Ni2+ inhibits the incidence and decreases both the magnitude and the duration of the responses, while nifedipine, verapamil, and Gd3+ have no effect. These measurements show that rabbit osteoclasts transduce a mechanical perturbation of the cell membrane into a [Ca2+]i signal via both a calcium influx and an internal calcium release.

  19. Automated Classification of Transient and Variable Sources

    NASA Astrophysics Data System (ADS)

    Donalek, Ciro; Graham, M.; Mahabal, A. A.; Djorgovski, S. G.; Drake, A. J.; Yang, M.; Maker, A.; Duan, V.

    2013-01-01

    Better and faster technology is increasing the amount of collected data in many scientific fields, all of them requiring a common task: extract knowledge from massive, multi parametric data sets, as rapidly and efficiently possible. Most systems today rely on a delayed human judgment and this “manual” approach will simply not scale to the next generation of surveys thus the need of a machine learning approach. We present a sleeping expert framework that makes use of many different ensembles of classifiers (eg, kNN, Neural Networks, Bayesian Networks, Decision Trees) that can be activated according to the input data; results from the single classifiers are then combined in order to achieve a better classification rate. Using data sets extracted from the ongoing Catalina Real-Time Transient Surveys (CRTS), we show the results obtained applying this framework to different astronomical problems (eg, classifying transients on the basis of features describing the light curves, systematic search of CV). Moreover, we illustrate a variety of feature selection strategies used to identify the subsets that give the most information; given the high number of parameters this is quickly becoming a crucial task in analyzing astronomical data sets.

  20. Compact Femtosecond-Millisecond Transient Absorption Spectrometer

    NASA Astrophysics Data System (ADS)

    Carroll, Elizabeth; Hill, Melissa; Madsen, Dorte; Malley, Konstantin; Larsen, Delmar

    2008-03-01

    The measurement of population dynamics in biological, chemical, and solid-state samples occurring over 10-15-10^1 seconds requires a combination of transient absorption techniques, typically involving different laser systems and detection electronics (e.g. femtosecond transient absorption and nanosecond flash photolysis). The difficulty in exactly matching excitation conditions often prohibits connecting ultrafast and longer time measurements, particularly in samples exhibiting nonlinear kinetics. We present a simple solution to bridge the femtosecond and microsecond domains with an inexpensive modification of a kHz amplified Ti:Sapphire laser. By introducing a secondary pulse-picker between the laser oscillator (75 MHz) and amplifier, we can electronically delay unamplified 800-nm probe pulses in 13.3-ns steps. The 5-nJ pulses seed a photonic crystal fiber to produce a supercontinuum (450-1100 nm) for broadband probing. We demonstrate the system capability by resolving formation and decay dynamics, spanning 10 decades (10-14-10-4 s), of photoexcited solvated electrons in sinapic acid, and triplet states and quinonoid intermediates in Vitamin B6.

  1. Aequorin response facilitation and intracellular calcium accumulation in molluscan neurones

    PubMed Central

    Smith, Stephen J.; Zucker, Robert S.

    1980-01-01

    indicates that the dye reports only about 1% of the calcium concentration increment expected from knowledge of cell volume and the charge carried by calcium current during a depolarizing pulse. This suggests that cytoplasmic buffering of free calcium must occur rapidly, on a time scale comparable to the response time of arsenazo III (about 1 msec) or more rapidly. 7. The slow potassium tail current following a depolarizing pulse is calcium-dependent and probably provides an approximate index of the internal sub-membrane calcium concentration. Increments in this current after repetitive pulses display a slight progressive depression rather than facilitation. 8. Since neither calcium currents nor the concentration transients show facilitation, we conclude that aequorin response facilitation is due to the non-linear dependence of aequorin photo-emissions on calcium concentration. This conclusion is supported by a finding that the very different kinetics of arsenazo III responses and aequorin responses can be reconciled by a simple model representing calcium accumulation and known response properties of the two indicator substances. 9. In a train of impulses evoked by injecting depolarizing current into a neurone, the successive action potentials grow in duration. Nevertheless, a nearly constant calcium influx signalled by arsenazo III accompanies broadening action potentials. PMID:6247486

  2. Rapid transcriptome changes induced by cytosolic Ca2+ transients reveal ABRE-related sequences as Ca2+-responsive cis elements in Arabidopsis.

    PubMed

    Kaplan, Boaz; Davydov, Olga; Knight, Heather; Galon, Yael; Knight, Marc R; Fluhr, Robert; Fromm, Hillel

    2006-10-01

    The regulation of gene expression by cellular calcium is crucial for plant defense against biotic and abiotic stresses. However, the number of genes known to respond to specific transient calcium signals is limited, and as yet there is no definition of a calcium-responsive cis element in plants. Here, we generated specific cytosolic calcium transients in intact Arabidopsis thaliana seedlings and linked them to early transcriptome changes, followed by bioinformatic analysis of the responsive genes. A cytosolic calcium transient induced by calmodulin antagonists and blocked by lanthanides was characterized using aequorin-based luminometry and photon imaging. Analysis of transcriptome changes revealed 230 calcium-responsive genes, of which 162 were upregulated and 68 were downregulated. These include known early stress-responsive genes as well as genes of unknown function. Analysis of their upstream regions revealed, exclusively in the upregulated genes, a highly significant occurrence of a consensus sequence (P < 10(-13)) comprising two abscisic acid-specific cis elements: the abscisic acid-responsive element (ABRE; CACGTG[T/C/G]) and its coupling element ([C/A]ACGCG[T/C/G]) [corrected] Finally, we show that a tetramer of the ABRE cis element is sufficient to confer transcriptional activation in response to cytosolic Ca(2+) transients. Thus, at least for some specific Ca(2+) transients and motif combinations, ABREs function as Ca(2+)-responsive cis elements. PMID:16980540

  3. Rapid transcriptome changes induced by cytosolic Ca2+ transients reveal ABRE-related sequences as Ca2+-responsive cis elements in Arabidopsis.

    PubMed

    Kaplan, Boaz; Davydov, Olga; Knight, Heather; Galon, Yael; Knight, Marc R; Fluhr, Robert; Fromm, Hillel

    2006-10-01

    The regulation of gene expression by cellular calcium is crucial for plant defense against biotic and abiotic stresses. However, the number of genes known to respond to specific transient calcium signals is limited, and as yet there is no definition of a calcium-responsive cis element in plants. Here, we generated specific cytosolic calcium transients in intact Arabidopsis thaliana seedlings and linked them to early transcriptome changes, followed by bioinformatic analysis of the responsive genes. A cytosolic calcium transient induced by calmodulin antagonists and blocked by lanthanides was characterized using aequorin-based luminometry and photon imaging. Analysis of transcriptome changes revealed 230 calcium-responsive genes, of which 162 were upregulated and 68 were downregulated. These include known early stress-responsive genes as well as genes of unknown function. Analysis of their upstream regions revealed, exclusively in the upregulated genes, a highly significant occurrence of a consensus sequence (P < 10(-13)) comprising two abscisic acid-specific cis elements: the abscisic acid-responsive element (ABRE; CACGTG[T/C/G]) and its coupling element ([C/A]ACGCG[T/C/G]) [corrected] Finally, we show that a tetramer of the ABRE cis element is sufficient to confer transcriptional activation in response to cytosolic Ca(2+) transients. Thus, at least for some specific Ca(2+) transients and motif combinations, ABREs function as Ca(2+)-responsive cis elements.

  4. Calcium signaling in taste cells.

    PubMed

    Medler, Kathryn F

    2015-09-01

    The sense of taste is a common ability shared by all organisms and is used to detect nutrients as well as potentially harmful compounds. Thus taste is critical to survival. Despite its importance, surprisingly little is known about the mechanisms generating and regulating responses to taste stimuli. All taste responses depend on calcium signals to generate appropriate responses which are relayed to the brain. Some taste cells have conventional synapses and rely on calcium influx through voltage-gated calcium channels. Other taste cells lack these synapses and depend on calcium release to formulate an output signal through a hemichannel. Beyond establishing these characteristics, few studies have focused on understanding how these calcium signals are formed. We identified multiple calcium clearance mechanisms that regulate calcium levels in taste cells as well as a calcium influx that contributes to maintaining appropriate calcium homeostasis in these cells. Multiple factors regulate the evoked taste signals with varying roles in different cell populations. Clearly, calcium signaling is a dynamic process in taste cells and is more complex than has previously been appreciated. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.

  5. Programmable Differential Delay Circuit With Fine Delay Adjustment

    DOEpatents

    DeRyckere, John F.; Jenkins, Philip Nord; Cornett, Frank Nolan

    2002-07-09

    Circuitry that provides additional delay to early arriving signals such that all data signals arrive at a receiving latch with same path delay. The delay of a forwarded clock reference is also controlled such that the capturing clock edge will be optimally positioned near quadrature (depending on latch setup/hold requirements). The circuitry continuously adapts to data and clock path delay changes and digital filtering of phase measurements reduce errors brought on by jittering data edges. The circuitry utilizes only the minimum amount of delay necessary to achieve objective thereby limiting any unintended jitter. Particularly, this programmable differential delay circuit with fine delay adjustment is designed to allow the skew between ASICS to be minimized. This includes skew between data bits, between data bits and clocks as well as minimizing the overall skew in a channel between ASICS.

  6. Fruit Calcium: Transport and Physiology.

    PubMed

    Hocking, Bradleigh; Tyerman, Stephen D; Burton, Rachel A; Gilliham, Matthew

    2016-01-01

    Calcium has well-documented roles in plant signaling, water relations and cell wall interactions. Significant research into how calcium impacts these individual processes in various tissues has been carried out; however, the influence of calcium on fruit ripening has not been thoroughly explored. Here, we review the current state of knowledge on how calcium may impact the development, physical traits and disease susceptibility of fruit through facilitating developmental and stress response signaling, stabilizing membranes, influencing water relations and modifying cell wall properties through cross-linking of de-esterified pectins. We explore the involvement of calcium in hormone signaling integral to the physiological mechanisms behind common disorders that have been associated with fruit calcium deficiency (e.g., blossom end rot in tomatoes or bitter pit in apples). This review works toward an improved understanding of how the many roles of calcium interact to influence fruit ripening, and proposes future research directions to fill knowledge gaps. Specifically, we focus mostly on grapes and present a model that integrates existing knowledge around these various functions of calcium in fruit, which provides a basis for understanding the physiological impacts of sub-optimal calcium nutrition in grapes. Calcium accumulation and distribution in fruit is shown to be highly dependent on water delivery and cell wall interactions in the apoplasm. Localized calcium deficiencies observed in particular species or varieties can result from differences in xylem morphology, fruit water relations and pectin composition, and can cause leaky membranes, irregular cell wall softening, impaired hormonal signaling and aberrant fruit development. We propose that the role of apoplasmic calcium-pectin crosslinking, particularly in the xylem, is an understudied area that may have a key influence on fruit water relations. Furthermore, we believe that improved knowledge of the calcium

  7. Fruit Calcium: Transport and Physiology

    PubMed Central

    Hocking, Bradleigh; Tyerman, Stephen D.; Burton, Rachel A.; Gilliham, Matthew

    2016-01-01

    Calcium has well-documented roles in plant signaling, water relations and cell wall interactions. Significant research into how calcium impacts these individual processes in various tissues has been carried out; however, the influence of calcium on fruit ripening has not been thoroughly explored. Here, we review the current state of knowledge on how calcium may impact the development, physical traits and disease susceptibility of fruit through facilitating developmental and stress response signaling, stabilizing membranes, influencing water relations and modifying cell wall properties through cross-linking of de-esterified pectins. We explore the involvement of calcium in hormone signaling integral to the physiological mechanisms behind common disorders that have been associated with fruit calcium deficiency (e.g., blossom end rot in tomatoes or bitter pit in apples). This review works toward an improved understanding of how the many roles of calcium interact to influence fruit ripening, and proposes future research directions to fill knowledge gaps. Specifically, we focus mostly on grapes and present a model that integrates existing knowledge around these various functions of calcium in fruit, which provides a basis for understanding the physiological impacts of sub-optimal calcium nutrition in grapes. Calcium accumulation and distribution in fruit is shown to be highly dependent on water delivery and cell wall interactions in the apoplasm. Localized calcium deficiencies observed in particular species or varieties can result from differences in xylem morphology, fruit water relations and pectin composition, and can cause leaky membranes, irregular cell wall softening, impaired hormonal signaling and aberrant fruit development. We propose that the role of apoplasmic calcium-pectin crosslinking, particularly in the xylem, is an understudied area that may have a key influence on fruit water relations. Furthermore, we believe that improved knowledge of the calcium

  8. Delay Choice vs. Delay Maintenance: Different Measures of Delayed Gratification in Capuchin Monkeys (Cebus apella)

    PubMed Central

    Addessi, Elsa; Paglieri, Fabio; Beran, Michael J.; Evans, Theodore A.; Macchitella, Luigi; De Petrillo, Francesca; Focaroli, Valentina

    2013-01-01

    Delaying gratification involves two components: (i) delay choice (selecting a delayed reward over an immediate one), and (ii) delay maintenance (sustaining the decision to delay gratification even if the immediate reward is available during the delay). In primates, two tasks most commonly have explored these components, the Intertemporal choice task and the Accumulation task. It is unclear whether these tasks provide equivalent measures of delay of gratification. Here, we compared the performance of the same capuchin monkeys, belonging to two study populations, between these tasks. We found only limited evidence of a significant correlation in performance. Consequently, in contrast to what is often assumed, our data provide only partial support to the hypothesis that these tasks provide equivalent measures of delay of gratification. PMID:23544770

  9. Complexometric Determination of Calcium

    NASA Astrophysics Data System (ADS)

    Nielsen, S. Suzanne

    Ethylenediaminetetraacetate (EDTA) complexes with numerous mineral ions, including calcium and magnesium. This reaction can be used to determine the amount of these minerals in a sample by a complexometric titration. Endpoints in the titration are detected using indicators that change color when they complex with mineral ions. Calmagite and eriochrome black T (EBT) are such indicators that change from blue to pink when they complex with calcium and magnesium. In the titration of a mineral-containing solution with EDTA, the solution turns from pink to blue at the endpoint with either indicator. The pH affects a complexometric EDTA titration in several ways, and must be carefully controlled. A major application of EDTA titration is testing the hardness of water, for which the method described is an official one (Standard Methods for the Examination of Water and Wastewater, Method 2340C; AOAC Method 920.196).

  10. DISTILLATION OF CALCIUM

    DOEpatents

    Barton, J.

    1954-07-27

    This invention relates to an improvement in the process for the purification of caicium or magnesium containing an alkali metal as impurity, which comprises distiiling a batch of the mixture in two stages, the first stage distillation being carried out in the presence of an inert gas at an absolute pressure substantially greater than the vapor pressure of calcium or maguesium at the temperature of distillation, but less than the vaper pressure at that temperature of the alkali metal impurity so that only the alkali metal is vaporized and condensed on a condensing surface. A second stage distilso that substantially only the calcium or magnesium distills under its own vapor pressure only and condenses in solid form on a lower condensing surface.

  11. Synthesis of calcium superoxide

    NASA Technical Reports Server (NTRS)

    Rewick, R. T.; Blucher, W. G.; Estacio, P. L.

    1972-01-01

    Efforts to prepare Ca(O2) sub 2 from reactions of calcium compounds with 100% O3 and with O(D-1) atoms generated by photolysis of O3 at 2537 A are described. Samples of Ca(OH) sub 2, CaO, CaO2, Ca metal, and mixtures containing suspected impurities to promote reaction have been treated with excess O3 under static and flow conditions in the presence and absence of UV irradiation. Studies with KO2 suggest that the superoxide anion is stable to radiation at 2537 A but reacts with oxygen atoms generated by the photolysis of O3 to form KO3. Calcium superoxide is expected to behave in an analogous.

  12. Delay-based reservoir computing using semiconductor ring lasers

    NASA Astrophysics Data System (ADS)

    Nguimdo, Romain Modeste; Danckaert, Jan; Verschaffelt, Guy; Van der Sande, Guy

    2014-05-01

    Delay systems subject to delayed optical feedback have recently shown great potential in solving computationally hard tasks. By implementing a neuro-inspired computational scheme relying on the transient response to optical data injection, high processing speeds have been demonstrated. However, reservoir computing systems based on delay dynamics discussed in the literature are designed by coupling many different stand-alone components which lead to bulky, lack of long-term stability, non-monolithic systems. Here we numerically investigate the possibility of implementing reservoir computing schemes based on semiconductor ring lasers as they are scalable and can be easily implemented on chip. We numerically benchmark our system on a chaotic time-series prediction task.

  13. A physiologic differentiation between delayed and immediate hypersensitivity

    PubMed Central

    Apicella, Michael A.; Allen, James C.

