Science.gov

Sample records for macronutrientes minerais ca

  1. Vacuolar Ca(2+) uptake.

    PubMed

    Pittman, Jon K

    2011-08-01

    Calcium transporters that mediate the removal of Ca(2+) from the cytosol and into internal stores provide a critical role in regulating Ca(2+) signals following stimulus induction and in preventing calcium toxicity. The vacuole is a major calcium store in many organisms, particularly plants and fungi. Two main pathways facilitate the accumulation of Ca(2+) into vacuoles, Ca(2+)-ATPases and Ca(2+)/H(+) exchangers. Here I review the biochemical and regulatory features of these transporters that have been characterised in yeast and plants. These Ca(2+) transport mechanisms are compared with those being identified from other vacuolated organisms including algae and protozoa. Studies suggest that Ca(2+) uptake into vacuoles and other related acidic Ca(2+) stores occurs by conserved mechanisms which developed early in evolution. PMID:21310481

  2. Mitochondrial Ca2+-induced Ca2+ Release Mediated by the Ca2+ Uniporter

    PubMed Central

    Montero, Mayte; Alonso, Maria Teresa; Albillos, Almudena; García-Sancho, Javier; Alvarez, Javier

    2001-01-01

    We have reported that a population of chromaffin cell mitochondria takes up large amounts of Ca2+ during cell stimulation. The present study focuses on the pathways for mitochondrial Ca2+ efflux. Treatment with protonophores before cell stimulation abolished mitochondrial Ca2+ uptake and increased the cytosolic [Ca2+] ([Ca2+]c) peak induced by the stimulus. Instead, when protonophores were added after cell stimulation, they did not modify [Ca2+]c kinetics and inhibited Ca2+ release from Ca2+-loaded mitochondria. This effect was due to inhibition of mitochondrial Na+/Ca2+ exchange, because blocking this system with CGP37157 produced no further effect. Increasing extramitochondrial [Ca2+]c triggered fast Ca2+ release from these depolarized Ca2+-loaded mitochondria, both in intact or permeabilized cells. These effects of protonophores were mimicked by valinomycin, but not by nigericin. The observed mitochondrial Ca2+-induced Ca2+ release response was insensitive to cyclosporin A and CGP37157 but fully blocked by ruthenium red, suggesting that it may be mediated by reversal of the Ca2+ uniporter. This novel kind of mitochondrial Ca2+-induced Ca2+ release might contribute to Ca2+ clearance from mitochondria that become depolarized during Ca2+ overload. PMID:11160823

  3. Routes of Ca2+ Shuttling during Ca2+ Oscillations

    PubMed Central

    Pecze, László; Blum, Walter; Schwaller, Beat

    2015-01-01

    In some cell types, Ca2+ oscillations are strictly dependent on Ca2+ influx across the plasma membrane, whereas in others, oscillations also persist in the absence of Ca2+ influx. We observed that, in primary mesothelial cells, the plasmalemmal Ca2+ influx played a pivotal role. However, when the Ca2+ transport across the plasma membrane by the “lanthanum insulation method” was blocked prior to the induction of the serum-induced Ca2+ oscillations, mitochondrial Ca2+ transport was found to be able to substitute for the plasmalemmal Ca2+ exchange function, thus rendering the oscillations independent of extracellular Ca2+. However, in a physiological situation, the Ca2+-buffering capacity of mitochondria was found not to be essential for Ca2+ oscillations. Moreover, brief spontaneous Ca2+ changes were observed in the mitochondrial Ca2+ concentration without apparent changes in the cytosolic Ca2+ concentration, indicating the presence of a mitochondrial autonomous Ca2+ signaling mechanism. In the presence of calretinin, a Ca2+-buffering protein, the amplitude of cytosolic spikes during oscillations was decreased, and the amount of Ca2+ ions taken up by mitochondria was reduced. Thus, the increased calretinin expression observed in mesothelioma cells and in certain colon cancer might be correlated to the increased resistance of these tumor cells to proapoptotic/pronecrotic signals. We identified and characterized (experimentally and by modeling) three Ca2+ shuttling pathways in primary mesothelial cells during Ca2+ oscillations: Ca2+ shuttled between (i) the endoplasmic reticulum (ER) and mitochondria, (ii) the ER and the extracellular space, and (iii) the ER and cytoplasmic Ca2+ buffers. PMID:26396196

  4. Topological organization of CA3-to-CA1 excitation.

    PubMed

    Hongo, Yoshie; Ogawa, Koichi; Takahara, Yuji; Takasu, Keiko; Royer, Sebastien; Hasegawa, Minoru; Sakaguchi, Gaku; Ikegaya, Yuji

    2015-09-01

    The CA1-projecting axons of CA3 pyramidal cells, called Schaffer collaterals, constitute one of the major information flow routes in the hippocampal formation. Recent anatomical studies have revealed the non-random structural connectivity between CA3 and CA1, but little is known regarding the functional connectivity (i.e. how CA3 network activity is functionally transmitted downstream to the CA1 network). Using functional multi-neuron calcium imaging of rat hippocampal slices, we monitored the spatiotemporal patterns of spontaneous CA3 and CA1 burst activity under pharmacological GABAergic blockade. We found that spatially clustered CA3 activity patterns were transformed into layered CA1 activity sequences. Specifically, synchronized bursts initiated from multiple hot spots in CA3 ensembles, and CA1 neurons located deeper in the pyramidal cell layer were recruited during earlier phases of the burst events. The order of these sequential activations was maintained across the bursts, but the sequence velocity varied depending on the inter-burst intervals. Thus, CA3 axons innervate CA1 neurons in a highly topographical fashion. PMID:26036915

  5. UV - RIVERSIDE CA

    EPA Science Inventory

    Brewer 112 is located in Riverside CA, measuring ultraviolet solar radiation. Irradiance and column ozone are derived from this data. Ultraviolet solar radiation is measured with a Brewer Mark IV, single-monochrometer, spectrophotometer manufactured by SCI-TEC Instruments, Inc. o...

  6. Intracellular BK(Ca) (iBK(Ca)) channels.

    PubMed

    Singh, Harpreet; Stefani, Enrico; Toro, Ligia

    2012-12-01

    The large conductance calcium- and voltage-activated potassium channel (BK(Ca)) is widely expressed at the plasma membrane. This channel is involved in a variety of fundamental cellular functions including excitability, smooth muscle contractility, and Ca(2+) homeostasis, as well as in pathological situations like proinflammatory responses in rheumatoid arthritis, and cancer cell proliferation. Immunochemical, biochemical and pharmacological studies from over a decade have intermittently shown the presence of BK(Ca) in intracellular organelles. To date, intracellular BK(Ca) (iBK(Ca)) has been localized in the mitochondria, endoplasmic reticulum, nucleus and Golgi apparatus but its functional role remains largely unknown except for the mitochondrial BK(Ca) whose opening is thought to play a role in protecting the heart from ischaemic injury. In the nucleus, pharmacology suggests a role in regulating nuclear Ca(2+), membrane potential and eNOS expression. Establishing the molecular correlates of iBK(Ca), the mechanisms defining iBK(Ca) organelle-specific targeting, and their modulation are challenging questions. This review summarizes iBK(Ca) channels, their possible functions, and efforts to identify their molecular correlates. PMID:22930268

  7. Cardiac Ca2+ signaling and Ca2+ sensitizers.

    PubMed

    Endoh, Masao

    2008-12-01

    The role of Ca2+ in cardiac excitation-contraction (E-C) coupling has been established by simultaneous measurements of contractility and Ca2+ transients by means of aequorin in intact myocardium and Ca2+ sensitive fluorescent dyes in single myocytes. The E-C coupling process can be classified into 3 processes: upstream (Ca2+ mobilization), central (Ca2+ binding to troponin C) and downstream mechanism (thin filament regulation and crossbridge cycling). These mechanisms are regulated differentially by various inotropic interventions. Positive force-frequency relationship and effects of beta-adrenoceptor stimulation, phosphodiesterase 3 inhibitors and digitalis are essentially exerted via upstream mechanism. Alpha-adrenoceptor stimulation, endothelin-1, angiotensin II, and clinically available Ca2+ sensitizers, such as levosimendan and pimobendan, act by a combination of the upstream and central/downstream mechanism. The Frank-Starling mechanism and effects of Ca2+ sensitizers such as EMD 57033 and Org 30029 are primarily induced via the central/downstream mechanism. Whereas the upstream and central mechanisms are markedly suppressed in failing myocytes and under acidotic conditions, Ca2+ sensitizers such as EMD 57033 and Org 30029 can induce cardiotonic effects under such conditions. Ca2+ sensitizers have high therapeutic potential for the treatment of contractile dysfunction in congestive heart failure and ischemic heart diseases, because they have energetic advantages and less risk of Ca2+ overload and can maintain effectiveness under pathological conditions. PMID:18981594

  8. Coachella Valley, CA

    NASA Technical Reports Server (NTRS)

    2001-01-01

    These band composites, acquired on June 4, 2000, cover a 11 by 13.5 km sub-scene in the Coachella Valley, CA. The area is shown by the yellow box on the full scene in the LOWER RIGHT corner, northwest of the Salton Sea. This is a major agricultural region of California, growing fruit and produce throughout the year. Different combinations of ASTER bands help identify the different crop types. UPPER LEFT: bands 3, 2, 1 as red, green, and blue (RGB); UPPER RIGHT: bands 4, 2, 1 as RGB; LOWER LEFT: bands 4, 3, 2 as RGB. The image is centered at 33.6 degrees north latitude, 116.1 degrees west longitude.

    The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  9. CA125 in Ovarian Cancer

    PubMed Central

    Urban, Nicole

    2009-01-01

    Summary Twenty five years after its discovery, circulating CA125 antigen is recommended for clinical use in the US for ovarian cancer (OC) screening of high risk women with ovaries despite its limited sensitivity and specificity. Recent findings suggest that CA125 might also serve as a predictive marker for pre-invasive OC. Methods to quantify circulating CA125 evolved towards sensitive and reliable double determinant ELISA assays. The CA125 gene, MUC16, was cloned 20 years after the protein discovery and revealed a very complex and unusual glycoprotein structure suggesting an immunological role. Recent evidence points toward CA125 function in the induction of materno-fetal tolerance through the alteration of NK phenotype. Two receptors for CA125 have been described: mesothelin and galectin-1. The specific location and functional proprieties of CA125 make it a therapeutic target of choice; clinical trials have demonstrated that anti-CA125 injections are well tolerated and suggest a potential survival benefit. PMID:20477371

  10. Dynamic buffering of mitochondrial Ca2+ during Ca2+ uptake and Na+-induced Ca2+ release

    PubMed Central

    Blomeyer, Christoph A.; Bazil, Jason N.; Stowe, David F.; Pradhan, Ranjan K.; Dash, Ranjan K.; Camara, Amadou K. S.

    2014-01-01

    In cardiac mitochondria, matrix free Ca2+ ([Ca2+]m) is primarily regulated by Ca2+ uptake and release via the Ca2+ uniporter (CU) and Na+/Ca2+ exchanger (NCE) as well as by Ca2+ buffering. Although experimental and computational studies on the CU and NCE dynamics exist, it is not well understood how matrix Ca2+ buffering affects these dynamics under various Ca2+ uptake and release conditions, and whether this influences the stoichiometry of the NCE. To elucidate the role of matrix Ca2+ buffering on the uptake and release of Ca2+, we monitored Ca2+ dynamics in isolated mitochondria by measuring both the extra-matrix free [Ca2+] ([Ca2+]e) and [Ca2+]m. A detailed protocol was developed and freshly isolated mitochondria from guinea pig hearts were exposed to five different [CaCl2] followed by ruthenium red and six different [NaCl]. By using the fluorescent probe indo-1, [Ca2+] and [Ca2+e]m were spectrofluorometrically quantified, and the stoichiometry of the NCE was determined. In addition, we measured NADH, membrane potential, matrix volume and matrix pH to monitor Ca2+-induced changes in mitochondrial bioenergetics. Our [Ca2+]e and [Ca2+]m measurements demonstrate that Ca2+ uptake and release do not show reciprocal Ca2+ dynamics in the extra-matrix and matrix compartments. This salient finding is likely caused by a dynamic Ca2+ buffering system in the matrix compartment. The Na+ - induced Ca2+ release demonstrates an electrogenic exchange via the NCE by excluding an electroneutral exchange. Mitochondrial bioenergetics were only transiently affected by Ca2+ uptake in the presence of large amounts of CaCl2, but not by Na+- induced Ca2+ release. PMID:23225099

  11. CaPTC Biennial Meetings

    Cancer.gov

    CaPTC hosts the 'Biennial Science of Global Prostate Cancer Disparities in Black Men' conference to address the growing global public health problem of prostate cancer among Black men in industrialized and developing countries.

  12. Mitochondrial Ca(2+) Processing by a Unit of Mitochondrial Ca(2+) Uniporter and Na(+)/Ca(2+) Exchanger Supports the Neuronal Ca(2+) Influx via Activated Glutamate Receptors.

    PubMed

    Strokin, Mikhail; Reiser, Georg

    2016-06-01

    The current study demonstrates that in hippocampal neurons mitochondrial Ca(2+) processing supports Ca(2+) influx via ionotropic glutamate (Glu) receptors. We define mitochondrial Ca(2+) processing as Ca(2+) uptake via mitochondrial Ca(2+) uniporter (MCU) combined with subsequent Ca(2+) release via mitochondrial Na(+)/Ca(2+) exchanger (NCX). Our tool is to measure the Ca(2+) influx rate in primary hippocampal co-cultures, i.e. neurons and astrocytes, by fluorescent digital microscopy, using a Fura-2-quenching method where we add small amounts of Mn(2+) in the superfusion medium. Thus, Ca(2+) influx is measured with Mn(2+) in the bath. Ru360 as inhibitor of mitochondrial Ca(2+) uptake through MCU strongly reduces the rate of Ca(2+) influx in Glu-stimulated primary hippocampal neurons. Similarly, the Ca(2+) influx rate in Glu-stimulated neurons declines after suppression of potential-dependent MCU, when we depolarize mitochondria with rotenone. With inhibition of Ca(2+) release from mitochondria via NCX using CGP-37157 the Ca(2+) influx via N-methyl-D-aspartate (NMDA)- and kainate-sensitive receptors is slowed down. Working jointly as mitochondrial Ca(2+) processing unit, MCU and NCX, apparently sustain the Ca(2+) throughput of activated Glu-sensitive receptors. Our results revise the role frequently attributed to mitochondria in neuronal Ca(2+) homeostasis, where mitochondria function mainly as Ca(2+) buffer, and prevent excessively high cytosolic Ca(2+) concentration increase during neuronal activity. The mechanism to control Ca(2+) influx in neurons, as discovered in this study, highlights mitochondrial Ca(2+) processing as a promising pharmacological target. We discuss this pathway in relation to the endoplasmic reticulum-related mechanisms of Ca(2+) processing. PMID:26842930

  13. The Influence of Ca2+ Buffers on Free [Ca2+] Fluctuations and the Effective Volume of Ca2+ Microdomains

    PubMed Central

    Weinberg, Seth H.; Smith, Gregory D.

    2014-01-01

    Intracellular calcium (Ca2+) plays a significant role in many cell signaling pathways, some of which are localized to spatially restricted microdomains. Ca2+ binding proteins (Ca2+ buffers) play an important role in regulating Ca2+ concentration ([Ca2+]). Buffers typically slow [Ca2+] temporal dynamics and increase the effective volume of Ca2+ domains. Because fluctuations in [Ca2+] decrease in proportion to the square-root of a domain’s physical volume, one might conjecture that buffers decrease [Ca2+] fluctuations and, consequently, mitigate the significance of small domain volume concerning Ca2+ signaling. We test this hypothesis through mathematical and computational analysis of idealized buffer-containing domains and their stochastic dynamics during free Ca2+ influx with passive exchange of both Ca2+ and buffer with bulk concentrations. We derive Langevin equations for the fluctuating dynamics of Ca2+ and buffer and use these stochastic differential equations to determine the magnitude of [Ca2+] fluctuations for different buffer parameters (e.g., dissociation constant and concentration). In marked contrast to expectations based on a naive application of the principle of effective volume as employed in deterministic models of Ca2+ signaling, we find that mobile and rapid buffers typically increase the magnitude of domain [Ca2+] fluctuations during periods of Ca2+ influx, whereas stationary (immobile) Ca2+ buffers do not. Also contrary to expectations, we find that in the absence of Ca2+ influx, buffers influence the temporal characteristics, but not the magnitude, of [Ca2+] fluctuations. We derive an analytical formula describing the influence of rapid Ca2+ buffers on [Ca2+] fluctuations and, importantly, identify the stochastic analog of (deterministic) effective domain volume. Our results demonstrate that Ca2+ buffers alter the dynamics of [Ca2+] fluctuations in a nonintuitive manner. The finding that Ca2+ buffers do not suppress intrinsic domain [Ca2

  14. Effects of Ca antagonists on Ca fluxes in resistance vessels

    SciTech Connect

    Cauvin, C.; Saida, K.; van Breemen, C.

    1982-01-01

    Researchers have examined contractions and /sup 45/Ca fluxes induced by norepinephrine (NE) and 80 mM potassium (high K) depolarization and their inhibition by dilitazem in rabbit mesenteric resistance vessels. Contraction induced by both NE and high K depended almost completely on extracellular Ca. Dose-response curves for diltiazem inhibition of NE (10(-5) M) and high K contractions showed ED50 values of 1 X 10(-8) and 6 X 10(-7) M, respectively, indicating that the receptor-operated channel (ROC) was more sensitive than the potential-operated channel (POC) to the action of diltiazem. Diltiazem (10(-6) M) was shown to inhibit NE- and 80 mM K-stimulated /sup 45/Ca influx effectively by 87 +/- 15 and 85 +/- 10%, respectively. Comparison of these data to those obtained from aorta suggest that although the sensitivity of the POC is approximately the same in aorta and mesenteric resistance vessels, the sensitivity of the ROC is much greater in the latter. This increased sensitivity is paralleled by a greatly decreased role of intracellular Ca release in NE contraction in mesenteric resistance vessels.

  15. Timing in Cellular Ca2+ signaling

    PubMed Central

    Boulware, Michael J.; Marchant, Jonathan S.

    2011-01-01

    Calcium (Ca2+) signals are generated across a broad time range. Kinetic considerations impact how information is processed to encode and decode Ca2+ signals, the choreography of responses that ensure specific and efficient signaling and the overall temporal gearing such that ephemeral Ca2+ signals have lasting physiological value. The reciprocal importance of timing for Ca2+ signaling, and Ca2+ signaling for timing is exemplified by the altered kinetic profiles of Ca2+ signals in certain diseases and the likely role of basal Ca2+ fluctuations in the perception of time itself. PMID:18786382

  16. Ca2+ waves in the heart

    PubMed Central

    Izu, Leighton T.; Xie, Yuanfang; Sato, Daisuke; Bányász, Tamás; Chen-Izu, Ye

    2013-01-01

    Ca2+ waves were probably first observed in the early 1940s. Since then Ca2+ waves have captured the attention of an eclectic mixture of mathematicians, neuroscientists, muscle physiologists, developmental biologists, and clinical cardiologists. This review discusses the current state of mathematical models of Ca2+ waves, the normal physiological functions Ca2+ waves might serve in cardiac cells, as well as how the spatial arrangement of Ca2+ release channels shape Ca2+ waves, and we introduce the idea of Ca2+ phase waves that might provide a useful framework for understanding triggered arrhythmias. This article is part of a Special Issue entitled ‘Calcium Signaling in Heart’. PMID:23220129

  17. Large Ca2+-dependent facilitation of CaV2.1 channels revealed by Ca2+ photo-uncaging

    PubMed Central

    Lee, Shin-Rong; Adams, Paul J; Yue, David T

    2015-01-01

    Key points CaV2.1 channels constitute a dominant Ca2+ entry pathway into brain neurons, triggering downstream Ca2+-dependent processes such as neurotransmitter release. CaV2.1 is itself modulated by Ca2+, resulting in activity-dependent enhancement of channel opening termed Ca2+-dependent facilitation (CDF). Real-time Ca2+ imaging and Ca2+ uncaging here reveal that CDF turns out to be strikingly faster, more Ca2+ sensitive, and larger than anticipated on previous grounds. Robust resolution of the quantitative profile of CDF enables deduction of a realistic biophysical model for this process. These results suggest that CaV2.1 CDF would figure most prominently in short-term synaptic plasticity and cerebellar Purkinje cell rhythmicity. Abstract CaV2.1 (P-type) voltage-gated Ca2+ channels constitute a major source of neuronal Ca2+ current, strongly influencing rhythmicity and triggering neurotransmitter release throughout the central nervous system. Fitting with such stature among Ca2+ entry pathways, CaV2.1 is itself feedback regulated by intracellular Ca2+, acting through calmodulin to facilitate channel opening. The precise neurophysiological role of this calcium-dependent facilitation (CDF) remains uncertain, however, in large measure because the very magnitude, Ca2+ dependence and kinetics of CDF have resisted quantification by conventional means. Here, we utilize the photo-uncaging of Ca2+ with CaV2.1 channels fluxing Li+ currents, so that voltage-dependent activation of channel gating is no longer conflated with Ca2+ entry, and CDF is then driven solely by light-induced increases in Ca2+. By using this strategy, we now find that CDF can be unexpectedly large, enhancing currents by as much as twofold at physiological voltages. CDF is steeply Ca2+ dependent, with a Hill coefficient of approximately two, a half-maximal effect reached by nearly 500 nm Ca2+, and Ca2+ on/off kinetics in the order of milliseconds to tens of milliseconds. These properties were

  18. Angular dependence in proton-proton correlation functions in central 40Ca + 40Ca and 48Ca + 48Ca reactions

    NASA Astrophysics Data System (ADS)

    Henzl, V.; Kilburn, M. A.; Chajęcki, Z.; Henzlova, D.; Lynch, W. G.; Brown, D.; Chbihi, A.; Coupland, D. D. S.; Danielewicz, P.; Desouza, R. T.; Famiano, M.; Herlitzius, C.; Hudan, S.; Lee, Jenny; Lukyanov, S.; Rogers, A. M.; Sanetullaev, A.; Sobotka, L. G.; Sun, Z. Y.; Tsang, M. B.; Vander Molen, A.; Verde, G.; Wallace, M. S.; Youngs, M.

    2012-01-01

    The angular dependence of proton-proton correlation functions is studied in central 40Ca+40Ca and 48Ca+48Ca nuclear reactions at E/A=80 MeV. Measurements were performed with the High Resolution Array (HiRA) complemented by the 4π Array at the National Superconducting Cyclotron Laboratory. A striking angular dependence in the laboratory frame is found within proton-proton correlation functions for both systems that greatly exceeds the measured and expected isospin dependent difference between the neutron-rich and neutron-deficient systems. Sources measured at backward angles reflect the participant zone of the reaction, while much larger sources observed at forward angles reflect the expanding, fragmenting, and evaporating projectile remnants. The decrease of the size of the source with increasing momentum is observed at backward angles while a weaker trend in the opposite direction is observed at forward angles. The results are compared to the theoretical calculations using the Boltzmann-Uehling-Uhlenbeck (BUU) transport model.

  19. STIM Is a Ca2+ Sensor Essential for Ca2+-Store-Depletion-Triggered Ca2+ Influx

    PubMed Central

    Liou, Jen; Kim, Man Lyang; Heo, Won Do; Jones, Joshua T.; Myers, Jason W.; Ferrell, James E.; Meyer, Tobias

    2011-01-01

    Summary Ca2+ signaling in nonexcitable cells is typically initiated by receptor-triggered production of inositol-1,4,5-trisphosphate and the release of Ca2+ from intracellular stores [1]. An elusive signaling process senses the Ca2+ store depletion and triggers the opening of plasma membrane Ca2+ channels [2–5]. The resulting sustained Ca2+ signals are required for many physiological responses, such as T cell activation and differentiation [6]. Here, we monitored receptor-triggered Ca2+ signals in cells transfected with siRNAs against 2,304 human signaling proteins, and we identified two proteins required for Ca2+-store-depletion-mediated Ca2+ influx, STIM1 and STIM2 [7–9]. These proteins have a single transmembrane region with a putative Ca2+ binding domain in the lumen of the endoplasmic reticulum. Ca2+ store depletion led to a rapid translocation of STIM1 into puncta that accumulated near the plasma membrane. Introducing a point mutation in the STIM1 Ca2+ binding domain resulted in prelocalization of the protein in puncta, and this mutant failed to respond to store depletion. Our study suggests that STIM proteins function as Ca2+ store sensors in the signaling pathway connecting Ca2+ store depletion to Ca2+ influx. PMID:16005298

  20. Decoding Ca2+ signals in plants

    NASA Technical Reports Server (NTRS)

    Sathyanarayanan, P. V.; Poovaiah, B. W.

    2004-01-01

    Different input signals create their own characteristic Ca2+ fingerprints. These fingerprints are distinguished by frequency, amplitude, duration, and number of Ca2+ oscillations. Ca(2+)-binding proteins and protein kinases decode these complex Ca2+ fingerprints through conformational coupling and covalent modifications of proteins. This decoding of signals can lead to a physiological response with or without changes in gene expression. In plants, Ca(2+)-dependent protein kinases and Ca2+/calmodulin-dependent protein kinases are involved in decoding Ca2+ signals into phosphorylation signals. This review summarizes the elements of conformational coupling and molecular mechanisms of regulation of the two groups of protein kinases by Ca2+ and Ca2+/calmodulin in plants.

  1. Decoding Ca2+ signals in plants.

    PubMed

    Sathyanarayanan, P V; Poovaiah, B W

    2004-01-01

    Different input signals create their own characteristic Ca2+ fingerprints. These fingerprints are distinguished by frequency, amplitude, duration, and number of Ca2+ oscillations. Ca(2+)-binding proteins and protein kinases decode these complex Ca2+ fingerprints through conformational coupling and covalent modifications of proteins. This decoding of signals can lead to a physiological response with or without changes in gene expression. In plants, Ca(2+)-dependent protein kinases and Ca2+/calmodulin-dependent protein kinases are involved in decoding Ca2+ signals into phosphorylation signals. This review summarizes the elements of conformational coupling and molecular mechanisms of regulation of the two groups of protein kinases by Ca2+ and Ca2+/calmodulin in plants. PMID:16044584

  2. A Devil in the Details: Matrix-Dependent 40Ca42Ca++/42Ca+ and Its Effects on Estimates of the Initial 41Ca/40Ca in the Solar System

    NASA Astrophysics Data System (ADS)

    McKeegan, K. D.; Liu, M.-C.

    2015-07-01

    Ian Hutcheon established that the molecular ion interference 40Ca42Ca++/42Ca+ on 41K+ is strongly dependent on the mineral analyzed. Correction for this "matrix effect" led to a downward revision of the initial 41Ca/40Ca of the solar system.

  3. Voltage-activated ion channels and Ca2+-induced Ca2+ release shape Ca2+ signaling in Merkel cells

    PubMed Central

    Piskorowski, Rebecca; Haeberle, Henry; Panditrao, Mayuri V.; Lumpkin, Ellen A.

    2008-01-01

    Ca2+ signaling and neurotransmission modulate touch-evoked responses in Merkel cell–neurite complexes. To identify mechanisms governing these processes, we analyzed voltage-activated ion channels and Ca2+ signaling in purified Merkel cells. Merkel cells in the intact skin were specifically labeled by antibodies against voltage-activated Ca2+ channels (CaV2.1) and voltage- and Ca2+-activated K+ (BKCa) channels. Voltage-clamp recordings revealed small Ca2+ currents, which produced Ca2+ transients that were amplified sevenfold by Ca2+-induced Ca2+ release. Merkel cells' voltage-activated K+ currents were carried predominantly by BKCa channels with inactivating and noninactivating components. Thus, Merkel cells, like hair cells, have functionally diverse BKCa channels. Finally, blocking K+ channels increased response magnitude and dramatically shortened Ca2+ transients evoked by mechanical stimulation. Together, these results demonstrate that Ca2+ signaling in Merkel cells is governed by the interplay of plasma membrane Ca2+ channels, store release and K+ channels, and they identify specific signaling mechanisms that may control touch sensitivity. PMID:18415122

  4. Fine tuning of cytosolic Ca 2+ oscillations

    PubMed Central

    Dupont, Geneviève; Combettes, Laurent

    2016-01-01

    Ca 2+ oscillations, a widespread mode of cell signaling, were reported in non-excitable cells for the first time more than 25 years ago. Their fundamental mechanism, based on the periodic Ca 2+ exchange between the endoplasmic reticulum and the cytoplasm, has been well characterized. However, how the kinetics of cytosolic Ca 2+ changes are related to the extent of a physiological response remains poorly understood. Here, we review data suggesting that the downstream targets of Ca 2+ are controlled not only by the frequency of Ca 2+ oscillations but also by the detailed characteristics of the oscillations, such as their duration, shape, or baseline level. Involvement of non-endoplasmic reticulum Ca 2+ stores, mainly mitochondria and the extracellular medium, participates in this fine tuning of Ca 2+ oscillations. The main characteristics of the Ca 2+ exchange fluxes with these compartments are also reviewed.

  5. CaMKII regulates intracellular Ca²⁺ dynamics in native endothelial cells.

    PubMed

    Toussaint, Fanny; Charbel, Chimène; Blanchette, Alexandre; Ledoux, Jonathan

    2015-09-01

    Localized endothelial Ca(2+) signalling, such as Ca(2+) pulsars, can modulate the contractile state of the underlying vascular smooth muscle cell through specific endothelial targets. In addition to K(Ca)3.1 as a target, Ca(2+) pulsars, an IP3R-dependent pulsatile Ca(2+) release from the endoplasmic reticulum (ER) could activate a frequency-sensitive Ca(2+)-dependent kinase such as CaMKII. In the absence of extracellular Ca(2+), acetylcholine increased endothelial CaMKII phosphorylation and activation, thereby suggesting CaMKII activation independently of Ca(2+) influx. Herein, a reciprocal relation where CaMKII controls endothelial Ca(2+) dynamics has been investigated in mesenteric arteries. Both CaMKIIα and β isoforms have been identified in endothelial cells and close proximity (<40 nm) suggests their association in heteromultimers. Intracellular Ca(2+) monitoring with high speed confocal microscopy then showed that inhibition of CaMKII with KN-93 significantly increased the population of Ca(2+) pulsars active sites (+89%), suggesting CaMKII as a major regulator of Ca(2+) pulsars in native endothelium. Mechanistic insights were then sought through the elucidation of the impact of CaMKII on ER Ca(2+) store. ER Ca(2+) emptying was accelerated by CaMKII inhibition and ER Ca(2+) content was assessed using ionomycin. Exposure to KN-93 strongly diminished ER Ca(2+) content (-61%) by relieving CaMKII-dependent inhibition of IP3 receptors (IP3R). Moreover, in situ proximity ligation assay suggested CaMKII-IP3R promiscuity, essential condition for a protein-protein interaction. Interestingly, segregation of IP3R within myoendothelial projection (MEP) appears to be isoform-specific. Hence, only IP3R type 1 and type 2 are detected within fenestrations of the internal elastic lamina, sites of MEP, whilst type 3 is absent from these structures. In summary, CaMKII seems to act as a Ca(2+)-sensitive switch of a negative feedback loop regulating endothelial Ca(2

  6. Potentiation of inositol trisphosphate-induced Ca2+ mobilization in Xenopus oocytes by cytosolic Ca2+.

    PubMed

    Yao, Y; Parker, I

    1992-12-01

    1. The ability of cytosolic Ca2+ ions to modulate inositol 1,4,5-trisphosphate (Insp3)-induced Ca2+ liberation from intracellular stores was studied in Xenopus oocytes using light flash photolysis of caged InsP3. Changes in cytosolic free Ca2+ level were effected by inducing Ca2+ entry through ionophore and voltage-gated plasma membrane channels and by injection of Ca2+ through a micropipette. Their effects on Ca2+ liberation were monitored by video imaging of Fluo-3 fluorescence and by voltage clamp recording of Ca(2+)-activated membrane Cl- currents. 2. Treatment of oocytes with the Ca2+ ionophores A23187 and ionomycin caused a transient elevation of cytosolic Ca2+ level when cells were bathed in Ca(2+)-free solution, which probably arose because of release of Ca2+ from intracellular stores. 3. Membrane current and Fluo-3 Ca2+ signals evoked by photoreleased InsP3 in ionophore-treated oocytes were potentiated when the intracellular Ca2+ level was elevated by raising the Ca2+ level in the bathing solution. 4. Responses to photoreleased InsP3 were similarly potentiated following activation of Ca2+ entry through voltage-gated Ca2+ channels expressed in the plasma membrane. 5. Ca(2+)-activated membrane currents evoked by depolarization developed a delayed 'hump' component during sustained photorelease of InsP3, probably because Ca2+ ions entering through the membrane channels triggered liberation of Ca2+ from intracellular stores. 6. Ba2+ and Sr2+ ions were able to substitute for Ca2+ in potentiating InsP3-mediated Ca2+ liberation. 7. Gradual photorelease of InsP3 by weak photolysis light evoked Ca2+ liberation that began at particular foci and then propagated throughout, but not beyond that area of the oocyte exposed to the light. Local elevations of intracellular Ca2+ produced by microinjection of Ca2+ acted as new foci for the initiation of Ca2+ liberation by InsP3. 8. In resting oocytes, intracellular injections of Ca2+ resulted only in localized elevation of

  7. Autonomous CaMKII requires further stimulation by Ca2+/calmodulin for enhancing synaptic strength

    PubMed Central

    Barcomb, Kelsey; Buard, Isabelle; Coultrap, Steven J.; Kulbe, Jacqueline R.; O'Leary, Heather; Benke, Timothy A.; Bayer, K. Ulrich

    2014-01-01

    A hallmark feature of Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) is generation of autonomous (Ca2+-independent) activity by T286 autophosphorylation. Biochemical studies have shown that “autonomous” CaMKII is ∼5-fold further stimulated by Ca2+/CaM, but demonstration of a physiological function for such regulation within cells has remained elusive. In this study, CaMKII-induced enhancement of synaptic strength in rat hippocampal neurons required both autonomous activity and further stimulation. Synaptic strength was decreased by CaMKIIα knockdown and rescued by reexpression, but not by mutants impaired for autonomy (T286A) or binding to NMDA-type glutamate receptor subunit 2B (GluN2B; formerly NR2B; I205K). Full rescue was seen with constitutively autonomous mutants (T286D), but only if they could be further stimulated (additional T305/306A mutation), and not with two other mutations that additionally impair Ca2+/CaM binding. Compared to rescue with wild-type CaMKII, the CaM-binding-impaired mutants even had reduced synaptic strength. One of these mutants (T305/306D) mimicked an inhibitory autophosphorylation of CaMKII, whereas the other one (Δstim) abolished CaM binding without introducing charged residues. Inhibitory T305/306 autophosphorylation also reduced GluN2B binding, but this effect was independent of reduced Ca2+/CaM binding and was not mimicked by T305/306D mutation. Thus, even autonomous CaMKII activity must be further stimulated by Ca2+/CaM for enhancement of synaptic strength.—Barcomb, K., Buard, I., Coultrap, S. J., Kulbe, J. R., O'Leary, H., Benke, T. A., Bayer, K. U. Autonomous CaMKII requires further stimulation by Ca2+/calmodulin for enhancing synaptic strength. PMID:24843070

  8. 46 CFR 7.125 - Point Vincente, CA to Point Conception, CA.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 1 2012-10-01 2012-10-01 false Point Vincente, CA to Point Conception, CA. 7.125 Section 7.125 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Pacific Coast § 7.125 Point Vincente, CA to Point Conception, CA. (a) A line drawn...

  9. Distinct Roles for Dorsal CA3 and CA1 in Memory for Sequential Nonspatial Events

    ERIC Educational Resources Information Center

    Farovik, Anja; Dupont, Laura M.; Eichenbaum, Howard

    2010-01-01

    Previous studies have suggested that dorsal hippocampal areas CA3 and CA1 are both involved in representing sequences of events that compose unique episodes. However, it is uncertain whether the contribution of CA3 is restricted to spatial information, and it is unclear whether CA1 encodes order per se or contributes by an active maintenance of…

  10. 46 CFR 7.130 - Point Conception, CA to Point Sur, CA.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Point Conception, CA to Point Sur, CA. 7.130 Section 7... LINES Pacific Coast § 7.130 Point Conception, CA to Point Sur, CA. (a) A line drawn from the southernmost extremity of Fossil Point at longitude 120°43.5′ W. to the seaward extremity of Whaler...

  11. 46 CFR 7.130 - Point Conception, CA to Point Sur, CA.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Point Conception, CA to Point Sur, CA. 7.130 Section 7... LINES Pacific Coast § 7.130 Point Conception, CA to Point Sur, CA. (a) A line drawn from the southernmost extremity of Fossil Point at longitude 120°43.5′ W. to the seaward extremity of Whaler...

  12. Expression and Localization of CaBP Ca2+ Binding Proteins in the Mouse Cochlea.

    PubMed

    Yang, Tian; Scholl, Elizabeth S; Pan, Ning; Fritzsch, Bernd; Haeseleer, Françoise; Lee, Amy

    2016-01-01

    CaBPs are a family of EF-hand Ca2+ binding proteins that are structurally similar to calmodulin. CaBPs can interact with, and yet differentially modulate, effectors that are regulated by calmodulin, such as Cav1 voltage-gated Ca2+ channels. Immunolabeling studies suggest that multiple CaBP family members (CaBP1, 2, 4, and 5) are expressed in the cochlea. To gain insights into the respective auditory functions of these CaBPs, we characterized the expression and cellular localization of CaBPs in the mouse cochlea. By quantitative reverse transcription PCR, we show that CaBP1 and CaBP2 are the major CaBPs expressed in mouse cochlea both before and after hearing onset. Of the three alternatively spliced variants of CaBP1 (caldendrin, CaBP1-L, and CaBP1-S) and CaBP2 (CaBP2-alt, CaBP2-L, CaBP2-S), caldendrin and CaBP2-alt are the most abundant. By in situ hybridization, probes recognizing caldendrin strongly label the spiral ganglion, while probes designed to recognize all three isoforms of CaBP1 weakly label both the inner and outer hair cells as well as the spiral ganglion. Within the spiral ganglion, caldendrin/CaBP1 labeling is associated with cells resembling satellite glial cells. CaBP2-alt is strongly expressed in inner hair cells both before and after hearing onset. Probes designed to recognize all three variants of CaBP2 strongly label inner hair cells before hearing onset and outer hair cells after the onset of hearing. Thus, CaBP1 and CaBP2 may have overlapping roles in regulating Ca2+ signaling in the hair cells, and CaBP1 may have an additional function in the spiral ganglion. Our findings provide a framework for understanding the role of CaBP family members in the auditory periphery. PMID:26809054

  13. Expression and Localization of CaBP Ca2+ Binding Proteins in the Mouse Cochlea

    PubMed Central

    Pan, Ning; Fritzsch, Bernd; Haeseleer, Françoise; Lee, Amy

    2016-01-01

    CaBPs are a family of EF-hand Ca2+ binding proteins that are structurally similar to calmodulin. CaBPs can interact with, and yet differentially modulate, effectors that are regulated by calmodulin, such as Cav1 voltage-gated Ca2+ channels. Immunolabeling studies suggest that multiple CaBP family members (CaBP1, 2, 4, and 5) are expressed in the cochlea. To gain insights into the respective auditory functions of these CaBPs, we characterized the expression and cellular localization of CaBPs in the mouse cochlea. By quantitative reverse transcription PCR, we show that CaBP1 and CaBP2 are the major CaBPs expressed in mouse cochlea both before and after hearing onset. Of the three alternatively spliced variants of CaBP1 (caldendrin, CaBP1-L, and CaBP1-S) and CaBP2 (CaBP2-alt, CaBP2-L, CaBP2-S), caldendrin and CaBP2-alt are the most abundant. By in situ hybridization, probes recognizing caldendrin strongly label the spiral ganglion, while probes designed to recognize all three isoforms of CaBP1 weakly label both the inner and outer hair cells as well as the spiral ganglion. Within the spiral ganglion, caldendrin/CaBP1 labeling is associated with cells resembling satellite glial cells. CaBP2-alt is strongly expressed in inner hair cells both before and after hearing onset. Probes designed to recognize all three variants of CaBP2 strongly label inner hair cells before hearing onset and outer hair cells after the onset of hearing. Thus, CaBP1 and CaBP2 may have overlapping roles in regulating Ca2+ signaling in the hair cells, and CaBP1 may have an additional function in the spiral ganglion. Our findings provide a framework for understanding the role of CaBP family members in the auditory periphery. PMID:26809054

  14. Levels of CEA, CA153, CA199, CA724 and AFP in nipple discharge of breast cancer patients

    PubMed Central

    Zhao, Song; Mei, Yu; Wang, Yongmei; Zhu, Jiang; Zheng, Guixi; Ma, Rong

    2015-01-01

    The distinction between breast cancer and benign breast diseases with nipple discharge remains an important diagnostic challenge. The purpose of this study was to predict the potential usefulness of tumor markers in nipple discharge and to investigate the relationship of tumor markers and clinical characteristics with breast cancer.One hundred and eleven patients with nipple discharge received breast surgery from November 2013 to December 2014 were included in the study. We evaluated levels of five tumor markers (CEA, CA153, CA199, CA724 and AFP) prior to treatment. Patients were divided into two groups according to postoperative pathological results: 30 cases in breast cancer group and 81 cases in benign group. The relationships of clinical characteristics with breast cancer were investigated by multivariate analysis with a logistic regression model.It showed significant differences in levels of nipple discharge CEA (P < 0.001) and CA153 (P = 0.014), but not CA199 (P = 0.856), CA724 (P = 0.171), AFP (P = 0.834) among two groups. Logistic regression analysis demonstrated complaint, age, menopause, abnormal palpable mass, CEA and CA153 were associated with breast cancer. In summary, measurements of CA199, CA724 and AFP in nipple discharge are not of great clinical value. Detecting CEA and CA153 in nipple dischargecould potentially be used for the early detection of breast cancer with in high-risk populations. PMID:26885008

  15. Voltage-gated Ca2+ entry and ryanodine receptor Ca2+-induced Ca2+ release in preglomerular arterioles.

    PubMed

    Fellner, Susan K; Arendshorst, William J

    2007-05-01

    We have previously shown that in afferent arterioles, angiotensin II (ANG II) involves activation of the inositol trisphosphate receptor (IP(3)R), activation of adenine diphosphoribose (ADPR) cyclase, and amplification of the initial IP(3)R-stimulated release of cytosolic Ca(2+) ([Ca(2+)](i)) from the sarcoplasmic reticulum (SR) (Fellner SK, Arendshorst WJ. Am J Physiol Renal Physiol 288: F785-F791, 2004). The response of the ryanodine receptor (RyR) to local increases in [Ca(2+)](i) is defined as calcium-induced calcium release (CICR). To investigate whether Ca(2+) entry via voltage-gated channels (VGCC) can stimulate CICR, we treated fura 2-loaded, freshly isolated afferent arterioles with KCl (40 mM; high KCl). In control arterioles, peak [Ca(2+)](i) increased by 165 +/- 10 nM. Locking the RyR in the closed position with ryanodine (100 microM) inhibited the [Ca(2+)](i) response by 59% (P < 0.01). 8-Br cADPR, a specific blocker of the ability of cyclic ADPR (cADPR) to sensitize the RyR to Ca(2+), caused a 43% inhibition. We suggest that the lower inhibition by 8-Br cADPR (P = 0.02, ryanodine vs. 8-Br cADPR) represents endogenously active ADPR cyclase. Depletion of SR Ca(2+) stores by inhibiting the SR Ca(2+)-ATPase with cyclopiazonic acid or thapsigargin blocked the [Ca(2+)](i) responses to KCl by 51% (P not significant vs. ryanodine or 8-Br cADPR). These data suggest that about half of the increase in [Ca(2+)](i) induced by high KCl is accomplished by activation of CICR through the ability of entered Ca(2+) to expose the RyR to high local concentrations of Ca(2+) and that endogenous cADPR contributes to the process. PMID:17190906

  16. Kinetic Study on Desulfurization of Hot Metal Using CaO and CaC2

    NASA Astrophysics Data System (ADS)

    Lindström, David; Sichen, Du

    2015-02-01

    The kinetics and reaction mechanisms of hot metal desulfurization using CaO and CaC2 were studied in a well-controlled atmosphere with a lab scale high temperature furnace. The growths of CaS around CaO and CaC2 were measured and compared at 1773 K (1500 °C). The parabolic rate constant was evaluated to be 5 × 10-7 (cm s-1) on CaO particles, and 2.4 × 10-7 (cm s-1) on CaC2. The bigger parabolic constant of CaO resulted in more efficient desulfurization. Agglomerates and big CaO particles led to 2CaO·SiO2 formation which hindered further utilization of CaO for desulfurization. The 2CaO·SiO2 formation was favoured by a high oxygen potential. Since the desulfurization reaction of CaO not only produced CaS but also oxygen, the local oxygen concentration around big CaO particles was higher than around small particles.

  17. Kinetic Study on Desulfurization of Hot Metal Using CaO and CaC2

    NASA Astrophysics Data System (ADS)

    Lindström, David; Sichen, Du

    2014-09-01

    The kinetics and reaction mechanisms of hot metal desulfurization using CaO and CaC2 were studied in a well-controlled atmosphere with a lab scale high temperature furnace. The growths of CaS around CaO and CaC2 were measured and compared at 1773 K (1500 °C). The parabolic rate constant was evaluated to be 5 × 10-7 (cm s-1) on CaO particles, and 2.4 × 10-7 (cm s-1) on CaC2. The bigger parabolic constant of CaO resulted in more efficient desulfurization. Agglomerates and big CaO particles led to 2CaO·SiO2 formation which hindered further utilization of CaO for desulfurization. The 2CaO·SiO2 formation was favoured by a high oxygen potential. Since the desulfurization reaction of CaO not only produced CaS but also oxygen, the local oxygen concentration around big CaO particles was higher than around small particles.

  18. Interplay Between Intracellular Ca(2+) Oscillations and Ca(2+)-stimulated Mitochondrial Metabolism.

    PubMed

    Wacquier, Benjamin; Combettes, Laurent; Van Nhieu, Guy Tran; Dupont, Geneviève

    2016-01-01

    Oscillations of cytosolic Ca(2+) concentration are a widespread mode of signalling. Oscillatory spikes rely on repetitive exchanges of Ca(2+) between the endoplasmic reticulum (ER) and the cytosol, due to the regulation of inositol 1,4,5-trisphosphate receptors. Mitochondria also sequester and release Ca(2+), thus affecting Ca(2+) signalling. Mitochondrial Ca(2+) activates key enzymes involved in ATP synthesis. We propose a new integrative model for Ca(2+) signalling and mitochondrial metabolism in electrically non-excitable cells. The model accounts for (1) the phase relationship of the Ca(2+) changes in the cytosol, the ER and mitochondria, (2) the dynamics of mitochondrial metabolites in response to cytosolic Ca(2+) changes, and (3) the impacts of cytosol/mitochondria Ca(2+) exchanges and of mitochondrial metabolism on Ca(2+) oscillations. Simulations predict that as expected, oscillations are slowed down by decreasing the rate of Ca(2+) efflux from mitochondria, but also by decreasing the rate of Ca(2+) influx through the mitochondrial Ca(2+) uniporter (MCU). These predictions were experimentally validated by inhibiting MCU expression. Despite the highly non-linear character of Ca(2+) dynamics and mitochondrial metabolism, bioenergetics were found to be robust with respect to changes in frequency and amplitude of Ca(2+) oscillations. PMID:26776859

  19. Interplay Between Intracellular Ca2+ Oscillations and Ca2+-stimulated Mitochondrial Metabolism

    PubMed Central

    Wacquier, Benjamin; Combettes, Laurent; Van Nhieu, Guy Tran; Dupont, Geneviève

    2016-01-01

    Oscillations of cytosolic Ca2+ concentration are a widespread mode of signalling. Oscillatory spikes rely on repetitive exchanges of Ca2+ between the endoplasmic reticulum (ER) and the cytosol, due to the regulation of inositol 1,4,5-trisphosphate receptors. Mitochondria also sequester and release Ca2+, thus affecting Ca2+ signalling. Mitochondrial Ca2+ activates key enzymes involved in ATP synthesis. We propose a new integrative model for Ca2+ signalling and mitochondrial metabolism in electrically non-excitable cells. The model accounts for (1) the phase relationship of the Ca2+ changes in the cytosol, the ER and mitochondria, (2) the dynamics of mitochondrial metabolites in response to cytosolic Ca2+ changes, and (3) the impacts of cytosol/mitochondria Ca2+ exchanges and of mitochondrial metabolism on Ca2+ oscillations. Simulations predict that as expected, oscillations are slowed down by decreasing the rate of Ca2+ efflux from mitochondria, but also by decreasing the rate of Ca2+ influx through the mitochondrial Ca2+ uniporter (MCU). These predictions were experimentally validated by inhibiting MCU expression. Despite the highly non-linear character of Ca2+ dynamics and mitochondrial metabolism, bioenergetics were found to be robust with respect to changes in frequency and amplitude of Ca2+ oscillations. PMID:26776859

  20. Ca isotope cycling in a forested ecosystem

    NASA Astrophysics Data System (ADS)

    Holmden, Chris; Bélanger, Nicolas

    2010-02-01

    Reports of large Ca isotope fractionations between trees and soils prompted this study of a Boreal forest ecosystem near La Ronge, Saskatchewan, to improve understanding of this phenomenon. The results on five tree species (black spruce, trembling aspen, white spruce, jack pine, balsam poplar) confirm that nutrient Ca uptake by plants favors the light isotopes, thus driving residual Ca in plant available soil pools towards enrichment in the heavy isotopes. Substantial within-tree fraction occurs in tissues formed along the transpiration stream, with low δ 44Ca values in fine roots (2 mm), intermediate values in stemwood, and high values in foliage. Separation factors between different plant tissues are similar between species, but the initial fractionation step in the tips of the fine roots is species specific, and/or sensitive to the local soil environment. Soil water δ 44Ca values appear to increase with depth to at least 35 cm below the top of the forest floor, which is close to the deepest level of fine roots. The heavy plant fractionated signature of Ca in the finely rooted upper soils filters downward where it is retained on ion exchange sites, leached into groundwater, and discharged into surface waters. The relationship between Ca uptake by tree fine roots and the pattern of δ 44Ca enrichment with soil depth was modeled for two Ca pools: the forest floor (litter) and the underlying (upper B) mineral soil. Six study plots were investigated along two hillside toposequences trending upwards from a first order stream. We used allometric equations describing the Ca distribution in boreal tree species to calculate weighted average δ 44Ca values for the stands in each plot and estimate Ca uptake rates. The δ 44Ca value of precipitation was measured, and soil weathering signatures deduced, by acid leaching of lower B mineral soils. Steady state equations were used to derive a set of model Ca fluxes and fractionation factors for each plot. The model reproduces

  1. Drugs preventing Na+ and Ca2+ overload.

    PubMed

    Ravens, U; Himmel, H M

    1999-03-01

    Cardiac intracellular Na+and Ca2+homeostasis is regulated by the concerted action of ion channels, pumps and exchangers. The Na+, K+-ATPase produces the electrochemical concentration gradient for Na+, which is the driving force for Ca2+removal from the cytosol via the Na+/Ca2+exchange. Reduction of this gradient by increased intracellular Na+concentration leads to cellular Ca2+overload resulting in arrhythmias and contractile dysfunction. Na+and Ca2+overload-associated arrhythmias can be produced experimentally by inhibition of Na+efflux (digitalis-induced intoxication) and by abnormal Na+influx via modulated Na+channels (veratridine, DPI 201-106; hypoxia) or via the Na+, H+exchanger. Theoretically, blockers of Na+and Ca2+channels, inhibitors of abnormal oscillatory release of Ca2+from internal stores or modulators of the Na+, Ca2+and Na+, H+exchanger activities could protect against cellular Na+and Ca2+overload. Three exemplary drugs that prevent Na+and Ca2+overload, i.e. the benzothiazolamine R56865, the methylenephenoxydioxy-derivative CP-060S, and the benzoyl-guanidine Hoe 642, a Na+, H+exchange blocker, are briefly reviewed with respect to their efficacy on digitalis-, veratridine- and ischaemia/reperfusion-induced arrhythmias. PMID:10094840

  2. Trace element proxies (Sr/Ca, Ba/Ca and Pb/Ca) in Bivalve shells: environmental signals or not?

    NASA Astrophysics Data System (ADS)

    Gillikin, D. P.; Dehairs, F.; Steenmans, D.; Meng, L.; Haifeng, T.; Navez, J.; Andre, L.; Baeyens, W.; Keppens, E.; Calmars Group,.

    2004-12-01

    Coral and sclerosponge skeletons have both been used as recorders of their environment. Sr/Ca, Ba/Ca and Pb/Ca have all shown to be useful in these substrates, giving insight into the past environment in which the skeleton grew (e.g., Lea et al., 1989, Nature 340, 373-376; Beck et al., 1992, Science 257, 644-647; Lazareth et al., 2000, Geology 28, 515-518; Rosenheim et al., 2004, Geology 32, 145-148). Although bivalves have not been studied as extensively as corals, these proxies are apparently not as reliable in bivalves (e.g., Vander Putten et al., 2000, GCA 64, 997-1011). We therefore investigate Sr/Ca and Pb/Ca in two species of aragonitic clams (Mercenaria mercenaria and Saxidomus giganteus) and Ba/Ca in the calcite layer of the mussel Mytilus edulis. Results indicate that Sr/Ca is primarily controlled by growth rate in S. giganteus whereas there was no relationship between these parameters in M. mercenaria. Pb/Ca is somewhat reproducible between specimens of S. giganteus, however long-term Pb/Ca records (1949-2003) in the shell of M. mercenaria did not show the expected curve of anthropogenically introduced lead, indicating that they are not recording environmental Pb concentrations. Therefore, Sr/Ca and Pb/Ca incorporation seem to be regulated by biological processes and not directly by environmental parameters. Ba/Ca in M. edulis shells on the other hand, does seem to be directly linked to the environment. Shells grown under laboratory and natural conditions both show the same linear relationship between dissolved Ba/Ca and shell Ba/Ca. Experiments involving manipulations of dissolved and particulate (i.e. food) Ba/Ca, suggest that the dominant pathway of barium into the shell is from the dissolved phase via the hemolymph. We were unable to explain the large peaks noted in the Ba/Ca profiles, however, they did not seem linked to phytoplankton blooms as has been previously suggested (Stecher et al., 1996, GCA 60, 3445-3456; Vander Putten et al., 2000

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

    PubMed

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

    1986-10-20

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

  4. Topographic specificity of functional connections from hippocampal CA3 to CA1

    NASA Astrophysics Data System (ADS)

    Brivanlou, Iman H.; Dantzker, Jami L. M.; Stevens, Charles F.; Callaway, Edward M.

    2004-02-01

    The hippocampus is a cortical region thought to play an important role in learning and memory. Most of our knowledge about the detailed organization of hippocampal circuitry responsible for these functions is derived from anatomical studies. These studies present an incomplete picture, however, because the functional character and importance of connections are often not revealed by anatomy. Here, we used a physiological method (photostimulation with caged glutamate) to probe the fine pattern of functional connectivity between the CA3 and CA1 subfields in the mouse hippocampal slice preparation. We recorded intracellularly from CA1 and CA3 pyramidal neurons while scanning with photostimulation across the entire CA3 subfield with high spatial resolution. Our results show that, at a given septotemporal level, nearby CA1 neurons receive synaptic inputs from neighboring CA3 neurons. Thus, the CA3 to CA1 mapping preserves neighbor relations.

  5. Impact of seawater [Ca2+] on the calcification and calciteMg / Ca of Amphistegina lessonii

    NASA Astrophysics Data System (ADS)

    Mewes, A.; Langer, G.; Thoms, S.; Nehrke, G.; Reichart, G.-J.; de Nooijer, L. J.; Bijma, J.

    2015-04-01

    Mg / Ca ratios in foraminiferal tests are routinely used as paleotemperature proxies, but on long timescales, they also hold the potential to reconstruct past seawater Mg / Ca. The impact of both temperature and seawater Mg / Ca on Mg incorporation in Foraminifera has been quantified by a number of studies. The underlying mechanism responsible for Mg incorporation in foraminiferal calcite and its sensitivity to environmental conditions, however, has not been fully identified. A recently published biomineralization model (Nehrke et al., 2013) proposes a combination of transmembrane transport and seawater leakage or vacuolization to link calcite Mg / Ca to seawater Mg / Ca and explains inter-species variability in Mg / Ca ratios. To test the assumptions of this model, we conducted a culture study in which seawater Mg / Ca was manipulated by varying [Ca2+] and keeping [Mg2+] constant. Foraminiferal growth rates, test thickness and calcite Mg / Ca of newly formed chambers were analyzed. Results showed optimum growth rates and test thickness at Mg / Ca closest to that of ambient seawater. Calcite Mg / Ca is positively correlated to seawater Mg / Ca, indicating that it is not absolute seawater [Ca2+] and [Mg2+] but their ratio that controls Mg / Ca in tests. These results demonstrate that the calcification process cannot be based only on seawater vacuolization, supporting the mixing model proposed by Nehrke et al. (2013). Here, however, we suggest transmembrane transport fractionation that is not as strong as suggested by Nehrke et al. (2013).

  6. Dietary calcium deficiency increases Ca2+ uptake and Ca2+ extrusion mechanisms in chick enterocytes.

    PubMed

    Centeno, Viviana A; Díaz de Barboza, Gabriela E; Marchionatti, Ana M; Alisio, Arturo E; Dallorso, Maria E; Nasif, Renée; Tolosa de Talamoni, Nori G

    2004-10-01

    Ca2+ uptake and Ca2+ extrusion mechanisms were studied in enterocytes with different degree of differentiation from chicks adapted to a low Ca2+ diet as compared to animals fed a normal diet. Chicks adapted to a low Ca2+ diet presented hypocalcemia, hypophosphatemia and increased serum 1,25(OH)2D3 and Ca2+ absorption. Low Ca2+ diet increased the alkaline phosphatase (AP) activity, independently of the cellular maturation, but it did not alter gamma-glutamyl-transpeptidase activity. Ca2+ uptake, Ca2+-ATPase and Na(+)/Ca2+ exchanger activities and expressions were increased by the mineral-deficient diet either in mature or immature enterocytes. Western blots analysis shows that vitamin D receptor (VDR) expression was much higher in crypt cells than in mature cells. Low Ca2+ diet decreased the number of vitamin D receptor units in both kinds of cells. In conclusion, changes in Ca2+ uptake and Ca2+ extrusion mechanisms in the enterocytes by a low Ca2+ diet appear to be a result of enhanced serum levels of 1,25(OH)2D3, which would promote cellular differentiation producing cells more efficient to express vitamin D dependent genes required for Ca2+ absorption. PMID:15528161

  7. Impact of seawater Ca2+ on the calcification and calcite Mg/Ca of Amphistegina lessonii

    NASA Astrophysics Data System (ADS)

    Mewes, A.; Langer, G.; Thoms, S.; Nehrke, G.; Reichart, G.-J.; de Nooijer, L. J.; Bijma, J.