    1969-01-01

    Studies have been made of movement of various macromolecules into and out of the pleural space of guinea pigs during the course of a delayed hypersensitivity reaction to purified protein derivative (PPD), and a passively transferred immediate hypersensitivity reaction to ovalbumin. While the immediate hypersensitivity reaction transiently alters vascular permeability as shown by increased movement of macromolecules into the chest, the delayed hypersensitivity reaction is marked by a decreased capacity to resorb macromolecules from the pleural space. The data suggest that the two hypersensitivity reactions may be distinguished by these physiologic differences. Additional data from studies of a chemically induced pleural effusion in these animals suggest that some type of outflow obstruction is necessary for the development of effusion, but that the outflow defect caused by the irritating chemical is based on a different mechanism than that seen during the delayed hypersensitivity reaction. PMID:4179171

  14. Effect of aspartame on circadian oscillations of calcium and inorganic phosphorus in rats.

    PubMed

    Rajasekar, P; Manivasagam, T; Subramanian, P

    2004-08-01

    The effect of aspartame on circadian rhythms of calcium and inorganic phosphorus levels was studied in rats. Acrophase delays in calcium rhythms and advances in inorganic phosphorus rhythms and alteration in mesor values in both rhythms were observed in aspartame-treated rats. However, no change in amplitude values was observed. Oral administration of aspartame leads to increased levels of aspartate in the brain, which could alter the characteristics of calcium and inorganic phosphorus rhythms, possibly by modulating transmission in several areas/nuclei in brain, including retinohypothalamic tract (RHT) and suprachiasmatic nuclei (SCN).

  15. Calcium hydroxylapatite: Radiesse.

    PubMed

    Ahn, Min S

    2007-02-01

    Among the array of choices for aesthetic soft tissue fillers, Radiesse occupies a unique niche as a safe, easily administered, "semi-permanent" material. Composed of calcium hydroxylapatite in a gel matrix, it has a proven safety profile and has been approved by the US Food and Drug Administration for use in the nasolabial folds and for HIV lipoatrophy. Radiesse have evolved quickly into a effective filler for moderately deep facial folds with high patient and physician approval.

  16. Adaptive Phase Delay Generator

    NASA Technical Reports Server (NTRS)

    Greer, Lawrence

    2013-01-01

    There are several experimental setups involving rotating machinery that require some form of synchronization. The adaptive phase delay generator (APDG) the Bencic-1000 is a flexible instrument that allows the user to generate pulses synchronized to the rising edge of a tachometer signal from any piece of rotating machinery. These synchronized pulses can vary by the delay angle, pulse width, number of pulses per period, number of skipped pulses, and total number of pulses. Due to the design of the pulse generator, any and all of these parameters can be changed independently, yielding an unparalleled level of versatility. There are two user interfaces to the APDG. The first is a LabVIEW program that has the advantage of displaying all of the pulse parameters and input signal data within one neatly organized window on the PC monitor. Furthermore, the LabVIEW interface plots the rpm of the two input signal channels in real time. The second user interface is a handheld portable device that goes anywhere a computer is not accessible. It consists of a liquid-crystal display and keypad, which enable the user to control the unit by scrolling through a host of command menus and parameter listings. The APDG combines all of the desired synchronization control into one unit. The experimenter can adjust the delay, pulse width, pulse count, number of skipped pulses, and produce a specified number of pulses per revolution. Each of these parameters can be changed independently, providing an unparalleled level of versatility when synchronizing hardware to a host of rotating machinery. The APDG allows experimenters to set up quickly and generate a host of synchronizing configurations using a simple user interface, which hopefully leads to faster results.

  17. Transient precursor strategy or very small biological apatite crystals?

    PubMed

    Grynpas, Marc D; Omelon, Sidney

    2007-08-01

    The mechanisms of skeletal mineralization have been studied and debated for decades. Recent Raman spectroscopic identification of octacalcium phosphate-like phosphate ions and possibly amorphous calcium phosphate ions in nascent bone mineral were claimed to support a transient precursor strategy for bone apatite formation. However, this data does not refute the theory that the newest, detectable bone mineral is very small, poorly crystalline biological apatite, because non-apatitic phosphate species have previously been identified in biological apatite and detected on the surfaces of nano-sized hydroxyapatite crystals.

  18. Summer 1993 Transient Student Report.

    ERIC Educational Resources Information Center

    Kent State Univ., Warren, OH. Office of Institutional Research.

    A study was conducted by the Trumbull Campus (TC) of Kent State University, in Ohio, to determine the motivations, objectives, and level of satisfaction of transient students, or students pursuing a degree at another institution but enrolled in courses at TC. Surveys were mailed to 50 transient students enrolled in summer 1993, with completed…

  19. Vehicle barrier with access delay

    DOEpatents

    Swahlan, David J; Wilke, Jason

    2013-09-03

    An access delay vehicle barrier for stopping unauthorized entry into secure areas by a vehicle ramming attack includes access delay features for preventing and/or delaying an adversary from defeating or compromising the barrier. A horizontally deployed barrier member can include an exterior steel casing, an interior steel reinforcing member and access delay members disposed within the casing and between the casing and the interior reinforcing member. Access delay members can include wooden structural lumber, concrete and/or polymeric members that in combination with the exterior casing and interior reinforcing member act cooperatively to impair an adversarial attach by thermal, mechanical and/or explosive tools.

  20. Delay reduction: current status.

    PubMed

    Fantino, E; Preston, R A; Dunn, R

    1993-07-01

    Delay-reduction theory states that the effectiveness of a stimulus as a conditioned reinforcer may be predicted most accurately by the reduction in time to primary reinforcement correlated with its onset. We review support for the theory and then discuss two new types of experiments that assess it. One compares models of choice in situations wherein the less preferred outcome is made more accessible; the other investigates whether frequency of conditioned reinforcement affects choice beyond the effect exerted by frequency of primary reinforcement.

  1. Calcium Signaling in Taste Cells

    PubMed Central

    Medler, Kathryn F.

    2014-01-01

    The sense of taste is a common ability shared by all organisms and is used to detect nutrients as well as potentially harmful compounds. Thus taste is critical to survival. Despite its importance, surprisingly little is known about the mechanisms generating and regulating responses to taste stimuli. All taste responses depend on calcium signals to generate appropriate responses which are relayed to the brain. Some taste cells have conventional synapses and rely on calcium influx through voltage-gated calcium channels. Other taste cells lack these synapses and depend on calcium release to formulate an output signal through a hemichannel. Beyond establishing these characteristics, few studies have focused on understanding how these calcium signals are formed. We identified multiple calcium clearance mechanisms that regulate calcium levels in taste cells as well as a calcium influx that contributes to maintaining appropriate calcium homeostasis in these cells. Multiple factors regulate the evoked taste signals with varying roles in different cell populations. Clearly, calcium signaling is a dynamic process in taste cells and is more complex than has previously been appreciated. PMID:25450977

  2. Biliary calcium and gallstone formation.

    PubMed

    Moore, E W

    1990-09-01

    The purpose of this paper is to present a brief overview of the current status of the field of biliary calcium and the role of calcium in the formation and maturation of gallstones. The study of free Ca+(+) ions in bile by electrochemical potentiometric measurements using Ca+(+)-selective ion-exchange electrodes is a relatively new field, but much progress has been made in the past few years. Using this powerful analytical tool, new concepts and findings have arisen in almost every aspect of biliary calcium. Although the current symposium is targeted primarily toward cholesterol gallstones, there are several areas in which understanding of biliary calcium may significantly contribute to a better understanding of the pathogenesis of cholesterol, as well as "pigment" (calcium salt), gallstones. Five broad areas are considered in relation to biliary calcium: (a) physiology (calcium entry into bile), (b) biophysics (the regulation of biliary free [Ca+(+)] as related to Gibbs-Donnan equilibria, (c) physical chemistry (the physicochemical state of calcium in bile, (d) thermodynamics (calcium solubility in bile), and (e) kinetics (pronucleating and antinucleating factors and metastable states). With more specific reference to cholesterol stones, consideration is also made of (a) the calcium salt "seed" hypothesis in cholesterol stone pathogenesis; (b) the interactions of Ca+(+) with phospholipid-cholesterol vesicles, with consideration of possible structural requirements and (c) thermodynamic and kinetic factors as related to peripheral or "eggshell" calcification of existing cholesterol stones. PMID:2210651

  3. Epidemiology of delayed ejaculation

    PubMed Central

    Di Sante, Stefania; Mollaioli, Daniele; Gravina, Giovanni Luca; Ciocca, Giacomo; Limoncin, Erika; Carosa, Eleonora; Lenzi, Andrea

    2016-01-01

    A large body of literature on diminished ejaculatory disorders has been generated without the use of a clear diagnostic definition. Many studies have not distinguished between the orgasm and ejaculation disorders leading to doubtful results. Delayed ejaculation (DE) is one of the diminished ejaculatory disorders, which range from varying delays in ejaculatory latency to a complete inability to ejaculate. The present review is aimed at providing a comprehensive overview of the current knowledge on the definition and epidemiology of diminished ejaculatory disorders. We focus on the acquired diseases, such as benign prostatic hyperplasia (BPH) and specific drug regimens that may cause an iatrogenic form of ejaculatory disorder. In addition, the impact of aging is discussed since the prevalence of DE appears to be moderately but positively related to age. Finally, we also focus on the importance of the hormonal milieu on male ejaculation. To date, evidence on the endocrine control of ejaculation is derived from small clinical trials, but the evidence suggests that hormones modulate the ejaculatory process by altering its overall latency. PMID:27652226

  4. Delayed rule following

    PubMed Central

    Schmitt, David R.

    2001-01-01

    Although the elements of a fully stated rule (discriminative stimulus [SD], some behavior, and a consequence) can occur nearly contemporaneously with the statement of the rule, there is often a delay between the rule statement and the SD. The effects of this delay on rule following have not been studied in behavior analysis, but they have been investigated in rule-like settings in the areas of prospective memory (remembering to do something in the future) and goal pursuit. Discriminative events for some behavior can be event based (a specific setting stimulus) or time based. The latter are more demanding with respect to intention following and show age-related deficits. Studies suggest that the specificity with which the components of a rule (termed intention) are stated has a substantial effect on intention following, with more detailed specifications increasing following. Reminders of an intention, too, are most effective when they refer specifically to both the behavior and its occasion. Covert review and written notes are two effective strategies for remembering everyday intentions, but people who use notes appear not to be able to switch quickly to covert review. By focusing on aspects of the setting and rule structure, research on prospective memory and goal pursuit expands the agenda for a more complete explanation of rule effects. PMID:22478363

  5. Epidemiology of delayed ejaculation

    PubMed Central

    Di Sante, Stefania; Mollaioli, Daniele; Gravina, Giovanni Luca; Ciocca, Giacomo; Limoncin, Erika; Carosa, Eleonora; Lenzi, Andrea

    2016-01-01

    A large body of literature on diminished ejaculatory disorders has been generated without the use of a clear diagnostic definition. Many studies have not distinguished between the orgasm and ejaculation disorders leading to doubtful results. Delayed ejaculation (DE) is one of the diminished ejaculatory disorders, which range from varying delays in ejaculatory latency to a complete inability to ejaculate. The present review is aimed at providing a comprehensive overview of the current knowledge on the definition and epidemiology of diminished ejaculatory disorders. We focus on the acquired diseases, such as benign prostatic hyperplasia (BPH) and specific drug regimens that may cause an iatrogenic form of ejaculatory disorder. In addition, the impact of aging is discussed since the prevalence of DE appears to be moderately but positively related to age. Finally, we also focus on the importance of the hormonal milieu on male ejaculation. To date, evidence on the endocrine control of ejaculation is derived from small clinical trials, but the evidence suggests that hormones modulate the ejaculatory process by altering its overall latency.

  6. Ageing is associated with deterioration of calcium homeostasis in isolated human right atrial myocytes

    PubMed Central

    Herraiz-Martínez, Adela; Álvarez-García, Jesus; Llach, Anna; Molina, Cristina E.; Fernandes, Jacqueline; Ferrero-Gregori, Andreu; Rodríguez, Cristina; Vallmitjana, Alexander; Benítez, Raúl; Padró, Josep M.; Martínez-González, José; Cinca, Juan; Hove-Madsen, Leif

    2015-01-01

    Aims Ageing-related cardiac disorders such as heart failure and atrial fibrillation often present with intracellular calcium homeostasis dysfunction. However, knowledge of the intrinsic effects of ageing on cellular calcium handling in the human heart is sparse. Therefore, this study aimed to analyse how ageing affects key mechanisms that regulate intracellular calcium in human atrial myocytes. Methods and results Whole membrane currents and intracellular calcium transients were measured in isolated human right atrial myocytes from 80 patients with normal left atrial dimensions and no history of atrial fibrillation. Patients were categorized as young (<55 years, n = 21), middle aged (55–74 years, n = 42), and old (≥75 years, n = 17). Protein levels were determined by western blot. Ageing was associated with the following electrophysiological changes: (i) a 3.2-fold decrease in the calcium transient (P < 0.01); (ii) reduction of the L-type calcium current (ICa) amplitude (2.4 ± 0.3 pA/pF vs. 1.4 ± 0.2 pA/pF, P < 0.01); (iii) lower levels of L-type calcium channel alpha-subunit (P < 0.05); (iv) lower rates of both fast (14.5 ± 0.9 ms vs. 20.9 ± 1.9, P < 0.01) and slow (73 ± 3 vs. 120 ± 12 ms, P < 0.001) ICa inactivation; and (v) a decrease in the sarcoplasmic reticulum calcium content (10.1 ± 0.8 vs. 6.4 ± 0.6 amol/pF, P < 0.005) associated with a significant decrease in both SERCA2 (P < 0.05) and calsequestrin-2 (P < 0.05) protein levels. In contrast, ageing did not affect spontaneous sarcoplasmic reticulum calcium release. Conclusion Ageing is associated with depression of SR calcium content, L-type calcium current, and calcium transient amplitude that may favour a progressive decline in right atrial contractile function with age. PMID:25712961

  7. Calcium and bone health--goodbye, calcium supplements?

    PubMed

    Ströhle, A; Hadji, P; Hahn, A

    2015-10-01

    This review assesses (1) the potential role of calcium supplements in the prevention and treatment of osteoporosis and osteoporotic fractures, and (2) the safety of calcium supplements with respect to cardiovascular health as well. With regard to (1), a total calcium intake of < 800 mg/day is associated with increased loss of bone mineral density in peri- and postmenopausal women with an increase in fracture risk. Hereby, the effect of calcium supplements on fracture prevention is dependent primary on baseline calcium intake. The strongest protective effect has been reported in individuals with a calcium intake < 700 mg/day and in high-risk groups. A calcium intake of about 1000-1200 mg/day seems to be sufficient for general fracture prevention. With regard to (2), an analysis of the data based on the Hill criteria does not demonstrate convincing evidence that calcium supplements increase cardiovascular risk. In the long term, total calcium intake of 2500 mg/day (from food and supplements) continues to be classified as safe. This value should not be exceeded for an extended period of time. PMID:25689871

  8. Stability and delay sensitivity of neutral fractional-delay systems.

    PubMed

    Xu, Qi; Shi, Min; Wang, Zaihua

    2016-08-01

    This paper generalizes the stability test method via integral estimation for integer-order neutral time-delay systems to neutral fractional-delay systems. The key step in stability test is the calculation of the number of unstable characteristic roots that is described by a definite integral over an interval from zero to a sufficient large upper limit. Algorithms for correctly estimating the upper limits of the integral are given in two concise ways, parameter dependent or independent. A special feature of the proposed method is that it judges the stability of fractional-delay systems simply by using rough integral estimation. Meanwhile, the paper shows that for some neutral fractional-delay systems, the stability is extremely sensitive to the change of time delays. Examples are given for demonstrating the proposed method as well as the delay sensitivity.

  9. Stability and delay sensitivity of neutral fractional-delay systems

    NASA Astrophysics Data System (ADS)

    Xu, Qi; Shi, Min; Wang, Zaihua

    2016-08-01

    This paper generalizes the stability test method via integral estimation for integer-order neutral time-delay systems to neutral fractional-delay systems. The key step in stability test is the calculation of the number of unstable characteristic roots that is described by a definite integral over an interval from zero to a sufficient large upper limit. Algorithms for correctly estimating the upper limits of the integral are given in two concise ways, parameter dependent or independent. A special feature of the proposed method is that it judges the stability of fractional-delay systems simply by using rough integral estimation. Meanwhile, the paper shows that for some neutral fractional-delay systems, the stability is extremely sensitive to the change of time delays. Examples are given for demonstrating the proposed method as well as the delay sensitivity.

  10. Stability and delay sensitivity of neutral fractional-delay systems.

    PubMed

    Xu, Qi; Shi, Min; Wang, Zaihua

    2016-08-01

    This paper generalizes the stability test method via integral estimation for integer-order neutral time-delay systems to neutral fractional-delay systems. The key step in stability test is the calculation of the number of unstable characteristic roots that is described by a definite integral over an interval from zero to a sufficient large upper limit. Algorithms for correctly estimating the upper limits of the integral are given in two concise ways, parameter dependent or independent. A special feature of the proposed method is that it judges the stability of fractional-delay systems simply by using rough integral estimation. Meanwhile, the paper shows that for some neutral fractional-delay systems, the stability is extremely sensitive to the change of time delays. Examples are given for demonstrating the proposed method as well as the delay sensitivity. PMID:27586618

  11. Endoplasmic Reticulum Calcium Regulates Epidermal Barrier Response and Desmosomal Structure

    PubMed Central

    Celli, Anna; Crumrine, Debra; Meyer, Jason M.; Mauro, Theodora M.