    2014-12-01

    Mg/Ca ratios in foraminiferal tests are routinely used as paleo temperature proxy, but on long timescales, also hold the potential to reconstruct past seawater Mg/Ca. Impact of both temperature and seawater Mg/Ca on Mg incorporation in foraminifera have been quantified by a number of studies. The underlying mechanism responsible for Mg incorporation in foraminiferal calcite and its sensitivity to environmental conditions, however, is not fully identified. A recently published biomineralization model (Nehrke et al., 2013) proposes a combination of transmembrane transport and seawater leakage or vacuolization to link calcite Mg/Ca to seawater Mg/Ca and explains inter-species variability in Mg/Ca ratios. To test the assumptions of this model, we conducted a culture study in which seawater Mg/Ca was manipulated by varying [Ca2+] and keeping [Mg2+] constant. Foraminiferal growth rates, test thickness and calcite Mg/Ca of newly formed chambers were analyzed. Results showed optimum growth rates and test thickness at Mg/Ca closest to that of ambient seawater. Calcite Mg/Ca is positively correlated to seawater Mg/Ca, indicating that not absolute seawater [Ca2+] and [Mg2+], but the telative ratio controls Mg/Ca in tests. These results demonstrate that the calcification process cannot be based only on seawater vacuolization, supporting the mixing model proposed by Nehrke et al. (2013). Here we, however, suggest a transmembrane transport fractionation that is not as strong as suggested by Nehrke et al. (2013).

  8. Ca2+ cycling in heart cells from ground squirrels: adaptive strategies for intracellular Ca2+ homeostasis.

    PubMed

    Li, Xiao-Chen; Wei, Ling; Zhang, Guang-Qin; Bai, Zai-Ling; Hu, Ying-Ying; Zhou, Peng; Bai, Shu-Hua; Chai, Zhen; Lakatta, Edward G; Hao, Xue-Mei; Wang, Shi-Qiang

    2011-01-01

    Heart tissues from hibernating mammals, such as ground squirrels, are able to endure hypothermia, hypoxia and other extreme insulting factors that are fatal for human and nonhibernating mammals. This study was designed to understand adaptive mechanisms involved in intracellular Ca(2+) homeostasis in cardiomyocytes from the mammalian hibernator, ground squirrel, compared to rat. Electrophysiological and confocal imaging experiments showed that the voltage-dependence of L-type Ca(2+) current (I(Ca)) was shifted to higher potentials in ventricular myocytes from ground squirrels vs. rats. The elevated threshold of I(Ca) did not compromise the Ca(2+)-induced Ca(2+) release, because a higher depolarization rate and a longer duration of action potential compensated the voltage shift of I(Ca). Both the caffeine-sensitive and caffeine-resistant components of cytosolic Ca(2+) removal were more rapid in ground squirrels. Ca(2+) sparks in ground squirrels exhibited larger amplitude/size and much lower frequency than in rats. Due to the high I(Ca) threshold, low SR Ca(2+) leak and rapid cytosolic Ca(2+) clearance, heart cells from ground squirrels exhibited better capability in maintaining intracellular Ca(2+) homeostasis than those from rats and other nonhibernating mammals. These findings not only reveal adaptive mechanisms of hibernation, but also provide novel strategies against Ca(2+) overload-related heart diseases. PMID:21935466

  9. TMCO1 Is an ER Ca(2+) Load-Activated Ca(2+) Channel.

    PubMed

    Wang, Qiao-Chu; Zheng, Qiaoxia; Tan, Haiyan; Zhang, Bing; Li, Xiaoling; Yang, Yuxiu; Yu, Jie; Liu, Yang; Chai, Hao; Wang, Xi; Sun, Zhongshuai; Wang, Jiu-Qiang; Zhu, Shu; Wang, Fengli; Yang, Maojun; Guo, Caixia; Wang, Heng; Zheng, Qingyin; Li, Yang; Chen, Quan; Zhou, Aimin; Tang, Tie-Shan

    2016-06-01

    Maintaining homeostasis of Ca(2+) stores in the endoplasmic reticulum (ER) is crucial for proper Ca(2+) signaling and key cellular functions. The Ca(2+)-release-activated Ca(2+) (CRAC) channel is responsible for Ca(2+) influx and refilling after store depletion, but how cells cope with excess Ca(2+) when ER stores are overloaded is unclear. We show that TMCO1 is an ER transmembrane protein that actively prevents Ca(2+) stores from overfilling, acting as what we term a "Ca(2+) load-activated Ca(2+) channel" or "CLAC" channel. TMCO1 undergoes reversible homotetramerization in response to ER Ca(2+) overloading and disassembly upon Ca(2+) depletion and forms a Ca(2+)-selective ion channel on giant liposomes. TMCO1 knockout mice reproduce the main clinical features of human cerebrofaciothoracic (CFT) dysplasia spectrum, a developmental disorder linked to TMCO1 dysfunction, and exhibit severe mishandling of ER Ca(2+) in cells. Our findings indicate that TMCO1 provides a protective mechanism to prevent overfilling of ER stores with Ca(2+) ions. PMID:27212239

  10. Allometric constraints on Sr/Ca and Ba/Ca partitioning in terrestrial mammalian trophic chains.

    PubMed

    Balter, Vincent

    2004-03-01

    In biological systems, strontium (Sr) and barium (Ba) are two non-essential elements, in comparison to calcium (Ca) which is essential. The Sr/Ca and Ba/Ca ratios tend to decrease in biochemical pathways which include Ca as an essential element, and these processes are termed biopurification of Ca. The quantitative pathway of the biopurification of Ca in relation to Sr and Ba between two biological reservoirs ( Rn and R(n -1)) is measured with an observed ratio (OR) expressed by the (Sr/Ca) Rn /(Sr/Ca)( Rn-1) and (Ba/Ca) Rn /(Ba/Ca)( Rn-1) ratios. For a mammalian organism, during the whole biopurification of Ca starting with the diet to the ultimate reservoir of Ca which is the bone, the mean values for ORSr and ORBa are 0.25 and 0.2, respectively. In this study, published Sr/Ca and Ba/Ca ratios are used for three sets of soils, plants, and bones of herbivorous and carnivorous mammals, each comprising a trophic chain, to illustrate the biopurification of Ca at the level of trophic chains. Calculated ORSr and ORBa of herbivore bones in relation to plants and of bones of carnivores in relation to bones of herbivores give ORSr=0.30+/-0.08 and ORBa=0.16+/-0.08, thus suggesting that trophic chains reflect the Sr/Ca and Ba/Ca fluxes that are prevalent at the level of a mammalian organism. The slopes of the three regression equations of log(Sr/Ca) vs. log(Ba/Ca) are similar, indicating that the process of biopurification of Ca with respect to Sr and Ba is due to biological processes and is independent of the geological settings. Modifications of the logarithmic expression of the Sr/Ca and Ba/Ca relationship allow a new formula of the biopurification process to be deduced, leading to the general equation ORBa=ORSr(1.79+/-0.33), where the allometric coefficient is the mean of the slopes of the three regression equations. Some recent examples are used to illustrate this new analysis of predator-prey relations between mammals. This opens up new possibilities for the

  11. Glutamate excitotoxicity and Ca2+-regulation of respiration: Role of the Ca2+ activated mitochondrial transporters (CaMCs).

    PubMed

    Rueda, Carlos B; Llorente-Folch, Irene; Traba, Javier; Amigo, Ignacio; Gonzalez-Sanchez, Paloma; Contreras, Laura; Juaristi, Inés; Martinez-Valero, Paula; Pardo, Beatriz; Del Arco, Araceli; Satrustegui, Jorgina

    2016-08-01

    Glutamate elicits Ca(2+) signals and workloads that regulate neuronal fate both in physiological and pathological circumstances. Oxidative phosphorylation is required in order to respond to the metabolic challenge caused by glutamate. In response to physiological glutamate signals, cytosolic Ca(2+) activates respiration by stimulation of the NADH malate-aspartate shuttle through Ca(2+)-binding to the mitochondrial aspartate/glutamate carrier (Aralar/AGC1/Slc25a12), and by stimulation of adenine nucleotide uptake through Ca(2+) binding to the mitochondrial ATP-Mg/Pi carrier (SCaMC-3/Slc25a23). In addition, after Ca(2+) entry into the matrix through the mitochondrial Ca(2+) uniporter (MCU), it activates mitochondrial dehydrogenases. In response to pathological glutamate stimulation during excitotoxicity, Ca(2+) overload, reactive oxygen species (ROS), mitochondrial dysfunction and delayed Ca(2+) deregulation (DCD) lead to neuronal death. Glutamate-induced respiratory stimulation is rapidly inactivated through a mechanism involving Poly (ADP-ribose) Polymerase-1 (PARP-1) activation, consumption of cytosolic NAD(+), a decrease in matrix ATP and restricted substrate supply. Glutamate-induced Ca(2+)-activation of SCaMC-3 imports adenine nucleotides into mitochondria, counteracting the depletion of matrix ATP and the impaired respiration, while Aralar-dependent lactate metabolism prevents substrate exhaustion. A second mechanism induced by excitotoxic glutamate is permeability transition pore (PTP) opening, which critically depends on ROS production and matrix Ca(2+) entry through the MCU. By increasing matrix content of adenine nucleotides, SCaMC-3 activity protects against glutamate-induced PTP opening and lowers matrix free Ca(2+), resulting in protracted appearance of DCD and protection against excitotoxicity in vitro and in vivo, while the lack of lactate protection during in vivo excitotoxicity explains increased vulnerability to kainite-induced toxicity in Aralar

  12. Exploring the Glycosylation of Serum CA125

    PubMed Central

    Saldova, Radka; Struwe, Weston B.; Wynne, Kieran; Elia, Giuliano; Duffy, Michael J.; Rudd, Pauline M.

    2013-01-01

    Ovarian cancer is the most lethal gynaecologic cancer affecting women. The most widely used biomarker for ovarian cancer, CA125, lacks sensitivity and specificity. Here, we explored differences in glycosylation of CA125 between serum from patients with ovarian cancer and healthy controls. We found differences between CA125 N-glycans from patient sera compared to controls. These include increases in core-fucosylated bi-antennary monosialylated glycans, as well as decreases in mostly bisecting bi-antennary and non-fucosylated glycans in patients compared to controls. Measurement of the glycosylated state of CA125 may therefore provide a more specific biomarker for patients with ovarian cancer. PMID:23896595

  13. Oxidized CaMKII Triggers Atrial Fibrillation

    PubMed Central

    Purohit, Anil; Rokita, Adam G.; Guan, Xiaoqun; Chen, Biyi; Koval, Olha M.; Voigt, Niels; Neef, Stefan; Sowa, Thomas; Gao, Zhan; Luczak, Elizabeth D.; Stefansdottir, Hrafnhildur; Behunin, Andrew C.; Li, Na; El-Accaoui, Ramzi N.; Yang, Baoli; Swaminathan, Paari Dominic; Weiss, Robert M.; Wehrens, Xander H.T.; Song, Long-Sheng; Dobrev, Dobromir; Maier, Lars S.; Anderson, Mark E.

    2013-01-01

    Background Atrial fibrillation is a growing public health problem without adequate therapies. Angiotensin II (Ang II) and reactive oxygen species (ROS) are validated risk factors for atrial fibrillation (AF) in patients, but the molecular pathway(s) connecting ROS and AF is unknown. The Ca2+/calmodulin-dependent protein kinase II (CaMKII) has recently emerged as a ROS activated proarrhythmic signal, so we hypothesized that oxidized CaMKIIδ(ox-CaMKII) could contribute to AF. Methods and Results We found ox-CaMKII was increased in atria from AF patients compared to patients in sinus rhythm and from mice infused with Ang II compared with saline. Ang II treated mice had increased susceptibility to AF compared to saline treated WT mice, establishing Ang II as a risk factor for AF in mice. Knock in mice lacking critical oxidation sites in CaMKIIδ (MM-VV) and mice with myocardial-restricted transgenic over-expression of methionine sulfoxide reductase A (MsrA TG), an enzyme that reduces ox-CaMKII, were resistant to AF induction after Ang II infusion. Conclusions Our studies suggest that CaMKII is a molecular signal that couples increased ROS with AF and that therapeutic strategies to decrease ox-CaMKII may prevent or reduce AF. PMID:24030498

  14. The State of the Ca Isotope Proxy

    NASA Astrophysics Data System (ADS)

    Fantle, M. S.; Tipper, E.

    2012-12-01

    At the Earth's surface, Ca is a critical element at a variety of scales. It is both a biological nutrient and water-soluble, and is a major constituent of the dominant mineral sink for carbon in the ocean. Additionally, the 5‰ range in the stable isotope ratios of Ca (44Ca/40Ca) suggests that Ca isotopes may be a promising tracer of the Ca cycle, specifically the oceanic budget over time. Despite ~15 years of concentrated effort on high-precision Ca isotope measurements, the utility of Ca isotopes as a proxy remains far from clear. A variety of basic questions have yet to be resolved, both in the marine and terrestrial realms. To provide perspective, the current work presents a data compilation of over 60 published Ca isotope studies. The compilation includes δ44/40CaSRM-915a measurements of the modern Ca cycle, including rivers and groundwater, dust, soils and soil pore fluids, vegetation, rainwater, silicate minerals/rocks, and marine carbonates. The focus of this work is to quantify the leverage of inputs to change the isotopic composition of the ocean. One of the tenets of the weathering proxy is that there is little isotopic leverage to change seawater. If this assumption is valid, then significant variations in the isotopic composition of seawater can be explained to some extent by mass flux imbalances between Ca inputs and outputs, requiring the Ca cycle to be out of steady state for significant periods of time. Despite evidence that Ca fractionates in the modern system during continental cycling, the δ44Ca range of riverine inputs to the ocean is very narrow (especially when compared to the spread in marine carbonates). Thus, there appears to be minimal isotopic leverage amongst inputs to shift the ocean δ44Ca. In order to develop our understanding of the Ca isotope proxy, we identify two probable mechanisms for shifting ocean δ44Ca and evaluate them using a series of simple box models. In the terrestrial realm, plants exhibit a wide range of

  15. Ca2+ influx into lily pollen grains through a hyperpolarization-activated Ca2+-permeable channel which can be regulated by extracellular CaM.

    PubMed

    Shang, Zhong-lin; Ma, Li-geng; Zhang, Hai-lin; He, Rui-rong; Wang, Xue-chen; Cui, Su-juan; Sun, Da-ye

    2005-04-01

    Confocal laser scanning microscopy (CLSM) and whole-cell patch-clamp were used to investigate the role of Ca2+ influx in maintaining the cytosolic Ca2+ concentration ([Ca2+]c) and the features of the Ca2+ influx pathway in germinating pollen grains of Lilium davidii D. [Ca2+]c decreased when Ca2+ influx was inhibited by EGTA or Ca2+ channel blockers. A hyperpolarization-activated Ca2+-permeable channel, which can be suppressed by trivalent cations, verapamil, nifedipine or diltiazem, was identified on the plasma membrane of pollen protoplasts with whole-cell patch-clamp recording. Calmodulin (CaM) antiserum and W7-agarose, both of which are cell-impermeable CaM antagonists, lead to a [Ca2+]c decrease, while exogenous purified CaM triggers a transient increase of [Ca2+]c and also remarkably activated the hyperpolarization-activated Ca2+ conductance on plasma membrane of pollen protoplasts in a dose-dependent manner. Both the increase of [Ca2+]c and the activation of Ca2+ conductance which were induced by exogenous CaM were inhibited by EGTA or Ca2+ channel blockers. This primary evidence showed the presence of a voltage-dependent Ca2+-permeable channel, whose activity may be regulated by extracellular CaM, in pollen cells. PMID:15695439

  16. Extrapolating microdomain Ca2+ dynamics using BK channels as a Ca2+ sensor

    PubMed Central

    Hou, Panpan; Xiao, Feng; Liu, Haowen; Yuchi, Ming; Zhang, Guohui; Wu, Ying; Wang, Wei; Zeng, Wenping; Ding, Mingyue; Cui, Jianming; Wu, Zhengxing; Wang, Lu-Yang; Ding, Jiuping

    2016-01-01

    Ca2+ ions play crucial roles in mediating physiological and pathophysiological processes, yet Ca2+ dynamics local to the Ca2+ source, either from influx via calcium permeable ion channels on plasmic membrane or release from internal Ca2+ stores, is difficult to delineate. Large-conductance calcium-activated K+ (BK-type) channels, abundantly distribute in excitable cells and often localize to the proximity of voltage-gated Ca2+ channels (VGCCs), spatially enabling the coupling of the intracellular Ca2+ signal to the channel gating to regulate membrane excitability and spike firing patterns. Here we utilized the sensitivity and dynamic range of BK to explore non-uniform Ca2+ local transients in the microdomain of VGCCs. Accordingly, we applied flash photolysis of caged Ca2+ to activate BK channels and determine their intrinsic sensitivity to Ca2+. We found that uncaging Ca2+ activated biphasic BK currents with fast and slow components (time constants being τf ≈ 0.2 ms and τs ≈ 10 ms), which can be accounted for by biphasic Ca2+ transients following light photolysis. We estimated the Ca2+-binding rate constant kb (≈1.8 × 108 M−1s−1) for mSlo1 and further developed a model in which BK channels act as a calcium sensor capable of quantitatively predicting local microdomain Ca2+ transients in the vicinity of VGCCs during action potentials. PMID:26776352

  17. EMRE is a Matrix Ca2+ Sensor that Governs Gatekeeping of the Mitochondrial Ca2+ Uniporter

    PubMed Central

    Vais, Horia; Mallilankaraman, Karthik; Mak, Don-On Daniel; Hoff, Henry; Payne, Riley; Tanis, Jessica; Foskett, J. Kevin

    2015-01-01

    SUMMARY The mitochondrial uniporter (MCU) is an ion channel that mediates Ca2+ uptake into the matrix to regulate metabolism, cell death and cytoplasmic Ca2+ signaling. Matrix Ca2+ concentration is similar to that in cytoplasm, despite an enormous driving force for entry, but the mechanisms that prevent mitochondrial Ca2+ overload are unclear. Here, we show that MCU channel activity is governed by matrix Ca2+ concentration through EMRE. Deletion or charge neutralization of its matrix-localized acidic carboxyl terminus abolishes matrix Ca2+ inhibition of MCU Ca2+ currents, resulting in MCU channel activation, enhanced mitochondrial Ca2+ uptake and constitutively elevated matrix Ca2+ concentration. EMRE-dependent regulation of MCU channel activity requires intermembrane space-localized MICU1, MICU2 and cytoplasmic Ca2+. Thus, mitochondria are protected from Ca2+ depletion and Ca2+ overload by a unique molecular complex that involves Ca2+ sensors on both sides of the inner mitochondrial membrane, coupled through EMRE. PMID:26774479

  18. Extrapolating microdomain Ca(2+) dynamics using BK channels as a Ca(2+) sensor.

    PubMed

    Hou, Panpan; Xiao, Feng; Liu, Haowen; Yuchi, Ming; Zhang, Guohui; Wu, Ying; Wang, Wei; Zeng, Wenping; Ding, Mingyue; Cui, Jianming; Wu, Zhengxing; Wang, Lu-Yang; Ding, Jiuping

    2016-01-01

    Ca(2+) ions play crucial roles in mediating physiological and pathophysiological processes, yet Ca(2+) dynamics local to the Ca(2+) source, either from influx via calcium permeable ion channels on plasmic membrane or release from internal Ca(2+) stores, is difficult to delineate. Large-conductance calcium-activated K(+) (BK-type) channels, abundantly distribute in excitable cells and often localize to the proximity of voltage-gated Ca(2+) channels (VGCCs), spatially enabling the coupling of the intracellular Ca(2+) signal to the channel gating to regulate membrane excitability and spike firing patterns. Here we utilized the sensitivity and dynamic range of BK to explore non-uniform Ca(2+) local transients in the microdomain of VGCCs. Accordingly, we applied flash photolysis of caged Ca(2+) to activate BK channels and determine their intrinsic sensitivity to Ca(2+). We found that uncaging Ca(2+) activated biphasic BK currents with fast and slow components (time constants being τf ≈ 0.2 ms and τs ≈ 10 ms), which can be accounted for by biphasic Ca(2+) transients following light photolysis. We estimated the Ca(2+)-binding rate constant kb (≈1.8 × 10(8)  M(-1) s(-1)) for mSlo1 and further developed a model in which BK channels act as a calcium sensor capable of quantitatively predicting local microdomain Ca(2+) transients in the vicinity of VGCCs during action potentials. PMID:26776352

  19. Topography of Place Maps along the CA3-to-CA2 Axis of the Hippocampus.

    PubMed

    Lu, Li; Igarashi, Kei M; Witter, Menno P; Moser, Edvard I; Moser, May-Britt

    2015-09-01

    We asked whether the structural heterogeneity of the hippocampal CA3-CA2 axis is reflected in how space is mapped onto place cells in CA3-CA2. Place fields were smaller and sharper in proximal CA3 than in distal CA3 and CA2. The proximodistal shift was accompanied by a progressive loss in the ability of place cells to distinguish configurations of the same spatial environment, as well as a reduction in the extent to which place cells formed uncorrelated representations for different environments. The transition to similar representations was nonlinear, with the sharpest drop in distal CA3. These functional changes along the CA3-CA2 axis mirror gradients in gene expression and connectivity that partly override cytoarchitectonic boundaries between the subfields of the hippocampus. The results point to the CA3-CA2 axis as a functionally graded system with powerful pattern separation at the proximal end, near the dentate gyrus, and stronger pattern completion at the CA2 end. PMID:26298277

  20. EMRE Is a Matrix Ca(2+) Sensor that Governs Gatekeeping of the Mitochondrial Ca(2+) Uniporter.

    PubMed

    Vais, Horia; Mallilankaraman, Karthik; Mak, Don-On Daniel; Hoff, Henry; Payne, Riley; Tanis, Jessica E; Foskett, J Kevin

    2016-01-26

    The mitochondrial uniporter (MCU) is an ion channel that mediates Ca(2+) uptake into the matrix to regulate metabolism, cell death, and cytoplasmic Ca(2+) signaling. Matrix Ca(2+) concentration is similar to that in cytoplasm, despite an enormous driving force for entry, but the mechanisms that prevent mitochondrial Ca(2+) overload are unclear. Here, we show that MCU channel activity is governed by matrix Ca(2+) concentration through EMRE. Deletion or charge neutralization of its matrix-localized acidic C terminus abolishes matrix Ca(2+) inhibition of MCU Ca(2+) currents, resulting in MCU channel activation, enhanced mitochondrial Ca(2+) uptake, and constitutively elevated matrix Ca(2+) concentration. EMRE-dependent regulation of MCU channel activity requires intermembrane space-localized MICU1, MICU2, and cytoplasmic Ca(2+). Thus, mitochondria are protected from Ca(2+) depletion and Ca(2+) overload by a unique molecular complex that involves Ca(2+) sensors on both sides of the inner mitochondrial membrane, coupled through EMRE. PMID:26774479

  1. Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak

    PubMed Central

    Sankaranarayanan, Rajiv; Li, Yatong; Greensmith, David J.; Eisner, David A.

    2016-01-01

    Key points Ca leak from the sarcoplasmic reticulum through the ryanodine receptor (RyR) reduces the amplitude of the Ca transient and slows its rate of decay.In the presence of β‐adrenergic stimulation, RyR‐mediated Ca leak produces a biphasic decay of the Ca transient with a fast early phase and a slow late phase.Two forms of Ca leak have been studied, Ca‐sensitising (induced by caffeine) and non‐sensitising (induced by ryanodine) and both induce biphasic decay of the Ca transient.Only Ca‐sensitising leak can be reversed by traditional RyR inhibitors such as tetracaine.Ca leak can also induce Ca waves. At low levels of leak, waves occur. As leak is increased, first biphasic decay and then slowed monophasic decay is seen. The level of leak has major effects on the shape of the Ca transient. Abstract In heart failure, a reduction in Ca transient amplitude and contractile dysfunction can by caused by Ca leak through the sarcoplasmic reticulum (SR) Ca channel (ryanodine receptor, RyR) and/or decreased activity of the SR Ca ATPase (SERCA). We have characterised the effects of two forms of Ca leak (Ca‐sensitising and non‐sensitising) on calcium cycling and compared with those of SERCA inhibition. We measured [Ca2+]i with fluo‐3 in voltage‐clamped rat ventricular myocytes. Increasing SR leak with either caffeine (to sensitise the RyR to Ca activation) or ryanodine (non‐sensitising) had similar effects to SERCA inhibition: decreased systolic [Ca2+]i, increased diastolic [Ca2+]i and slowed decay. However, in the presence of isoproterenol, leak produced a biphasic decay of the Ca transient in the majority of cells while SERCA inhibition produced monophasic decay. Tetracaine reversed the effects of caffeine but not of ryanodine. When caffeine (1 mmol l−1) was added to a cell which displayed Ca waves, the wave frequency initially increased before waves disappeared and biphasic decay developed. Eventually (at higher caffeine concentrations), the

  2. Effects of Mg2+ on Ca2+ waves and Ca2+ transients of rat ventricular myocytes.

    PubMed

    Terada, H; Hayashi, H; Noda, N; Satoh, H; Katoh, H; Yamazaki, N

    1996-03-01

    It has been shown that the occurrence of the transient inward current, which is responsible for triggered activity, was often associated with propagating regions of increased intracellular Ca2+ concentration ([Ca2+]i), i.e., the "Ca2+ wave." To investigate the mechanism of antiarrhythmic action of Mg2+, we have studied effects of high concentrations of Mg2+ on Ca2+ waves in isolated rat ventricular myocytes. [Ca2+]i was estimated using the Ca(2+)-indicating probe indo 1. Ca2+ waves in myocytes, stimulated at 0.2 Hz, were induced by perfusion of isoproterenol (10(-7) M). High Mg2+ concentration suppressed Ca2+ waves in a concentration-dependent manner (36% at 4 mM, 70% at 8 mM, and 82% at 12 mM). The Ca2+ channel blocker verapamil also suppressed Ca2+ waves in a similar way. In contrast with marked depression of Ca2+ transients by verapamil, Ca2+ transients were not affected by high Mg2+ concentration (8 mM). High Mg2+ concentration also reduced frequencies of Ca2+ waves in the absence of electrical stimulation, whereas verapamil failed to reduce frequencies of Ca2+ waves. Reduction in frequency of Ca2+ waves by high Mg2+ concentration was associated with slowing of propagation velocity of Ca2+ waves. To examine whether suppressive effects of high Mg2+ concentration on Ca2+ waves were related to an increase in intracellular Mg2+ concentration ([Mg2+]i), the effect of high-Mg2+ solution on [Mg2+]i was examined in myocytes loaded with mag-fura 2. An increase in extracellular Mg2+ concentration from 1 to 12 mM increased [Mg2+]i from 1.06 +/- 0.16 to 1.87 +/- 0.22 mM (P < 0.01) in 30 min. To examine the effect of high Mg2+ concentration on amount of releasable Ca2+ in the sarcoplasmic reticulum, the effect of high Mg2+ concentration on the Ca2+ transient induced by a rapid application of caffeine was examined. High-Mg2+ solution increased the peak of the caffeine-induced Ca2+ transient. These results suggest that the inhibitory effect of Mg2+ on Ca2+ waves was not due

  3. Ca2+-regulated structural changes in troponin

    NASA Astrophysics Data System (ADS)

    Vinogradova, Maia V.; Stone, Deborah B.; Malanina, Galina G.; Karatzaferi, Christina; Cooke, Roger; Mendelson, Robert A.; Fletterick, Robert J.

    2005-04-01

    Troponin senses Ca2+ to regulate contraction in striated muscle. Structures of skeletal muscle troponin composed of TnC (the sensor), TnI (the regulator), and TnT (the link to the muscle thin filament) have been determined. The structure of troponin in the Ca2+-activated state features a nearly twofold symmetrical assembly of TnI and TnT subunits penetrated asymmetrically by the dumbbell-shaped TnC subunit. Ca ions are thought to regulate contraction by controlling the presentation to and withdrawal of the TnI inhibitory segment from the thin filament. Here, we show that the rigid central helix of the sensor binds the inhibitory segment of TnI in the Ca2+-activated state. Comparison of crystal structures of troponin in the Ca2+-activated state at 3.0 Å resolution and in the Ca2+-free state at 7.0 Å resolution shows that the long framework helices of TnI and TnT, presumed to be a Ca2+-independent structural domain of troponin are unchanged. Loss of Ca ions causes the rigid central helix of the sensor to collapse and to release the inhibitory segment of TnI. The inhibitory segment of TnI changes conformation from an extended loop in the presence of Ca2+ to a short -helix in its absence. We also show that Anapoe, a detergent molecule, increases the contractile force of muscle fibers and binds specifically, together with the TnI switch helix, in a hydrophobic pocket of TnC upon activation by Ca ions. Ca | muscle | regulation | structure

  4. Basal Ca2+ and the oscillation of Ca2+ in caffeine-treated bullfrog sympathetic neurones.

    PubMed Central

    Nohmi, M; Hua, S Y; Kuba, K

    1992-01-01

    1. Effects of caffeine on the intracellular free Ca2+ concentration ([Ca2+]i) in single bullfrog sympathetic neurones in excised tissue were studied by recording Fura-2 fluorescence excited at 340, 361 or 380 nm and taking their ratios (R340/380 or R361/380). 2. Caffeine (3-10 mM) produced oscillation of [Ca2+]i and an 'apparent' decrease in the basal level of [Ca2+]i during a period between phasic rises. The mechanism of the latter effect was analysed in relation to the mechanism of the former. 3. Caffeine (3-10 mM) increased Fura-2 fluorescence in a range of excitation wavelength from 330 to 390 nm. The ratios of fluorescences, R340/380 and R361/380, however, were not significantly affected by caffeine. These results suggest that the 'apparent' reduction in the basal [Ca2+]i seen as a decrease in R340/380 or R361/380 results from a true decrease in [Ca2+]i. 4. Caffeine-induced decrease in [Ca2+]i persisted for every period between phasic rises of [Ca2+]i during [Ca2+]i oscillation, and after the blockade of [Ca2+]i oscillation by ryanodine. The decrease in the latter condition lasted for more than 20 min. 5. The decrease in the basal [Ca2+]i depended on the external Ca2+ concentration and was not mimicked by the action of cyclic nucleotides. 6. Possible mechanisms underlying the decrease in the basal [Ca2+]i produced by caffeine (effects on Ca2+ transport at the cell or Ca(2+)-storing organelle membrane) and their significance in relation to the [Ca2+]i oscillation were discussed. PMID:1432716

  5. Coupled Ca2+/H+ transport by cytoplasmic buffers regulates local Ca2+ and H+ ion signaling.

    PubMed

    Swietach, Pawel; Youm, Jae-Boum; Saegusa, Noriko; Leem, Chae-Hun; Spitzer, Kenneth W; Vaughan-Jones, Richard D

    2013-05-28

    Ca(2+) signaling regulates cell function. This is subject to modulation by H(+) ions that are universal end-products of metabolism. Due to slow diffusion and common buffers, changes in cytoplasmic [Ca(2+)] ([Ca(2+)]i) or [H(+)] ([H(+)]i) can become compartmentalized, leading potentially to complex spatial Ca(2+)/H(+) coupling. This was studied by fluorescence imaging of cardiac myocytes. An increase in [H(+)]i, produced by superfusion of acetate (salt of membrane-permeant weak acid), evoked a [Ca(2+)]i rise, independent of sarcolemmal Ca(2+) influx or release from mitochondria, sarcoplasmic reticulum, or acidic stores. Photolytic H(+) uncaging from 2-nitrobenzaldehyde also raised [Ca(2+)]i, and the yield was reduced following inhibition of glycolysis or mitochondrial respiration. H(+) uncaging into buffer mixtures in vitro demonstrated that Ca(2+) unloading from proteins, histidyl dipeptides (HDPs; e.g., carnosine), and ATP can underlie the H(+)-evoked [Ca(2+)]i rise. Raising [H(+)]i tonically at one end of a myocyte evoked a local [Ca(2+)]i rise in the acidic microdomain, which did not dissipate. The result is consistent with uphill Ca(2+) transport into the acidic zone via Ca(2+)/H(+) exchange on diffusible HDPs and ATP molecules, energized by the [H(+)]i gradient. Ca(2+) recruitment to a localized acid microdomain was greatly reduced during intracellular Mg(2+) overload or by ATP depletion, maneuvers that reduce the Ca(2+)-carrying capacity of HDPs. Cytoplasmic HDPs and ATP underlie spatial Ca(2+)/H(+) coupling in the cardiac myocyte by providing ion exchange and transport on common buffer sites. Given the abundance of cellular HDPs and ATP, spatial Ca(2+)/H(+) coupling is likely to be of general importance in cell signaling. PMID:23676270

  6. By Regulating Mitochondrial Ca2+-Uptake UCP2 Modulates Intracellular Ca2+

    PubMed Central

    Gebing, Tina; Reda, Sara; Schwaiger, Astrid; Leitner, Johannes; Wolny, Martin; Eckardt, Lars; Hoppe, Uta C.

    2016-01-01

    Introduction The possible role of UCP2 in modulating mitochondrial Ca2+-uptake (mCa2+-uptake) via the mitochondrial calcium uniporter (MCU) is highly controversial. Methods Thus, we analyzed mCa2+-uptake in isolated cardiac mitochondria, MCU single-channel activity in cardiac mitoplasts, dual Ca2+-transients from mitochondrial ((Ca2+)m) and intracellular compartment ((Ca2+)c) in the whole-cell configuration in cardiomyocytes of wild-type (WT) and UCP2-/- mice. Results Isolated mitochondria showed a Ru360 sensitive mCa2+-uptake, which was significantly decreased in UCP2-/- (229.4±30.8 FU vs. 146.3±23.4 FU, P<0.05). Single-channel registrations confirmed a Ru360 sensitive voltage-gated Ca2+-channel in mitoplasts, i.e. mCa1, showing a reduced single-channel activity in UCP2-/- (Po,total: 0.34±0.05% vs. 0.07±0.01%, P<0.05). In UCP2-/- cardiomyocytes (Ca2+)m was decreased (0.050±0.009 FU vs. 0.021±0.005 FU, P<0.05) while (Ca2+)c was unchanged (0.032±0.002 FU vs. 0.028±0.004 FU, P>0.05) and transsarcolemmal Ca2+-influx was inhibited suggesting a possible compensatory mechanism. Additionally, we observed an inhibitory effect of ATP on mCa2+-uptake in WT mitoplasts and (Ca2+)m of cardiomyocytes leading to an increase of (Ca2+)c while no ATP dependent effect was observed in UCP2-/-. Conclusion Our results indicate regulatory effects of UCP2 on mCa2+-uptake. Furthermore, we propose, that previously described inhibitory effects on MCU by ATP may be mediated via UCP2 resulting in changes of excitation contraction coupling. PMID:26849136

  7. CA-MRSA. The new sports pathogen.

    PubMed

    Kurkowski, Christina

    2007-01-01

    Skin infections in athletes caused by community-associated Methicillin-resistant Staphylococcus aureus (CA-MRSA) have been observed within many cities throughout the United States and within many countries throughout the world (Centers for Disease Control and Prevention [CDC], 2003). As the incidence rises in the athletic population, clinicians must learn to identify risk factors for CA-MRSA, diagnosis and treat infections with judicious use of antimicrobial agents and facilitate strategies to limit transmission. Recently, a new consensus guideline for handling CA-MRSA outbreaks in sports has been released by the CDC (Gorwitz et al., 2006). This article includes a review of the evolution of MRSA; distinguishes between healthcare associated Methicillin-resistant Staphylococcus aureus (HA-MRSA) and CA-MRSA; and reviews the diagnosis, management, and prevention strategies to limit transmission of CA-MRSA. PMID:17921891

  8. Ca-Dependent Folding of Human Calumenin

    PubMed Central

    Mazzorana, Marco; Hussain, Rohanah; Sorensen, Thomas

    2016-01-01

    Human calumenin (hCALU) is a six EF-hand protein belonging to the CREC family. As other members of the family, it is localized in the secretory pathway and regulates the activity of SERCA2a and of the ryanodine receptor in the endoplasmic reticulum (ER). We have studied the effects of Ca2+ binding to the protein and found it to attain a more compact structure upon ion binding. Circular Dichroism (CD) measurements suggest a major rearrangement of the protein secondary structure, which reversibly switches from disordered at low Ca2+ concentrations to predominantly alpha-helical when Ca2+ is added. SAXS experiments confirm the transition from an unfolded to a compact structure, which matches the structural prediction of a trilobal fold. Overall our experiments suggest that calumenin is a Ca2+ sensor, which folds into a compact structure, capable of interacting with its molecular partners, when Ca2+ concentration within the ER reaches the millimolar range. PMID:26991433

  9. Ppp2ca knockout in mice spermatogenesis.

    PubMed

    Pan, Xiaoyun; Chen, Xia; Tong, Xin; Tang, Chao; Li, Jianmin

    2015-04-01

    Protein phosphatase 2A (PP2A) is a ubiquitous serine/threonine phosphatase involved in meiosis, mitosis, sperm capacitation, and apoptosis. Abberant activity of PP2A has been associated with a number of diseases. The homolog PPP2CA and PPP2CB can each function as the phosphatase catalytic subunit generally referred to as PP2AC. We generated a Ppp2ca conditional knockout (CKO) in C57BL/6J mice. Exon 2 of Ppp2ca was knocked out in a spatial or temporal-specific manner in primordial germ cells at E12.5. This Ppp2ca-null mutation caused infertility in male C57BL/6J mice. These CKO mice provide a powerful tool to study the mechanisms of Ppp2ca in development and disease. PMID:25628439

  10. The role of luminal Ca2+ in the generation of Ca2+ waves in rat ventricular myocytes

    PubMed Central

    Lukyanenko, Valeriy; Subramanian, Saisunder; Györke, Inna; Wiesner, Theodore F; Györke, Sandor

    1999-01-01

    We used confocal Ca2+ imaging and fluo-3 to investigate the transition of localized Ca2+ releases induced by focal caffeine stimulation into propagating Ca2+ waves in isolated rat ventricular myocytes. Self-sustaining Ca2+ waves could be initiated when the cellular Ca2+ load was increased by elevating the extracellular [Ca2+] ([Ca2+]o) and they could also be initiated at normal Ca2+ loads when the sensitivity of the release sites to cytosolic Ca2+ was enhanced by low doses of caffeine. When we prevented the accumulation of extra Ca2+ in the luminal compartment of the sarcoplasmic reticulum (SR) with thapsigargin, focal caffeine pulses failed to trigger self-sustaining Ca2+ waves on elevation of [Ca2+]o. Inhibition of SR Ca2+ uptake by thapsigargin in cells already preloaded with Ca2+ above normal levels did not prevent local Ca2+ elevations from triggering propagating waves. Moreover, wave velocity increased by 20 %. Tetracaine (0·75 mM) caused transient complete inhibition of both local and propagating Ca2+ signals, followed by full recovery of the responses due to increased SR Ca2+ accumulation. Computer simulations using a numerical model with spatially distinct Ca2+ release sites suggested that increased amounts of releasable Ca2+ might not be sufficient to generate self-sustaining Ca2+ waves under conditions of Ca2+ overload unless the threshold of release site Ca2+ activation was set at relatively low levels (< 1·5 μM). We conclude that the potentiation of SR Ca2+ release channels by luminal Ca2+ is an important factor in Ca2+ wave generation. Wave propagation does not require the translocation of Ca2+ from the spreading wave front into the SR. Instead, it relies on luminal Ca2+ sensitizing Ca2+ release channels to cytosolic Ca2+. PMID:10373699

  11. Main determinants of presynaptic Ca2+ dynamics at individual mossy fiber - CA3 pyramidal cell synapses

    PubMed Central

    Scott, Ricardo; Rusakov, Dmitri A.

    2009-01-01

    Synaptic transmission between hippocampal mossy fibers (MFs) and CA3 pyramidal cells exhibits remarkable use-dependent plasticity. The underlying presynaptic mechanisms, however, remain poorly understood. Here we have used fluorescent Ca2+ indicators Fluo-4, Fluo-5F and Oregon Green BAPTA-1 to investigate Ca2+ dynamics in individual giant MF boutons (MFBs) in area CA3 traced from the somata of granule cells held in whole-cell mode. In an individual MFB, a single action potential induces a brief peak of free Ca2+ (estimated in the range of 8-9 μM) followed by an elevation to ~320 nM which slowly decays to its resting level of ~110 nM. Changes in the somatic membrane potential influence presynaptic Ca2+ entry at proximal MFBs in the hilus. This influence decays with distance along the axon, with a length constant of approximately 200 μm. In giant MFBs in CA3, progressive saturation of endogenous Ca2+ buffers during repetitive spiking amplifies rapid Ca2+ peaks and the residual Ca2+ several-fold, suggesting a causal link to synaptic facilitation. We find that internal Ca2+ stores contribute to maintaining the low resting Ca2+ providing ~22% of the buffering/extrusion capacity of giant MFBs. Rapid Ca2+ release from stores represents up to 20% of the presynaptic Ca2+ transient evoked by a brief train of action potentials. The results identify the main components of presynaptic Ca2+ dynamics at this important cortical synapse. PMID:16807336

  12. Isospin effects in 40,48Ca+40,48Ca collisions

    NASA Astrophysics Data System (ADS)

    Henzl, V.; Henzlova, D.; Kilburn, M.; Verde, G.; Brown, D.; Chbihi, A.; Coupland, D.; Elson, J.; Famiano, M.; Herlitzius, C.; Hudan, S.; Lee, J.; Lukyanov, S.; Lynch, W.; Rogers, A.; Sanetullaev, A.; Sobotka, L.; de Souza, R. T.; Sun, Z. Y.; Tsang, B.; Wallace, M.; Xu, K.; Youngs, M.

    2010-03-01

    The isospin dependence of two proton correlations is studied in 40Ca+40Ca and 48Ca+48Ca collisions at E/A=80MeV. Measurements were performed with the HiRA detector array complemented by the 4π Ball at NSCL. We observe a strong isospin dependence of the pp-correlation functions; however the emitting source radius extracted using the imaging technique yields no sensitivity to the isospin of the reaction system. We interpret this result as a consequence of smaller fraction of fast proton emission in the neutron rich 48Ca system.

  13. Fusion hindrance for Ca+Ca systems: Influence of neutron excess

    NASA Astrophysics Data System (ADS)

    Jiang, C. L.; Stefanini, A. M.; Esbensen, H.; Rehm, K. E.; Corradi, L.; Fioretto, E.; Mason, P.; Montagnoli, G.; Scarlassara, F.; Silvestri, R.; Singh, P. P.; Szilner, S.; Tang, X. D.; Ur, C. A.

    2010-10-01

    The measurement of the excitation function for fusion evaporation reactions in the system Ca40+Ca48 (Q= 4.56 MeV) has been extended downward by two orders of magnitude with respect to previous cross section data. A first indication of an S-factor maximum in a system with a positive Q value has been observed. In addition a correlation between fusion hindrance and neutron excess N-Z has been found for the Ca + Ca, Ni + Ni, and Ca + Zr systems.

  14. Na+/Ca2+ exchangers: three mammalian gene families control Ca2+ transport.

    PubMed

    Lytton, Jonathan

    2007-09-15

    Mammalian Na+/Ca2+ exchangers are members of three branches of a much larger family of transport proteins [the CaCA (Ca2+/cation antiporter) superfamily] whose main role is to provide control of Ca2+ flux across the plasma membranes or intracellular compartments. Since cytosolic levels of Ca2+ are much lower than those found extracellularly or in sequestered stores, the major function of Na+/Ca2+ exchangers is to extrude Ca2+ from the cytoplasm. The exchangers are, however, fully reversible and thus, under special conditions of subcellular localization and compartmentalized ion gradients, Na+/Ca2+ exchangers may allow Ca2+ entry and may play more specialized roles in Ca2+ movement between compartments. The NCX (Na+/Ca2+ exchanger) [SLC (solute carrier) 8] branch of Na+/Ca2+ exchangers comprises three members: NCX1 has been most extensively studied, and is broadly expressed with particular abundance in heart, brain and kidney, NCX2 is expressed in brain, and NCX3 is expressed in brain and skeletal muscle. The NCX proteins subserve a variety of roles, depending upon the site of expression. These include cardiac excitation-contraction coupling, neuronal signalling and Ca2+ reabsorption in the kidney. The NCKX (Na2+/Ca2+-K+ exchanger) (SLC24) branch of Na+/Ca2+ exchangers transport K+ and Ca2+ in exchange for Na+, and comprises five members: NCKX1 is expressed in retinal rod photoreceptors, NCKX2 is expressed in cone photoreceptors and in neurons throughout the brain, NCKX3 and NCKX4 are abundant in brain, but have a broader tissue distribution, and NCKX5 is expressed in skin, retinal epithelium and brain. The NCKX proteins probably play a particularly prominent role in regulating Ca2+ flux in environments which experience wide and frequent fluctuations in Na+ concentration. Until recently, the range of functions that NCKX proteins play was generally underappreciated. This situation is now changing rapidly as evidence emerges for roles including photoreceptor

  15. Ca2+ microdomains near plasma membrane Ca2+ channels: impact on cell function.

    PubMed

    Parekh, Anant B

    2008-07-01

    In eukaryotic cells, a rise in cytoplasmic Ca(2+) can activate a plethora of responses that operate on time scales ranging from milliseconds to days. Inherent to the use of a promiscuous signal like Ca(2+) is the problem of specificity: how can Ca(2+) activate some responses but not others? We now know that the spatial profile of the Ca(2+) signal is important Ca(2+) does not simply rise uniformly throughout the cytoplasm upon stimulation but can reach very high levels locally, creating spatial gradients. The most fundamental local Ca(2+) signal is the Ca(2+) microdomain that develops rapidly near open plasmalemmal Ca(2+) channels like voltage-gated L-type (Cav1.2) and store-operated CRAC channels. Recent work has revealed that Ca(2+) microdomains arising from these channels are remarkably versatile in triggering a range of responses that differ enormously in both temporal and spatial profile. Here, I delineate basic features of Ca(2+) microdomains and then describe how these highly local signals are used by Ca(2+)-permeable channels to drive cellular responses. PMID:18467365

  16. Ca Cycle Constraints from the Ca Isotope Composition of Precambrian Sedimentary Carbonates

    NASA Astrophysics Data System (ADS)

    Blättler, C. L.; Higgins, J. A.

    2014-12-01

    The geochemical cycle of Ca in seawater is relatively straightforward - Ca is ultimately sourced from the weathering of silicates and largely removed as carbonates. Most of these carbonates are then recycled through subsequent uplift and weathering, but some are metamorphosed or returned to the mantle via subduction. Ca isotopes in sedimentary marine carbonates can provide new insights into the global Ca (and by corollary, C) cycle by constraining the flux and isotopic composition of the recycled and subducted Ca sinks on billion-year timescales. Precambrian applications of Ca isotopes have so far been limited to relatively small datasets which cover unusual, dynamic intervals of the Proterozoic. In order to address questions about long-timescale Ca cycling, Ca isotopes were measured on an extensive suite of Precambrian carbonates (n > 300) which represent environments, textures, and morphologies that are typical for their age, and whose carbon isotope values have been interpreted as reflecting precipitation from seawater. Because marine carbonates constitute the dominant geological sink for Ca, this representative sample set places specific limits on the evolution of the sedimentary and crustal Ca reservoirs and suggests further applications for Ca isotopes in Precambrian time.

  17. (47)Ca production for (47)Ca/(47)Sc generator system using electron linacs.

    PubMed

    Rane, Shraddha; Harris, Jason T; Starovoitova, Valeriia N

    2015-03-01

    In this work we have studied the feasibility of photonuclear production of (47)Ca from (48)Ca for (47)Ca/(47)Sc generators. Photon flux distribution for electron beams of different energies incident on a tungsten converter was calculated using the MCNPX radiation transport code. The (47)Ca production rate dependence on electron beam energy was found and (47)Ca/(47)Sc yields were estimated for a 40MeV electron beam. It was shown that irradiating enriched targets with a 40MeV, 1mA beam will result in tens of MBq g(-1) (few mCi g(-1)) activity of (47)Sc. The results of the simulations were benchmarked by irradiating 22.5g of CaCl2 powder with a 39MeV electron beam incident on a tungsten converter. Measured (47)Ca/(47)Sc activities were found to be in very good agreement with the predictions. PMID:25600103

  18. Ferromagnetic CaRuO3

    PubMed Central

    Tripathi, Shivendra; Rana, Rakesh; Kumar, Sanjay; Pandey, Parul; Singh, R. S.; Rana, D. S.

    2014-01-01

    The non-magnetic and non-Fermi-liquid CaRuO3 is the iso-structural analog of the ferromagnetic (FM) and Fermi-liquid SrRuO3. We show that an FM order in the orthorhombic CaRuO3 can be established by the means of tensile epitaxial strain. The structural and magnetic property correlations in the CaRuO3 films formed on SrTiO3 (100) substrate establish a scaling relation between the FM moment and the tensile strain. The strain dependent crossover from non-magnetic to FM CaRuO3 was observed to be associated with switching of non-Fermi liquid to Fermi-liquid behavior. The intrinsic nature of this strain-induced FM order manifests in the Hall resistivity too; the anomalous Hall component realizes in FM tensile-strained CaRuO3 films on SrTiO3 (100) whereas the non-magnetic compressive-strained films on LaAlO3 (100) exhibit only the ordinary Hall effect. These observations of an elusive FM order are consistent with the theoretical predictions of scaling of the tensile epitaxial strain and the magnetic order in tensile CaRuO3. We further establish that the tensile strain is more efficient than the chemical route to induce FM order in CaRuO3. PMID:24464302

  19. Predicting Ca(2+)-binding sites in proteins.

    PubMed Central

    Nayal, M; Di Cera, E

    1994-01-01

    The coordination shell of Ca2+ ions in proteins contains almost exclusively oxygen atoms supported by an outer shell of carbon atoms. The bond-strength contribution of each ligating oxygen in the inner shell can be evaluated by using an empirical expression successfully applied in the analysis of crystals of metal oxides. The sum of such contributions closely approximates the valence of the bound cation. When a protein is embedded in a very fine grid of points and an algorithm is used to calculate the valence of each point representing a potential Ca(2+)-binding site, a typical distribution of valence values peaked around 0.4 is obtained. In 32 documented Ca(2+)-binding proteins, containing a total of 62 Ca(2+)-binding sites, a very small fraction of points in the distribution has a valence close to that of Ca2+. Only 0.06% of the points have a valence > or = 1.4. These points share the remarkable tendency to cluster around documented Ca2+ ions. A high enough value of the valence is both necessary (58 out of 62 Ca(2+)-binding sites have a valence > or = 1.4) and sufficient (87% of the grid points with a valence > or = 1.4 are within 1.0 A from a documented Ca2+ ion) to predict the location of bound Ca2+ ions. The algorithm can also be used for the analysis of other cations and predicts the location of Mg(2+)- and Na(+)-binding sites in a number of proteins. The valence is, therefore, a tool of pinpoint accuracy for locating cation-binding sites, which can also be exploited in engineering high-affinity binding sites and characterizing the linkage between structural components and functional energetics for molecular recognition of metal ions by proteins. Images Fig. 4 PMID:8290605

  20. Involvement of the Ca2+/calmodulin-dependent protein kinase II pathway in the Ca2+-mediated regulation of the capacitative Ca2+ entry in Xenopus oocytes.

    PubMed Central

    Matifat, F; Fournier, F; Lorca, T; Capony, J P; Brûlé, G; Collin, T

    1997-01-01

    Activation of the phosphoinositide transduction pathway induces capacitative Ca2+ entry in Xenopus oocytes. This can also be evoked by intracellular injection of Ins(1,4.5)P3, external application of thapsigargin and/or incubation in a Ca2+-free medium. Readmission of Ca2+ to voltage-clamped, thapsigargin-treated Xenopus oocytes triggers Ca2+-dependent Cl- current variations that reflect capacitative Ca2+ entry. Inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) by specific peptides markedly increased the amplitude of the transients, suggesting an involvement of the CaMKII pathway in the regulation of capacitative Ca2+ entry. Biochemical studies provide evidence for the activation of CaMKII in response to the development of capacitative Ca2+ entry. In effect, a CaMKII assay in vivo allows us to postulate that readmission of Ca2+ to thapsigargin-treated oocytes can induce a burst of CaMKII activity. Finally, analysis of the Cl- transient kinetics at high resolution of time suggests that CaMKII inhibition blocks the onset of the inactivation process without affecting the activation rate. We therefore postulate that CaMKII might participate in a negative feedback regulation of store-depletion-evoked Ca2+ entry in Xenopus oocytes. PMID:9078272

  1. Yeast as a tool for plant Ca(2+) transporter research

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To maintain optimal cytosolic Ca(2+) concentrations, cells employ three distinct strategies: 1) tightly regulated influx of Ca(2+); 2) efficient efflux of Ca(2+) from the cell; and 3) sequestration of Ca(2+) in organelles. Ca(2+)efflux and influx are mediated by diverse transporter systems, such as ...

  2. Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling.

    PubMed

    Delvendahl, Igor; Jablonski, Lukasz; Baade, Carolin; Matveev, Victor; Neher, Erwin; Hallermann, Stefan

    2015-06-01

    Fast synchronous neurotransmitter release at the presynaptic active zone is triggered by local Ca(2+) signals, which are confined in their spatiotemporal extent by endogenous Ca(2+) buffers. However, it remains elusive how rapid and reliable Ca(2+) signaling can be sustained during repetitive release. Here, we established quantitative two-photon Ca(2+) imaging in cerebellar mossy fiber boutons, which fire at exceptionally high rates. We show that endogenous fixed buffers have a surprisingly low Ca(2+)-binding ratio (∼ 15) and low affinity, whereas mobile buffers have high affinity. Experimentally constrained modeling revealed that the low endogenous buffering promotes fast clearance of Ca(2+) from the active zone during repetitive firing. Measuring Ca(2+) signals at different distances from active zones with ultra-high-resolution confirmed our model predictions. Our results lead to the concept that reduced Ca(2+) buffering enables fast active zone Ca(2+) signaling, suggesting that the strength of endogenous Ca(2+) buffering limits the rate of synchronous synaptic transmission. PMID:26015575

  3. Isoflurane inhibits synaptic vesicle exocytosis through reduced Ca2+ influx, not Ca2+-exocytosis coupling

    PubMed Central

    Baumgart, Joel P.; Zhou, Zhen-Yu; Hara, Masato; Cook, Daniel C.; Hoppa, Michael B.; Ryan, Timothy A.; Hemmings, Hugh C.

    2015-01-01

    Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca2+ influx without significantly altering the Ca2+ sensitivity of SV exocytosis. A clinically relevant concentration of isoflurane (0.7 mM) inhibited changes in [Ca2+]i driven by single action potentials (APs) by 25 ± 3%, which in turn led to 62 ± 3% inhibition of single AP-triggered exocytosis at 4 mM extracellular Ca2+ ([Ca2+]e). Lowering external Ca2+ to match the isoflurane-induced reduction in Ca2+ entry led to an equivalent reduction in exocytosis. These data thus indicate that anesthetic inhibition of neurotransmitter release from small SVs occurs primarily through reduced axon terminal Ca2+ entry without significant direct effects on Ca2+-exocytosis coupling or on the SV fusion machinery. Isoflurane inhibition of exocytosis and Ca2+ influx was greater in glutamatergic compared with GABAergic nerve terminals, consistent with selective inhibition of excitatory synaptic transmission. Such alteration in the balance of excitatory to inhibitory transmission could mediate reduced neuronal interactions and network-selective effects observed in the anesthetized central nervous system. PMID:26351670

  4. Isoflurane inhibits synaptic vesicle exocytosis through reduced Ca2+ influx, not Ca2+-exocytosis coupling.

    PubMed

    Baumgart, Joel P; Zhou, Zhen-Yu; Hara, Masato; Cook, Daniel C; Hoppa, Michael B; Ryan, Timothy A; Hemmings, Hugh C

    2015-09-22

    Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca(2+) influx without significantly altering the Ca(2+) sensitivity of SV exocytosis. A clinically relevant concentration of isoflurane (0.7 mM) inhibited changes in [Ca(2+)]i driven by single action potentials (APs) by 25 ± 3%, which in turn led to 62 ± 3% inhibition of single AP-triggered exocytosis at 4 mM extracellular Ca(2+) ([Ca(2+)]e). Lowering external Ca(2+) to match the isoflurane-induced reduction in Ca(2+) entry led to an equivalent reduction in exocytosis. These data thus indicate that anesthetic inhibition of neurotransmitter release from small SVs occurs primarily through reduced axon terminal Ca(2+) entry without significant direct effects on Ca(2+)-exocytosis coupling or on the SV fusion machinery. Isoflurane inhibition of exocytosis and Ca(2+) influx was greater in glutamatergic compared with GABAergic nerve terminals, consistent with selective inhibition of excitatory synaptic transmission. Such alteration in the balance of excitatory to inhibitory transmission could mediate reduced neuronal interactions and network-selective effects observed in the anesthetized central nervous system. PMID:26351670

  5. Tetraspanin-13 modulates voltage-gated CaV2.2 Ca2+ channels

    PubMed Central

    Mallmann, Robert T.; Wilmes, Thomas; Lichvarova, Lucia; Bührer, Anja; Lohmüller, Barbara; Castonguay, Jan; Lacinova, Lubica; Klugbauer, Norbert

    2013-01-01

    Integration of voltage-gated Ca2+ channels in a network of protein-interactions is a crucial requirement for proper regulation of channel activity. In this study, we took advantage of the specific properties of the yeast split-ubiquitin system to search for and characterize so far unknown interaction partners of CaV2 Ca2+ channels. We identified tetraspanin-13 (TSPAN-13) as an interaction partner of the α1 subunit of N-type CaV2.2, but not of P/Q-type CaV2.1 or L- and T-type Ca2+ channels. Interaction could be located between domain IV of CaV2.2 and transmembrane segments S1 and S2 of TSPAN-13. Electrophysiological analysis revealed that TSPAN-13 specifically modulates the efficiency of coupling between voltage sensor activation and pore opening of the channel and accelerates the voltage-dependent activation and inactivation of the Ba2+ current through CaV2.2. These data indicate that TSPAN-13 might regulate CaV2.2 Ca2+ channel activity in defined synaptic membrane compartments and thereby influences transmitter release. PMID:23648579

  6. Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila melanogaster.