    2016-01-01

    Ca2+ fluxes direct keratinocyte differentiation, cell-to-cell adhesion, migration, and epidermal barrier homeostasis. We previously showed that intracellular Ca2+ stores constitute a major portion of the calcium gradient especially in the stratum granulosum. Loss of the calcium gradient triggers epidermal barrier homeostatic responses. In this report, using unfixed ex vivo epidermis and human epidermal equivalents we show that endoplasmic reticulum (ER) Ca2+ is released in response to barrier perturbation, and that this release constitutes the major shift in epidermal Ca2+ seen after barrier perturbation. We find that ER Ca2+ release correlates with a transient increase in extracellular Ca2+. Lastly, we show that ER calcium release resulting from barrier perturbation triggers transient desmosomal remodeling, seen as an increase in extracellular space and a loss of the desmosomal intercellular midline. Topical application of thapsigargin, which inhibits the ER Ca2+ ATPase activity without compromising barrier integrity, also leads to desmosomal remodeling and loss of the midline structure. These experiments establish the ER Ca2+ store as a master regulator of the Ca2+ gradient response to epidermal barrier perturbation, and suggest that ER Ca2+ homeostasis also modulates normal desmosomal reorganization, both at rest and after acute barrier perturbation. PMID:27255610

  12. Do the adjusting-delay and increasing-delay tasks measure the same construct: delay discounting?

    PubMed

    Craig, Andrew R; Maxfield, Adam D; Stein, Jeffrey S; Renda, C Renee; Madden, Gregory J

    2014-08-01

    Delay discounting describes the subjective devaluation of a reward when it is delayed. In animals, the adjusting-delay (AD) and increasing-delay (ID) tasks often are used to assess individual differences in, and drug effects on, delay discounting. No study to date, however, has compared systematically the measures of discounting produced in these tasks. The current study examined the correlation between measures of delay discounting derived from AD and ID procedures. Twenty rats completed 30 sessions under each task (order counterbalanced across rats). Quantitative measures of delay discounting produced by the two tasks were positively correlated, suggesting that the AD and ID tasks measure the same underlying facet of impulsive choice (i.e. individual or conjoint sensitivities to reward delay and magnitude). The measures derived from either task, however, depended on the sequences in which the tasks were experienced. That is, pre-exposure to one task decreased discounting of delayed rewards in the second task. Consistent with other published findings, exposure to delayed consequences during the initial discounting assessment might explain this effect. Despite the observed correlation between ID and AD indifference delays, we suggest that the ID procedure might be a more appropriate procedure for pharmacological studies.

  13. Prehospital and in-hospital delays in acute stroke care.

    PubMed

    Evenson, K R; Rosamond, W D; Morris, D L

    2001-05-01

    Current guidelines emphasize the need for early stroke care. However, significant delays occur during both the prehospital and in-hospital phases of care, making many patients ineligible for stroke therapies. The purpose of this study was to systematically review and summarize the existing scientific literature reporting prehospital and in-hospital stroke delay times in order to assist future delivery of effective interventions to reduce delay time and to raise several key issues which future studies should consider. A comprehensive search was performed to find all published journal articles which reported on the prehospital or in-hospital delay time for stroke, including intervention studies. Since 1981, at least 48 unique reports of prehospital delay time for patients with stroke, transient ischemic attack, or stroke-like symptoms were published from 17 different countries. In the majority of studies which reported median delay times, the median time from symptom onset to arrival in the emergency department was between 3 and 6 h. The in-hospital times from emergency department arrival to being seen by an emergency department physician, initiation and interpretation of a computed tomography (CT) scan, and being seen by a neurologist were consistently longer than recommended. However, prehospital delay comprised the majority of time from symptom onset to potential treatment. Definitions and methodologies differed across studies, making direct comparisons difficult. This review suggests that the majority of stroke patients are unlikely to arrive at the emergency department and receive a diagnostic evaluation in under 3 h. Further studies of stroke delay and corresponding interventions are needed, with careful attention to definitions and methodologies. PMID:11359072

  14. Sustained Perceptual Deficits from Transient Sensory Deprivation

    PubMed Central

    Sanes, Dan H.

    2015-01-01

    displays an increased vulnerability to the sensory environment. Here, we identify a precise developmental window during which mild hearing loss affects the maturation of an auditory perceptual cue that is known to support animal communication, including human speech. Furthermore, animals reared with transient hearing loss display deficits in perceptual learning. Our results suggest that speech and language delays associated with transient or permanent childhood hearing loss may be accounted for, in part, by deficits in central auditory processing mechanisms. PMID:26224865

  15. [Renal calcium excretion and urolithiasis].

    PubMed

    Aruga, Seiji; Honma, Yukio

    2011-10-01

    Patients with urolithiasis have been increasing in the world, especially morbidity of calcium nephrolithiasis has been increasing in the advanced countries. The changes in the environmental factors including alternation of diet are said to be associated with the increment of morbidity of kidney stone. Idiopathic hypercalciuria is one of the most important risk factor of calcium nephrolithiasis and is classified into absorptive, resorptive, and renal leak. Though the origins of these three types of hypercalciuria are different, increased bone resorption and increased calcium absorption from gut tend to be observed simultaneously. Not only genetic abnormalities in the proteins which are involved in calcium metabolisms but environmental factors such as high sodium intake and chronic acid load caused by increased ingestion of animal protein have been considered to be associated with increased urinary calcium excretion. Renal metabolisms of oxalate and phosphate which are important compositions of calcium containing stone, uric acid as a promoter and citrate as a inhibitor of nephrolithiasis are also described.

  16. Spatiotemporal properties of high-speed calcium oscillations in the pedunculopontine nucleus

    PubMed Central

    Hyde, James; Kezunovic, Nebojsa; Urbano, Francisco J.

    2013-01-01

    The pedunculopontine nucleus (PPN) is a component of the reticular activating system (RAS), and is involved in the activated states of waking and rapid eye movement (REM) sleep. Gamma oscillations (approximately 30–80 Hz) are evident in all PPN neurons and are mediated by high-threshold voltage-dependent N- and P/Q-type calcium channels. We tested the hypothesis that high-speed calcium imaging would reveal calcium-mediated oscillations in dendritic compartments in synchrony with patch-clamp recorded oscillations during depolarizing current ramps. Patch-clamped 8- to 16-day-old rat PPN neurons (n = 67 out of 121) were filled with Fura 2, Bis Fura, or OGB1/CHR. This study also characterized a novel ratiometric technique using Oregon Green BAPTA-1 (OGB1) with coinjections of a new long-stokes-shift dye, Chromeo 494 (CHR). Fluorescent calcium transients were blocked with the nonspecific calcium channel blocker cadmium, or by the combination of ω-agatoxin-IVA, a specific P/Q-type calcium channel blocker, and ω-conotoxin-GVIA, a specific N-type calcium channel blocker. The calcium transients were evident in different dendrites (suggesting channels are present throughout the dendritic tree) along the sampled length without interruption (suggesting channels are evenly distributed), and appeared to represent a summation of oscillations present in the soma. We confirm that PPN calcium channel-mediated oscillations are due to P/Q- and N-type channels, and reveal that these channels are distributed along the dendrites of PPN cells. PMID:23990242

  17. Dietary calcium and 1,25-dihydroxyvitamin D3 regulate transcription of calcium transporter genes in calbindin-D9k knockout mice.

    PubMed

    Ko, Sang-Hwan; Lee, Geun-Shik; Vo, Thuy T B; Jung, Eui-Man; Choi, Kyung-Chul; Cheung, Ki-Wha; Kim, Jae Wha; Park, Jong-Gil; Oh, Goo Taeg; Jeung, Eui-Bae

    2009-04-01

    The effect(s) of oral calcium and vitamin D(3) were examined on the expression of duodenal and renal active calcium transport genes, i.e., calbindin-D9k (CaBP-9k) and calbindin-D28k (CaBP-28k), transient receptor potential cation channels (TRPV5 and TRPV6), Na(+)/Ca(2+) exchanger 1 (NCX1) and plasma membrane calcium ATPase 1b (PMCA1b), in CaBP-9k KO mice. Wild-type (WT) and KO mice were provided with calcium and vitamin D(3)-deficient diets for 10 weeks. The deficient diet significantly decreased body weights compared with the normal diet groups. The serum calcium concentration of the WT mice was decreased by the deficient diet but was unchanged in the KO mice. The deficient diet significantly increased duodenal transcription of CaBP-9k and TRPV6 in the WT mice, but no alteration was observed in the KO mice. In the kidney, the deficient diet significantly increased renal transcripts of CaBP-9k, TRPV6, PMCA1b, CaBP-28k and TRPV5 in the WT mice but did not alter calcium-relating genes in the KO mice. Two potential mediators of calcium-processing genes, vitamin D receptor (VDR) and parathyroid hormone receptor (PTHR), have been suggested to be useful for elucidating these differential regulations in the calcium-related genes of the KO mice. Expression of VDR was not significantly affected by diet or the KO mutation. Renal PTHR mRNA levels were reduced by the diet, and reduced expression was also seen in the KO mice given the normal diet. Taken together, these results suggest that the active calcium transporting genes in KO mice may have resistance to the deficiency diet of calcium and vitamin D(3).

  18. Calcium Kinetics During Space Flight

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Wastney, Meryl E.; OBrien, Kimberly O.; Lane, Helen W.

    1999-01-01

    Bone loss is one of the most detrimental effects of space flight, threatening to limit the duration of human space missions. The ability to understand and counteract this loss will be critical for crew health and safety during and after extended-duration missions. The hypotheses to be tested in this project are that space flight alters calcium homeostasis and bone mineral metabolism, and that calcium homeostasis and bone mineral metabolism will return to baseline within days to weeks of return to Earth. These hypotheses will be evidenced by elevated rates of bone mineral resorption and decreased bone mineral deposition, decreased absorption of dietary calcium, altered calcitropic endocrine profiles, elevated excretion of calcium in urine and feces, and elevated excretion of markers of bone resorption. The second hypothesis will be evidenced by return of indices of calcium homeostasis and bone metabolism to preflight levels within days to weeks of return to Earth. Studies will be conducted on International Space Station astronauts before, during, and after extended-duration flights. Measurements of calcium kinetics, bone mass, and endocrine/biochemical markers of bone and calcium homeostasis will be conducted. Kinetic studies utilizing dual isotope tracer kinetic studies and mathematical modeling techniques will allow for determination of bone calcium deposition, bone calcium resorption, dietary calcium absorption and calcium excretion (both urinary and endogenous fecal excretion). These studies will build upon preliminary work conducted on the Russian Mir space station. The results from this project will be critical for clarifying how microgravity affects bone and calcium homeostasis, and will provide an important control point for assessment of countermeasure efficacy. These results are expected to aid in developing countermeasures for bone loss, both for space crews and for individuals on Earth who have metabolic bone diseases.

  19. Transient critical heat flux and blowdown heat-transfer studies

    SciTech Connect

    Leung, J.C.

    1980-05-01

    Objective of this study is to give a best-estimate prediction of transient critical heat flux (CHF) during reactor transients and hypothetical accidents. To accomplish this task, a predictional method has been developed. Basically it involves the thermal-hydraulic calculation of the heated core with boundary conditions supplied from experimental measurements. CHF predictions were based on the instantaneous ''local-conditions'' hypothesis, and eight correlations (consisting of round-tube, rod-bundle, and transient correlations) were tested against most recent blowdown heat-transfer test data obtained in major US facilities. The prediction results are summarized in a table in which both CISE and Biasi correlations are found to be capable of predicting the early CHF of approx. 1 s. The Griffith-Zuber correlation is credited for its prediction of the delay CHF that occurs in a more tranquil state with slowly decaying mass velocity. In many instances, the early CHF can be well correlated by the x = 1.0 criterion; this is certainly indicative of an annular-flow dryout-type crisis. The delay CHF occurred at near or above 80% void fraction, and the success of the modified Zuber pool-boiling correlation suggests that this CHF is caused by flooding and pool-boiling type hydrodynamic crisis.

  20. Reactor transient analyses with KIN3D/PARTISN

    SciTech Connect

    Gabrielli, F.; Rineiski, A.; Maschek, W.; Marchetti, M.

    2013-07-01

    Efforts are going on at the Karlsruhe Institute of Technology (KIT) to extend the kinetics capability of the PARTISN code in order to run in parallel two- and three-dimensional transient analyses with the quasistatic method, while taking into account delayed neutrons. In the original code version, time-dependent transport problems are solved by employing a semi-implicit direct kinetics option, the delayed neutrons being not taken into account. The PARTISN 5.97 code has been extended and then coupled with KIN3D, a time-dependent model embedded in the ERANOS code system. In the coupled code, PARTISN 5.97 is used as neutron transport solver to perform transient analyses while employing direct and quasi-static kinetics options of KIN3D. The coupled code can be also applied for first-order and exact perturbation theory calculations. In the paper, the PARTISN 5.97 extensions and coupling procedure are described and the performances of the KIN3D/PARTISN coupled code are investigated by analyzing transients induced by a source-jerk in a three-dimensional ADS model driven by an external source. (authors)

  1. Transient upsets in microprocessor controllers

    NASA Technical Reports Server (NTRS)

    Glaser, R. E.; Masson, G. M.

    1981-01-01

    The modeling and analysis of transient faults in microprocessor based controllers are discussed. Such controllers typically consist of a microprocessor, read only memory storing and application program, random access memory for data storage, and input/output devices for external communications. The effects of transient faults on the performance of the controller are reviewed. An instruction level perspective of performance is taken which is the basis of a useful high level program state description of the microprocessor controller. A transition matrix is defined which determines the controller's response to transient fault arrivals.

  2. Transient overvoltages on cable sheaths

    NASA Astrophysics Data System (ADS)

    Dabringhaus, H. G.

    1983-08-01

    Transient overvoltage on the sheaths of high voltage cables with single point sheath earthing or cross bonding of the cable sheaths involve danger for the cable and the joints. The investigations of transient overvoltages in the case of a switching operation on a 110 kV single core oil filled cable with single sided sheath earthing are reported. A comparison between measured transient voltage variations and those calculated with the help of a traveling wave analyzer program shows very good agreement. The investigations showed that with single point sheath earthing, the unearthed sheath end ought to be protected against overvoltages.

  3. Transient characteristics of rocket turbopumps

    NASA Astrophysics Data System (ADS)

    Shimura, Takashi; Watanabe, Mitsuo

    Transient characteristics of high-speed, high-pressure cryogenic turbopumps for rocket engines were examined experimentally by starting and stopping several rocket turbopumps rapidly by gas turbine drive. Aspects of transient characteristics studied were instantaneous pump head coefficient and pump efficiency, cavitation growth in the inducer during rapid acceleration, effects of the starting mode related to the propulsion system mission, and transient behavior of a self-balancing type axial thrust balancing system. Based on the test results, the feasibility of definite starting modes for the LE-5 turbopump was confirmed and the self-balancing type axial thrust balancing system for the LE-7 LOX turbopump was completed.

  4. Depolarization and calcium entry in squid giant axons

    PubMed Central

    Baker, P. F.; Hodgkin, A. L.; Ridgway, E. B.

    1971-01-01

    1. Changes in ionized calcium in giant axons were followed by recording the light produced by injected aequorin. 2. From the effect of injecting calcium buffers the internal concentration of ionized calcium was found to be about the same as in a mixture of 45 Ca EGTA:55 free EGTA, i.e. about 0·3 μM. 3. After an axon had been exposed to cyanide for 50-100 min the velocity of the aequorin reaction increased about 500 times. This effect, which could be reversed rapidly by removing cyanide, was probably brought about by release of calcium from an internal store. 4. Injecting 30 μmole ATP per litre of axoplasm into a cyanide-poisoned axon caused a transient lowering of light intensity; oligomycin blocked the effect. 5. Raising external calcium or replacing external sodium by choline or lithium reversibly increased the light produced by axons injected with aequorin. 6. Stimulation at 50-200 impulses/sec in a solution containing 112 mM-Ca caused the light intensity to increase to a new steady level; after stimulation the light intensity returned to its original level with a time constant of 10-30 sec. Similar but smaller effects were seen in solutions containing less external calcium. The recovery after stimulation is probably due to uptake of calcium by the internal store. 7. Injecting 3 m-mole EGTA per litre axoplasm lowered the resting glow and abolished the aequorin response to stimulation. 8. There was no light response to stimulation immediately after an axial injection of aequorin and the effect increased to a `steady' level with a half-time of about 5 min. The conclusion is that the rise in calcium concentration resulting from stimulation is confined to the peripheral part of the axon and that the diffusion coefficient of aequorin in axoplasm is about 4 × 10-7 cm2/sec. 9. The increment in light per impulse often increased markedly during the course of a long experiment and there was also considerable variation between axons. 10. If the light response to

  5. [Measurement of the concentration of free cytoplasmic calcium in the process of platelet aggregation using a fluorescent method].

    PubMed

    Popov, E G; Gavrilov, I Iu; Pozin, E Ia; Gabbasov, Z A

    1989-01-01

    A multiwavelength method for measuring free cytosolic calcium concentration is proposed. It is based on the registration of the fluorescent spectrum of calcium--sensitive probe indo-1 and deconvolution of the spectrum into components corresponding to free and bound forms of the probe. Calcium concentration is calculated as a product of calcium-probe dissociation constant by calcium-bound to free form concentration ratio. The obtained values are independent of variations in light-scattering properties of the medium and total dye concentration in the optical channel. It is shown that during ADP-induced platelet aggregation calcium concentration rises without measurable delay after the addition of the inducer and significantly decreases by the time the aggregation begins.