    PubMed

    Santalla, Manuela; Valverde, Carlos A; Harnichar, Ezequiel; Lacunza, Ezequiel; Aguilar-Fuentes, Javier; Mattiazzi, Alicia; Ferrero, Paola

    2014-01-01

    Aging is associated to disrupted contractility and rhythmicity, among other cardiovascular alterations. Drosophila melanogaster shows a pattern of aging similar to human beings and recapitulates the arrhythmogenic conditions found in the human heart. Moreover, the kinase CaMKII has been characterized as an important regulator of heart function and an arrhythmogenic molecule that participate in Ca2+ handling. Using a genetically engineered expressed Ca2+ indicator, we report changes in cardiac Ca2+ handling at two different ages. Aging prolonged relaxation, reduced spontaneous heart rate (HR) and increased the occurrence of arrhythmias, ectopic beats and asystoles. Alignment between Drosophila melanogaster and human CaMKII showed a high degree of conservation and indicates that relevant phosphorylation sites in humans are also present in the fruit fly. Inhibition of CaMKII by KN-93 (CaMKII-specific inhibitor), reduced HR without significant changes in other parameters. By contrast, overexpression of CaMKII increased HR and reduced arrhythmias. Moreover, it increased fluorescence amplitude, maximal rate of rise of fluorescence and reduced time to peak fluorescence. These results suggest that CaMKII in Drosophila melanogaster acts directly on heart function and that increasing CaMKII expression levels could be beneficial to improve contractility. PMID:25003749

  7. Aging and CaMKII Alter Intracellular Ca2+ Transients and Heart Rhythm in Drosophila melanogaster

    PubMed Central

    Santalla, Manuela; Valverde, Carlos A.; Harnichar, Ezequiel; Lacunza, Ezequiel; Aguilar-Fuentes, Javier; Mattiazzi, Alicia; Ferrero, Paola

    2014-01-01

    Aging is associated to disrupted contractility and rhythmicity, among other cardiovascular alterations. Drosophila melanogaster shows a pattern of aging similar to human beings and recapitulates the arrhythmogenic conditions found in the human heart. Moreover, the kinase CaMKII has been characterized as an important regulator of heart function and an arrhythmogenic molecule that participate in Ca2+ handling. Using a genetically engineered expressed Ca2+ indicator, we report changes in cardiac Ca2+ handling at two different ages. Aging prolonged relaxation, reduced spontaneous heart rate (HR) and increased the occurrence of arrhythmias, ectopic beats and asystoles. Alignment between Drosophila melanogaster and human CaMKII showed a high degree of conservation and indicates that relevant phosphorylation sites in humans are also present in the fruit fly. Inhibition of CaMKII by KN-93 (CaMKII-specific inhibitor), reduced HR without significant changes in other parameters. By contrast, overexpression of CaMKII increased HR and reduced arrhythmias. Moreover, it increased fluorescence amplitude, maximal rate of rise of fluorescence and reduced time to peak fluorescence. These results suggest that CaMKII in Drosophila melanogaster acts directly on heart function and that increasing CaMKII expression levels could be beneficial to improve contractility. PMID:25003749

  8. Regulated release of Ca2+ from respiring mitochondria by Ca2+/2H+ antiport.

    PubMed

    Fiskum, G; Lehninger, A L

    1979-07-25

    Simultaneous measurements of oxygen consumption and transmembrane transport of Ca2+, H+, and phosphate show that the efflux of Ca2+ from respiring tightly coupled rat liver mitochondria takes place by an electroneutral Ca2+/2H+ antiport process that is ruthenium red-insensitive and that is regulated by the oxidation-reduction state of the mitochondrial pyridine nucleotides. When mitochondrial pyridine nucleotides are kept in a reduced steady state, the efflux of Ca2+ is inhibited; when they are in an oxidized state, Ca2+ efflux is activated. These processes were demonstrated by allowing phosphate-depleted mitochondria respiring on succinate in the presence of rotenone to take up Ca2+ from the medium. Upon subsequent addition of ruthenium red to block Ca2+ transport via the electrophoretic influx pathway, and acetoacetate, to bring mitochondrial pyridine nucleotides into the oxidized state, Ca2+ efflux and H+ influx ensued. The observed H+ influx/Ca2+ efflux ratio was close to the value 2.0 predicted for the operation of an electrically neutral Ca2+/2H+ antiport process. PMID:36390

  9. Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling

    PubMed Central

    Delvendahl, Igor; Jablonski, Lukasz; Baade, Carolin; Matveev, Victor; Neher, Erwin; Hallermann, Stefan

    2015-01-01

    Fast synchronous neurotransmitter release at the presynaptic active zone is triggered by local Ca2+ signals, which are confined in their spatiotemporal extent by endogenous Ca2+ buffers. However, it remains elusive how rapid and reliable Ca2+ signaling can be sustained during repetitive release. Here, we established quantitative two-photon Ca2+ imaging in cerebellar mossy fiber boutons, which fire at exceptionally high rates. We show that endogenous fixed buffers have a surprisingly low Ca2+-binding ratio (∼15) and low affinity, whereas mobile buffers have high affinity. Experimentally constrained modeling revealed that the low endogenous buffering promotes fast clearance of Ca2+ from the active zone during repetitive firing. Measuring Ca2+ signals at different distances from active zones with ultra-high-resolution confirmed our model predictions. Our results lead to the concept that reduced Ca2+ buffering enables fast active zone Ca2+ signaling, suggesting that the strength of endogenous Ca2+ buffering limits the rate of synchronous synaptic transmission. PMID:26015575

  10. Genetical and comparative genomics of Brassica under altered Ca supply identifies Arabidopsis Ca-transporter orthologs.

    PubMed

    Graham, Neil S; Hammond, John P; Lysenko, Artem; Mayes, Sean; O Lochlainn, Seosamh; Blasco, Bego; Bowen, Helen C; Rawlings, Chris J; Rios, Juan J; Welham, Susan; Carion, Pierre W C; Dupuy, Lionel X; King, Graham J; White, Philip J; Broadley, Martin R

    2014-07-01

    Although Ca transport in plants is highly complex, the overexpression of vacuolar Ca(2+) transporters in crops is a promising new technology to improve dietary Ca supplies through biofortification. Here, we sought to identify novel targets for increasing plant Ca accumulation using genetical and comparative genomics. Expression quantitative trait locus (eQTL) mapping to 1895 cis- and 8015 trans-loci were identified in shoots of an inbred mapping population of Brassica rapa (IMB211 × R500); 23 cis- and 948 trans-eQTLs responded specifically to altered Ca supply. eQTLs were screened for functional significance using a large database of shoot Ca concentration phenotypes of Arabidopsis thaliana. From 31 Arabidopsis gene identifiers tagged to robust shoot Ca concentration phenotypes, 21 mapped to 27 B. rapa eQTLs, including orthologs of the Ca(2+) transporters At-CAX1 and At-ACA8. Two of three independent missense mutants of BraA.cax1a, isolated previously by targeting induced local lesions in genomes, have allele-specific shoot Ca concentration phenotypes compared with their segregating wild types. BraA.CAX1a is a promising target for altering the Ca composition of Brassica, consistent with prior knowledge from Arabidopsis. We conclude that multiple-environment eQTL analysis of complex crop genomes combined with comparative genomics is a powerful technique for novel gene identification/prioritization. PMID:25082855

  11. Calcium transport in bovine rumen epithelium as affected by luminal Ca concentrations and Ca sources

    PubMed Central

    Schröder, Bernd; Wilkens, Mirja R; Ricken, Gundula E; Leonhard-Marek, Sabine; Fraser, David R; Breves, Gerhard

    2015-01-01

    The quantitative role of different segments of the gastrointestinal tract for Ca absorption, the respective mechanisms, and their regulation are not fully identified for ruminants, that is, cattle. In different in vitro experiments the forestomach wall has been demonstrated to be a major site for active Ca absorption in sheep and goats. In order to further clarify the role of the bovine rumen for Ca transport with special attention to luminal Ca concentrations, its ionic form, and pH, electrophysiological and unidirectional flux rate measurements were performed with isolated bovine rumen epithelial tissues. For Ca flux studies (Jms, Jsm) in vitro Ussing chamber technique was applied. Standard RT-PCR method was used to characterize TRPV6 and PMCA1 as potential contributors to transepithelial active Ca transport. At Ca concentrations of 1.2 mmol L−1 on both sides of the tissues, Jms were higher than Jsm resulting under some conditions in significant Ca net flux rates (Jnet), indicating the presence of active Ca transport. In the absence of an electrical gradient, Jnet could significantly be stimulated in the presence of luminal short-chain fatty acids (SCFAs). Increasing the luminal Ca concentrations up to 11.2 mmol L−1 resulted in significant increases in Jms without influencing Jsm. Providing Ca in its form as respective chloride, formate, or propionate salts there was no significant effect on Jms. No transcripts specific for Ca channel TRPV6 could be demonstrated. Our results indicate different mechanisms for Ca absorption in bovine rumen as compared with those usually described for the small intestines. PMID:26564067

  12. Calcium transport in bovine rumen epithelium as affected by luminal Ca concentrations and Ca sources.

    PubMed

    Schröder, Bernd; Wilkens, Mirja R; Ricken, Gundula E; Leonhard-Marek, Sabine; Fraser, David R; Breves, Gerhard

    2015-11-01

    The quantitative role of different segments of the gastrointestinal tract for Ca absorption, the respective mechanisms, and their regulation are not fully identified for ruminants, that is, cattle. In different in vitro experiments the forestomach wall has been demonstrated to be a major site for active Ca absorption in sheep and goats. In order to further clarify the role of the bovine rumen for Ca transport with special attention to luminal Ca concentrations, its ionic form, and pH, electrophysiological and unidirectional flux rate measurements were performed with isolated bovine rumen epithelial tissues. For Ca flux studies (Jms, Jsm) in vitro Ussing chamber technique was applied. Standard RT-PCR method was used to characterize TRPV6 and PMCA1 as potential contributors to transepithelial active Ca transport. At Ca concentrations of 1.2 mmol L(-1) on both sides of the tissues, Jms were higher than Jsm resulting under some conditions in significant Ca net flux rates (Jnet), indicating the presence of active Ca transport. In the absence of an electrical gradient, Jnet could significantly be stimulated in the presence of luminal short-chain fatty acids (SCFAs). Increasing the luminal Ca concentrations up to 11.2 mmol L(-1) resulted in significant increases in Jms without influencing Jsm. Providing Ca in its form as respective chloride, formate, or propionate salts there was no significant effect on Jms. No transcripts specific for Ca channel TRPV6 could be demonstrated. Our results indicate different mechanisms for Ca absorption in bovine rumen as compared with those usually described for the small intestines. PMID:26564067

  13. Selective Na+/Ca2+ exchanger inhibition prevents Ca2+ overload-induced triggered arrhythmias

    PubMed Central

    Nagy, Norbert; Kormos, Anita; Kohajda, Zsófia; Szebeni, Áron; Szepesi, Judit; Pollesello, Piero; Levijoki, Jouko; Acsai, Károly; Virág, László; Nánási, Péter P; Papp, Julius Gy; Varró, András; Tóth, András

    2014-01-01

    Background and Purpose Augmented Na+/Ca2+ exchanger (NCX) activity may play a crucial role in cardiac arrhythmogenesis; however, data regarding the anti-arrhythmic efficacy of NCX inhibition are debatable. Feasible explanations could be the unsatisfactory selectivity of NCX inhibitors and/or the dependence of the experimental model on the degree of Ca2+i overload. Hence, we used NCX inhibitors SEA0400 and the more selective ORM10103 to evaluate the efficacy of NCX inhibition against arrhythmogenic Ca2+i rise in conditions when [Ca2+]i was augmented via activation of the late sodium current (INaL) or inhibition of the Na+/K+ pump. Experimental Approach Action potentials (APs) were recorded from canine papillary muscles and Purkinje fibres by microelectrodes. NCX current (INCX) was determined in ventricular cardiomyocytes utilizing the whole-cell patch clamp technique. Ca2+i transients (CaTs) were monitored with a Ca2+-sensitive fluorescent dye, Fluo-4. Key Results Enhanced INaL increased the Ca2+ load and AP duration (APD). SEA0400 and ORM10103 suppressed INCX and prevented/reversed the anemone toxin II (ATX-II)-induced [Ca2+]i rise without influencing APD, CaT or cell shortening, or affecting the ATX-II-induced increased APD. ORM10103 significantly decreased the number of strophanthidin-induced spontaneous diastolic Ca2+ release events; however, SEA0400 failed to restrict the veratridine-induced augmentation in Purkinje-ventricle APD dispersion. Conclusions and Implications Selective NCX inhibition – presumably by blocking revINCX (reverse mode NCX current) – is effective against arrhythmogenesis caused by [Na+]i-induced [Ca2+]i elevation, without influencing the AP waveform. Therefore, selective INCX inhibition, by significantly reducing the arrhythmogenic trigger activity caused by the perturbed Ca2+i handling, should be considered as a promising anti-arrhythmic therapeutic strategy. PMID:25073832

  14. The caBIG terminology review process.

    PubMed

    Cimino, James J; Hayamizu, Terry F; Bodenreider, Olivier; Davis, Brian; Stafford, Grace A; Ringwald, Martin

    2009-06-01

    The National Cancer Institute (NCI) is developing an integrated biomedical informatics infrastructure, the cancer Biomedical Informatics Grid (caBIG), to support collaboration within the cancer research community. A key part of the caBIG architecture is the establishment of terminology standards for representing data. In order to evaluate the suitability of existing controlled terminologies, the caBIG Vocabulary and Data Elements Workspace (VCDE WS) working group has developed a set of criteria that serve to assess a terminology's structure, content, documentation, and editorial process. This paper describes the evolution of these criteria and the results of their use in evaluating four standard terminologies: the Gene Ontology (GO), the NCI Thesaurus (NCIt), the Common Terminology for Adverse Events (known as CTCAE), and the laboratory portion of the Logical Objects, Identifiers, Names and Codes (LOINC). The resulting caBIG criteria are presented as a matrix that may be applicable to any terminology standardization effort. PMID:19154797

  15. Role of Ca++ in Shoot Gravitropism. [avena

    NASA Technical Reports Server (NTRS)

    Rayle, D. L.

    1985-01-01

    A cornerstone in the argument that Ca(2+) levels may regulate growth is the finding the EGTA promotes straight growth. The usual explanation for these results is that Ca(2+) chelation from cell walls results in wall loosening and thus accelerated straight growth. The ability of frozen-thawed Avena coleoptile tissue (subjected to 15g tension) to extend in response to EGTA and Quin II was examined. The EGTA when applied in weakly buffered (i.e., 0.1mM) neutral solutions initiates rapid extension. When the buffer strength is increased, similar concentrations of EGTA produce no growth response. This implies when EGTA liberated protons are released upon Ca(2+) chelation they can either initiate acid growth (low buffer conditions) or if consumed (high buffer conditions) have no effect. Thus Ca(2+) chelation in itself apparently does not result in straight growth.

  16. The caBIG Terminology Review Process

    PubMed Central

    Cimino, James J.; Hayamizu, Terry F.; Bodenreider, Olivier; Davis, Brian; Stafford, Grace A.; Ringwald, Martin

    2009-01-01

    The National Cancer Institute (NCI) is developing an integrated biomedical informatics infrastructure, the cancer Biomedical Informatics Grid (caBIG®), to support collaboration within the cancer research community. A key part of the caBIG architecture is the establishment of terminology standards for representing data. In order to evaluate the suitability of existing controlled terminologies, the caBIG Vocabulary and Data Elements Workspace (VCDE WS) working group has developed a set of criteria that serve to assess a terminology's structure, content, documentation, and editorial process. This paper describes the evolution of these criteria and the results of their use in evaluating four standard terminologies: the Gene Ontology (GO), the NCI Thesaurus (NCIt), the Common Terminology for Adverse Events (known as CTCAE), and the laboratory portion of the Logical Objects, Identifiers, Names and Codes (LOINC). The resulting caBIG criteria are presented as a matrix that may be applicable to any terminology standardization effort. PMID:19154797

  17. Motion of the Ca2+-pump captured.

    PubMed

    Yokokawa, Masatoshi; Takeyasu, Kunio

    2011-09-01

    Studies of ion pumps, such as ATP synthetase and Ca(2+)-ATPase, have a long history. The crystal structures of several kinds of ion pump have been resolved, and provide static pictures of mechanisms of ion transport. In this study, using fast-scanning atomic force microscopy, we have visualized conformational changes in the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) in real time at the single-molecule level. The analyses of individual SERCA molecules in the presence of both ATP and free Ca(2+) revealed up-down structural changes corresponding to the Albers-Post scheme. This fluctuation was strongly affected by the ATP and Ca(2+) concentrations, and was prevented by an inhibitor, thapsigargin. Interestingly, at a physiological ATP concentrations, the up-down motion disappeared completely. These results indicate that SERCA does not transit through the shortest structure, and has a catalytic pathway different from the ordinary Albers-Post scheme under physiological conditions. PMID:21707923

  18. Ca channel gating during cardiac action potentials.

    PubMed

    Mazzanti, M; DeFelice, L J

    1990-10-01

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

  19. PIK3CA in Colorectal Cancer

    PubMed Central

    Cathomas, Gieri

    2014-01-01

    PIK3CA, the catalytic subunit of PI3K, is mutated in many different tumors, including colorectal cancer (CRC). Mutations of PIK3CA have been reported in 10–20% of CRC, about 80% of mutations found in two hot spots in exon 9 and exon 20. In RAS wild-type CRC, PIK3CA mutations have been associated with a worse clinical outcome and with a negative prediction of a response to targeted therapy by anti-EGFR monoclonal antibodies. However, these findings have not been confirmed in all studies and subsequent more detailed analysis has revealed that these effects may be restricted to mutations in Exon 20. Finally, mutations in PIK3CA may be the long sought biomarker for successful adjuvant therapy with aspirin in patients with CRC. Therefore, PIK3CA mutations appear to be a promising predictive biomarker; however, further data are needed to conclusively define the impact of somatic mutations in the PIK3CA gene for the management of patients with CRC. PMID:24624362

  20. Ca(5)Zr(3)F(22).

    PubMed

    Oudahmane, Abdelghani; El-Ghozzi, Malika; Avignant, Daniel

    2012-04-01

    Single crystals of Ca(5)Zr(3)F(22), penta-calcium trizirconium docosafluoride, were obtained unexpectedly by solid-state reaction between CaF(2) and ZrF(4) in the presence of AgF. The structure of the title compound is isotypic with that of Sr(5)Zr(3)F(22) and can be described as being composed of layers with composition [Zr(3)F(20)](8-) made up from two different [ZrF(8)](4-) square anti-prisms (one with site symmetry 2) by corner-sharing. The layers extending parallel to the (001) plane are further linked by Ca(2+) cations, forming a three-dimensional network. Amongst the four crystallographically different Ca(2+) ions, three are located on twofold rotation axes. The Ca(2+) ions exhibit coordination numbers ranging from 8 to 12, depending on the cut off, with very distorted fluorine environments. Two of the Ca(2+) ions occupy inter-stices between the layers whereas the other two are located in void spaces of the [Zr(3)F(20)](8-) layer and alternate with the two Zr atoms along [010]. The crystal under investigation was an inversion twin. PMID:22589749

  1. Effect of morphine on synaptosomal Ca++ uptake.

    PubMed

    Guerrero-Munoz, F; Cerreta, K V; Guerrero, M L; Way, E L

    1979-04-01

    The effect of morphine on the uptake of 45Ca++ was studied in synaptosomes from mouse brain using two procedures, centrifugation and filtration. The addition of morphine (1.7 x 10(-7) or 3.4 x 10(-7) M) reduced 45CA++ uptake by either technique, although the basal 45Ca++ uptake by the filtration method was approximately 7-fold higher than that by the centrifugation procedure. Similar effects were obtained after acute morphine treatment with 10 mg/kg s.c. Previous naloxone in vitro treatment (1.9 x 10(-8) M) or in vivo administration (2 mg/kg s.c.) reversed the morphine inhibition of the 45Ca++ uptake. On the other hand, after the animal was rendered tolerant and dependent by morphine pellet implantation, an enhancement of the synaptosomal 45Ca++ uptake was observed. It is concluded that changes in Ca++ fluxes in synaptosomes observed after acute and chronic morphine treatment may be involved with morphine pharmacological action related with analgesia, tolerance and physical dependence. PMID:571016

  2. Efficient 41Ca measurements for biomedical applications

    NASA Astrophysics Data System (ADS)

    Vockenhuber, C.; Schulze-König, T.; Synal, H.-A.; Aeberli, I.; Zimmermann, M. B.

    2015-10-01

    We present the performance of 41Ca measurements using low-energy Accelerator Mass Spectrometry (AMS) at the 500 kV facility TANDY at ETH Zurich. We optimized the measurement procedure for biomedical applications where reliability and high sample throughput is required. The main challenge for AMS measurements of 41Ca is the interfering stable isobar 41K. We use a simplified sample preparation procedure to produce calcium fluoride (CaF2) and extract calcium tri-fluoride ions (CaF3-) ions to suppress the stable isobar 41K. Although 41K is not completely suppressed we reach 41Ca/40Ca background level in the 10-12 range which is adequate for biomedical studies. With helium as a stripper gas we can use charge state 2+ at high transmission (∼50%). The new measurement procedure with the approximately 10 × improved efficiency and the higher accuracy due to 41K correction allowed us to measure more than 600 samples for a large biomedical study within only a few weeks of measurement time.

  3. Regulation of RYR1 activity by Ca(2+) and calmodulin

    NASA Technical Reports Server (NTRS)

    Rodney, G. G.; Williams, B. Y.; Strasburg, G. M.; Beckingham, K.; Hamilton, S. L.

    2000-01-01

    The skeletal muscle calcium release channel (RYR1) is a Ca(2+)-binding protein that is regulated by another Ca(2+)-binding protein, calmodulin. The functional consequences of calmodulin's interaction with RYR1 are dependent on Ca(2+) concentration. At nanomolar Ca(2+) concentrations, calmodulin is an activator, but at micromolar Ca(2+) concentrations, calmodulin is an inhibitor of RYR1. This raises the question of whether the Ca(2+)-dependent effects of calmodulin on RYR1 function are due to Ca(2+) binding to calmodulin, RYR1, or both. To distinguish the effects of Ca(2+) binding to calmodulin from those of Ca(2+) binding to RYR1, a mutant calmodulin that cannot bind Ca(2+) was used to evaluate the effects of Ca(2+)-free calmodulin on Ca(2+)-bound RYR1. We demonstrate that Ca(2+)-free calmodulin enhances the affinity of RYR1 for Ca(2+) while Ca(2+) binding to calmodulin converts calmodulin from an activator to an inhibitor. Furthermore, Ca(2+) binding to RYR1 enhances its affinity for both Ca(2+)-free and Ca(2+)-bound calmodulin.

  4. Pumping Ca2+ up H+ gradients: a Ca2(+)-H+ exchanger without a membrane.

    PubMed

    Swietach, Pawel; Leem, Chae-Hun; Spitzer, Kenneth W; Vaughan-Jones, Richard D

    2014-08-01

    Cellular processes are exquisitely sensitive to H+ and Ca2+ ions because of powerful ionic interactions with proteins. By regulating the spatial and temporal distribution of intracellular [Ca2+] and [H+], cells such as cardiac myocytes can exercise control over their biological function. A well-established paradigm in cellular physiology is that ion concentrations are regulated by specialized, membrane-embedded transporter proteins. Many of these couple the movement of two or more ionic species per transport cycle, thereby linking ion concentrations among neighbouring compartments. Here, we compare and contrast canonical membrane transport with a novel type of Ca(2+)-H+ coupling within cytoplasm, which produces uphill Ca2+ transport energized by spatial H+ ion gradients, and can result in the cytoplasmic compartmentalization of Ca2+ without requiring a partitioning membrane. The mechanism, demonstrated in mammalian myocytes, relies on diffusible cytoplasmic buffers, such as carnosine, homocarnosine and ATP, to which Ca2+ and H+ ions bind in an apparently competitive manner. These buffer molecules can actively recruit Ca2+ to acidic microdomains, in exchange for the movement of H+ ions. The resulting Ca2+ microdomains thus have the potential to regulate function locally. Spatial cytoplasmic Ca(2+)-H+ exchange (cCHX) acts like a 'pump' without a membrane and may be operational in many cell types. PMID:24514908

  5. Ca2+ homeostasis and regulation of ER Ca2+ in mammalian oocytes/eggs

    PubMed Central

    Wakai, Takuya; Fissore, Rafael A.

    2014-01-01

    The activation of the developmental program in mammalian eggs relies on the initiation at the time of fertilization of repeated rises in the intracellular concentration of free calcium ([Ca2+]i), also known as [Ca2+]i oscillations. The ability to mount the full complement of oscillations is only achieved at the end of oocyte maturation, at the metaphase stage of meiosis II (MII). Over the last decades research has focused on addressing the mechanisms by which the sperm initiates the oscillations and identification of the channels that mediate intracellular Ca2+ release. This review will describe the up-to-date knowledge of other aspects of Ca2+ homeostasis in mouse such as the mechanisms that transport Ca2+ out of the cytosol into the endoplasmic reticulum (ER), the Ca2+ store of the oocyte/egg, into other organelles and also those extrude Ca2+. Evidence pointing to channels in the plasma membrane that mediate Ca2+ entry from the extracellular milieu, which is required for the persistence of the oscillations, is also discussed, along with the modifications that these mechanisms undergo during maturation. Lastly, we highlight areas where additional research is needed to obtain a better understating of the molecules and mechanisms that regulate homeostasis in this unique Ca2+ signaling system. PMID:23260016

  6. Negative feedback from CaSR signaling to aquaporin-2 sensitizes vasopressin to extracellular Ca2.

    PubMed

    Ranieri, Marianna; Tamma, Grazia; Di Mise, Annarita; Russo, Annamaria; Centrone, Mariangela; Svelto, Maria; Calamita, Giuseppe; Valenti, Giovanna

    2015-07-01

    We previously described that high luminal Ca(2+) in the renal collecting duct attenuates short-term vasopressin-induced aquaporin-2 (AQP2) trafficking through activation of the Ca(2+)-sensing receptor (CaSR). Here, we evaluated AQP2 phosphorylation and permeability, in both renal HEK-293 cells and in the dissected inner medullary collecting duct, in response to specific activation of CaSR with NPS-R568. In CaSR-transfected cells, CaSR activation drastically reduced the basal levels of AQP2 phosphorylation at S256 (AQP2-pS256), thus having an opposite effect to vasopressin action. When forskolin stimulation was performed in the presence of NPS-R568, the increase in AQP2-pS256 and in the osmotic water permeability were prevented. In the freshly isolated inner mouse medullar collecting duct, stimulation with forskolin in the presence of NPS-R568 prevented the increase in AQP2-pS256 and osmotic water permeability. Our data demonstrate that the activation of CaSR in the collecting duct prevents the cAMP-dependent increase in AQP2-pS256 and water permeability, counteracting the short-term vasopressin response. By extension, our results suggest the attractive concept that CaSR expressed in distinct nephron segments exerts a negative feedback on hormones acting through cAMP, conferring high sensitivity of hormone to extracellular Ca(2+). PMID:25977473

  7. Sr / Ca and Mg / Ca ratios in polygenetic carbonate allochems from a Michigan marl lake

    NASA Astrophysics Data System (ADS)

    Treese, Thomas N.; Owen, Robert M.; Wilkinson, Bruce H.

    1981-03-01

    Rapid accumulation of CaCO 3 is occurring in Littlefield Lake, a marl lake located in central Michigan. The sediment, which is 95% CaCO 3, primarily consists of eight different genetic groups of carbonate allochems. These include calcite muds, sands, algal oncoids and Chara encrustations, as well as the dominant aragonitic gastropods Valvota tricarinota. Gyraulus deflectus and Amnicola integra. and the dominant aragonitic pelecypod Sphaerium partumeium. Samples of each of these groups were analyzed for Ca, Sr and Mg. Molar Mg/Ca ratios are primarily controlled by allochem mineralogy, with calcitic forms having Mg/Ca ratios 5-10 times larger than aragonitic (shelled) forms. The Sr/Ca ratios are primarily controlled by biochemical fractionation, and are significantly lower than Sr/Ca ratios of inorganically precipitated aragonite from other settings. Partition coefficients were determined for both Sr and Mg for each carbonate allochem group and, based on comparisons with results reported by other workers, the partition coefficients determined here are generally considered 'typical' or representative values for biogeneous freshwater carbonates. An analysis of variance of the data indicates that most genera and species of carbonate-secreting organisms in marl lakes have highly characteristic Sr/Ca and Mg/Ca ratios. These ratios can potentially serve as geochemical tracers in future investigations of lacustrine carbonate diagenesis. Both Sr and Mg are influenced by grain size and/or surface area, probably due to the presence of these elements in non-lattice-held (exchangeable) positions.

  8. L-type and Ca2+ release channel-dependent hierarchical Ca2+ signalling in rat portal vein myocytes.

    PubMed

    Arnaudeau, S; Boittin, F X; Macrez, N; Lavie, J L; Mironneau, C; Mironneau, J

    1997-11-01

    Ca2+ signalling events and whole-cell Ca2+ currents were analyzed in single myocytes from rat portal vein by using a laser scanning confocal microscope combined with the patch-clamp technique. In myocytes in which the intracellular Ca2+ store was depleted or Ca2+ release channels were blocked by 10 microM ryanodine, inward Ca2+ currents induced slow and sustained elevations of [Ca2+]i. These Ca2+ responses were suppressed by 1 microM oxodipine and by depolarizations to +120 mV, a potential close to the reversal potential for Ca2+ ions, suggesting that they reflected Ca2+ influx through L-type Ca2+ channels. With functioning intracellular Ca2+ stores, flash photolysis of caged Ca2+ gave rise to a small increase in [Ca2+]i with superimposed Ca2+ sparks, reflecting the opening of clustered Ca2+ release channels. Brief Ca2+ currents in the voltage range from -30 to +10 mV triggered Ca2+ sparks or macrosparks that did not propagate in the entire line-scan image. Increasing the duration of Ca2+ current for 100 ms or more allowed the trigger of propagating Ca2+ waves which originated from the same initiation sites as the caffeine-activated response. Both Ca2+ sparks and initiation sites of Ca2+ waves activated by Ca2+ currents were observed in the vicinity of areas that excluded the Ca2+ probes, reflecting infoldings of the plasma membrane close to the sarcoplasmic reticulum, as revealed by fluorescent markers. The hierarchy of Ca2+ signalling events, from submicroscopic fundamental events to elementary events (sparks) and propagated waves, provides an integrated mechanism to regulate vascular tone. PMID:9448946

  9. A caffeine- and ryanodine-sensitive Ca2+ store in bullfrog sympathetic neurones modulates effects of Ca2+ entry on [Ca2+]i.