  6. Soviet delays raise prices

    SciTech Connect

    Young, I.

    1992-01-15

    The breakup of the Soviet Union is causing massive disruptions to methanol exports. The changeover to a Commonwealth of independent States has created logistical problems which have led some shipments of Russian methanol to be cancelled and delayed other deliveries by up to two weeks. In recent years the Soviet Union has exported 700,000 m.t./year-900,000 m.t./year of methanol, mainly to Western Europe. The product is made at 750,000-m.t./year plants at Tomsk and Gubakha in Russia and transported by rail for shipment from the ports of Ventspils, Latvia, on the Baltic Sea and Yuzhnyy in Ukraine, on the Black Sea. The exports were handled by state export agency Soyuzagrochim, mainly under contract to West European traders and consumers in areas like Scandinavia and France.

  7. Delayed cure bismaleimide resins

    DOEpatents

    Adams, Johnnie E.; Jamieson, Donald R.

    1984-08-07

    Polybismaleimides prepared by delayed curing of bis-imides having the formula ##STR1## wherein R.sub.1 and R.sub.2 each independently is H, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, Cl or Br, or R.sub.1 and R.sub.2 together form a fused 6-membered hydrocarbon aromatic ring, with the proviso that R.sub.1 and R.sub.2 are not t-butyl or t-butoxy; X is O, S or Se; n is 1-3; and the --(CH.sub.2).sub.n -- group, optionally, is substituted by 1-3 methyl groups or by fluorine.

  8. Compact Dielectric-Rod White-Light Delay Lines

    NASA Technical Reports Server (NTRS)

    Maleki, Lute; Matsko, Andrey; Savchenkov, Anatoliy; Strekalov, Dmitry

    2008-01-01

    Optical delay lines of a proposed type would be made from rods of such dielectric materials as calcium fluoride, fused silica, or sapphire. These would offer advantages over prior optical delay lines, as summarized below. Optical delay lines are key components of opto-electronic microwave oscillators, narrow-band opto-electronic microwave filters, evanescent-field optical biochemical detectors, and some Fourier-Transform spectrum analyzers. Heretofore, optical delay lines used in such applications have been of two types: resonators and coiled long optical fibers, both of which have disadvantages: Resonators are compact, but excitation must be provided by narrow-band lasers. Wide-band (including noisy) laser light cannot be coupled efficiently to narrow-band resonators. When light is coupled into a narrowband resonator from a source of reasonably high power, a significant amount of optical energy circulates within the resonator, causing nonlinear loss and significant noise. Typically, a coil-type optical delay line is made of fused-silica fiber, which exhibits fundamental loss. To overcome the limit imposed by the optical loss in fused silica, it would be necessary to use fibers having crystalline cores. Although space is saved by winding fibers into coils, fiber-coil delay lines are still inconveniently bulky. The proposed compact dielectric-rod delay lines would exploit the special class of non-diffracting light beams that are denoted Bessel beams because their amplitudes are proportional to Bessel functions of the radii from their central axes. High-order Bessel beams can have large values of angular momentum. They can be generated with the help of whispering-gallery-mode optical resonators, as described, for example, in "Simplified Generation of High-Angular-Momentum Light Beams" (NPO-42965) NASA Tech Briefs, Vol. 31, No. 3 (March 2007), page 8a. In a delay line according to the proposal, the dielectric rod would be dimensioned to function as a multimode

  9. 21 CFR 184.1187 - Calcium alginate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Calcium alginate. 184.1187 Section 184.1187 Food... GRAS § 184.1187 Calcium alginate. (a) Calcium alginate (CAS Reg. No. 9005-35-0) is the calcium salt of alginic acid, a natural polyuronide constituent of certain brown algae. Calcium alginate is prepared...

  10. Transient Features in Nanosecond Pulsed Electric Fields Differentially Modulate Mitochondria and Viability

    PubMed Central

    Beebe, Stephen J.; Chen, Yeong-Jer; Sain, Nova M.; Schoenbach, Karl H.; Xiao, Shu

    2012-01-01

    It is hypothesized that high frequency components of nanosecond pulsed electric fields (nsPEFs), determined by transient pulse features, are important for maximizing electric field interactions with intracellular structures. For monopolar square wave pulses, these transient features are determined by the rapid rise and fall of the pulsed electric fields. To determine effects on mitochondria membranes and plasma membranes, N1-S1 hepatocellular carcinoma cells were exposed to single 600 ns pulses with varying electric fields (0–80 kV/cm) and short (15 ns) or long (150 ns) rise and fall times. Plasma membrane effects were evaluated using Fluo-4 to determine calcium influx, the only measurable source of increases in intracellular calcium. Mitochondria membrane effects were evaluated using tetramethylrhodamine ethyl ester (TMRE) to determine mitochondria membrane potentials (ΔΨm). Single pulses with short rise and fall times caused electric field-dependent increases in calcium influx, dissipation of ΔΨm and cell death. Pulses with long rise and fall times exhibited electric field-dependent increases in calcium influx, but diminished effects on dissipation of ΔΨm and viability. Results indicate that high frequency components have significant differential impact on mitochondria membranes, which determines cell death, but lesser variances on plasma membranes, which allows calcium influxes, a primary determinant for dissipation of ΔΨm and cell death. PMID:23284682

  11. Transient features in nanosecond pulsed electric fields differentially modulate mitochondria and viability.

    PubMed

    Beebe, Stephen J; Chen, Yeong-Jer; Sain, Nova M; Schoenbach, Karl H; Xiao, Shu

    2012-01-01

    It is hypothesized that high frequency components of nanosecond pulsed electric fields (nsPEFs), determined by transient pulse features, are important for maximizing electric field interactions with intracellular structures. For monopolar square wave pulses, these transient features are determined by the rapid rise and fall of the pulsed electric fields. To determine effects on mitochondria membranes and plasma membranes, N1-S1 hepatocellular carcinoma cells were exposed to single 600 ns pulses with varying electric fields (0-80 kV/cm) and short (15 ns) or long (150 ns) rise and fall times. Plasma membrane effects were evaluated using Fluo-4 to determine calcium influx, the only measurable source of increases in intracellular calcium. Mitochondria membrane effects were evaluated using tetramethylrhodamine ethyl ester (TMRE) to determine mitochondria membrane potentials (ΔΨm). Single pulses with short rise and fall times caused electric field-dependent increases in calcium influx, dissipation of ΔΨm and cell death. Pulses with long rise and fall times exhibited electric field-dependent increases in calcium influx, but diminished effects on dissipation of ΔΨm and viability. Results indicate that high frequency components have significant differential impact on mitochondria membranes, which determines cell death, but lesser variances on plasma membranes, which allows calcium influxes, a primary determinant for dissipation of ΔΨm and cell death.

  12. Extracellular calcium sensing and extracellular calcium signaling

    NASA Technical Reports Server (NTRS)

    Brown, E. M.; MacLeod, R. J.; O'Malley, B. W. (Principal Investigator)

    2001-01-01

    , localized changes in Ca(o)(2+) within the ECF can originate from several mechanisms, including fluxes of calcium ions into or out of cellular or extracellular stores or across epithelium that absorb or secrete Ca(2+). In any event, the CaR and other receptors/sensors for Ca(o)(2+) and probably for other extracellular ions represent versatile regulators of numerous cellular functions and may serve as important therapeutic targets.

  13. Demographic determinants of delayed divorce.

    PubMed

    Chan, L Y; Heaton, T B

    1989-01-01

    This study identifies factors that predict delayed divorce in the US. The findings show that factors which influence marital stability in general also correlate with delayed divorce in the same direction. Wife's age at marriage, age of the youngest child, wife's religion, region of residence, and metropolitan residence have substantial effects of delayed divorce, but the effects of race, parental divorce, premarital pregnancy, and socioeconomic status are small.

  14. Modeling delay in genetic networks: From delay birth-death processes to delay stochastic differential equations

    SciTech Connect

    Gupta, Chinmaya; López, José Manuel; Azencott, Robert; Ott, William; Bennett, Matthew R.; Josić, Krešimir

    2014-05-28

    Delay is an important and ubiquitous aspect of many biochemical processes. For example, delay plays a central role in the dynamics of genetic regulatory networks as it stems from the sequential assembly of first mRNA and then protein. Genetic regulatory networks are therefore frequently modeled as stochastic birth-death processes with delay. Here, we examine the relationship between delay birth-death processes and their appropriate approximating delay chemical Langevin equations. We prove a quantitative bound on the error between the pathwise realizations of these two processes. Our results hold for both fixed delay and distributed delay. Simulations demonstrate that the delay chemical Langevin approximation is accurate even at moderate system sizes. It captures dynamical features such as the oscillatory behavior in negative feedback circuits, cross-correlations between nodes in a network, and spatial and temporal information in two commonly studied motifs of metastability in biochemical systems. Overall, these results provide a foundation for using delay stochastic differential equations to approximate the dynamics of birth-death processes with delay.

  15. Modeling delay in genetic networks: From delay birth-death processes to delay stochastic differential equations

    NASA Astrophysics Data System (ADS)

    Gupta, Chinmaya; López, José Manuel; Azencott, Robert; Bennett, Matthew R.; Josić, Krešimir; Ott, William

    2014-05-01

    Delay is an important and ubiquitous aspect of many biochemical processes. For example, delay plays a central role in the dynamics of genetic regulatory networks as it stems from the sequential assembly of first mRNA and then protein. Genetic regulatory networks are therefore frequently modeled as stochastic birth-death processes with delay. Here, we examine the relationship between delay birth-death processes and their appropriate approximating delay chemical Langevin equations. We prove a quantitative bound on the error between the pathwise realizations of these two processes. Our results hold for both fixed delay and distributed delay. Simulations demonstrate that the delay chemical Langevin approximation is accurate even at moderate system sizes. It captures dynamical features such as the oscillatory behavior in negative feedback circuits, cross-correlations between nodes in a network, and spatial and temporal information in two commonly studied motifs of metastability in biochemical systems. Overall, these results provide a foundation for using delay stochastic differential equations to approximate the dynamics of birth-death processes with delay.

  16. Modeling delay in genetic networks: from delay birth-death processes to delay stochastic differential equations.

    PubMed

    Gupta, Chinmaya; López, José Manuel; Azencott, Robert; Bennett, Matthew R; Josić, Krešimir; Ott, William

    2014-05-28

    Delay is an important and ubiquitous aspect of many biochemical processes. For example, delay plays a central role in the dynamics of genetic regulatory networks as it stems from the sequential assembly of first mRNA and then protein. Genetic regulatory networks are therefore frequently modeled as stochastic birth-death processes with delay. Here, we examine the relationship between delay birth-death processes and their appropriate approximating delay chemical Langevin equations. We prove a quantitative bound on the error between the pathwise realizations of these two processes. Our results hold for both fixed delay and distributed delay. Simulations demonstrate that the delay chemical Langevin approximation is accurate even at moderate system sizes. It captures dynamical features such as the oscillatory behavior in negative feedback circuits, cross-correlations between nodes in a network, and spatial and temporal information in two commonly studied motifs of metastability in biochemical systems. Overall, these results provide a foundation for using delay stochastic differential equations to approximate the dynamics of birth-death processes with delay.

  17. The effects of thermal stimuli on intracellular calcium change and histamine releases in rat basophilic leukemia mast cells

    NASA Astrophysics Data System (ADS)

    Wu, Zu-Hui; Zhu, Dan; Chen, Ji-Yao; Zhou, Lu-Wei

    2012-05-01

    The effects of thermal stimuli on rat basophilic leukemia mast cells were studied. The cells in calcium-contained or calcium-free buffers were thermally stimulated in the temperature range of 25-60 °C. The corresponding calcium ion concentration in cells [Ca2+]i as well as the released histamine from cells was measured with fluorescence staining methods. The ruthenium red (RR), a block of membrane calcium channels (transient receptor potential family V (TRPV)), was used in experiments. Under the stimulus of 25-50 °C, no significant difference on [Ca2+]i was found between these three groups of the cells in calcium-contained buffer without or with RR and cells in calcium-free saline, indicating that the increased calcium in cytosol did not result from the extracellular buffer but came from the intracellular calcium stores. The [Ca2+]i continuously increased under the temperature of 50-60 °C, but the RR and calcium-free saline can obviously diminish the [Ca2+]i increase at these high temperatures, reflecting that the opening of the TRPV2 channels leads to a calcium influx resulting in the [Ca2+]i increment. The histamine release also became significant in these cases. Since the released histamine is a well-known mediator for the microcirculation promotion, the histamine release from mast cells could be one of the mechanisms of thermal therapy.

  18. Cytosolic calcium rises and related events in ergosterol-treated Nicotiana cells.

    PubMed

    Vatsa, Parul; Chiltz, Annick; Luini, Estelle; Vandelle, Elodie; Pugin, Alain; Roblin, Gabriel

    2011-07-01

    The typical fungal membrane component ergosterol was previously shown to trigger defence responses and protect plants against pathogens. Most of the elicitors mobilize the second messenger calcium, to trigger plant defences. We checked the involvement of calcium in response to ergosterol using Nicotiana plumbaginifolia and Nicotiana tabacum cv Xanthi cells expressing apoaequorin in the cytosol. First, it was verified if ergosterol was efficient in these cells inducing modifications of proton fluxes and increased expression of defence-related genes. Then, it was shown that ergosterol induced a rapid and transient biphasic increase of free [Ca²⁺](cyt) which intensity depends on ergosterol concentration in the range 0.002-10 μM. Among sterols, this calcium mobilization was specific for ergosterol and, ergosterol-induced pH and [Ca²⁺](cyt) changes were specifically desensitized after two subsequent applications of ergosterol. Specific modulators allowed elucidating some events in the signalling pathway triggered by ergosterol. The action of BAPTA, LaCl₃, nifedipine, verapamil, neomycin, U73122 and ruthenium red suggested that the first phase was linked to calcium influx from external medium which subsequently triggered the second phase linked to calcium release from internal stores. The calcium influx and the [Ca²⁺](cyt) increase depended on upstream protein phosphorylation. The extracellular alkalinization and ROS production depended on calcium influx but, the ergosterol-induced MAPK activation was calcium-independent. ROS were not involved in cytosolic calcium rise as described in other models, indicating that ROS do not systematically participate in the amplification of calcium signalling. Interestingly, ergosterol-induced ROS production is not linked to cell death and ergosterol does not induce any calcium elevation in the nucleus.

  19. A programmable-delay line.

    PubMed

    Schiano, J L; Trahiotis, C

    1987-01-01

    A relatively simple circuit is described which delays audio signals in 5 microseconds steps from 0 microsecond to 4000 microseconds. Delays are programmed via twelve TTL-level data lines. The magnitude response is flat and the phase response is linear from DC to 5 kHz. The gain of the circuit is fixed and independent of the selected delay. Delays are accurate to within 1 microsecond of the programmed value. The device is a nice alternative to other methods which have diverse shortcomings.

  20. Time Delay of CGM Sensors

    PubMed Central

    Schmelzeisen-Redeker, Günther; Schoemaker, Michael; Kirchsteiger, Harald; Freckmann, Guido; Heinemann, Lutz; del Re, Luigi

    2015-01-01

    Background: Continuous glucose monitoring (CGM) is a powerful tool to support the optimization of glucose control of patients with diabetes. However, CGM systems measure glucose in interstitial fluid but not in blood. Rapid changes in one compartment are not accompanied by similar changes in the other, but follow with some delay. Such time delays hamper detection of, for example, hypoglycemic events. Our aim is to discuss the causes and extent of time delays and approaches to compensate for these. Methods: CGM data were obtained in a clinical study with 37 patients with a prototype glucose sensor. The study was divided into 5 phases over 2 years. In all, 8 patients participated in 2 phases separated by 8 months. A total number of 108 CGM data sets including raw signals were used for data analysis and were processed by statistical methods to obtain estimates of the time delay. Results: Overall mean (SD) time delay of the raw signals with respect to blood glucose was 9.5 (3.7) min, median was 9 min (interquartile range 4 min). Analysis of time delays observed in the same patients separated by 8 months suggests a patient dependent delay. No significant correlation was observed between delay and anamnestic or anthropometric data. The use of a prediction algorithm reduced the delay by 4 minutes on average. Conclusions: Prediction algorithms should be used to provide real-time CGM readings more consistent with simultaneous measurements by SMBG. Patient specificity may play an important role in improving prediction quality. PMID:26243773

  1. Transient nucleation in condensed systems

    NASA Technical Reports Server (NTRS)

    Kelton, K. F.; Greer, A. L.; Thompson, C. V.

    1983-01-01

    Using classical nucleation theory we consider transient nucleation occurring in a one-component, condensed system under isothermal conditions. We obtain an exact closed-form expression for the time dependent cluster populations. In addition, a more versatile approach is developed: a numerical simulation technique which models directly the reactions by which clusters are produced. This simulation demonstrates the evolution of cluster populations and nucleation rate in the transient regime. Results from the simulation are verified by comparison with exact analytical solutions for the steady state. Experimental methods for measuring transient nucleation are assessed, and it is demonstrated that the observed behavior depends on the method used. The effect of preexisting cluster distributions is studied. Previous analytical and numerical treatments of transient nucleation are compared to the solutions obtained from the simulation. The simple expressions of Kashchiev are shown to give good descriptions of the nucleation behavior.

  2. Differential Diagnosis of Transient Amnesia

    PubMed Central

    Croft, P. B.; Heathfield, K. W. G.; Swash, M.

    1973-01-01

    In a group of 39 consecutive patients attending neurological clinics with transient amnesia patients with transient global amnesia formed the largest group; others suffered from epilepsy, migraine, temporal lobe encephalitis, or psychogenic fugues. In most cases the clinical features suggested the aetiology, but an electroencephalogram recorded as soon after the attack as possible may help in distinguishing amnesia due to temporal lobe epilepsy. PMID:4758521

  3. AMPA receptor exchange underlies transient memory destabilization on retrieval.

    PubMed

    Hong, Ingie; Kim, Jeongyeon; Kim, Jihye; Lee, Sukwon; Ko, Hyoung-Gon; Nader, Karim; Kaang, Bong-Kiun; Tsien, Richard W; Choi, Sukwoo

    2013-05-14

    A consolidated memory can be transiently destabilized by memory retrieval, after which memories are reconsolidated within a few hours; however, the molecular substrates underlying this destabilization process remain essentially unknown. Here we show that at lateral amygdala synapses, fear memory consolidation correlates with increased surface expression of calcium-impermeable AMPA receptors (CI-AMPARs), which are known to be more stable at the synapse, whereas memory retrieval induces an abrupt exchange of CI-AMPARs to calcium-permeable AMPARs (CP-AMPARs), which are known to be less stable at the synapse. We found that blockade of either CI-AMPAR endocytosis or NMDA receptor activity during memory retrieval, both of which blocked the exchange to CP-AMPARs, prevented memory destabilization, indicating that this transient exchange of AMPARs may underlie the transformation of a stable memory into an unstable memory. These newly inserted CP-AMPARs gradually exchanged back to CI-AMPARs within hours, which coincided with the course of reconsolidation. Furthermore, blocking the activity of these newly inserted CP-AMPARs after retrieval impaired reconsolidation, suggesting that they serve as synaptic "tags" that support synapse-specific reconsolidation. Taken together, our results reveal unexpected physiological roles of CI-AMPARs and CP-AMPARs in transforming a consolidated memory into an unstable memory and subsequently guiding reconsolidation. PMID:23630279

  4. 21 CFR 172.330 - Calcium pantothenate, calcium chloride double salt.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Calcium pantothenate, calcium chloride double salt..., calcium chloride double salt. The food additive calcium chloride double salt of calcium pantothenate may... information required by the Act, the following: (1) The name of the additive “calcium chloride double salt...

  5. 21 CFR 172.330 - Calcium pantothenate, calcium chloride double salt.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Calcium pantothenate, calcium chloride double salt... Dietary and Nutritional Additives § 172.330 Calcium pantothenate, calcium chloride double salt. The food additive calcium chloride double salt of calcium pantothenate may be safely used in foods for...

  6. 21 CFR 172.330 - Calcium pantothenate, calcium chloride double salt.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium pantothenate, calcium chloride double salt..., calcium chloride double salt. The food additive calcium chloride double salt of calcium pantothenate may... information required by the Act, the following: (1) The name of the additive “calcium chloride double salt...

  7. 21 CFR 172.330 - Calcium pantothenate, calcium chloride double salt.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Calcium pantothenate, calcium chloride double salt..., calcium chloride double salt. The food additive calcium chloride double salt of calcium pantothenate may... information required by the Act, the following: (1) The name of the additive “calcium chloride double salt...

  8. 21 CFR 172.330 - Calcium pantothenate, calcium chloride double salt.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Calcium pantothenate, calcium chloride double salt..., calcium chloride double salt. The food additive calcium chloride double salt of calcium pantothenate may... information required by the Act, the following: (1) The name of the additive “calcium chloride double salt...

  9. Transient Tsunamis in Lakes

    NASA Astrophysics Data System (ADS)

    Couston, L.; Mei, C.; Alam, M.

    2013-12-01

    A large number of lakes are surrounded by steep and unstable mountains with slopes prone to failure. As a result, landslides are likely to occur and impact water sitting in closed reservoirs. These rare geological phenomena pose serious threats to dam reservoirs and nearshore facilities because they can generate unexpectedly large tsunami waves. In fact, the tallest wave experienced by contemporary humans occurred because of a landslide in the narrow bay of Lituya in 1958, and five years later, a deadly landslide tsunami overtopped Lake Vajont's dam, flooding and damaging villages along the lakefront and in the Piave valley. If unstable slopes and potential slides are detected ahead of time, inundation maps can be drawn to help people know the risks, and mitigate the destructive power of the ensuing waves. These maps give the maximum wave runup height along the lake's vertical and sloping boundaries, and can be obtained by numerical simulations. Keeping track of the moving shorelines along beaches is challenging in classical Eulerian formulations because the horizontal extent of the fluid domain can change over time. As a result, assuming a solid slide and nonbreaking waves, here we develop a nonlinear shallow-water model equation in the Lagrangian framework to address the problem of transient landslide-tsunamis. In this manner, the shorelines' three-dimensional motion is part of the solution. The model equation is hyperbolic and can be solved numerically by finite differences. Here, a 4th order Runge-Kutta method and a compact finite-difference scheme are implemented to integrate in time and spatially discretize the forced shallow-water equation in Lagrangian coordinates. The formulation is applied to different lake and slide geometries to better understand the effects of the lake's finite lengths and slide's forcing mechanism on the generated wavefield. Specifically, for a slide moving down a plane beach, we show that edge-waves trapped by the shoreline and free

  10. Delay modeling of bipolar ECL/EFL (Emitter-Coupled Logic/Emitter-Follower-Logic) circuits

    NASA Astrophysics Data System (ADS)

    Yang, Andrew T.

    1986-08-01

    This report deals with the development of a delay-time model for timing simulation of large circuits consisting of Bipolar ECL(Emitter-Coupled Logic) and EFL (Emitter-Follower-Logic) networks. This model can provide adequate information on the performance of the circuits with a minimum expenditure of computation time. This goal is achieved by the use of proper circuit transient models on which analytical delay expressions can be derived with accurate results. The delay-model developed in this report is general enough to handle complex digital circuits with multiple inputs or/and multiple levels. The important effects of input slew rate are also included in the model.

  11. Superfluorescence from optically trapped calcium atoms

    NASA Astrophysics Data System (ADS)

    Kumarakrishnan, A.; Han, X. L.

    1998-11-01

    We have studied superfluorescence (SF) under highly unfavorable conditions of rapid collisional and radiative distribution in a Doppler-broadened medium. Nanosecond SF pulses at 5.5 μm were generated on the Ca 4s4p 1P1-3d4s 1D2 transition from a column of calcium vapor buffered with Ar by optically pumping the 4s2 1S0-4s4p 1P1 transition. The Rabi frequency associated with the intense pump pulse prevents the occurrence of SF while the pump laser is on. As a result, the predicted scaling laws that describe the properties of SF in a transversely excited system, such as peak heights, pulse widths, and delay times, are shown to apply in our situation in which the conditions resemble swept excitation. The delay times were found to be in agreement with a fully quantum mechanical calculation which describes the initiation of SF. Measurements of the densities of the three levels, the absolute SF photon yield, and the spatial distribution of the excited states indicate that the system has a quantum yield of unity. The SF intensity increases with an increase in Ar pressure due to collisional redistribution until the collisional dephasing rate inhibits SF. The conditions describing the transition of SF to amplified spontaneous emission allow us to measure the collisional broadening rate for the SF transition.

  12. Detecting aseismic transients using seismicity

    NASA Astrophysics Data System (ADS)

    Reverso, T.; Marsan, D.; Helmstetter, A.

    2013-12-01

    Aseismic deformation transients occur in different tectonic context. In subduction zones, aseismic slip events are of paramount importance for understanding earthquake hazard, and for estimating the potential for future mega-thrust events. Aseismic slip is however difficult to detect except for the largest cases using GPS data. Here, we propose a systematic detection of aseismic deformation transients based on seismicity data alone. We search for transient increases in background seismicity rate, that would indicate the presence of an aseismic event. To that purpose, we make use of an ETAS model in space and time, to distinguish earthquakes due to background processes from aftershocks. We optimize the model parameters, and test the sensitivity of the results with changes in parameters. Given the 'best' model, we measure the statistical significance of the departure of the local (in time and space) background rate with the 'normal' background rate. Significant departure then indicates the need to temporary increase the background rate in order to explain the observed earthquake occurrences. We thus can single out such episodes of aseismic transients, and characterize their duration and spatial extent. Applying this method to the Aleutian subduction zone reveals several instances of aseismic deformation transients, at various spatial and temporal scales. We further investigate how these transients are organized along the subduction interface, and in time.

  13. Chaotic simulated annealing by a neural network with a variable delay: design and application.

    PubMed

    Chen, Shyan-Shiou

    2011-10-01

    In this paper, we have three goals: the first is to delineate the advantages of a variably delayed system, the second is to find a more intuitive Lyapunov function for a delayed neural network, and the third is to design a delayed neural network for a quadratic cost function. For delayed neural networks, most researchers construct a Lyapunov function based on the linear matrix inequality (LMI) approach. However, that approach is not intuitive. We provide a alternative candidate Lyapunov function for a delayed neural network. On the other hand, if we are first given a quadratic cost function, we can construct a delayed neural network by suitably dividing the second-order term into two parts: a self-feedback connection weight and a delayed connection weight. To demonstrate the advantage of a variably delayed neural network, we propose a transiently chaotic neural network with variable delay and show numerically that the model should possess a better searching ability than Chen-Aihara's model, Wang's model, and Zhao's model. We discuss both the chaotic and the convergent phases. During the chaotic phase, we simply present bifurcation diagrams for a single neuron with a constant delay and with a variable delay. We show that the variably delayed model possesses the stochastic property and chaotic wandering. During the convergent phase, we not only provide a novel Lyapunov function for neural networks with a delay (the Lyapunov function is independent of the LMI approach) but also establish a correlation between the Lyapunov function for a delayed neural network and an objective function for the traveling salesman problem.

  14. Parameter identification in periodic delay differential equations with distributed delay

    NASA Astrophysics Data System (ADS)

    Torkamani, Shahab; Butcher, Eric A.; Khasawneh, Firas A.

    2013-04-01

    In this study, a parameter identification approach for identifying the parameters of a periodic delayed system with distributed delay is introduced based on time series analysis and spectral element analysis. Using this approach the parameters of the distributed delayed system can be identified from the time series of the response of the system. The experimental or numerical data of the response is examined with Floquet theory and time series analysis techniques to estimate a reduced order dynamics, or truncated state space to identify the Floquet multipliers. Parameter identification is then completed using a dynamic map developed for the assumed model of the system which can relate the Floquet multipliers to the unknown parameters in the model. The parameter identification technique is validated numerically for first and second order delay differential equations with distributed delay.

  15. Amplitude death in networks of delay-coupled delay oscillators.

    PubMed

    Höfener, Johannes M; Sethia, Gautam C; Gross, Thilo

    2013-09-28

    Amplitude death is a dynamical phenomenon in which a network of oscillators settles to a stable state as a result of coupling. Here, we study amplitude death in a generalized model of delay-coupled delay oscillators. We derive analytical results for degree homogeneous networks which show that amplitude death is governed by certain eigenvalues of the network's adjacency matrix. In particular, these results demonstrate that in delay-coupled delay oscillators amplitude death can occur for arbitrarily large coupling strength k. In this limit, we find a region of amplitude death which already occurs at small coupling delays that scale with 1/k. We show numerically that these results remain valid in random networks with heterogeneous degree distribution.

  16. The calcium sensor synaptotagmin 7 is required for synaptic facilitation.

    PubMed

    Jackman, Skyler L; Turecek, Josef; Belinsky, Justine E; Regehr, Wade G

    2016-01-01

    It has been known for more than 70 years that synaptic strength is dynamically regulated in a use-dependent manner. At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement in which each subsequent action potential evokes greater neurotransmitter release. Facilitation can enhance neurotransmitter release considerably and can profoundly influence information transfer across synapses, but the underlying mechanism remains a mystery. One proposed mechanism is that a specialized calcium sensor for facilitation transiently increases the probability of release, and this sensor is distinct from the fast sensors that mediate rapid neurotransmitter release. Yet such a sensor has never been identified, and its very existence has been disputed. Here we show that synaptotagmin 7 (Syt7) is a calcium sensor that is required for facilitation at several central synapses. In Syt7-knockout mice, facilitation is eliminated even though the initial probability of release and the presynaptic residual calcium signals are unaltered. Expression of wild-type Syt7 in presynaptic neurons restored facilitation, whereas expression of a mutated Syt7 with a calcium-insensitive C2A domain did not. By revealing the role of Syt7 in synaptic facilitation, these results resolve a longstanding debate about a widespread form of short-term plasticity, and will enable future studies that may lead to a deeper understanding of the functional importance of facilitation.

  17. The calcium sensor synaptotagmin 7 is required for synaptic facilitation

    PubMed Central

    Jackman, Skyler L.; Turecek, Josef; Belinsky, Justine E.

    2015-01-01

    It has been known for over 70 years that synaptic strength is dynamically regulated in a use-dependent manner1. At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement where each subsequent action potential evokes greater neurotransmitter release2. Facilitation can enhance neurotransmitter release manyfold and profoundly influence information transfer across synapses3, but the underlying mechanism remains a mystery. Among the proposed mechanisms is that a specialized calcium sensor for facilitation transiently increases the probability of release2,4 and is distinct from the fast sensors that mediate rapid neurotransmitter release. Yet such a sensor has never been identified, and its very existence has been disputed5,6. Here we show that synaptotagmin 7 (syt7) is a calcium sensor that is required for facilitation at multiple central synapses. In syt7 knockout mice, facilitation is eliminated even though the initial probability of release and presynaptic residual calcium signals are unaltered. Expression of wild-type syt7 in presynaptic neurons restored facilitation, whereas expression of a mutated syt7 with a calcium-insensitive C2A domain did not. By revealing the role of syt7 in synaptic facilitation, these results resolve a longstanding debate about a widespread form of short-term plasticity, and will enable future studies that may lead to a deeper understanding of the functional importance of facilitation. PMID:26738595

  18. The Transient Radio Sky

    NASA Astrophysics Data System (ADS)

    Keane, E. F.

    2010-11-01

    The high time-resolution radio sky represents unexplored astronomical territory where the discovery potential is high. In this thesis I have studied the transient radio sky, focusing on millisecond scales. As such, this work is concerned primarily with neutron stars, the mostpopulous member of the radio transient parameter space. In particular, I have studied the well known radio pulsars and the recently identified group of neutron stars which show erratic radio emission, known as RRATs, which show radio bursts every few minutes to every few hours. When RRATs burst onto the scene in 2006, it was thought that they represented a previously unknown, distinct class of sporadically emitting sources. The difficulty in their identification implies a large underlying population, perhaps larger than the radio pulsars. The first question investigated in this thesis was whether the large projected population of RRATs posed a problem, i.e. could the observed supernova rate account for so many sources. In addition to pulsars and RRATs, the various other known neutron star manifestations were considered, leading to the conclusion that distinct populations would result in a `birthrate problem'. Evolution between the classes could solve this problem -- the RRATs are not a distinct population ofneutron stars.Alternatively, perhaps the large projected population of RRATs is an overestimate. To obtain an improved estimate, the best approach is to find more sources. The Parkes Multi-beam Pulsar Survey, wherein the RRATs were initially identified, offered an opportunity to do just this. Abouthalf of the RRATs showing bursts during the survey were thought to have been missed, due to the deleterious effects of impulsive terrestrial interference signals. To remove these unwanted signals, so that we could identify the previously shrouded RRATs, we developed newinterference mitigation software and processing techniques. Having done this, the survey was completely re-processed, resulting in

  19. Vitamin D, Calcium, and Bone Health

    MedlinePlus

    ... Balance › Vitamin D, Calcium, and Bone Health Vitamin D, Calcium, and Bone Health March 2012 Download PDFs ... helps keep your bones strong. Why are vitamin D and calcium important to bone health? Vitamin D ...

  20. Electrochemical cell with calcium anode

    DOEpatents

    Cooper, John F.; Hosmer, Pamela K.; Kelly, Benjamin E.

    1979-01-01

    An electrochemical cell comprising a calcium anode and a suitable cathode in an alkaline electrolyte consisting essentially of an aqueous solution of an hydroxide and a chloride. Specifically disclosed is a mechanically rechargeable calcium/air fuel cell with an aqueous NaOH/NaCl electrolyte.

  1. An Improved Calcium Flame Test.

    ERIC Educational Resources Information Center

    Pearson, Robert S.

    1985-01-01

    Indicates that the true red color of calcium can be obtained (using the procedure described by Sorm and Logowski) if the calcium ion solution is mixed with an equal volume of saturated ammonium bromide solution. Suggestions for flame tests of other elements are also noted. (JN)

  2. Calcium Intake: A Lifelong Proposition.

    ERIC Educational Resources Information Center

    Amschler, Denise H.

    1985-01-01

    This article reviews the current problem of low calcium intake in the United States among all age groups, the role of calcium in the formation and maintenance of bone mass, and major factors influencing absorption. Osteoporosis is discussed, and current recommendations for Recommended Dietary allowance are provided. (Author/MT)

  3. Major Minerals - Calcium, Magnesium, Phosphorus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Calcium, magnesium and phosphorus are essential elements critically important for the function of the musculoskeletal system, including the formation and transduction of energy and the maintenance of healthy bone. The major calcium concern for physically active healthy middle-aged adults is to consu...