    PubMed Central

    Friel, D D; Tsien, R W

    1992-01-01

    1. We studied how in changes in cytosolic free Ca2+ concentration ([Ca2+]i) produced by voltage-dependent Ca2+ entry are influenced by a caffeine-sensitive Ca2+ store in bullfrog sympathetic neurones. Ca2+ influx was elicited by K+ depolarization and the store was manipulated with either caffeine or ryanodine. 2. For a time after discharging the store with caffeine and switching to a caffeine-free medium: (a) [Ca2+]i was depressed by up to 40-50 nM below the resting level, (b) caffeine responsiveness was diminished, and (c) brief K+ applications elicited [Ca2+]i responses with slower onset and faster recovery than controls. These effects were more pronounced as the conditioning caffeine concentration was increased over the range 1-30 mM. 3. [Ca2+]i, caffeine and K+ responsiveness recovered in parallel with a half-time of approximately 2 min. Recovery required external Ca2+ and was speeded by increasing the availability of cytosolic Ca2+, suggesting that it reflected replenishment of the store at the expense of cytosolic Ca2+. 4. During recovery, Ca2+ entry stimulated by depolarization had the least effect on [Ca2+]i when the store was filling most rapidly. This suggests that the effect of Ca2+ entry on [Ca2+]i is modified, at least in part, because some of the Ca2+ which enters the cytosol during stimulation is taken up by the store as it refills. 5. Further experiments were carried out to investigate whether the store can also release Ca2+ in response to stimulated Ca2+ entry. In the continued presence of caffeine at a low concentration (1 mM), high K+ elicited a faster and larger [Ca2+]i response compared to controls; at higher concentrations of caffeine (10 and 30 mM) responses were depressed. 6. Ryanodine (1 microM) reduced the rate at which [Ca2+]i increased with Ca2+ entry, but not to the degree observed after discharging the store. At this concentration, ryanodine completely blocked responses to caffeine but had no detectable effect on Ca2+ channel current

  10. CaMKII regulation in information processing and storage

    PubMed Central

    Coultrap, Steven J.; Bayer, K. Ulrich

    2012-01-01

    The Ca2+/Calmodulin(CaM)-dependent protein kinase II (CaMKII) is activated by Ca2+/CaM, but becomes partially autonomous (Ca2+-independent) upon autophosphorylation at T286. This hallmark feature of CaMKII regulation provides a form of molecular memory and is indeed important in long-term potentiation (LTP) of excitatory synapse strength and memory formation. However, emerging evidence supports a direct role in information processing, while storage of synaptic information may instead be mediated by regulated interaction of CaMKII with the NMDA receptor (NMDAR) complex. These and other CaMKII regulation mechanisms are discussed here in the context of the kinase structure and their impact on post-synaptic functions. Recent findings also implicate CaMKII in long-term depression (LTD), as well as functional roles at inhibitory synapses, lending renewed emphasis on better understanding the spatio-temporal control of CaMKII regulation. PMID:22717267

  11. Ultrastructural and immunohistochemical localization of plasma membrane Ca2+-ATPase 4 in Ca2+-transporting epithelia.

    PubMed

    Alexander, R Todd; Beggs, Megan R; Zamani, Reza; Marcussen, Niels; Frische, Sebastian; Dimke, Henrik

    2015-10-01

    Plasma membrane Ca(2+)-ATPases (PMCAs) participate in epithelial Ca(2+) transport and intracellular Ca(2+) signaling. The Pmca4 isoform is enriched in distal nephron isolates and decreased in mice lacking the epithelial transient receptor potential vanilloid 5 Ca(2+) channel. We therefore hypothesized that Pmca4 plays a significant role in transcellular Ca(2+) flux and investigated the localization and regulation of Pmca4 in Ca(2+)-transporting epithelia. Using antibodies directed specifically against Pmca4, we found it expressed only in the smooth muscle layer of mouse and human intestines, whereas pan-specific Pmca antibodies detected Pmca1 in lateral membranes of enterocytes. In the kidney, Pmca4 showed broad localization to the distal nephron. In the mouse, expression was most abundant in segments coexpressing the epithelial ransient receptor potential vanilloid 5 Ca(2+) channel. Significant, albeit lower, expression was also evident in the region encompassing the cortical thick ascending limbs, macula densa, and early distal tubules as well as smooth muscle layers surrounding renal vessels. In the human kidney, a similar pattern of distribution was observed, with the highest PMCA4 expression in Na(+)-Cl(-) cotransporter-positive tubules. Electron microscopy demonstrated Pmca4 localization in distal nephron cells at both the basolateral membrane and intracellular perinuclear compartments but not submembranous vesicles, suggesting rapid trafficking to the plasma membrane is unlikely to occur in vivo. Pmca4 expression was not altered by perturbations in Ca(2+) balance, pointing to a housekeeping function of the pump in Ca(2+)-transporting epithelia. In conclusion, Pmca4 shows a divergent expression pattern in Ca(2+)-transporting epithelia, inferring diverse roles for this isoform not limited to transepithelial Ca(2+) transport. PMID:26180241

  12. Swelling-Activated Ca2+ Channels Trigger Ca2+ Signals in Merkel Cells

    PubMed Central

    Haeberle, Henry; Bryan, Leigh A.; Vadakkan, Tegy J.; Dickinson, Mary E.; Lumpkin, Ellen A.

    2008-01-01

    Merkel cell-neurite complexes are highly sensitive touch receptors comprising epidermal Merkel cells and sensory afferents. Based on morphological and molecular studies, Merkel cells are proposed to be mechanosensory cells that signal afferents via neurotransmission; however, functional studies testing this hypothesis in intact skin have produced conflicting results. To test this model in a simplified system, we asked whether purified Merkel cells are directly activated by mechanical stimulation. Cell shape was manipulated with anisotonic solution changes and responses were monitored by Ca2+ imaging with fura-2. We found that hypotonic-induced cell swelling, but not hypertonic solutions, triggered cytoplasmic Ca2+ transients. Several lines of evidence indicate that these signals arise from swelling-activated Ca2+-permeable ion channels. First, transients were reversibly abolished by chelating extracellular Ca2+, demonstrating a requirement for Ca2+ influx across the plasma membrane. Second, Ca2+ transients were initially observed near the plasma membrane in cytoplasmic processes. Third, voltage-activated Ca2+ channel (VACC) antagonists reduced transients by half, suggesting that swelling-activated channels depolarize plasma membranes to activate VACCs. Finally, emptying internal Ca2+ stores attenuated transients by 80%, suggesting Ca2+ release from stores augments swelling-activated Ca2+ signals. To identify candidate mechanotransduction channels, we used RT-PCR to amplify ion-channel transcripts whose pharmacological profiles matched those of hypotonic-evoked Ca2+ signals in Merkel cells. We found 11 amplicons, including PKD1, PKD2, and TRPC1, channels previously implicated in mechanotransduction in other cells. Collectively, these results directly demonstrate that Merkel cells are activated by hypotonic-evoked swelling, identify cellular signaling mechanisms that mediate these responses, and support the hypothesis that Merkel cells contribute to touch reception

  13. Acidic Ca(2+) stores come to the fore.

    PubMed

    Patel, Sandip; Muallem, Shmuel

    2011-08-01

    Changes in the concentration of cytosolic Ca(2+) form the basis of a ubiquitous signal transduction pathway. Accumulating evidence implicates acidic organelles in the control of Ca(2+) dynamics in organisms across phyla. In this special issue, we discuss Ca(2+) signalling by these "acidic Ca(2+) stores" which include acidocalcisomes, vacuoles, the endo-lysosomal system, lysosome-related organelles, secretory vesicles and the Golgi complex. Ca(2+) release from these morphologically very different organelles is mediated by members of the TRP channel superfamily and two-pore channels. Inositol trisphosphate and ryanodine receptors which are traditionally viewed as endoplasmic reticulum Ca(2+) release channels can also mobilize acidic Ca(2+) stores. Ca(2+) uptake into acidic Ca(2+) stores is driven by Ca(2+) ATPases and Ca(2+)/H(+) exchangers. In animal cells, the Ca(2+)-mobilizing messenger NAADP plays a central role in mediating Ca(2+) signals from acidic Ca(2+) stores through activation of two-pore channels. These signals are important for several physiological processes including muscle contraction and differentiation. Dysfunctional acidic Ca(2+) stores have been implicated in diseases such as acute pancreatitis and lysosomal storage disorders. Acidic Ca(2+) stores are therefore emerging as essential components of the Ca(2+) signalling network and merit extensive further study. PMID:21497395

  14. Control of ciliary motility by Ca sup 2+ : Integration of Ca sup 2+ -dependent functions and targets for Ca sup 2+ action

    SciTech Connect

    Evans, T.C.

    1988-01-01

    To identify functions that regulate Ca{sup 2+}-induced ciliary reversal in Paramecium, mutants defective in terminating depolarization-induced backward swimming were selected. Six independent recessive mutations (k-shy) comprising two complementation groups, k-shyA and k-shyB, were identified. All mutants exhibited prolonged backward swimming in depolarizing solutions. Voltage clamp studies revealed that mutant Ca{sup 2+} current amplitudes were reduced, but could be restored to wild type levels by EGTA injection. The recovery of the mutant Ca{sup 2+} current from Ca{sup 2+}-dependent inactivation, and the decay of the Ca{sup 2+}-dependent K{sup +} and Ca{sup 2+}-dependent Na{sup +} currents after depolarization were slow in k-shy compared to wild type. To identify protein targets of Ca{sup 2+} action, ciliary proteins that interact with calmodulin (CaM) were characterized. With a {sup 125}I-CaM blot assay, several CaM-binding proteins were identified including axonemal, soluble, and membrane-bound polypeptides. Competitive displacement studies with unlabeled Paramecium CaM, bovine CaM, and troponinC suggested that both protein types bind CaM with high affinity and specificity. To examine the presence of CaM-binding sites in intact axonemes, a filtration binding assay was developed.

  15. Diffusion of Ca and Mg in Calcite

    SciTech Connect

    Cygan, R.T.; Fisler, D.K.

    1999-02-10

    The self-diffusion of Ca and the tracer diffusion of Mg in calcite have been experimentally measured using isotopic tracers of {sup 25}Mg and {sup 44}Ca. Natural single crystals of calcite were coated with a thermally-sputtered oxide thin film and then annealed in a CO{sub 2} gas at one atmosphere total pressure and temperatures from 550 to 800 C. Diffusion coefficient values were derived from the depth profiles obtained by ion microprobe analysis. The resultant activation energies for Mg tracer diffusion and Ca self-diffusion are respectively: E{sub a}(Mg) = 284 {+-} 74 kJ/mol and E{sub a}(Ca) = 271 {+-} 80 kJ/mol. For the temperature ranges in these experiments, the diffusion of Mg is faster than Ca. The results are generally consistent in magnitude with divalent cation diffusion rates obtained in previous studies and provide a means of interpreting the thermal histories of carbonate minerals, the mechanism of dolomitization, and other diffusion-controlled processes. The results indicate that cation diffusion in calcite is relatively slow and cations are the rate-limiting diffusing species for the deformation of calcite and carbonate rocks. Application of the calcite-dolomite geothermometer to metamorphic assemblages will be constrained by cation diffusion and cooling rates. The direct measurement of Mg tracer diffusion in calcite indicates that dolomitization is unlikely to be accomplished by Mg diffusion in the solid state but by a recrystallization process.

  16. Ca2+ signaling during vertebrate somitogenesis.

    PubMed

    Webb, Sarah E; Miller, Andrew L

    2006-07-01

    A variety of Ca2+ signals, in the form of intercellular pulses and waves, have been reported to be associated with the various sequential stages of somitogenesis: from convergent extension and the formation of the paraxial mesoderm; during the patterning of the paraxial mesoderm to establish segmental units; throughout the formation of the morphological boundaries that delineate the segmental units, and finally from within the maturing somites as they undergo subsequent development and differentiation. Due to both the technical challenges presented in imaging intact, developing embryos, and the subtle nature of the Ca2+ transients generated, they have proved to be difficult to visualize. However, a combination of cultured cell preparations and improvements in explant and whole embryo imaging techniques has begun to reveal a new and exciting class of developmental Ca2+ signals. In this chapter, we review the small, but expanding, number of reports in the literature and attempt to identify common characteristics of the somitogenic Ca2+ transients, such as their mode of generation, as well as their spatial and temporal features. This may help to elucidate the significance and function of these intriguing Ca2+ transients and thus integrate them into the complex signaling networks that orchestrate early developmental events. PMID:16787560

  17. CaF2:Yb laser ceramics

    NASA Astrophysics Data System (ADS)

    Akchurin, M. Sh.; Basiev, T. T.; Demidenko, A. A.; Doroshenko, M. E.; Fedorov, P. P.; Garibin, E. A.; Gusev, P. E.; Kuznetsov, S. V.; Krutov, M. A.; Mironov, I. A.; Osiko, V. V.; Popov, P. A.

    2013-01-01

    CaF2:Yb fluoride laser ceramics, prepared by hot-forming, exhibit the same optical properties as starting single crystals. Slope efficiency of the Сa0.95Yb0.05F2.05 is equal to 35% in the pulsed mode of laser operation. Decrease of ytterbium concentration in CaF2:Yb samples down to 3 mol.% resulted in the essential improvement of Сa0.97Yb0.03F2.03 thermal conductivity from 3.5 to 4.5 W/m K, but slightly decreased (down to 30%) slope efficiency of the samples under both pulsed and CW mode of operation. Alternative hot-pressing synthesis of CaF2:Yb fluoride laser ceramics provided materials with superior mechanical properties (microhardness Н = 3.2 GPa and fracture toughness К1С = 0.65 МPа m1/2) in comparison with hot-formed and/or single crystal CaF2:Yb specimens. For the first time, lasing has been observed for the novel aforementioned hot-pressed CaF2:Yb ceramics.

  18. Serum CA 242 in pancreatic cancer. Comparison with CA 19-9 and CEA.

    PubMed

    Pezzilli, R; Billi, P; Plate, L; Laudadio, M A; Sprovieri, G

    1995-01-01

    Serum CA 242, CA 19-9 and CEA concentrations were determined in 94 subjects divided into 5 groups: Group 1 consisted of 22 healthy subjects; Group 2 consisted of 40 patients with pancreatic adenocarcinoma; according to Cubilla and Fitzgerald's classification, 11 tumours were Stage I, 4 were Stage II, and 25 were Stage III. Group 3 consisted of 10 chronic pancreatitis patients, group 4 of 10 acute pancreatitis patients, group 5 of 12 patients with nonpancreatic digestive carcinomas. Ten of these 12 patients had distant metastases. The sensitivity of CA 19-9 in the diagnosis of pancreatic cancer was higher than that of CEA and CA 242 (p < 0.05 and p < 0.005, respectively). In Stage I cancer patients the sensitivity of the markers studied was less than 50% (45% for CA 19-9, 18% for CEA, and 9% for CA 242) whereas most of the 25 patients with metastatic tumours of the pancreas had elevated serum levels of all 3 markers. The various combinations of the three markers did not significantly improve the sensitivity in diagnosing pancreatic cancer. No relationship was found between the localization of the tumour and the serum levels of the 3 markers studied. Similarly, no differences were found between patients with cholestasis and those without. The specificity of the 3 markers, evaluated in patients with benign pancreatic diseases, was 100% for CA 242, 90% for CA 199 and 70% for CEA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8562994

  19. Multifaceted plasma membrane Ca(2+) pumps: From structure to intracellular Ca(2+) handling and cancer.

    PubMed

    Padányi, Rita; Pászty, Katalin; Hegedűs, Luca; Varga, Karolina; Papp, Béla; Penniston, John T; Enyedi, Ágnes

    2016-06-01

    Plasma membrane Ca(2+) ATPases (PMCAs) are intimately involved in the control of intracellular Ca(2+) concentration. They reduce Ca(2+) in the cytosol not only by direct ejection, but also by controlling the formation of inositol-1,4,5-trisphosphate and decreasing Ca(2+) release from the endoplasmic reticulum Ca(2+) pool. In mammals four genes (PMCA1-4) are expressed, and alternative RNA splicing generates more than twenty variants. The variants differ in their regulatory characteristics. They localize into highly specialized membrane compartments and respond to the incoming Ca(2+) with distinct temporal resolution. The expression pattern of variants depends on cell type; a change in this pattern can result in perturbed Ca(2+) homeostasis and thus altered cell function. Indeed, PMCAs undergo remarkable changes in their expression pattern during tumorigenesis that might significantly contribute to the unbalanced Ca(2+) homeostasis of cancer cells. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen. PMID:26707182

  20. Characterizing CA{sub 2} and CA{sub 6} using ELNES

    SciTech Connect

    Altay, A.; Carter, C.B.; Rulis, P.; Ching, W.-Y.; Arslan, I.; Guelguen, M.A.

    2010-08-15

    Calcium aluminates, compounds in the CaO-Al{sub 2}O{sub 3} phase system, are used in high-temperature cements and refractory oxides and have wide range of potential technological applications due to their interesting optical, electrical, thermal, and mechanical properties. They are used in both crystalline and glassy form; the glass is an isotropic material while the crystalline materials may be highly anisotropic. This paper will consider two particular crystalline materials, CA{sub 2} and CA{sub 6}, but the results should be applicable to all calcium aluminates. Although CA{sub 2} and CA{sub 6} crystals contain the same chemical species, Ca, Al, and O, the coordination and local environments of these species are different in the two structures and hence they show very different energy-loss near-edge structures (ELNES) when examined by electron energy-loss spectroscopy (EELS) in the TEM. The data obtained using ELNES can effectively provide a fingerprint for each compound and a map for their electronic structure. Once such fingerprints are obtained, they can be used to identify nano-sized particles/grains or material at interfaces and grain boundaries. In the present study, the local symmetry fingerprints for CA{sub 2} and CA{sub 6} structures are reported combining experimental spectra with electronic-structure calculations that allow the different features in the spectra to be interpreted. Al-L{sub 2,3} and O-K edge core-loss spectra from CA{sub 2} and CA{sub 6} were measured experimentally using electron energy-loss spectroscopy in a monochromated scanning transmission electron microscope. The near-edge structures were calculated for the different phases using the orthogonalized linear combination of atomic-orbitals method, and took account of core-hole interactions. It is shown that CA{sub 2} and CA{sub 6} structures exhibit distinctive experimental ELNES fingerprints so that these two phases can be separately identified even when present in small volumes

  1. Hg2+ signaling in trout hepatoma (RTH-149) cells: involvement of Ca2+-induced Ca2+ release.

    PubMed

    Burlando, Bruno; Bonomo, Marco; Fabbri, Elena; Dondero, Francesco; Viarengo, Aldo

    2003-09-01

    Mercury is a non-essential heavy metal affecting intracellular Ca2+ dynamics. We studied the effects of Hg2+ on [Ca2+]i in trout hepatoma cells (RTH-149). Confocal imaging of fluo-3-loaded cells showed that Hg2+ induced dose-dependent, sustained [Ca2+]i transient, triggered intracellular Ca2+ waves, stimulated Ca2+-ATPase activity, and promoted InsP3 production. The effect of Hg2+ was reduced by the Ca2+ channel blocker verapamil and totally abolished by extracellular GSH, but was almost unaffected by cell loading with the heavy metal chelator TPEN or esterified GSH. In a Ca2+-free medium, Hg2+ induced a smaller [Ca2+]i transient, that was unaffected by TPEN, but was abolished by U73122, a PLC inhibitor, and by cell loading with GDP-betaS, a G protein inhibitor, or heparin, a blocker of intracellular Ca2+ release. Data indicate that Hg2+ induces Ca2+ entry through verapamil-sensitive channels, and intracellular Ca2+ release via a G protein-PLC-InsP3 mechanism. However, in cells loaded with heparin and exposed to Hg2+ in the presence of external Ca2+, the [Ca2+]i rise was maximally reduced, indicating that the global effect of Hg2+ is not a mere sum of Ca2+ entry plus Ca2+ release, but involves an amplification of Ca2+ release operated by Ca2+ entry through a CICR mechanism. PMID:12887976

  2. Mitochondrial Ca(2+) uptake in skeletal muscle health and disease.

    PubMed

    Zhou, Jingsong; Dhakal, Kamal; Yi, Jianxun

    2016-08-01

    Muscle uses Ca(2+) as a messenger to control contraction and relies on ATP to maintain the intracellular Ca(2+) homeostasis. Mitochondria are the major sub-cellular organelle of ATP production. With a negative inner membrane potential, mitochondria take up Ca(2+) from their surroundings, a process called mitochondrial Ca(2+) uptake. Under physiological conditions, Ca(2+) uptake into mitochondria promotes ATP production. Excessive uptake causes mitochondrial Ca(2+) overload, which activates downstream adverse responses leading to cell dysfunction. Moreover, mitochondrial Ca(2+) uptake could shape spatio-temporal patterns of intracellular Ca(2+) signaling. Malfunction of mitochondrial Ca(2+) uptake is implicated in muscle degeneration. Unlike non-excitable cells, mitochondria in muscle cells experience dramatic changes of intracellular Ca(2+) levels. Besides the sudden elevation of Ca(2+) level induced by action potentials, Ca(2+) transients in muscle cells can be as short as a few milliseconds during a single twitch or as long as minutes during tetanic contraction, which raises the question whether mitochondrial Ca(2+) uptake is fast and big enough to shape intracellular Ca(2+) signaling during excitation-contraction coupling and creates technical challenges for quantification of the dynamic changes of Ca(2+) inside mitochondria. This review focuses on characterization of mitochondrial Ca(2+) uptake in skeletal muscle and its role in muscle physiology and diseases. PMID:27430885

  3. Growth rate effects on Mg/Ca and Sr/Ca ratios constrained by belemnite calcite

    NASA Astrophysics Data System (ADS)

    Vinzenz Ullmann, Clemens

    2016-04-01

    Multiple temperature proxies from single species are important to achieve robust palaeotemperature estimates. Besides the commonly employed oxygen isotope thermometer, also Mg/Ca and Sr/Ca ratios perform well as proxies for calcification temperature in the shells of some species. While salinity changes affect the ratios of earth alkaline elements much less than the δ18O thermometer, metabolic effects may exert a strong control on the expression of element ratios. Such effects are hard to study because biomineralization experiments have to overcome large intraspecific variability and can hardly ever isolate the controls of a single parameter on shell geochemistry. The unique geometry of the belemnite rostrum constitutes an exception to this rule. Its shape, large size, and the visibility of growth increments as bands enable the analysis of multiple, correlatable, high resolution geochemical profiles in a single fossil. The effects of the growth rate variability amongst these profiles on Mg/Ca and Sr/Ca ratios has been tested here. Within a specimen of Passaloteuthis bisulcata (Early Toarcian, Cleveland Basin, UK), Mg/Ca and Sr/Ca data were obtained from four profiles. With respect to growth rate in the first profile, which was taken as a reference, the relative growth rates in the remaining three profiles varied by a factor of 0.9 to 2.7. Results suggest that relative growth rate is linearly correlated with Mg/Ca and Sr/Ca, with a decrease of Mg/Ca by 8 % and increase of Sr/Ca by 6 % per 100 % increase in relative growth rate. The observed trends are consistent with abiogenic precipitation experiments and suggest that crystal precipitation rate exerts a significant, predictable control on the element distribution in biogenic calcite.

  4. Materials compatibility during the chlorination of molten CaCl/sub 2/. CaO salts. [CaCl/sub 2/. CaO salt

    SciTech Connect

    Rense, C.E.C.; Fife, K.W.; Bowersox, D.F.; Ferran, M.D.

    1987-01-01

    As part of our effort to develop a semicontinuous PuO/sub 2/ reduction process, we are investigating promising materials for containing a 900/sup 0/C molten CaCl/sub 2/ . CaO chlorination reaction. We want the material to contain this reaction and to be reusable. We tested candidate materials in a simulated salt (no plutonium) using anhydrous HCl as the chlorinating agent. Data are presented on the performance of 36 metals and alloys, 9 ceramics, and 3 coatings.

  5. Gonadotropin-releasing hormone-induced Ca2+ transients in single identified gonadotropes require both intracellular Ca2+ mobilization and Ca2+ influx.

    PubMed Central

    Shangold, G A; Murphy, S N; Miller, R J

    1988-01-01

    We examined the effects of gonadotropin-releasing hormone (GnRH) on the intracellular free Ca2+ concentration ([Ca2+]i) in single rat anterior pituitary gonadotropes identified by a reverse hemolytic plaque assay. Concentrations of GnRH greater than 10 pM elicited increases in [Ca2+]i in identified cells but not in others. In contrast, depolarization induced by 50 mM K+ increased [Ca2+]i in all cells. Ca2+ transients induced by GnRH exhibited a complex time course. After an initial rapid rise, the [Ca2+]i fell to near basal levels only to be followed by a secondary extended rise and fall. Analysis of the Ca2+ transients on a rapid time base revealed that responses frequently consisted of several rapid oscillations in [Ca2+]i. Removal of extracellular Ca2+ or addition of the dihydropyridine Ca2+-channel blocker nitrendipine completely blocked the secondary rise in [Ca2+]i but had no effect whatsoever on the initial spike. Nitrendipine also blocked 50 mM K+-induced increases in [Ca2+]i in identified gonadotropes. The secondary rise induced by GnRH could be enhanced by a phorbol ester in a nitrendipine-sensitive fashion. Multiple spike responses to GnRH stimulation of the same cell could only be obtained if subsequent Ca2+ influx was permitted either by allowing a secondary rise to occur or by producing a Ca2+ transient by depolarizing the cells with 50 mM K+. It therefore appears that the response to GnRH consists of an initial phase of Ca2+ mobilization, probably mediated by inositol trisphosphate, and a subsequent phase of Ca2+ influx through nitrendipine-sensitive Ca2+ channels that may be activated by protein kinase C. The relative roles of these phases in the control of gonadotropin secretion are discussed. Images PMID:3045819

  6. Inhibitors of the Ca{sup 2+}/calmodulin-dependent protein kinase phosphatase family (CaMKP and CaMKP-N)

    SciTech Connect

    Sueyoshi, Noriyuki; Takao, Toshihiko; Nimura, Takaki; Sugiyama, Yasunori; Numano, Takamasa; Shigeri, Yasushi; Taniguchi, Takanobu; Kameshita, Isamu Ishida, Atsuhiko

    2007-11-23

    Ca{sup 2+}/calmodulin-dependent protein kinase phosphatase (CaMKP) and its nuclear isoform CaMKP-N are unique Ser/Thr protein phosphatases that negatively regulate the Ca{sup 2+}/calmodulin-dependent protein kinase (CaMK) cascade by dephosphorylating multifunctional CaMKI, II, and IV. However, the lack of specific inhibitors of these phosphatases has hampered studies on these enzymes in vivo. In an attempt to obtain specific inhibitors, we searched inhibitory compounds and found that Evans Blue and Chicago Sky Blue 6B served as effective inhibitors for CaMKP. These compounds also inhibited CaMKP-N, but inhibited neither protein phosphatase 2C, another member of PPM family phosphatase, nor calcineurin, a typical PPP family phosphatase. The minimum structure required for the inhibition was 1-amino-8-naphthol-4-sulfonic acid. When Neuro2a cells cotransfected with CaMKIV and CaMKP-N were treated with these compounds, the dephosphorylation of CaMKIV was strongly suppressed, suggesting that these compounds could be used as potent inhibitors of CaMKP and CaMKP-N in vivo as well as in vitro.

  7. Mitochondrial Ryanodine Receptors and Other Mitochondrial Ca2+ Permeable Channels

    PubMed Central

    Ryu, Shin-Young; Beutner, Gisela; Dirksen, Robert T.; Kinnally, Kathleen W.; Sheu, Shey-Shing

    2010-01-01

    Ca2+ channels that underlie mitochondrial Ca2+ transport first reported decades ago have now just recently been precisely characterized electrophysiologically. Numerous data indicate that mitochondrial Ca2+ uptake via these channels regulates multiple intracellular processes by shaping cytosolic and mitochondrial Ca2+ transients, as well as altering the cellular metabolic and redox state. On the other hand, mitochondrial Ca2+ overload also initiates a cascade of events that leads to cell death. Thus, characterization of mitochondrial Ca2+ channels is central to a comprehensive understanding of cell signaling. Here, we discuss recent progresses in the biophysical and electrophysiological characterization of several distinct mitochondrial Ca2+ channels. PMID:20096690

  8. Regulation and roles of Ca2+ stores in human sperm

    PubMed Central

    Correia, Joao; Michelangeli, Francesco; Publicover, Stephen

    2015-01-01

    [Ca2 +]i signalling is a key regulatory mechanism in sperm function. In mammalian sperm the Ca2 +-permeable plasma membrane ion channel CatSper is central to [Ca2 +]i signalling, but there is good evidence that Ca2 + stored in intracellular organelles is also functionally important. Here we briefly review the current understanding of the diversity of Ca2 + stores and the mechanisms for the regulation of their activity. We then consider the evidence for the involvement of these stores in [Ca2 +]i signalling in mammalian (primarily human) sperm, the agonists that may activate these stores and their role in control of sperm function. Finally we consider the evidence that membrane Ca2 + channels and stored Ca2 + may play discrete roles in the regulation of sperm activities and propose a mechanism by which these different components of the sperm Ca2 +-signalling apparatus may interact to generate complex and spatially diverse [Ca2 +]i signals. PMID:25964382

  9. Solution NMR Structure of the Ca2+-bound N-terminal Domain of CaBP7

    PubMed Central

    McCue, Hannah V.; Patel, Pryank; Herbert, Andrew P.; Lian, Lu-Yun; Burgoyne, Robert D.; Haynes, Lee P.