  4. Space shuttle observation of an unusual transient atmospheric emission

    NASA Astrophysics Data System (ADS)

    Yair, Yoav; Price, Colin; Ziv, Baruch; Israelevich, Peter L.; Sentman, Davis D.; São-Sabbas, Fernanda T.; Devir, Adam D.; Sato, Mitsuteru; Rodger, Craig J.; Moalem, Meir; Greenberg, Eran; Yaron, Ofer

    2005-01-01

    We report an observation of an unusual transient luminous event (TLE) detected in the near IR, south of Madagascar above the Indian Ocean. The event was imaged from the space shuttle Columbia during the MEIDEX sprite campaign [Yair et al., 2004]. It was delayed 0.23 seconds from a preceding visual lightning flash which was horizontally displaced >1000 km from the event. The calculated brightness in the 860 (+/-50) nm filter was ~310 +/- 30 kR, and the morphology of the emitting volume did not resemble any known class of TLE (i.e., sprites, ELVES or halos). This TIGER event (Transient Ionospheric Glow Emission in Red) may constitute a new class of TLE, not necessarily induced by a near-by thunderstorm. We discuss possible generation mechanisms, including the conjugate sprite hypothesis caused by lightning at the magnetic mirror point, lightning-induced electron precipitation and an extraterrestrial source, meteoric or cometary.

  5. Complexity in electro-optic delay dynamics: modelling, design and applications.

    PubMed

    Larger, Laurent

    2013-09-28

    Nonlinear delay dynamics have found during the last 30 years a particularly prolific exploration area in the field of photonic systems. Besides the popular external cavity laser diode set-ups, we focus in this article on another experimental realization involving electro-optic (EO) feedback loops, with delay. This approach has strongly evolved with the important technological progress made on broadband photonic and optoelectronic devices dedicated to high-speed optical telecommunications. The complex dynamical systems performed by nonlinear delayed EO feedback loop architectures were designed and explored within a huge range of operating parameters. Thanks to the availability of high-performance photonic devices, these EO delay dynamics led also to many successful, efficient and diverse applications, beyond the many fundamental questions raised from the observation of experimental behaviours. Their chaotic motion allowed for a physical layer encryption method to secure optical data, with a demonstrated capability to operate at the typical speed of modern optical telecommunications. Microwave limit cycles generated in similar EO delay oscillators showed significantly improved spectral purity thanks to the use of a very long fibre delay line. Last but not least, a novel brain inspired computational principle has been recently implemented physically in photonics for the first time, again on the basis of an EO delay dynamical system. In this latter emerging application, the computed result is obtained by a proper 'read-out' of the complex nonlinear transients emerging from a fixed point, the transient being issued by the injection of the information signal to be processed.

  6. Geometric time delay interferometry

    NASA Astrophysics Data System (ADS)

    Vallisneri, Michele

    2005-08-01

    The space-based gravitational-wave observatory LISA, a NASA-ESA mission to be launched after 2012, will achieve its optimal sensitivity using time delay interferometry (TDI), a LISA-specific technique needed to cancel the otherwise overwhelming laser noise in the interspacecraft phase measurements. The TDI observables of the Michelson and Sagnac types have been interpreted physically as the virtual measurements of a synthesized interferometer. In this paper, I present Geometric TDI, a new and intuitive approach to extend this interpretation to all TDI observables. Unlike the standard algebraic formalism, Geometric TDI provides a combinatorial algorithm to explore exhaustively the space of second-generation TDI observables (i.e., those that cancel laser noise in LISA-like interferometers with time-dependent arm lengths). Using this algorithm, I survey the space of second-generation TDI observables of length (i.e., number of component phase measurements) up to 24, and I identify alternative, improved forms of the standard second-generation TDI observables. The alternative forms have improved high-frequency gravitational-wave sensitivity in realistic noise conditions (because they have fewer nulls in the gravitational-wave and noise response functions), and are less susceptible to instrumental gaps and glitches (because their component phase measurements span shorter time periods).

  7. Delayed traumatic intracerebral haemorrhage

    PubMed Central

    Baratham, Gopal; Dennyson, William G.

    1972-01-01

    Twenty-one out of 7,866 head injuries were complicated by the development of delayed intracerebral haematomata. The age distribution of patients with this condition closely resembled that of patients with subdural haematomata and differed sharply from patients with extradural haemorrhage. This finding, combined with the fact that the two conditions often coexisted, suggests the possibility of similar aetiological factors operating in their production. The injury producing the lesion was often minor and the larger haematomata appeared to be associated with longer `asymptomatic' intervals. The neurological deterioration was in most instances clearly the result of an increase in intracranial pressure. When possible, angiography followed by definitive craniotomy was the most satisfactory method of management and multiple burr holes even when combined with needling of the hemisphere yielded unsatisfactory results. The distribution of lesions tended to confirm their traumatic origin. On no occasion was there a vascular abnormality to account for the haemorrhage and, despite the fact that the ages of most patients were in the seventh and eighth decades, the incidence of degenerative vascular disease was small. Contusional injury causes a local failure of the mechanisms that regulate cerebral blood flow. Hypoxia, hypercapnia, and venous congestion produce cerebral hyperaemia which encourages gradual haematoma formation particularly at the sites of injury. This explains not only the situation of the lesions but also the latency between the trauma and their development. PMID:5084138

  8. Delay Adjusted Incidence Infographic

    Cancer.gov

    This Infographic shows the National Cancer Institute SEER Incidence Trends. The graphs show the Average Annual Percent Change (AAPC) 2002-2011. For Men, Thyroid: 5.3*,Liver & IBD: 3.6*, Melanoma: 2.3*, Kidney: 2.0*, Myeloma: 1.9*, Pancreas: 1.2*, Leukemia: 0.9*, Oral Cavity: 0.5, Non-Hodgkin Lymphoma: 0.3*, Esophagus: -0.1, Brain & ONS: -0.2*, Bladder: -0.6*, All Sites: -1.1*, Stomach: -1.7*, Larynx: -1.9*, Prostate: -2.1*, Lung & Bronchus: -2.4*, and Colon & Rectum: -3/0*. For Women, Thyroid: 5.8*, Liver & IBD: 2.9*, Myeloma: 1.8*, Kidney: 1.6*, Melanoma: 1.5, Corpus & Uterus: 1.3*, Pancreas: 1.1*, Leukemia: 0.6*, Brain & ONS: 0, Non-Hodgkin Lymphoma: -0.1, All Sites: -0.1, Breast: -0.3, Stomach: -0.7*, Oral Cavity: -0.7*, Bladder: -0.9*, Ovary: -0.9*, Lung & Bronchus: -1.0*, Cervix: -2.4*, and Colon & Rectum: -2.7*. * AAPC is significantly different from zero (p<.05). Rates were adjusted for reporting delay in the registry. www.cancer.gov Source: Special section of the Annual Report to the Nation on the Status of Cancer, 1975-2011.

  9. Delayed unlatching mechanism

    DOEpatents

    Bzorgi, Fariborz M.

    2015-05-19

    In various embodiments an apparatus is presented for securing a structure such as a door, window, hatch, or gate that moves between an open and a closed position relative to a fixed structure to provide or deny access to a compartment, a room, an outdoor area, or a facility. Various embodiments provide a delay in opening the closure of sufficient duration to frustrate a rapid activation that might be desired by a person who is attempting to pass through the closure for some illicit purpose. Typically, hydraulics are used to activate the apparatus and no electrical energy or electronic signals are employed. In one embodiment, a plurality of actuations of a hand lever operates a hydraulic pump that moves a locking bolt from a first position in which a locking bolt is engaged with a recess in the fixed structure (preventing opening of a gate) to a second position in which the locking bolt is disengaged from the recess to permit opening of the gate.

  10. Phorbol ester stimulates calcium sequestration in saponized human platelets

    SciTech Connect

    Yoshida, K.; Nachmias, V.T.

    1987-11-25

    When platelets are activated by agonists, calcium (Ca2+) is released from an intracellular storage site. Recent studies using fura-2 show that, after thrombin stimulation, the rise in free calcium is transient and returns to base-line levels in 2-3 min, while the transient following ADP stimulation lasts only 15-20 s. We reported previously that the phorbol ester 12,13-phorbol myristate acetate (PMA), added at nanomolar levels after thrombin, immediately accelerated the rate of return of calcium to the base line severalfold. In the present study, we used both intact and saponized platelets to determine whether this is due to stimulation of calcium sequestration. Using fura-2 and intact platelets, we found 1) that PMA stimulated the restoration of free Ca2+ levels after ADP as well as after thrombin, and 2) that H-7, an inhibitor of protein kinase C (Ca2+/phospholipid-dependent enzyme), slowed the return of Ca2+ to baseline levels. Using saponized platelets, we also found 3) that pretreatment of platelets with PMA before saponin treatment increased the ATP-dependent /sup 45/Ca2+ uptake 2-fold, with a half-maximal effect at 5 nm; 4) that most of the Ca2+ released by ionomycin or by myoinositol 1,4,5-trisphosphate; and 5) that a GTP-binding protein inhibitor, guanosine 5'-O-(2-thiodiphosphate), decreased basal or PMA-stimulated /sup 45/Ca2+ uptake in saponin-treated platelets. Our data suggest that activation of protein kinase C stimulates the sequestration of Ca2+ independently of cAMP or myoinositol 1,4,5-trisphosphate.

  11. High resolution digital delay timer

    DOEpatents

    Martin, Albert D.

    1988-01-01

    Method and apparatus are provided for generating an output pulse following a trigger pulse at a time delay interval preset with a resolution which is high relative to a low resolution available from supplied clock pulses. A first lumped constant delay (20) provides a first output signal (24) at predetermined interpolation intervals corresponding to the desired high resolution time interval. Latching circuits (26, 28) latch the high resolution data (24) to form a first synchronizing data set (60). A selected time interval has been preset to internal counters (142, 146, 154) and corrected for circuit propagation delay times having the same order of magnitude as the desired high resolution. Internal system clock pulses (32, 34) count down the counters to generate an internal pulse delayed by an interval which is functionally related to the preset time interval. A second LCD (184) corrects the internal signal with the high resolution time delay. A second internal pulse is then applied to a third LCD (74) to generate a second set of synchronizing data (76) which is complementary with the first set of synchronizing data (60) for presentation to logic circuits (64). The logic circuits (64) further delay the internal output signal (72) to obtain a proper phase relationship of an output signal (80) with the internal pulses (32, 34). The final delayed output signal (80) thereafter enables the output pulse generator (82) to produce the desired output pulse (84) at the preset time delay interval following input of the trigger pulse (10, 12).

  12. Delayed Auditory Feedback and Movement

    ERIC Educational Resources Information Center

    Pfordresher, Peter Q.; Dalla Bella, Simone

    2011-01-01

    It is well known that timing of rhythm production is disrupted by delayed auditory feedback (DAF), and that disruption varies with delay length. We tested the hypothesis that disruption depends on the state of the movement trajectory at the onset of DAF. Participants tapped isochronous rhythms at a rate specified by a metronome while hearing DAF…

  13. Delayed Reinforcement of Operant Behavior

    ERIC Educational Resources Information Center

    Lattal, Kennon A.

    2010-01-01

    The experimental analysis of delay of reinforcement is considered from the perspective of three questions that seem basic not only to understanding delay of reinforcement but also, by implication, the contributions of temporal relations between events to operant behavior. The first question is whether effects of the temporal relation between…

  14. Activation of transient receptor potential ankyrin 1 by eugenol.

    PubMed

    Chung, G; Im, S T; Kim, Y H; Jung, S J; Rhyu, M-R; Oh, S B

    2014-03-01

    Eugenol is a bioactive plant extract used as an analgesic agent in dentistry. The structural similarity of eugenol to cinnamaldehyde, an active ligand for transient receptor potential ankyrin 1 (TRPA1), suggests that eugenol might produce its effect via TRPA1, in addition to TRPV1 as we reported previously. In this study, we investigated the effect of eugenol on TRPA1, by fura-2-based calcium imaging and patch clamp recording in trigeminal ganglion neurons and in a heterologous expression system. As the result, eugenol induced robust calcium responses in rat trigeminal ganglion neurons that responded to a specific TRPA1 agonist, allyl isothiocyanate (AITC), and not to capsaicin. Capsazepine, a TRPV1 antagonist failed to inhibit eugenol-induced calcium responses in AITC-responding neurons. In addition, eugenol response was observed in trigeminal ganglion neurons from TRPV1 knockout mice and human embryonic kidney 293 cell lines that express human TRPA1, which was inhibited by TRPA1-specific antagonist HC-030031. Eugenol-evoked TRPA1 single channel activity and eugenol-induced TRPA1 currents were dose-dependent with EC50 of 261.5μM. In summary, these results demonstrate that the activation of TRPA1 might account for another molecular mechanism underlying the pharmacological action of eugenol.

  15. Effect of dietary calcium and 1,25-(OH)2D3 on the expression of calcium transport genes in calbindin-D9k and -D28k double knockout mice.

    PubMed

    Ko, Sang-Hwan; Choi, Kyung-Chul; Oh, Goo Taeg; Jeung, Eui-Bae

    2009-02-01

    The phenotypes of calbindin-D9k (CaBP-9k) and -28k (CaBP-28k) single knockout (KO) mice are similar to wild-type (WT) mice due to the compensatory action of other calcium transport proteins. In this study, we generated CaBP-9k/CaBP-28k double knockout (DKO) mice in order to investigate the importance of CaBP-9k and CaBP-28k in active calcium processing. Under normal dietary conditions, DKO mice did not exhibit any changes in phenotype or the expression of active calcium transport genes as compared to WT or CaBP-28k KO mice. Under calcium-deficient dietary conditions, the phenotype and expression of calcium transport genes in CaBP-28k KO mice were similar to WT, whereas in DKO mice, serum calcium levels and bone length were decreased. The intestinal and renal expression of transient receptor potential vanilloid member 6 (TRPV6) mRNA was significantly decreased in DKO mice fed a calcium-deficient diet as compared to CaBP-28k KO or WT mice, and DKO mice died after 4 weeks on a calcium-deficient diet. Body weight, bone mineral density (BMD) and bone length were significantly reduced in all mice fed a calcium and 1,25-(OH)(2)D(3)-deficient diet, as compared to a normal diet, and none of the mice survived more than 4 weeks. These results indicate that deletion of CaBP-28k alone does not affect body calcium homeostasis, but that deletion of CaBP-9k and CaBP-28k has a significant effect on calcium processing under calcium-deficient conditions, confirming the importance of dietary calcium and 1,25-(OH)(2)D(3) during growth and development.

  16. Calcium signaling mediates antifungal activity of triazole drugs in the Aspergilli.

    PubMed

    Liu, Fei-fei; Pu, Li; Zheng, Qing-qing; Zhang, Yuan-wei; Gao, Rong-sui; Xu, Xu-shi; Zhang, Shi-zhu; Lu, Ling

    2015-08-01

    Azoles are widely applied and largely effective as antifungals; however, the increasing prevalence of clinically resistant isolates has yet to be matched by approaches to improve the efficacy of antimicrobial therapy. In this study, using the model fungus Aspergillus nidulans and one of the most common human pathogen Aspergillus fumigatus as research materials, we present the evidence that calcium signaling is involved in the azole-antifungals-induced stress-response reactions. In normal media, antifungal-itraconazole (ITZ) is able to induce the [Ca(2+)]c increased sharply but the addition of calcium chelator-EGTA or BAPTA almost blocks the calcium influx responses, resulted in the dramatically decreasing of [Ca(2+)]c transient. Real-time PCR analysis verified that six-tested Ca(2+)-inducible genes-two calcium channels (cchA/midA), a calmodulin-dependent phosphatase-calcineurin (cnaA), a transcription factor-crzA, and two calcium transporters (pmrA/pmcA)-could be transiently up-regulated by adding ITZ, indicating these components are involved in the azole stress-response reaction. Defect of cnaA or crzA caused more susceptibility to azole antifungals than did single mutants or double deletions of midA and cchA. Notably, EGTA may influence Rh123 accumulation as an azole-mimicking substrate through the process of the drug absorption. In vivo studies of a Galleria mellonella model identified that the calcium chelator works as an adjunct antifungal agent with azoles for invasive aspergillosis. Most importantly, combination of ITZ and EGTA or ITZ with calcium signaling inhibitor-FK506 greatly enhances the ITZ efficacy. Thus, our study provides potential clues that specific inhibitors of calcium signaling could be clinically useful adjuncts to conventional azole antifungals in the Aspergilli.

  17. The cardiac L-type calcium channel distal carboxy terminus autoinhibition is regulated by calcium.

    PubMed

    Crump, Shawn M; Andres, Douglas A; Sievert, Gail; Satin, Jonathan

    2013-02-01

    The L-type calcium channel (LTCC) provides trigger Ca(2+) for sarcoplasmic reticulum Ca-release, and LTCC function is influenced by interacting proteins including the LTCC distal COOH terminus (DCT) and calmodulin. DCT is proteolytically cleaved and reassociates with the LTCC complex to regulate calcium channel function. DCT reduces LTCC barium current (I(Ba,L)) in reconstituted channel complexes, yet the contribution of DCT to LTCC Ca(2+) current (I(Ca,L)) in cardiomyocyte systems is unexplored. This study tests the hypothesis that DCT attenuates cardiomyocyte I(Ca,L). We measured LTCC current and Ca(2+) transients with DCT coexpressed in murine cardiomyocytes. We also heterologously coexpressed DCT and Ca(V)1.2 constructs with truncations corresponding to the predicted proteolytic cleavage site, Ca(V)1.2Δ1801, and a shorter deletion corresponding to well-studied construct, Ca(V)1.2Δ1733. DCT inhibited I(Ba,L) in cardiomyocytes, and in human embryonic kidney (HEK) 293 cells expressing Ca(V)1.2Δ1801 and Ca(V)1.2Δ1733. Ca(2+)-CaM relieved DCT block in cardiomyocytes and HEK cells. The selective block of I(Ba,L) combined with Ca(2+)-CaM effects suggested that DCT-mediated blockade may be relieved under conditions of elevated Ca(2+). We therefore tested the hypothesis that DCT block is dynamic, increasing under relatively low Ca(2+), and show that DCT reduced diastolic Ca(2+) at low stimulation frequencies but spared high frequency Ca(2+) entry. DCT reduction of diastolic Ca(2+) and relief of block at high pacing frequencies and under conditions of supraphysiological bath Ca(2+) suggests that a physiological function of DCT is to increase the dynamic range of Ca(2+) transients in response to elevated pacing frequencies. Our data motivate the new hypothesis that DCT is a native reverse use-dependent inhibitor of LTCC current.

  18. Calcium in Plants

    PubMed Central

    WHITE, PHILIP J.; BROADLEY, MARTIN R.

    2003-01-01

    Calcium is an essential plant nutrient. It is required for various structural roles in the cell wall and membranes, it is a counter‐cation for inorganic and organic anions in the vacuole, and the cytosolic Ca2+ concentration ([Ca2+]cyt) is an obligate intracellular messenger coordinating responses to numerous developmental cues and environmental challenges. This article provides an overview of the nutritional requirements of different plants for Ca, and how this impacts on natural flora and the Ca content of crops. It also reviews recent work on (a) the mechanisms of Ca2+ transport across cellular membranes, (b) understanding the origins and specificity of [Ca2+]cyt signals and (c) characterizing the cellular [Ca2+]cyt‐sensors (such as calmodulin, calcineurin B‐like proteins and calcium‐dependent protein kinases) that allow plant cells to respond appropriately to [Ca2+]cyt signals. PMID:12933363

  19. Communication: XUV transient absorption spectroscopy of iodomethane and iodobenzene photodissociation

    NASA Astrophysics Data System (ADS)

    Drescher, L.; Galbraith, M. C. E.; Reitsma, G.; Dura, J.; Zhavoronkov, N.; Patchkovskii, S.; Vrakking, M. J. J.; Mikosch, J.

    2016-07-01

    Time-resolved extreme ultraviolet (XUV) transient absorption spectroscopy of iodomethane and iodobenzene photodissociation at the iodine pre-N4,5 edge is presented, using femtosecond UV pump pulses and XUV probe pulses from high harmonic generation. For both molecules the molecular core-to-valence absorption lines fade immediately, within the pump-probe time-resolution. Absorption lines converging to the atomic iodine product emerge promptly in CH3I but are time-delayed in C6H5I. We attribute this delay to the initial π → σ* excitation in iodobenzene, which is distant from the iodine reporter atom. We measure a continuous shift in energy of the emerging atomic absorption lines in CH3I, attributed to relaxation of the excited valence shell. An independent particle model is used to rationalize the observed experimental findings.

  20. Calcium-sensing receptor and calcium kidney stones.

    PubMed

    Vezzoli, Giuseppe; Terranegra, Annalisa; Rainone, Francesco; Arcidiacono, Teresa; Cozzolino, Mario; Aloia, Andrea; Dogliotti, Elena; Cusi, Daniele; Soldati, Laura

    2011-11-22

    Calcium nephrolithiasis may be considered as a complex disease having multiple pathogenetic mechanisms and characterized by various clinical manifestations. Both genetic and environmental factors may increase susceptibility to calcium stones; therefore, it is crucial to characterize the patient phenotype to distinguish homogeneous groups of stone formers. Family and twin studies have shown that the stone transmission pattern is not mendelian, but complex and polygenic. In these studies, heritability of calcium stones was calculated around 50%Calcium-sensing receptor (CaSR) is mostly expressed in the parathyroid glands and in renal tubules. It regulates the PTH secretion according to the serum calcium concentration. In the kidney, it modulates electrolyte and water excretion regulating the function of different tubular segments. In particular, CaSR reduces passive and active calcium reabsorption in distal tubules, increases phosphate reabsorption in proximal tubules and stimulates proton and water excretion in collecting ducts. Therefore, it is a candidate gene for calcium nephrolithiasis.In a case-control study we found an association between the normocitraturic stone formers and two SNPs of CaSR, located near the promoters region (rs7652589 and rs1501899). This result was replicated in patients with primary hyperparathyroidism, comparing patients with or without kidney stones. Bioinformatic analysis suggested that the minor alleles at these polymorphisms were able to modify the binding sites of specific transcription factors and, consequently, CaSR expression.Our studies suggest that CaSR is one of the candidate genes explaining individual predisposition to calcium nephrolithiasis. Stone formation may be favored by an altered CaSR expression in kidney medulla involving the normal balance among calcium, phosphate, protons and water excretion.

  1. Delayed Adrenarche may be an Additional Feature of Immunoglobulin Super Family Member 1 Deficiency Syndrome.

    PubMed

    Van Hulle, Severine; Craen, Margarita; Callewaert, Bert; Joustra, Sjoerd; Oostdijk, Wilma; Losekoot, Monique; Wit, Jan Maarten; Turgeon, Marc Olivier; Bernard, Daniel J; De Schepper, Jean

    2016-03-01

    Immunoglobulin super family member 1 (IGSF1) deficiency syndrome is characterized by central hypothyroidism, delayed surge in testosterone during puberty, macro-orchidism, and in some cases, hypoprolactinemia and/or transient growth hormone (GH) deficiency. Our patient was a 19-year-old male adolescent who had been treated since the age of 9 years with GH and thyroxine for an idiopathic combined GH, thyroid-stimulating hormone (TSH), and prolactin (PRL) deficiency. His GH deficiency proved to be transient, but deficiencies of TSH and PRL persisted, and he had developed macro-orchidism since the end of puberty. Brain magnetic resonance imaging and PROP1 and POU1F1 sequencing were normal. A disharmonious puberty (delayed genital and pubic hair development, bone maturation, and pubertal growth spurt, despite normal testicular growth) was observed as well as a delayed adrenarche, as reflected by very low dehydroepiandrosterone sulfate and delayed pubarche. Direct sequencing of the IGSF1 gene revealed a novel hemizygous mutation, c.3127T>C, p.Cys1043Arg. Pathogenicity of the mutation was demonstrated in vitro. Male children with an idiopathic combined GH, PRL, and TSH deficiency, showing persistent central hypothyroidism but transient GH deficiency upon retesting at adult height, should be screened for mutations in the IGSF1 gene, especially when macro-orchidism and/or hypoprolactinemia are present. We suspect that delayed adrenarche, as a consequence of PRL deficiency, might be part of the clinical phenotype of patients with IGSF1 deficiency. PMID:26757742

  2. Delayed Adrenarche may be an Additional Feature of Immunoglobulin Super Family Member 1 Deficiency Syndrome

    PubMed Central

    Hulle, Severine Van; Craen, Margarita; Callewaert, Bert; Joustra, Sjoerd; Oostdijk, Wilma; Losekoot, Monique; Wit, Jan Maarten; Turgeon, Marc Olivier; Bernard, Daniel J.; Schepper, Jean De

    2016-01-01

    Immunoglobulin super family member 1 (IGSF1) deficiency syndrome is characterized by central hypothyroidism, delayed surge in testosterone during puberty, macro-orchidism, and in some cases, hypoprolactinemia and/or transient growth hormone (GH) deficiency. Our patient was a 19-year-old male adolescent who had been treated since the age of 9 years with GH and thyroxine for an idiopathic combined GH, thyroid-stimulating hormone (TSH), and prolactin (PRL) deficiency. His GH deficiency proved to be transient, but deficiencies of TSH and PRL persisted, and he had developed macro-orchidism since the end of puberty. Brain magnetic resonance imaging and PROP1 and POU1F1 sequencing were normal. A disharmonious puberty (delayed genital and pubic hair development, bone maturation, and pubertal growth spurt, despite normal testicular growth) was observed as well as a delayed adrenarche, as reflected by very low dehydroepiandrosterone sulfate and delayed pubarche. Direct sequencing of the IGSF1 gene revealed a novel hemizygous mutation, c.3127T>C, p.Cys1043Arg. Pathogenicity of the mutation was demonstrated in vitro. Male children with an idiopathic combined GH, PRL, and TSH deficiency, showing persistent central hypothyroidism but transient GH deficiency upon retesting at adult height, should be screened for mutations in the IGSF1 gene, especially when macro-orchidism and/or hypoprolactinemia are present. We suspect that delayed adrenarche, as a consequence of PRL deficiency, might be part of the clinical phenotype of patients with IGSF1 deficiency. PMID:26757742

  3. Sensitivity to calcium intake in calcium stone forming patients.

    PubMed

    Heilberg, I P; Martini, L A; Draibe, S A; Ajzen, H; Ramos, O L; Schor, N

    1996-01-01

    The absorptive or renal origin of hypercalciuria can be discriminated using an acute oral calcium load test (ACLT). Of 86 patients with calcium oxalate kidney stones, 28 (23%) were found to be hypercalciuric (HCa) and 58 (67%) normocalciuric (NCa) on their customary free diet, containing 542 +/- 29 mg/day (mean +/- SE) of calcium. Since the apparently normal 24-hour calcium excretion of many calcium stone formers (CSF) may be due to a combination of high calcium absorption with moderately low calcium intake, all patients were investigated by ACLT. Of 28 HCa patients, 13 (46%) were classified as absorptive (AH) and 15 (54%) as renal hypercalciuria (RH). Of the 58 NCa patients, 38 (65%) presented features of intestinal hyperabsorption and were therefore designated as AH-like, and 20 (35%) as RH-like. To further elucidate the role of dietary calcium in these CSF, a chronic calcium load test (CCLT), consisting of 1 g/day of oral Ca for 7 days, was designed. A positive response to the CCLT was considered to occur when urinary calcium (uCa) was > or = 4 mg/ kg/24 h on the 7th day. Among NCa patients, 29% of AH-like subjects responded to the CCLT and 71% did not; 50% of RH-like subjects also responded and 50% did not. In HCa patients, 85% of AH and 67% of RH subjects maintained uCa > or = 4 mg/kg/24 h after the CCLT and 15% of AH and 23% of RH subjects did not. However, a significant additional increase in mean uCa was not observed among HCa patients. All patients were submitted to a second evaluation of fasting calciuria (Ca/Cr). A modification of this parameter was noticed in 89% of RH-like and 78% of RH patients. In conclusion, these data suggest the presence of subpopulations of patients sensitive or not to calcium intake, regardless of whether the acute response to a calcium overload test suggested AH or RH. The CCLT disclosed dietary hypercalciuria in 21/58 (36%) of previously NCa patients. In these NCa patients, the ACLT may be replaced by the CCLT. The distinction

  4. Limestone reaction in calcium aluminate cement–calcium sulfate systems

    SciTech Connect

    Bizzozero, Julien Scrivener, Karen L.

    2015-10-15

    This paper reports a study of ternary blends composed of calcium aluminate cement, calcium sulfate hemihydrate and limestone. Compressive strength tests and hydration kinetics were studied as a function of limestone and calcium sulfate content. The phase evolution and the total porosity were followed and compared to thermodynamic simulation to understand the reactions involved and the effect of limestone on these binders. The reaction of limestone leads to the formation of hemicarboaluminate and monocarboaluminate. Increasing the ratio between sulfate and aluminate decreases the extent of limestone reaction.

  5. Calcium orthophosphate coatings on magnesium and its biodegradable alloys.

    PubMed

    Dorozhkin, Sergey V

    2014-07-01

    Biodegradable metals have been suggested as revolutionary biomaterials for bone-grafting therapies. Of these metals, magnesium (Mg) and its biodegradable alloys appear to be particularly attractive candidates due to their non-toxicity and as their mechanical properties match those of bones better than other metals do. Being light, biocompatible and biodegradable, Mg-based metallic implants have several advantages over other implantable metals currently in use, such as eliminating both the effects of stress shielding and the requirement of a second surgery for implant removal. Unfortunately, the fast degradation rates of Mg and its biodegradable alloys in the aggressive physiological environment impose limitations on their clinical applications. This necessitates development of implants with controlled degradation rates to match the kinetics of bone healing. Application of protective but biocompatible and biodegradable coatings able to delay the onset of Mg corrosion appears to be a reasonable solution. Since calcium orthophosphates are well tolerated by living organisms, they appear to be the excellent candidates for such coatings. Nevertheless, both the high chemical reactivity and the low melting point of Mg require specific parameters for successful deposition of calcium orthophosphate coatings. This review provides an overview of current coating techniques used for deposition of calcium orthophosphates on Mg and its biodegradable alloys. The literature analysis revealed that in all cases the calcium orthophosphate protective coatings both increased the corrosion resistance of Mg-based metallic biomaterials and improved their surface biocompatibility.

  6. Delayed Geodynamo in Hadean

    NASA Astrophysics Data System (ADS)

    Arkani-Hamed, J.

    2014-12-01

    Paleointensity measurements of Archean rocks reveal a strong geodynamo at ~3.45 Ga, while excess nitrogen content of lunar soil samples implies no geodynamo at ~3.9 Ga. Here I propose that initiation of a strong geodynamo is delayed due to accretion style of Earth, involving collision and merging of a few dozen Moon to Mars size planetary embryos. Two accretion scenarios consisting of 25 and 50 embryos are investigated. The collision of an embryo heats the proto-Earth's core differentially and the rotating low-viscosity core stably stratifies, creating a spherically symmetric and radially increasing temperature distribution. Convection starts in the outer core after each impact but is destroyed by the next impact. The iron core of an impacting embryo descends in the mantle and merges to the proto-Earth's core. Both adiabatic and non-adiabatic merging cases are studied. A major part of the gravitational energy released due to core merging is used to lift up the upper portion of the core to emplace the impactor core material at the neutrally buoyant level in the proto-Earth's core. The remaining energy is converted to heat. In the adiabatic case the merging embryo's core retains all of the remaining energy, while in the non-adiabatic merging 50% of the remaining energy is shared with the outer part of the proto-Earth's core where the embryo's core descends. The two merging models result in significantly different temperature distributions in the core at the end of accretion. After the accretion, the convecting shell in the outer core grows monotonically and generates geodynamo gradually. It takes about 50-100 Myr for the convecting shell to generate a strong dipole field at the surface, 50,000 to 100,000 nT, in the presence of a large stably stratified liquid inner core when the convecting outer core thickness exceeds about one half the radius of the Earth's core.

  7. Delayed drug hypersensitivity reactions.

    PubMed

    Pichler, Werner J

    2003-10-21

    Immune reactions to small molecular compounds, such as drugs, can cause a variety of diseases involving the skin, liver, kidney, and lungs. In many drug hypersensitivity reactions, drug-specific CD4+ and CD8+ T cells recognize drugs through their alphabeta T-cell receptors in an MHC-dependent way. Drugs stimulate T cells if they act as haptens and bind covalently to peptides or if they have structural features that allow them to interact with certain T-cell receptors directly. Immunohistochemical and functional studies of drug-reactive T cells in patients with distinct forms of exanthema reveal that distinct T-cell functions lead to different clinical phenotypes. In maculopapular exanthema, perforin-positive and granzyme B-positive CD4+ T cells kill activated keratinocytes, while a large number of cytotoxic CD8+ T cells in the epidermis is associated with formation of vesicles and bullae. Drug-specific T cells also orchestrate inflammatory skin reactions through the release of various cytokines (for example, interleukin-5, interferon) and chemokines (such as interleukin-8). Activation of T cells with a particular function seems to lead to a specific clinical picture (for example, bullous or pustular exanthema). Taken together, these data allow delayed hypersensitivity reactions (type IV) to be further subclassified into T-cell reactions, which through the release of certain cytokines and chemokines preferentially activate and recruit monocytes (type IVa), eosinophils (type IVb), or neutrophils (type IVd). Moreover, cytotoxic functions by either CD4+ or CD8+ T cells (type IVc) seem to participate in all type IV reactions.

  8. Calcium wave propagation by calcium-induced calcium release: an unusual excitable system.

    PubMed

    Sneyd, J; Girard, S; Clapham, D

    1993-03-01

    We discuss in detail the behaviour of a model, proposed by Goldbeter et al. (1990. Proc. natn. Acad. Sci. 87, 1461-1465), for intracellular calcium wave propagation by calcium-induced calcium release, focusing our attention on excitability and the propagation of waves in one spatial dimension. The model with no diffusion behaves like a generic excitable system, and threshold behaviour, excitability and oscillations can be understood within this general framework. However, when diffusion is included, the model no longer behaves like a generic excitable system; the fast and slow variables are not distinct and previous results on excitable systems do not necessarily apply. We consider a piecewise linear simplification of the model, and construct travelling pulse and periodic plane wave solutions to the simplified model. The analogous behaviour in the full model is studied numerically. Goldbeter's model for calcium-induced calcium release is an excitable system of a type not previously studied in detail.