    2012-01-01

    Calcium-binding protein 7 (CaBP7) is a member of the calmodulin (CaM) superfamily that harbors two high affinity EF-hand motifs and a C-terminal transmembrane domain. CaBP7 has been previously shown to interact with and modulate phosphatidylinositol 4-kinase III-β (PI4KIIIβ) activity in in vitro assays and affects vesicle transport in neurons when overexpressed. Here we show that the N-terminal domain (NTD) of CaBP7 is sufficient to mediate the interaction of CaBP7 with PI4KIIIβ. CaBP7 NTD encompasses the two high affinity Ca2+ binding sites, and structural characterization through multiangle light scattering, circular dichroism, and NMR reveals unique properties for this domain. CaBP7 NTD binds specifically to Ca2+ but not Mg2+ and undergoes significant conformational changes in both secondary and tertiary structure upon Ca2+ binding. The Ca2+-bound form of CaBP7 NTD is monomeric and exhibits an open conformation similar to that of CaM. Ca2+-bound CaBP7 NTD has a solvent-exposed hydrophobic surface that is more expansive than observed in CaM or CaBP1. Within this hydrophobic pocket, there is a significant reduction in the number of methionine residues that are conserved in CaM and CaBP1 and shown to be important for target recognition. In CaBP7 NTD, these residues are replaced with isoleucine and leucine residues with branched side chains that are intrinsically more rigid than the flexible methionine side chain. We propose that these differences in surface hydrophobicity, charge, and methionine content may be important in determining highly specific interactions of CaBP7 with target proteins, such as PI4KIIIβ. PMID:22989873

  10. CaV1.2 beta-subunit coordinates CaMKII-triggered cardiomyocyte death and afterdepolarizations.

    PubMed

    Koval, Olha M; Guan, Xiaoquan; Wu, Yuejin; Joiner, Mei-Ling; Gao, Zhan; Chen, Biyi; Grumbach, Isabella M; Luczak, Elizabeth D; Colbran, Roger J; Song, Long-Sheng; Hund, Thomas J; Mohler, Peter J; Anderson, Mark E

    2010-03-16

    Excessive activation of calmodulin kinase II (CaMKII) causes arrhythmias and heart failure, but the cellular mechanisms for CaMKII-targeted proteins causing disordered cell membrane excitability and myocardial dysfunction remain uncertain. Failing human cardiomyocytes exhibit increased CaMKII and voltage-gated Ca(2+) channel (Ca(V)1.2) activity, and enhanced expression of a specific Ca(V)1.2 beta-subunit protein isoform (beta(2a)). We recently identified Ca(V)1.2 beta(2a) residues critical for CaMKII phosphorylation (Thr 498) and binding (Leu 493), suggesting the hypothesis that these amino acids are crucial for cardiomyopathic consequences of CaMKII signaling. Here we show WT beta(2a) expression causes cellular Ca(2+) overload, arrhythmia-triggering cell membrane potential oscillations called early afterdepolarizations (EADs), and premature death in paced adult rabbit ventricular myocytes. Prevention of intracellular Ca(2+) release by ryanodine or global cellular CaMKII inhibition reduced EADs and improved cell survival to control levels in WT beta(2a)-expressing ventricular myocytes. In contrast, expression of beta(2a) T498A or L493A mutants mimicked the protective effects of ryanodine or global cellular CaMKII inhibition by reducing Ca(2+) entry through Ca(V)1.2 and inhibiting EADs. Furthermore, Ca(V)1.2 currents recorded from cells overexpressing CaMKII phosphorylation- or binding-incompetent beta(2a) subunits were incapable of entering a CaMKII-dependent high-activity gating mode (mode 2), indicating that beta(2a) Thr 498 and Leu 493 are required for Ca(V)1.2 activation by CaMKII in native cells. These data show that CaMKII binding and phosphorylation sites on beta(2a) are concise but pivotal components of a molecular and biophysical and mechanism for EADs and impaired survival in adult cardiomyocytes. PMID:20194790

  11. The CAR that drives Ca2+ to Orai1.

    PubMed

    Jha, Archana; Muallem, Shmuel

    2016-03-01

    How Ca(2+) permeates the Orai1 channel and the mechanism by which the channel achieves high Ca(2+) selectivity remain critical questions in understanding store-operated Ca(2+) influx. In research published in Science Signaling, Frischauf et al. identified a Ca(2+)-accumulating region (CAR) in the extracellular opening of Orai1, which explains how concentrating Ca(2+) at the mouth of Orai1 facilitates channel permeation and contributes to selectivity. PMID:26956483

  12. Fine-tuning synaptic plasticity by modulation of Ca(V)2.1 channels with Ca2+ sensor proteins.

    PubMed

    Leal, Karina; Mochida, Sumiko; Scheuer, Todd; Catterall, William A

    2012-10-16

    Modulation of P/Q-type Ca(2+) currents through presynaptic voltage-gated calcium channels (Ca(V)2.1) by binding of Ca(2+)/calmodulin contributes to short-term synaptic plasticity. Ca(2+)-binding protein-1 (CaBP1) and Visinin-like protein-2 (VILIP-2) are neurospecific calmodulin-like Ca(2+) sensor proteins that differentially modulate Ca(V)2.1 channels, but how they contribute to short-term synaptic plasticity is unknown. Here, we show that activity-dependent modulation of presynaptic Ca(V)2.1 channels by CaBP1 and VILIP-2 has opposing effects on short-term synaptic plasticity in superior cervical ganglion neurons. Expression of CaBP1, which blocks Ca(2+)-dependent facilitation of P/Q-type Ca(2+) current, markedly reduced facilitation of synaptic transmission. VILIP-2, which blocks Ca(2+)-dependent inactivation of P/Q-type Ca(2+) current, reduced synaptic depression and increased facilitation under conditions of high release probability. These results demonstrate that activity-dependent regulation of presynaptic Ca(V)2.1 channels by differentially expressed Ca(2+) sensor proteins can fine-tune synaptic responses to trains of action potentials and thereby contribute to the diversity of short-term synaptic plasticity. PMID:23027954

  13. Detection of Ca(2+)-binding proteins by electrophoretic migration in the presence of Ca2+ combined with 45Ca2+ overlay of protein blots

    SciTech Connect

    Garrigos, M.; Deschamps, S.; Viel, A.; Lund, S.; Champeil, P.; Moller, J.V.; le Maire, M. , Gif-sur-Yvette )

    1991-04-01

    When high affinity Ca(2+)-binding proteins like calmodulin, or proteins with a high Ca(2+)-binding capacity like calsequestrin, underwent sodium dodecyl sulfate-gel electrophoresis in Laemmli systems, their electrophoretic migration rates were much higher in gels containing 1 mM Ca2+ than in gels containing ethylene glycol bis(beta-aminoethyl ether) N,N{prime}-tetraacetic acid (EGTA). Replacement of EGTA by Ca2+ in the gel, combined with the blotting of electrophoretically separated proteins on polyvinylidene difluoride membranes and subsequent 45Ca2+ overlay, proved a very effective means of detecting Ca(2+)-binding proteins. This combined approach is important since artifacts occur in both techniques when used separately. We found that the usual procedure of adding Ca2+ to the sample before electrophoresis without including it in the gel itself permitted the detection of only very high affinity Ca(2+)-binding proteins.

  14. Developmental changes in Ca(2+)-uptake, Na+,Ca(2+)-exchange and Ca(2+)-ATPase in freshly isolated embryonic, newborn and adult chicken heart.

    PubMed

    Prakash, P; Meera, P; Tripathi, O

    1996-01-01

    Developmental changes in cellular Ca(2+)-transport mechanisms were studied in chick heart by determining cellular Ca(2+)-uptake and Na+,Ca(2+)-exchange activity in freshly isolated ventricular tissues of embryonic (5-18 days old), newborn (1-2 days old) and young adult (90-100 days old) heart by monitoring 45Ca influx. Ca(2+)-ATPase activity was determined in microsomal fractions at different stages of development. The Ca(2+)-uptake (per g wet tissue weight) increased with the development of embryonic as well as post-hatch chick heart, reaching a maximum in the young adult chicken. The overall increase in Ca(2+)-uptake, from embryonic day 5 to young-adult stage, was more than 3 fold. The Na+,Ca(2+)-exchange activity, determined as Na(+)-gradient-induced Ca(2+)-uptake in presence of either ouabain or zero [Na+]0, showed a 6-fold increase during development of heart from the embryonic day 5 to the young adult stage. Amiloride, an inhibitor of Na+,Ca(2+)-exchange, caused a dose-dependent reduction in a ouabain-induced rise in 45Ca influx at different stages of development. The inhibitory effect of amiloride was, however, greater during later stages of development. A progressive increase in Ca(2+)-ATPase activity was also seen during development. Ca(2+)-ATPase exhibited about a 4-fold increase in activity from embryonic day 7 to the young adult. The concomitant increase in Ca(2+)-uptake, Na+,Ca(2+)-exchange and Ca(2+)-ATPase activities suggests age-dependent changes in Ca(2+)-transport and storage systems of developing heart during embryogenesis and post-embryonic life. During embryogenesis the developmental increase in Na+,Ca(2+)-exchange activity was greater than that during post-hatch development of heart. However, the increase in Ca(2+)-ATPase activity was greater during post-hatch development than during embryogenesis. It is suggested that Na+,Ca(2+)-exchange and Ca(2+)-ATPase play a prominent role in maintaining cellular Ca2+ homeostasis during embryogenesis and

  15. Mitochondrial and sarcolemmal Ca2+ transport reduce [Ca2+]i during caffeine contractures in rabbit cardiac myocytes.

    PubMed Central

    Bassani, R A; Bassani, J W; Bers, D M

    1992-01-01

    1. Contraction and intracellular Ca2+ (Ca2+i) transients were measured in isolated rabbit ventricular myocytes during twitches and contractures induced by rapid application of 10 mM-caffeine. 2. The amplitude of caffeine-induced contractures and the accompanying Ca2+i transients were larger than during normal twitches and also declined more slowly. This may be because only a fraction of sarcoplasmic reticulum (SR) Ca2+ is released during a normal twitch, or because of a temporal overlap of SR Ca2+ release and uptake during the twitch. 3. When a caffeine contracture was initiated in Na(+)-free, Ca(2+)-free medium (to prevent sarcolemmal Na(+)-Ca2+ exchange) the contracture and Ca2+i transient were larger and decreased much more slowly. Thus, Ca2+ extrusion via Na(+)-Ca2+ exchange may limit the amplitude of caffeine-induced contractures. 4. Relaxation half-time (t1/2) for the twitch (0.17 +/- 0.03 s) was increased to 0.54 +/- 0.07 s for caffeine contractures in control solution and 8.8 +/- 1 s for caffeine-induced contractures in Na(+)-free, Ca(2+)-free solution. These results confirm that the SR Ca2+ pump and Na(+)-Ca2+ exchange are the predominant mechanisms for cytoplasmic Ca2+ removal during relaxation. However slower mechanisms can still reduce intracellular [Ca2+]. 5. Relaxation of caffeine contractures in Na(+)-free solution was further slowed when (a) mitochondrial Ca2+ uptake was inhibited with the oxidative phosphorylation uncoupler, FCCP (t1/2 = 19.7 +/- 3.2 s), or (b) the sarcolemmal Ca(2+)-ATPase pumping ability was depressed by a large transmembrane [Ca2+] gradient (t1/2 = 27.5 +/- 6.9 s). 6. When the four Ca2+ transport systems were simultaneously inhibited (i.e. SR Ca2+ pump, Na(+)-Ca2+ exchange, mitochondrial Ca2+ uptake and sarcolemmal Ca2+ pump), relaxation was practically abolished, but the cell could recover quickly when Na+ was reintroduced and caffeine removed. 7. We conclude that, under our experimental conditions, the sarcolemmal Ca2+ pump

  16. Ca2+ signaling in the myocardium by (redox) regulation of PKA/CaMKII

    PubMed Central

    Johnston, Alex S.; Lehnart, Stephan E.; Burgoyne, Joseph R.

    2015-01-01

    Homeostatic cardiac function is maintained by a complex network of interdependent signaling pathways which become compromised during disease progression. Excitation-contraction-coupling, the translation of an electrical signal to a contractile response is critically dependent on a tightly controlled sequence of events culminating in a rise in intracellular Ca2+ and subsequent contraction of the myocardium. Dysregulation of this Ca2+ handling system as well as increases in the production of reactive oxygen species (ROS) are two major contributing factors to myocardial disease progression. ROS, generated by cellular oxidases and by-products of cellular metabolism, are highly reactive oxygen derivatives that function as key secondary messengers within the heart and contribute to normal homeostatic function. However, excessive production of ROS, as in disease, can directly interact with kinases critical for Ca2+ regulation. This post-translational oxidative modification therefore links changes in the redox status of the myocardium to phospho-regulated pathways essential for its function. This review aims to describe the oxidative regulation of the Ca2+/calmodulin-dependent kinase II (CaMKII) and cAMP-dependent protein kinase A (PKA), and the subsequent impact this has on Ca2+ handling within the myocardium. Elucidating the impact of alterations in intracellular ROS production on Ca2+ dynamics through oxidative modification of key ROS sensing kinases, may provide novel therapeutic targets for preventing myocardial disease progression. PMID:26321952

  17. Measuring spatial and temporal Ca2+ signals in Arabidopsis plants.

    PubMed

    Zhu, Xiaohong; Taylor, Aaron; Zhang, Shenyu; Zhang, Dayong; Feng, Ying; Liang, Gaimei; Zhu, Jian-Kang

    2014-01-01

    Developmental and environmental cues induce Ca(2+) fluctuations in plant cells. Stimulus-specific spatial-temporal Ca(2+) patterns are sensed by cellular Ca(2+) binding proteins that initiate Ca(2+) signaling cascades. However, we still know little about how stimulus specific Ca(2+) signals are generated. The specificity of a Ca(2+) signal may be attributed to the sophisticated regulation of the activities of Ca(2+) channels and/or transporters in response to a given stimulus. To identify these cellular components and understand their functions, it is crucial to use systems that allow a sensitive and robust recording of Ca(2+) signals at both the tissue and cellular levels. Genetically encoded Ca(2+) indicators that are targeted to different cellular compartments have provided a platform for live cell confocal imaging of cellular Ca(2+) signals. Here we describe instructions for the use of two Ca(2+) detection systems: aequorin based FAS (film adhesive seedlings) luminescence Ca(2+) imaging and case12 based live cell confocal fluorescence Ca(2+) imaging. Luminescence imaging using the FAS system provides a simple, robust and sensitive detection of spatial and temporal Ca(2+) signals at the tissue level, while live cell confocal imaging using Case12 provides simultaneous detection of cytosolic and nuclear Ca(2+) signals at a high resolution. PMID:25226381

  18. Apocalmodulin Itself Promotes Ion Channel Opening and Ca2+ Regulation

    PubMed Central

    Adams, Paul J.; Ben-Johny, Manu; Dick, Ivy E.; Inoue, Takanari; Yue, David T.

    2014-01-01

    SUMMARY The Ca2+-free form of calmodulin (apoCaM) often appears inert, modulating target molecules only upon conversion to its Ca2+-bound form. This schema has appeared to govern voltage-gated Ca2+ channels, where apoCaM has been considered a dormant Ca2+ sensor, associated with channels, but awaiting the binding of Ca2+ ions before inhibiting channel opening to provide vital feedback inhibition. Using single-molecule measurements of channels and chemical dimerization to elevate apoCaM, we find that apoCaM binding on its own markedly upregulates opening, rivaling the strongest forms of modulation. Upon Ca2+ binding to this CaM, inhibition may simply reverse the initial upregulation. As RNA edited and spliced channel variants show different affinities for apoCaM, the apoCaM-dependent control mechanisms may underlie the functional diversity of these variants and explain an elongation of neuronal action potentials by apoCaM. More broadly, voltage-gated Na channels adopt this same modulatory principle. ApoCaM thus imparts potent and pervasive ion-channel regulation. PMID:25417111

  19. 77 FR 58901 - California Disaster #CA-00190

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-24

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION California Disaster CA-00190 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... Application Deadline Date: 06/14/2013. ADDRESSES: Submit completed loan applications to: U.S. Small...

  20. literacy.ca EXPRESS. December 2010

    ERIC Educational Resources Information Center

    Canadian Literacy and Learning Network, 2010

    2010-01-01

    This issue of "literacy.ca EXPRESS" features new and exciting developments, updates and exciting new resources. Articles included in this issue are: (1) Introducing CLLN (Canadian Literacy and Learning Network)!; (2) Supporting Learner Leadership; (3) Involving Learners by Patricia Ashie; (4) Catching Confidence; (5) CALL (Committee of Adult…

  1. Hippocampal CA1 Ripples as Inhibitory Transients.

    PubMed

    Malerba, Paola; Krishnan, Giri P; Fellous, Jean-Marc; Bazhenov, Maxim

    2016-04-01

    Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep. Neurons active during behavior reactivate in both structures during sleep, in conjunction with characteristic brain oscillations that may form the neural substrate of memory consolidation. In the hippocampus, replay occurs within sharp wave-ripples: short bouts of high-frequency activity in area CA1 caused by excitatory activation from area CA3. In this work, we develop a computational model of ripple generation, motivated by in vivo rat data showing that ripples have a broad frequency distribution, exponential inter-arrival times and yet highly non-variable durations. Our study predicts that ripples are not persistent oscillations but result from a transient network behavior, induced by input from CA3, in which the high frequency synchronous firing of perisomatic interneurons does not depend on the time scale of synaptic inhibition. We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration. Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network. PMID:27093059

  2. Exchange stiffness of Ca-doped YIG

    NASA Astrophysics Data System (ADS)

    Avgin, I.; Huber, D. L.

    1994-05-01

    An effective medium theory for the zero-temperature exchange stiffness of uncompensated Ca-doped YIG is presented. The theory is based on the assumption that the effect of the Ca impurities is to produce strong, random ferromagnetic interactions between spins on the a and d sublattices. In the simplest version of the theory, a fraction, x, of the ad exchange integrals are large and positive, x being related to the Ca concentration. The stiffness is calculated as function of x for arbitrary perturbed ad exchange integral, Jxad. For Jxad≳(1/5)‖8Jaa+3Jdd‖, with Jaa and Jdd denoting the aa and dd exchange integrals, respectively, there is a critical concentration, Xc, such that when x≳Xc, the stiffness is complex. It is suggested that Xc delineates the region where there are significant departures from colinearity in the ground state of the Fe spins. Extension of the theory to a model where the Ca doping is assumed to generate Fe4+ ions on the tetrahedral sites is discussed. Possible experimental tests of the theory are mentioned.

  3. literacy.ca EXPRESS. October 2009

    ERIC Educational Resources Information Center

    Movement for Canadian Literacy, 2009

    2009-01-01

    This issue of "literacy.ca EXPRESS" focuses on the topic of promising practice. Promising or good practice and lessons learned are used to describe useful practices, approaches or ideas. Articles included in this issue: (1) Practitioner Profile: Meet Connie Jones; (2) Highlights from the LAN (Learner Advisory Network); (3) In the Works... Projects…

  4. Interlamellar CA1 network in the hippocampus

    PubMed Central

    Yang, Sunggu; Yang, Sungchil; Moreira, Thais; Hoffman, Gloria; Carlson, Greg C.; Bender, Kevin J.; Alger, Bradley E.; Tang, Cha-Min

    2014-01-01

    To understand the cellular basis of learning and memory, the neurophysiology of the hippocampus has been largely examined in thin transverse slice preparations. However, the synaptic architecture along the longitudinal septo-temporal axis perpendicular to the transverse projections in CA1 is largely unknown, despite its potential significance for understanding the information processing carried out by the hippocampus. Here, using a battery of powerful techniques, including 3D digital holography and focal glutamate uncaging, voltage-sensitive dye, two-photon imaging, electrophysiology, and immunohistochemistry, we show that CA1 pyramidal neurons are connected to one another in an associational and well-organized fashion along the longitudinal axis of the hippocampus. Such CA1 longitudinal connections mediate reliable signal transfer among the pyramidal cells and express significant synaptic plasticity. These results illustrate a need to reconceptualize hippocampal CA1 network function to include not only processing in the transverse plane, but also operations made possible by the longitudinal network. Our data will thus provide an essential basis for future computational modeling studies on information processing operations carried out in the full 3D hippocampal network that underlies its complex cognitive functions. PMID:25139992

  5. literacy.ca EXPRESS. April 2010

    ERIC Educational Resources Information Center

    Movement for Canadian Literacy, 2010

    2010-01-01

    This issue of "literacy.ca EXPRESS" focuses on poverty. The articles included in this issue are: (1) Poverty Overview; (2) Tony's Story; (3) LAN (Learner Advisory Network) Member's Story (Dianne Smith); (4) Linking Adult Literacy to Poverty Reduction; (5) MCL (Movement for Canadian Literacy) Update; (6) Highlights from the LAN; (7) Good to Know...…

  6. SNL/CA Cultural Resources Management Plan.

    SciTech Connect

    Larsen, Barbara L.

    2005-11-01

    The SNL/CA Cultural Resources Management Plan satisfies the site's Environmental Management System requirement to promote long-term stewardship of cultural resources. The plan summarizes the cultural and historical setting of the site, identifies existing procedures and processes that support protection and preservation of resources, and outlines actions that would be initiated if cultural resources were discovered onsite in the future.3

  7. 78 FR 39821 - California Disaster #CA-00202

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION California Disaster CA-00202 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... Deadline Date: 03/25/2014. ADDRESSES: Submit completed loan applications to: U.S. Small...

  8. 78 FR 60366 - California Disaster #CA-00212

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION California Disaster CA-00212 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY...: 06/24/2014. ADDRESSES: Submit completed loan applications to: U.S. Small Business...

  9. Inositol Trisphosphate Receptor Ca2+ Release Channels

    PubMed Central

    FOSKETT, J. KEVIN; WHITE, CARL; CHEUNG, KING-HO; MAK, DON-ON DANIEL

    2010-01-01

    The inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are a family of Ca2+ release channels localized predominately in the endoplasmic reticulum of all cell types. They function to release Ca2+ into the cytoplasm in response to InsP3 produced by diverse stimuli, generating complex local and global Ca2+ signals that regulate numerous cell physiological processes ranging from gene transcription to secretion to learning and memory. The InsP3R is a calcium-selective cation channel whose gating is regulated not only by InsP3, but by other ligands as well, in particular cytoplasmic Ca2+. Over the last decade, detailed quantitative studies of InsP3R channel function and its regulation by ligands and interacting proteins have provided new insights into a remarkable richness of channel regulation and of the structural aspects that underlie signal transduction and permeation. Here, we focus on these developments and review and synthesize the literature regarding the structure and single-channel properties of the InsP3R. PMID:17429043

  10. Hippocampal CA1 Ripples as Inhibitory Transients

    PubMed Central

    Krishnan, Giri P; Fellous, Jean-Marc; Bazhenov, Maxim

    2016-01-01

    Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep. Neurons active during behavior reactivate in both structures during sleep, in conjunction with characteristic brain oscillations that may form the neural substrate of memory consolidation. In the hippocampus, replay occurs within sharp wave-ripples: short bouts of high-frequency activity in area CA1 caused by excitatory activation from area CA3. In this work, we develop a computational model of ripple generation, motivated by in vivo rat data showing that ripples have a broad frequency distribution, exponential inter-arrival times and yet highly non-variable durations. Our study predicts that ripples are not persistent oscillations but result from a transient network behavior, induced by input from CA3, in which the high frequency synchronous firing of perisomatic interneurons does not depend on the time scale of synaptic inhibition. We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration. Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network. PMID:27093059

  11. Interlamellar CA1 network in the hippocampus.

    PubMed

    Yang, Sunggu; Yang, Sungchil; Moreira, Thais; Hoffman, Gloria; Carlson, Greg C; Bender, Kevin J; Alger, Bradley E; Tang, Cha-Min

    2014-09-01

    To understand the cellular basis of learning and memory, the neurophysiology of the hippocampus has been largely examined in thin transverse slice preparations. However, the synaptic architecture along the longitudinal septo-temporal axis perpendicular to the transverse projections in CA1 is largely unknown, despite its potential significance for understanding the information processing carried out by the hippocampus. Here, using a battery of powerful techniques, including 3D digital holography and focal glutamate uncaging, voltage-sensitive dye, two-photon imaging, electrophysiology, and immunohistochemistry, we show that CA1 pyramidal neurons are connected to one another in an associational and well-organized fashion along the longitudinal axis of the hippocampus. Such CA1 longitudinal connections mediate reliable signal transfer among the pyramidal cells and express significant synaptic plasticity. These results illustrate a need to reconceptualize hippocampal CA1 network function to include not only processing in the transverse plane, but also operations made possible by the longitudinal network. Our data will thus provide an essential basis for future computational modeling studies on information processing operations carried out in the full 3D hippocampal network that underlies its complex cognitive functions. PMID:25139992

  12. Ca2+-Dependent Regulation of Ca2+ Currents in Rat Primary Afferent Neurons: Role of CaMKII and the Effect of Injury

    PubMed Central

    Tang, Qingbo; Bangaru, Madhavi Latha Yadav; Kostic, Sandra; Pan, Bin; Wu, Hsiang-En; Koopmeiners, Andrew S.; Yu, Hongwei; Fischer, Gregory J.; McCallum, J. Bruce; Kwok, Wai-Meng; Hudmon, Andy

    2012-01-01

    Currents through voltage-gated Ca2+ channels (ICa) may be regulated by cytoplasmic Ca2+ levels ([Ca2+]c), producing Ca2+-dependent inactivation (CDI) or facilitation (CDF). Since ICa regulates sensory neuron excitability, altered CDI or CDF could contribute to pain generation after peripheral nerve injury. We explored this by manipulating [Ca2+]c while recording ICa in rat sensory neurons. In uninjured neurons, elevating [Ca2+]c with a conditioning prepulse (−15 mV, 2 s) inactivated ICa measured during subsequent test pulses (−15 mV, 5 ms). This inactivation was Ca2+-dependent (CDI), since it was decreased with elimination of Ca2+ influx by depolarization to above the ICa reversal potential, with high intracellular Ca2+ buffering (EGTA 10 mm or BAPTA 20 mm), and with substitution of Ba2+ for extracellular Ca2+, revealing a residual voltage-dependent inactivation. At longer latencies after conditioning (>6 s), ICa recovered beyond baseline. This facilitation also proved to be Ca2+-dependent (CDF) using the protocols limiting cytoplasmic Ca2+ elevation. Ca2+/calmodulin-dependent protein kinase II (CaMKII) blockers applied by bath (KN-93, myristoyl-AIP) or expressed selectively in the sensory neurons (AIP) reduced CDF, unlike their inactive analogues. Protein kinase C inhibition (chelerythrine) had no effect. Selective blockade of N-type Ca2+ channels eliminated CDF, whereas L-type channel blockade had no effect. Following nerve injury, CDI was unaffected, but CDF was eliminated in axotomized neurons. Excitability of sensory neurons in intact ganglia from control animals was diminished after a similar conditioning pulse, but this regulation was eliminated by injury. These findings indicate that ICa in sensory neurons is subject to both CDI and CDF, and that hyperexcitability following injury-induced loss of CDF may result from diminished CaMKII activity. PMID:22915116

  13. ASteCA: Automated Stellar Cluster Analysis

    NASA Astrophysics Data System (ADS)

    Perren, G. I.; Vázquez, R. A.; Piatti, A. E.

    2015-04-01

    We present the Automated Stellar Cluster Analysis package (ASteCA), a suit of tools designed to fully automate the standard tests applied on stellar clusters to determine their basic parameters. The set of functions included in the code make use of positional and photometric data to obtain precise and objective values for a given cluster's center coordinates, radius, luminosity function and integrated color magnitude, as well as characterizing through a statistical estimator its probability of being a true physical cluster rather than a random overdensity of field stars. ASteCA incorporates a Bayesian field star decontamination algorithm capable of assigning membership probabilities using photometric data alone. An isochrone fitting process based on the generation of synthetic clusters from theoretical isochrones and selection of the best fit through a genetic algorithm is also present, which allows ASteCA to provide accurate estimates for a cluster's metallicity, age, extinction and distance values along with its uncertainties. To validate the code we applied it on a large set of over 400 synthetic MASSCLEAN clusters with varying degrees of field star contamination as well as a smaller set of 20 observed Milky Way open clusters (Berkeley 7, Bochum 11, Czernik 26, Czernik 30, Haffner 11, Haffner 19, NGC 133, NGC 2236, NGC 2264, NGC 2324, NGC 2421, NGC 2627, NGC 6231, NGC 6383, NGC 6705, Ruprecht 1, Tombaugh 1, Trumpler 1, Trumpler 5 and Trumpler 14) studied in the literature. The results show that ASteCA is able to recover cluster parameters with an acceptable precision even for those clusters affected by substantial field star contamination. ASteCA is written in Python and is made available as an open source code which can be downloaded ready to be used from its official site.

  14. The Electronic Spectra of CaN2(+) and Ca(N2)2(+)

    NASA Technical Reports Server (NTRS)

    Rodriguez-Santiago, Luis; Bauschlicher, Charles W., Jr.; Arnold, James (Technical Monitor)

    1998-01-01

    The ground and low-lying electronic states of CaN2(+) are studied at several levels of theory. The results for the X(sup 2)Sigma(+) state and the excited (2)(sup 2)Pi state, arising from occupying the Ca 4p orbital, are in good agreement with experiment. The analogous states of Ca(N2)2(+) are studied using the same theoretical approaches, and predictions are made as to the changes caused by the addition of the second N2 ligand.

  15. A study of the low-lying states of CaAr + and CaKr +

    NASA Astrophysics Data System (ADS)

    Heinemann, Christoph; Koch, Wolfram; Partridge, Harry

    1998-04-01

    The spectroscopic constants of the ground 2Σ + states of CaAr + and CaKr + are determined using high quality ab initio methods. The computed binding energies are 789 and 1252 cm -1, respectively, in good agreement with the experimental determination of Pullins, Scurlock, Reddic and Duncan (J. Chem. Phys. 104 (1996) 7518). The much smaller CaKr + binding energy determined by Buthelezi, Bellert, Lewis and Brucat (Chem. Phys. Lett. 246 (1995) 145) is shown to be due to deficiencies in the method used to approximate the binding energy of the excited state.