  9. Neocortical GABA release at high intracellular sodium and low extracellular calcium: an anti-seizure mechanism.

    PubMed

    Rassner, Michael P; Moser, Andreas; Follo, Marie; Joseph, Kevin; van Velthoven-Wurster, Vera; Feuerstein, Thomas J

    2016-04-01

    In epilepsy, the GABA and glutamate balance may be disrupted and a transient decrease in extracellular calcium occurs before and during a seizure. Flow Cytometry based fluorescence activated particle sorting experiments quantified synaptosomes from human neocortical tissue, from both epileptic and non-epileptic patients (27.7% vs. 36.9% GABAergic synaptosomes, respectively). Transporter-mediated release of GABA in human and rat neocortical synaptosomes was measured using the superfusion technique for the measurement of endogenous GABA. GABA release was evoked by either a sodium channel activator or a sodium/potassium-ATPase inhibitor when exocytosis was possible or prevented, and when the sodium/calcium exchanger was active or inhibited. The transporter-mediated release of GABA is because of elevated intracellular sodium. A reduction in the extracellular calcium increased this release (in both non-epileptic and epileptic, except Rasmussen encephalitis, synaptosomes). The inverse was seen during calcium doubling. In humans, GABA release was not affected by exocytosis inhibition, that is, it was solely transporter-mediated. However, in rat synaptosomes, an increase in GABA release at zero calcium was only exhibited when the exocytosis was prevented. The absence of calcium amplified the sodium/calcium exchanger activity, leading to elevated intracellular sodium, which, together with the stimulation-evoked intracellular sodium increment, enhanced GABA transporter reversal. Sodium/calcium exchange inhibitors diminished GABA release. Thus, an important seizure-induced extracellular calcium reduction might trigger a transporter- and sodium/calcium exchanger-related anti-seizure mechanism by augmenting transporter-mediated GABA release, a mechanism absent in rats. Uniquely, the additional increase in GABA release because of calcium-withdrawal dwindled during the course of illness in Rasmussen encephalitis. Seizures cause high Na(+) influx through action potentials. A

  10. Impaired Cellular Bioenergetics Causes Mitochondrial Calcium Handling Defects in MT-ND5 Mutant Cybrids

    PubMed Central

    Duchen, Michael R.

    2016-01-01

    Mutations in mitochondrial DNA (mtDNA) can cause mitochondrial disease, a group of metabolic disorders that affect both children and adults. Interestingly, individual mtDNA mutations can cause very different clinical symptoms, however the factors that determine these phenotypes remain obscure. Defects in mitochondrial oxidative phosphorylation can disrupt cell signaling pathways, which may shape these disease phenotypes. In particular, mitochondria participate closely in cellular calcium signaling, with profound impact on cell function. Here, we examined the effects of a homoplasmic m.13565C>T mutation in MT-ND5 on cellular calcium handling using transmitochondrial cybrids (ND5 mutant cybrids). We found that the oxidation of NADH and mitochondrial membrane potential (Δψm) were significantly reduced in ND5 mutant cybrids. These metabolic defects were associated with a significant decrease in calcium uptake by ND5 mutant mitochondria in response to a calcium transient. Inhibition of glycolysis with 2-deoxy-D-glucose did not affect cytosolic calcium levels in control cybrids, but caused an increase in cytosolic calcium in ND5 mutant cybrids. This suggests that glycolytically-generated ATP is required not only to maintain Δψm in ND5 mutant mitochondria but is also critical for regulating cellular calcium homeostasis. We conclude that the m.13565C>T mutation in MT-ND5 causes defects in both mitochondrial oxidative metabolism and mitochondrial calcium sequestration. This disruption of mitochondrial calcium handling, which leads to defects in cellular calcium homeostasis, may be an important contributor to mitochondrial disease pathogenesis. PMID:27110715

  11. Delay of Gratification and Delay Discounting: A Unifying Feedback Model of Delay-Related Impulsive Behavior

    ERIC Educational Resources Information Center

    Reynolds, Brady; Schiffbauer, Ryan

    2005-01-01

    Delay of Gratification (DG) and Delay Discounting (DD) represent two indices of impulsive behavior often treated as though they represent equivalent or the same underlying processes. However, there are key differences between DG and DD procedures, and between certain research findings with each procedure, that suggest they are not equivalent. In…

  12. Calcium Signaling throughout the Toxoplasma gondii Lytic Cycle: A STUDY USING GENETICALLY ENCODED CALCIUM INDICATORS.

    PubMed

    Borges-Pereira, Lucas; Budu, Alexandre; McKnight, Ciara A; Moore, Christina A; Vella, Stephen A; Hortua Triana, Miryam A; Liu, Jing; Garcia, Celia R S; Pace, Douglas A; Moreno, Silvia N J

    2015-11-01

    Toxoplasma gondii is an obligate intracellular parasite that invades host cells, creating a parasitophorous vacuole where it communicates with the host cell cytosol through the parasitophorous vacuole membrane. The lytic cycle of the parasite starts with its exit from the host cell followed by gliding motility, conoid extrusion, attachment, and invasion of another host cell. Here, we report that Ca(2+) oscillations occur in the cytosol of the parasite during egress, gliding, and invasion, which are critical steps of the lytic cycle. Extracellular Ca(2+) enhances each one of these processes. We used tachyzoite clonal lines expressing genetically encoded calcium indicators combined with host cells expressing transiently expressed calcium indicators of different colors, and we measured Ca(2+) changes in both parasites and host simultaneously during egress. We demonstrated a link between cytosolic Ca(2+) oscillations in the host and in the parasite. Our approach also allowed us to measure two new features of motile parasites, which were enhanced by Ca(2+) influx. This is the first study showing, in real time, Ca(2+) signals preceding egress and their direct link with motility, an essential virulence trait.

  13. Identification of a Calcium Signalling Pathway of S-[6]-Gingerol in HuH-7 Cells

    PubMed Central

    McGrath, Kristine C. Y.; Tran, Van H.; Li, Yi-Ming; Duke, Colin C.; Heather, Alison K.; Roufogalis, Basil D.

    2013-01-01

    Calcium signals in hepatocytes control cell growth, proliferation, and death. Members of the transient receptor potential (TRP) cation channel superfamily are candidate calcium influx channels. NFκB activation strictly depends on calcium influx and often induces antiapoptotic genes favouring cell survival. Previously, we reported that S-[6]-gingerol is an efficacious agonist of the transient receptor potential cation channel subfamily V member 1 (TRPV1) in neurones. In this study, we tested the effect of S-[6]-gingerol on HuH-7 cells using the Fluo-4 calcium assay, RT-qPCR, transient cell transfection, and luciferase measurements. We found that S-[6]-gingerol induced a transient rise in [Ca2+]i in HuH-7 cells. The increase in [Ca2+]i induced by S-[6]-gingerol was abolished by preincubation with EGTA and was also inhibited by the TRPV1 channel antagonist capsazepine. Expression of TRPV1 in HuH-7 cells was confirmed by mRNA analysis as well as a test for increase of [Ca2+]i by TRPV1 agonist capsaicin and its inhibition by capsazepine. We found that S-[6]-gingerol induced rapid NFκB activation through TRPV1 in HuH-7 cells. Furthermore, S-[6]-gingerol-induced NFκB activation was dependent on the calcium gradient and TRPV1. The rapid NFκB activation by S-[6]-gingerol was associated with an increase in mRNA levels of NFκB-target genes: cIAP-2, XIAP, and Bcl-2 that encode antiapoptotic proteins. PMID:23956783

  14. Nuclear calcium signaling induces expression of the synaptic organizers Lrrtm1 and Lrrtm2.

    PubMed

    Hayer, Stefanie N; Bading, Hilmar

    2015-02-27

    Calcium transients in the cell nucleus evoked by synaptic activity in hippocampal neurons function as a signaling end point in synapse-to-nucleus communication. As an important regulator of neuronal gene expression, nuclear calcium is involved in the conversion of synaptic stimuli into functional and structural changes of neurons. Here we identify two synaptic organizers, Lrrtm1 and Lrrtm2, as targets of nuclear calcium signaling. Expression of both Lrrtm1 and Lrrtm2 increased in a synaptic NMDA receptor- and nuclear calcium-dependent manner in hippocampal neurons within 2-4 h after the induction of action potential bursting. Induction of Lrrtm1 and Lrrtm2 occurred independently of the need for new protein synthesis and required calcium/calmodulin-dependent protein kinases and the nuclear calcium signaling target CREB-binding protein. Analysis of reporter gene constructs revealed a functional cAMP response element in the proximal promoter of Lrrtm2, indicating that at least Lrrtm2 is regulated by the classical nuclear Ca(2+)/calmodulin-dependent protein kinase IV-CREB/CREB-binding protein pathway. These results suggest that one mechanism by which nuclear calcium signaling controls neuronal network function is by regulating the expression of Lrrtm1 and Lrrtm2.

  15. Role of the JP45-Calsequestrin Complex on Calcium Entry in Slow Twitch Skeletal Muscles.

    PubMed

    Mosca, Barbara; Eckhardt, Jan; Bergamelli, Leda; Treves, Susan; Bongianino, Rossana; De Negri, Marco; Priori, Silvia G; Protasi, Feliciano; Zorzato, Francesco

    2016-07-01

    We exploited a variety of mouse models to assess the roles of JP45-CASQ1 (CASQ, calsequestrin) and JP45-CASQ2 on calcium entry in slow twitch muscles. In flexor digitorum brevis (FDB) fibers isolated from JP45-CASQ1-CASQ2 triple KO mice, calcium transients induced by tetanic stimulation rely on calcium entry via La(3+)- and nifedipine-sensitive calcium channels. The comparison of excitation-coupled calcium entry (ECCE) between FDB fibers from WT, JP45KO, CASQ1KO, CASQ2KO, JP45-CASQ1 double KO, JP45-CASQ2 double KO, and JP45-CASQ1-CASQ2 triple KO shows that ECCE enhancement requires ablation of both CASQs and JP45. Calcium entry activated by ablation of both JP45-CASQ1 and JP45-CASQ2 complexes supports tetanic force development in slow twitch soleus muscles. In addition, we show that CASQs interact with JP45 at Ca(2+) concentrations similar to those present in the lumen of the sarcoplasmic reticulum at rest, whereas Ca(2+) concentrations similar to those present in the SR lumen after depolarization-induced calcium release cause the dissociation of JP45 from CASQs. Our results show that the complex JP45-CASQs is a negative regulator of ECCE and that tetanic force development in slow twitch muscles is supported by the dynamic interaction between JP45 and CASQs. PMID:27189940

  16. Regulation of Multi-drug Resistance in hepatocellular carcinoma cells is TRPC6/Calcium Dependent

    PubMed Central

    Wen, Liang; Liang, Chao; Chen, Enjiang; Chen, Wei; Liang, Feng; Zhi, Xiao; Wei, Tao; Xue, Fei; Li, Guogang; Yang, Qi; Gong, Weihua; Feng, Xinhua; Bai, Xueli; Liang, Tingbo

    2016-01-01

    Hepatocellular carcinoma (HCC) is notoriously refractory to chemotherapy because of its tendency to develop multi-drug resistance (MDR), whose various underlying mechanisms make it difficult to target. The calcium signalling pathway is associated with many cellular biological activities, and is also a critical player in cancer. However, its role in modulating tumour MDR remains unclear. In this study, stimulation by doxorubicin, hypoxia and ionizing radiation was used to induce MDR in HCC cells. A sustained aggregation of intracellular calcium was observed upon these stimuli, while inhibition of calcium signalling enhanced the cells’ sensitivity to various drugs by attenuating epithelial-mesenchymal transition (EMT), Hif1-α signalling and DNA damage repair. The effect of calcium signalling is mediated via transient receptor potential canonical 6 (TRPC6), a subtype of calcium-permeable channel. An in vivo xenograft model of HCC further confirmed that inhibiting TRPC6 enhanced the efficacy of doxorubicin. In addition, we deduced that STAT3 activation is a downstream signalling pathway in MDR. Collectively, this study demonstrated that the various mechanisms regulating MDR in HCC cells are calcium dependent through the TRPC6/calcium/STAT3 pathway. We propose that targeting TRPC6 in HCC may be a novel antineoplastic strategy, especially combined with chemotherapy. PMID:27011063

  17. Altered mechanical properties of titin immunoglobulin domain 27 in the presence of calcium.

    PubMed

    DuVall, Michael M; Gifford, Jessica L; Amrein, Matthias; Herzog, Walter

    2013-04-01

    Titin (connectin) based passive force regulation has been an important physiological mechanism to adjust to varying muscle stretch conditions. Upon stretch, titin behaves as a spring capable of modulating its elastic response in accordance with changes in muscle biochemistry. One such mechanism has been the calcium-dependent stiffening of titin domains that renders the spring inherently more resistant to stretch. This transient titin-calcium interaction may serve a protective function in muscle, which could preclude costly unfolding of select domains when muscles elongate to great lengths. To test this idea, fluorescence spectroscopy was performed revealing a change in the microenvironment of the investigated immunoglobulin domain 27 (I27) of titin with calcium. Additionally, an atomic force microscope was used to evaluate the calcium-dependent regulation of passive force by stretching eight linked titin I27 domains until they unfolded. When stretching in the presence of calcium, the I27 homopolymer chain became stabilized, displaying three novel properties: (1) higher stretching forces were needed to unfold the domains, (2) the stiffness, measured as a persistence length (PL), increased and (3) the peak-to-peak distance between adjacent I27 domains increased. Furthermore, a peak order dependence became apparent for both force and PL, reflecting the importance of characterizing the dynamic unfolding history of a polymer with this approach. Together, this novel titin Ig-calcium interaction may serve to stabilize the I27 domain permitting titin to tune passive force within stretched muscle in a calcium-dependent manner. PMID:23224300

  18. Calcium metabolism in health and disease.

    PubMed

    Peacock, Munro

    2010-01-01

    This brief review focuses on calcium balance and homeostasis and their relationship to dietary calcium intake and calcium supplementation in healthy subjects and patients with chronic kidney disease and mineral bone disorders (CKD-MBD). Calcium balance refers to the state of the calcium body stores, primarily in bone, which are largely a function of dietary intake, intestinal absorption, renal excretion, and bone remodeling. Bone calcium balance can be positive, neutral, or negative, depending on a number of factors, including growth, aging, and acquired or inherited disorders. Calcium homeostasis refers to the hormonal regulation of serum ionized calcium by parathyroid hormone, 1,25-dihydroxyvitamin D, and serum ionized calcium itself, which together regulate calcium transport at the gut, kidney, and bone. Hypercalcemia and hypocalcemia indicate serious disruption of calcium homeostasis but do not reflect calcium balance on their own. Calcium balance studies have determined the dietary and supplemental calcium requirements needed to optimize bone mass in healthy subjects. However, similar studies are needed in CKD-MBD, which disrupts both calcium balance and homeostasis, because these data in healthy subjects may not be generalizable to this patient group. Importantly, increasing evidence suggests that calcium supplementation may enhance soft tissue calcification and cardiovascular disease in CKD-MBD. Further research is needed to elucidate the risks and mechanisms of soft tissue calcification with calcium supplementation in both healthy subjects and CKD-MBD patients.

  19. Attosecond Delays in Molecular Photoionization

    NASA Astrophysics Data System (ADS)

    Huppert, Martin; Jordan, Inga; Baykusheva, Denitsa; von Conta, Aaron; Wörner, Hans Jakob

    2016-08-01

    We report measurements of energy-dependent photoionization delays between the two outermost valence shells of N2O and H2O . The combination of single-shot signal referencing with the use of different metal foils to filter the attosecond pulse train enables us to extract delays from congested spectra. Remarkably large delays up to 160 as are observed in N2O , whereas the delays in H2O are all smaller than 50 as in the photon-energy range of 20-40 eV. These results are interpreted by developing a theory of molecular photoionization delays. The long delays measured in N2O are shown to reflect the population of molecular shape resonances that trap the photoelectron for a duration of up to ˜110 as. The unstructured continua of H2O result in much smaller delays at the same photon energies. Our experimental and theoretical methods make the study of molecular attosecond photoionization dynamics accessible.

  20. Attosecond Delays in Molecular Photoionization.

    PubMed

    Huppert, Martin; Jordan, Inga; Baykusheva, Denitsa; von Conta, Aaron; Wörner, Hans Jakob

    2016-08-26

    We report measurements of energy-dependent photoionization delays between the two outermost valence shells of N_{2}O and H_{2}O. The combination of single-shot signal referencing with the use of different metal foils to filter the attosecond pulse train enables us to extract delays from congested spectra. Remarkably large delays up to 160 as are observed in N_{2}O, whereas the delays in H_{2}O are all smaller than 50 as in the photon-energy range of 20-40 eV. These results are interpreted by developing a theory of molecular photoionization delays. The long delays measured in N_{2}O are shown to reflect the population of molecular shape resonances that trap the photoelectron for a duration of up to ∼110 as. The unstructured continua of H_{2}O result in much smaller delays at the same photon energies. Our experimental and theoretical methods make the study of molecular attosecond photoionization dynamics accessible. PMID:27610849