  16. Exercise training reverses myocardial dysfunction induced by CaMKIIδC overexpression by restoring Ca2+ homeostasis.

    PubMed

    Høydal, Morten A; Stølen, Tomas O; Kettlewell, Sarah; Maier, Lars S; Brown, Joan Heller; Sowa, Tomas; Catalucci, Daniele; Condorelli, Gianluigi; Kemi, Ole J; Smith, Godfrey L; Wisløff, Ulrik

    2016-07-01

    Several conditions of heart disease, including heart failure and diabetic cardiomyopathy, are associated with upregulation of cytosolic Ca(2+)/calmodulin-dependent protein kinase II (CaMKIIδC) activity. In the heart, CaMKIIδC isoform targets several proteins involved in intracellular Ca(2+) homeostasis. We hypothesized that high-intensity endurance training activates mechanisms that enable a rescue of dysfunctional cardiomyocyte Ca(2+) handling and thereby ameliorate cardiac dysfunction despite continuous and chronic elevated levels of CaMKIIδC CaMKIIδC transgenic (TG) and wild-type (WT) mice performed aerobic interval exercise training over 6 wk. Cardiac function was measured by echocardiography in vivo, and cardiomyocyte shortening and intracellular Ca(2+) handling were measured in vitro. TG mice had reduced global cardiac function, cardiomyocyte shortening (47% reduced compared with WT, P < 0.01), and impaired Ca(2+) homeostasis. Despite no change in the chronic elevated levels of CaMKIIδC, exercise improved global cardiac function, restored cardiomyocyte shortening, and reestablished Ca(2+) homeostasis to values not different from WT. The key features to explain restored Ca(2+) homeostasis after exercise training were increased L-type Ca(2+) current density and flux by 79 and 85%, respectively (P < 0.01), increased sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a) function by 50% (P < 0.01), and reduced diastolic SR Ca(2+) leak by 73% (P < 0.01), compared with sedentary TG mice. In conclusion, exercise training improves global cardiac function as well as cardiomyocyte function in the presence of a maintained high CaMKII activity. The main mechanisms of exercise-induced improvements in TG CaMKIIδC mice are mediated via increased L-type Ca(2+) channel currents and improved SR Ca(2+) handling by restoration of SERCA2a function in addition to reduced diastolic SR Ca(2+) leak. PMID:27231311

  17. Regulation of endoplasmic reticulum Ca2+ oscillations in mammalian eggs

    PubMed Central

    Wakai, Takuya; Zhang, Nan; Vangheluwe, Peter; Fissore, Rafael A.

    2013-01-01

    Summary Changes in the intracellular concentration of free calcium ([Ca2+]i) regulate diverse cellular processes including fertilization. In mammalian eggs, the [Ca2+]i changes induced by the sperm unfold in a pattern of periodical rises, also known as [Ca2+]i oscillations. The source of Ca2+ during oscillations is the endoplasmic reticulum ([Ca2+]ER), but it is presently unknown how [Ca2+]ER is regulated. Here, we show using mouse eggs that [Ca2+]i oscillations induced by a variety of agonists, including PLCζ, SrCl2 and thimerosal, provoke simultaneous but opposite changes in [Ca2+]ER and cause differential effects on the refilling and overall load of [Ca2+]ER. We also found that Ca2+ influx is required to refill [Ca2+]ER, because the loss of [Ca2+]ER was accelerated in medium devoid of Ca2+. Pharmacological inactivation of the function of the mitochondria and of the Ca2+-ATPase pumps PMCA and SERCA altered the pattern of oscillations and abruptly reduced [Ca2+]ER, especially after inactivation of mitochondria and SERCA functions. We also examined the expression of SERCA2b protein and found that it was expressed throughout oocyte maturation and attained a conspicuous cortical cluster organization in mature eggs. We show that its overexpression reduces the duration of inositol-1,4,5-trisphosphate-induced [Ca2+]i rises, promotes initiation of oscillations and enhances refilling of [Ca2+]ER. Collectively, our results provide novel insights on the regulation of [Ca2+]ER oscillations, which underlie the unique Ca2+-signalling system that activates the developmental program in mammalian eggs. PMID:24101727

  18. Ca2+ signals regulate mitochondrial metabolism by stimulating CREB-mediated expression of the mitochondrial Ca2+ uniporter gene mcu

    PubMed Central

    Shanmughapriya, Santhanam; Rajan, Sudarsan; Hoffman, Nicholas E.; Zhang, Xueqian; Guo, Shuchi; Kolesar, Jill E.; Hines, Kevin J.; Ragheb, Jonathan; Jog, Neelakshi R.; Caricchio, Roberto; Baba, Yoshihiro; Zhou, Yandong; Kaufman, Brett; Cheung, Joseph Y.; Kurosaki, Tomohiro; Gill, Donald L.; Madesh, Muniswamy

    2016-01-01

    Cytosolic Ca2+ signals, generated through the coordinated translocation of Ca2+ across the plasma membrane (PM) and endoplasmic reticulum (ER) membrane, mediate diverse cellular responses. Mitochondrial Ca2+ is important for mitochondrial function and, when cytosolic Ca2+ concentrations become too high, mitochondria function as cellular Ca2+ sinks. By measuring mitochondrial Ca2+ currents, we found that mitochondrial Ca2+ uptake was reduced in chicken DT40 B lymphocytes lacking either the ER-localized inositol trisphosphate receptor (IP3R), which releases Ca2+ from the ER, or Orai1 or STIM1, components of the PM-localized Ca2+-permeable channel complex that mediates store-operated calcium entry (SOCE) in response to depletion of ER Ca2+ stores. The abundance of MCU, the pore-forming subunit of the mitochondrial Ca2+ uniporter, was reduced in cells deficient in IP3R, STIM1, or Orai1. Chromatin immunoprecipitation and promoter reporter analyses revealed that the Ca2+-regulated transcription factor CREB directly bound the mcu promoter and stimulated expression. Lymphocytes deficient in IP3R, STIM1, or Orai1 exhibited altered mitochondrial metabolism, indicating that Ca2+ released from the ER and SOCE-mediated signals modulate mitochondrial function. Thus, our results showed that a transcriptional regulatory circuit involving Ca2+-dependent activation of CREB controls the Ca2+-uptake capability of mitochondria and hence regulates mitochondrial metabolism. PMID:25737585

  19. Activation of the Ca2+-sensing receptor increases renal claudin-14 expression and urinary Ca2+ excretion

    PubMed Central

    Dimke, Henrik; Desai, Prajakta; Borovac, Jelena; Lau, Alyssa; Pan, Wanling; Alexander, R. Todd

    2016-01-01

    Kidney stones are a prevalent clinical condition imposing a large economic burden on the health-care system. Hypercalciuria remains the major risk factor for development of a Ca2+-containing stone. The kidney’s ability to alter Ca2+ excretion in response to changes in serum Ca2+ is in part mediated by the Ca2+-sensing receptor (CaSR). Recent studies revealed renal claudin-14 (Cldn14) expression localized to the thick ascending limb (TAL) and its expression to be regulated via the CaSR. We find that Cldn14 expression is increased by high dietary Ca2+ intake and by elevated serum Ca2+ levels induced by prolonged 1,25-dihydroxyvitamin D3 administration. Consistent with this, activation of the CaSR in vivo via administration of the calcimimetic cinacalcet hydrochloride led to a 40-fold increase in Cldn14 mRNA. Moreover, overexpression of Cldn14 in two separate cell culture models decreased paracellular Ca2+ flux by preferentially decreasing cation permeability, thereby increasing transepithelial resistance. These data support the existence of a mechanism whereby activation of the CaSR in the TAL increases Cldn14 expression, which in turn blocks the paracellular reabsorption of Ca2+. This molecular mechanism likely facilitates renal Ca2+ losses in response to elevated serum Ca2+. Moreover, dys-regulation of the newly described CaSR-Cldn14 axis likely contributes to the development of hypercalciuria and kidney stones. PMID:23283989

  20. Ca2+ signals regulate mitochondrial metabolism by stimulating CREB-mediated expression of the mitochondrial Ca2+ uniporter gene MCU.

    PubMed

    Shanmughapriya, Santhanam; Rajan, Sudarsan; Hoffman, Nicholas E; Zhang, Xueqian; Guo, Shuchi; Kolesar, Jill E; Hines, Kevin J; Ragheb, Jonathan; Jog, Neelakshi R; Caricchio, Roberto; Baba, Yoshihiro; Zhou, Yandong; Kaufman, Brett A; Cheung, Joseph Y; Kurosaki, Tomohiro; Gill, Donald L; Madesh, Muniswamy

    2015-03-01

    Cytosolic Ca2+ signals, generated through the coordinated translocation of Ca2+ across the plasma membrane (PM) and endoplasmic reticulum (ER) membrane, mediate diverse cellular responses. Mitochondrial Ca2+ is important for mitochondrial function, and when cytosolic Ca2+ concentration becomes too high, mitochondria function as cellular Ca2+ sinks. By measuring mitochondrial Ca2+ currents, we found that mitochondrial Ca2+ uptake was reduced in chicken DT40 B lymphocytes lacking either the ER-localized inositol trisphosphate receptor (IP3R), which releases Ca2+ from the ER, or Orai1 or STIM1, components of the PM-localized Ca2+ -permeable channel complex that mediates store-operated calcium entry (SOCE) in response to depletion of ER Ca2+ stores. The abundance of MCU, the pore-forming subunit of the mitochondrial Ca2+ uniporter, was reduced in cells deficient in IP3R, STIM1, or Orai1. Chromatin immunoprecipitation and promoter reporter analyses revealed that the Ca2+ -regulated transcription factor CREB (cyclic adenosine monophosphate response element-binding protein) directly bound the MCU promoter and stimulated expression. Lymphocytes deficient in IP3R, STIM1, or Orai1 exhibited altered mitochondrial metabolism, indicating that Ca2+ released from the ER and SOCE-mediated signals modulates mitochondrial function. Thus, our results showed that a transcriptional regulatory circuit involving Ca2+ -dependent activation of CREB controls the Ca2+ uptake capability of mitochondria and hence regulates mitochondrial metabolism. PMID:25737585

  1. Imaging intraorganellar Ca2+ at subcellular resolution using CEPIA

    PubMed Central

    Suzuki, Junji; Kanemaru, Kazunori; Ishii, Kuniaki; Ohkura, Masamichi; Okubo, Yohei; Iino, Masamitsu

    2014-01-01

    The endoplasmic reticulum (ER) and mitochondria accumulate Ca2+ within their lumens to regulate numerous cell functions. However, determining the dynamics of intraorganellar Ca2+ has proven to be difficult. Here we describe a family of genetically encoded Ca2+ indicators, named calcium-measuring organelle-entrapped protein indicators (CEPIA), which can be utilized for intraorganellar Ca2+ imaging. CEPIA, which emit green, red or blue/green fluorescence, are engineered to bind Ca2+ at intraorganellar Ca2+ concentrations. They can be targeted to different organelles and may be used alongside other fluorescent molecular markers, expanding the range of cell functions that can be simultaneously analysed. The spatiotemporal resolution of CEPIA makes it possible to resolve Ca2+ import into individual mitochondria while simultaneously measuring ER and cytosolic Ca2+. We have used these imaging capabilities to reveal differential Ca2+ handling in individual mitochondria. CEPIA imaging is a useful new tool to further the understanding of organellar functions. PMID:24923787

  2. Phosphorylation and activation of nuclear Ca{sup 2+}/calmodulin-dependent protein kinase phosphatase (CaMKP-N/PPM1E) by Ca{sup 2+}/calmodulin-dependent protein kinase I (CaMKI)

    SciTech Connect

    Onouchi, Takashi; Sueyoshi, Noriyuki; Ishida, Atsuhiko; Kameshita, Isamu

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer CaMKP-N/PPM1E underwent proteolytic processing and translocated to cytosol. Black-Right-Pointing-Pointer The proteolysis was effectively inhibited by the proteasome inhibitors. Black-Right-Pointing-Pointer Ser-480 of zebrafish CaMKP-N was phosphorylated by cytosolic CaMKI. Black-Right-Pointing-Pointer Phosphorylation-mimic mutants of CaMKP-N showed enhanced activity. Black-Right-Pointing-Pointer These results suggest that CaMKP-N is regulated by CaMKI. -- Abstract: Nuclear Ca{sup 2+}/calmodulin-dependent protein kinase phosphatase (CaMKP-N/PPM1E) is an enzyme that dephosphorylates and downregulates multifunctional Ca{sup 2+}/calmodulin-dependent protein kinases (CaMKs) as well as AMP-dependent protein kinase. In our previous study, we found that zebrafish CaMKP-N (zCaMKP-N) underwent proteolytic processing and translocated to cytosol in a proteasome inhibitor-sensitive manner. In the present study, we found that zCaMKP-N is regulated by phosphorylation at Ser-480. When zCaMKP-N was incubated with the activated CaMKI, time-dependent phosphorylation of the enzyme was observed. This phosphorylation was significantly reduced when Ser-480 was replaced by Ala, suggesting that CaMKI phosphorylates Ser-480 of zCaMKP-N. Phosphorylation-mimic mutants, S480D and S480E, showed higher phosphatase activities than those of wild type and S480A mutant in solution-based phosphatase assay using various substrates. Furthermore, autophosphorylation of CaMKII after ionomycin treatment was more severely attenuated in Neuro2a cells when CaMKII was cotransfected with the phosphorylation-mimic mutant of zCaMKP-N than with the wild-type or non-phosphorylatable zCaMKP-N. These results strongly suggest that phosphorylation of zCaMKP-N at Ser-480 by CaMKI activates CaMKP-N catalytic activity and thereby downregulates multifunctional CaMKs in the cytosol.

  3. Acidic intracellular Ca(2+) stores and caveolae in Ca(2+) signaling and diabetes.

    PubMed

    Guerrero-Hernandez, Agustin; Gallegos-Gomez, Martin Leonardo; Sanchez-Vazquez, Victor Hugo; Lopez-Mendez, Maria Cristina

    2014-11-01

    Acidic Ca(2+) stores, particularly lysosomes, are newly discovered players in the well-orchestrated arena of Ca(2+) signaling and we are at the verge of understanding how lysosomes accumulate Ca(2+) and how they release it in response to different chemical, such as NAADP, and physical signals. Additionally, it is now clear that lysosomes play a key role in autophagy, a process that allows cells to recycle components or to eliminate damaged structures to ensure cellular well-being. Moreover, lysosomes are being unraveled as hubs that coordinate both anabolism via insulin signaling and catabolism via AMPK. These acidic vesicles have close contact with the ER and there is a bidirectional movement of information between these two organelles that exquisitely regulates cell survival. Lysosomes also connect with plasma membrane where caveolae are located as specialized regions involved in Ca(2+) and insulin signaling. Alterations of all these signaling pathways are at the core of insulin resistance and diabetes. PMID:25182518

  4. Fabrication aspects of PLA-CaP/PLGA-CaP composites for orthopedic applications: a review.

    PubMed

    Zhou, Huan; Lawrence, Joseph G; Bhaduri, Sarit B

    2012-07-01

    For several decades, composites made of polylactic acid-calcium phosphates (PLA-CaP) and polylactic acid-co-glycolic acid-calcium phosphates (PLGA-CaP) have seen widespread uses in orthopedic applications. This paper reviews the fabrication aspects of these composites, following the ubiquitous materials science approach by studying "processing-structure-property" correlations. Various fabrication processes such as microencapsulation, phase separation, electrospinning, supercritical gas foaming, etc., are reviewed, with specific examples of their applications in fabricating these composites. The effect of the incorporation of CaP materials on the mechanical and biological performance of PLA/PLGA is addressed. In addition, this paper describes the state of the art on challenges and innovations concerning CaP dispersion, incorporation of biomolecules/stem cells and long-term degradation of the composites. PMID:22342596

  5. Sarcoplasmic reticulum Ca2+ content, L-type Ca2+ current and the Ca2+ transient in rat myocytes during beta-adrenergic stimulation.

    PubMed Central

    Hussain, M; Orchard, C H

    1997-01-01

    1. The effect of beta-adrenergic stimulation on the relationship between the intracellular Ca2+ transient and the amplitude of the L-type Ca2+ current (ICa) has been investigated in ventricular myocytes isolated from rat hearts. Intracellular [Ca2+] was monitored using fura-2 during field stimulation and while membrane potential was controlled using voltage clamp techniques. 2. The increase in the amplitude, and the rate of decline, of the Ca2+ transient produced by isoprenaline (1.0 mumol l-1) was not significantly different in myocytes generating action potentials and in those voltage clamped with pulses of constant duration and amplitude. 3. Under control conditions, the current-voltage (I-V) relationship for ICa was bell shaped. The amplitude of the Ca2+ transient also showed a bell-shaped voltage dependence. In the presence of isoprenaline, the amplitude of both ICa and the Ca2+ transient was greater at all test potentials and the I-V relationship maintained its bell-shaped voltage dependence. However, the size of the Ca2+ transient was no longer graded with changes in the amplitude of ICa: a small ICa could now elicit a maximal Ca2+ transient. 4. Rapid application of caffeine (10 mmol l-1) was used to elicit Ca2+ release from the sarcoplasmic reticulum (SR). Isoprenaline increased the integral of the subsequent rise in cytoplasmic [Ca2+] to 175 +/- 13% of control. 5. Abbreviation of conditioning pulse duration in the presence of isoprenaline was used to reduce the amplitude of the Ca2+ transient to control levels. Under these conditions, the amplitude of the Ca2+ transient was again graded with the amplitude of ICa in the same way as under control conditions. 6. Nifedipine (2 mumol l-1) was also used to decrease Ca2+ transient amplitude in the presence of isoprenaline. In the presence of isoprenaline and nifedipine, the amplitude of the Ca2+ transient again showed a bell-shaped voltage dependence. 7. The SR Ca(2+)-ATPase inhibitor thapsigargin (2.5 mumol l-1

  6. Role of Ca2+ entry and Ca2+ stores in atypical smooth muscle cell autorhythmicity in the mouse renal pelvis

    PubMed Central

    Lang, R J; Hashitani, H; Tonta, M A; Suzuki, H; Parkington, H C

    2007-01-01

    Background and purpose: Electrically active atypical smooth muscle cells (ASMCs) within the renal pelvis have long been considered to act as pacemaker cells driving pelviureteric peristalsis. We have investigated the role of Ca2+ entry and uptake into and release from internal stores in the generation of Ca2+ transients and spontaneous transient depolarizations (STDs) in ASMCs. Experimental approach: The electrical activity and separately visualized changes in intracellular Ca2+ concentration in typical smooth muscle cells (TSMCs), ASMCs and interstitial cells of Cajal-like cells (ICC-LCs) were recorded using intracellular microelectrodes and a fluorescent Ca2+ indicator, fluo-4. Results: In 1 μM nifedipine, high frequency (10–30 min−1) Ca2+ transients and STDs were recorded in ASMCs, while ICC-LCs displayed low frequency (1–3 min−1) Ca2+ transients. All spontaneous electrical activity and Ca2+ transients were blocked upon removal of Ca2+ from the bathing solution, blockade of Ca2+ store uptake with cyclopiazonic acid (CPA) and with 2-aminoethoxy-diphenylborate (2-APB). STD amplitudes were reduced upon removal of the extracellular Na+ or blockade of IP3 dependent Ca2+ store release with neomycin or U73122. Blockade of ryanodine-sensitive Ca2+ release blocked ICC-LC Ca2+ transients but only reduced Ca2+ transient discharge in ASMCs. STDs in ASMCS were also little affected by DIDS, La3+, Gd3+ or by the replacement of extracellular Cl- with isethionate. Conclusions: ASMCs generated Ca2+ transients and cation-selective STDs via mechanisms involving Ca2+ release from IP3-dependent Ca2+ stores, STD stimulation of TSMCs was supported by Ca2+ entry through L type Ca2+ channels and Ca2+ release from ryanodine-sensitive stores. PMID:17965738

  7. Dual Effect of Phosphate Transport on Mitochondrial Ca2+ Dynamics*

    PubMed Central

    Wei, An-Chi; Liu, Ting; O'Rourke, Brian

    2015-01-01

    The large inner membrane electrochemical driving force and restricted volume of the matrix confer unique constraints on mitochondrial ion transport. Cation uptake along with anion and water movement induces swelling if not compensated by other processes. For mitochondrial Ca2+ uptake, these include activation of countertransporters (Na+/Ca2+ exchanger and Na+/H+ exchanger) coupled to the proton gradient, ultimately maintained by the proton pumps of the respiratory chain, and Ca2+ binding to matrix buffers. Inorganic phosphate (Pi) is known to affect both the Ca2+ uptake rate and the buffering reaction, but the role of anion transport in determining mitochondrial Ca2+ dynamics is poorly understood. Here we simultaneously monitor extra- and intra-mitochondrial Ca2+ and mitochondrial membrane potential (ΔΨm) to examine the effects of anion transport on mitochondrial Ca2+ flux and buffering in Pi-depleted guinea pig cardiac mitochondria. Mitochondrial Ca2+ uptake proceeded slowly in the absence of Pi but matrix free Ca2+ ([Ca2+]mito) still rose to ∼50 μm. Pi (0.001–1 mm) accelerated Ca2+ uptake but decreased [Ca2+]mito by almost 50% while restoring ΔΨm. Pi-dependent effects on Ca2+ were blocked by inhibiting the phosphate carrier. Mitochondrial Ca2+ uptake rate was also increased by vanadate (Vi), acetate, ATP, or a non-hydrolyzable ATP analog (AMP-PNP), with differential effects on matrix Ca2+ buffering and ΔΨm recovery. Interestingly, ATP or AMP-PNP prevented the effects of Pi on Ca2+ uptake. The results show that anion transport imposes an upper limit on mitochondrial Ca2+ uptake and modifies the [Ca2+]mito response in a complex manner. PMID:25963147

  8. Epithelial Ca2+ entry channels: transcellular Ca2+ transport and beyond

    PubMed Central

    Peng, Ji-Bin; Brown, Edward M; Hediger, Matthias A

    2003-01-01

    The recently discovered apical calcium channels CaT1 (TRPV6) and ECaC (TRPV5) belong to a family of six members called the ‘TRPV family’. Unlike the other four members which are nonselective cation channels functioning as heat or osmolarity sensors in the body, CaT1 and ECaC are remarkably calcium-selective channels which serve as apical calcium entry mechanisms in absorptive and secretory tissues. CaT1 is highly expressed in the proximal intestine, placenta and exocrine tissues, whereas ECaC expression is most prominent in the distal convoluted and connecting tubules of the kidney. CaT1 in the intestine is highly responsive to 1,25-dihydroxyvitamin D3 and shows both fast and slow calcium-dependent feedback inhibition to prevent calcium overload. In contrast, ECaC only shows slow inactivation kinetics and appears to be mostly regulated by the calcium load in the kidney. Outside the calcium-transporting epithelia, CaT1 is highly expressed in exocrine tissues such as pancreas, prostate and salivary gland. In these tissues it probably mediates re-uptake of calcium following its release by secretory vesicles. CaT1 also contributes to store-operated calcium entry in Jurkat T-lymphocytes and prostate cancer LNCaP cells, possibly in conjunction with other cellular components which link CaT1 activity to the filling state of the calcium stores. Finally, CaT1 expression is upregulated in prostate cancer and other cancers of epithelial origin, highlighting its potential as a target for cancer therapy. PMID:12869611

  9. Ca-α1T, a fly T-type Ca2+ channel, negatively modulates sleep

    PubMed Central

    Jeong, Kyunghwa; Lee, Soyoung; Seo, Haengsoo; Oh, Yangkyun; Jang, Donghoon; Choe, Joonho; Kim, Daesoo; Lee, Jung-Ha; Jones, Walton D.

    2015-01-01

    Mammalian T-type Ca2+ channels are encoded by three separate genes (Cav3.1, 3.2, 3.3). These channels are reported to be sleep stabilizers important in the generation of the delta rhythms of deep sleep, but controversy remains. The identification of precise physiological functions for the T-type channels has been hindered, at least in part, by the potential for compensation between the products of these three genes and a lack of specific pharmacological inhibitors. Invertebrates have only one T-type channel gene, but its functions are even less well-studied. We cloned Ca-α1T, the only Cav3 channel gene in Drosophila melanogaster, expressed it in Xenopus oocytes and HEK-293 cells, and confirmed it passes typical T-type currents. Voltage-clamp analysis revealed the biophysical properties of Ca-α1T show mixed similarity, sometimes falling closer to Cav3.1, sometimes to Cav3.2, and sometimes to Cav3.3. We found Ca-α1T is broadly expressed across the adult fly brain in a pattern vaguely reminiscent of mammalian T-type channels. In addition, flies lacking Ca-α1T show an abnormal increase in sleep duration most pronounced during subjective day under continuous dark conditions despite normal oscillations of the circadian clock. Thus, our study suggests invertebrate T-type Ca2+ channels promote wakefulness rather than stabilizing sleep. PMID:26647714

  10. Isotope ratios measured in symmetric and asymmetric ^40,48Ca+^40,48Ca collisions

    NASA Astrophysics Data System (ADS)

    Henzlova, D.; Brown, D.; Charity, B.; Chbihi, A.; Coupland, D.; de Souza, R.; Elson, J.; Famiano, M.; Henzl, V.; Hudan, S.; Kilburn, M.; Lee, J.; Lukyanov, S.; Lynch, B.; Rogers, A.; Sanetullaev, A.; Sobotka, L.; Sun, Z.; Tsang, B.; Verde, G.; Wallace, M.; Youngs, M.; Westfall, G.; Vander Molen, A.

    2008-04-01

    In a recent experiment performed at NSCL MSU three reaction systems with very different isospin contents were investigated at incident energy of 80A MeV -- ^40Ca+^40Ca, ^48Ca+^40Ca and ^48Ca+^48Ca. The reactions were studied in a 4pi geometry using an MSU 4pi detector (array of 224 phoswitch scintillators) in combination with HiRA (High Resolution Array, a high granularity Si strip/CsI detector array). The former was used to determine the centrality of the collision, while the latter gave precise energy and angular information of the emitted light fragments. The measured reactions span a wide range of system isospin (N/Z=1 to 1.4) and thus serve as an important source of information on the influence of isospin of the reaction system on some of the basic properties of the dense and highly excited system formed in these collisions. Preliminary results on isotope ratios and isoscaling will be presented. This work is supported by the National Science Foundation under Grant Nos. PHY-0606007 and PHY-9977707.

  11. Ca-α1T, a fly T-type Ca2+ channel, negatively modulates sleep.

    PubMed

    Jeong, Kyunghwa; Lee, Soyoung; Seo, Haengsoo; Oh, Yangkyun; Jang, Donghoon; Choe, Joonho; Kim, Daesoo; Lee, Jung-Ha; Jones, Walton D

    2015-01-01

    Mammalian T-type Ca(2+) channels are encoded by three separate genes (Cav3.1, 3.2, 3.3). These channels are reported to be sleep stabilizers important in the generation of the delta rhythms of deep sleep, but controversy remains. The identification of precise physiological functions for the T-type channels has been hindered, at least in part, by the potential for compensation between the products of these three genes and a lack of specific pharmacological inhibitors. Invertebrates have only one T-type channel gene, but its functions are even less well-studied. We cloned Ca-α1T, the only Cav3 channel gene in Drosophila melanogaster, expressed it in Xenopus oocytes and HEK-293 cells, and confirmed it passes typical T-type currents. Voltage-clamp analysis revealed the biophysical properties of Ca-α1T show mixed similarity, sometimes falling closer to Cav3.1, sometimes to Cav3.2, and sometimes to Cav3.3. We found Ca-α1T is broadly expressed across the adult fly brain in a pattern vaguely reminiscent of mammalian T-type channels. In addition, flies lacking Ca-α1T show an abnormal increase in sleep duration most pronounced during subjective day under continuous dark conditions despite normal oscillations of the circadian clock. Thus, our study suggests invertebrate T-type Ca(2+) channels promote wakefulness rather than stabilizing sleep. PMID:26647714

  12. Effect of sophoridine on Ca(2+) induced Ca(2+) release during heart failure.

    PubMed

    Hu, S-T; Shen, Y-F; Gong, J-M; Yang, Y-J

    2016-03-14

    Sophoridine is a type of alkaloid extract derived from the Chinese herb Sophora flavescens Ait (kushen) and possess a variety of pharmacological effects including anti-inflammation, anti-anaphylaxis, anti-cancer, anti-arrhythmic and so on. However, the effect of sophoridine on heart failure has not been known yet. In this study, the effect of sophoridine on heart failure was investigated using Sprague-Dawley (SD) rat model of chronic heart failure. Morphological results showed that in medium and high dose group, myofilaments were arranged orderly and closely, intermyofibrillar lysis disappeared and mitochondria contained tightly packed cristae compared with heart failure group. We investigated the Ca(2+) induced Ca(2+) transients and assessed the expression of ryanodine receptor (RyR2) and L-type Ca(2+) channel (dihydropyridine receptor, DHPR). We found that the cytosolic Ca(2+) transients were markedly increased in amplitude in medium (deltaF/F(0)=43.33+/-1.92) and high dose groups (deltaF/F(0)=47.21+/-1.25) compared with heart failure group (deltaF/F(0)=16.7+/-1.29, P<0.01), Moreover, we demonstrated that the expression of cardiac DHPR was significantly increased in medium- and high dose-group compared with heart failure rats. Our results suggest that sophoridine could improve heart failure by ameliorating cardiac Ca(2+) induced Ca(2+) transients, and that this amelioration is associated with upregulation of DHPR. PMID:26596316

  13. Rediscovering area CA2: unique properties and functions

    PubMed Central

    Dudek, Serena M.; Alexander, Georgia M.; Farris, Shannon

    2016-01-01

    Hippocampal area CA2 has several features that distinguish it from CA1 and CA3, including a unique gene expression profile, failure to display long-term potentiation and relative resistance to cell death. A recent increase in interest in the CA2 region, combined with the development of new methods to define and manipulate its neurons, has led to some exciting new discoveries on the properties of CA2 neurons and their role in behaviour. Here, we review these findings and call attention to the idea that the definition of area CA2 ought to be revised in light of gene expression data. PMID:26806628

  14. 41Ca in Circumstellar Graphite from Supernovae

    NASA Astrophysics Data System (ADS)

    Amari, S.; Zinner, E.; Lewis, R. S.

    1995-09-01

    We have measured isotopic ratios of C, N, O, Si, K, Ca, and Ti in 13 carbon grains from the low density graphite fraction KE3 (1.65-1.72g/cm3). These grains show the same isotopic signatures as KE3 grains previously measured [1]. Many of them have isotopically heavy C (up to x13 solar) and heavy N (up to x9.7 solar); nine have ^18O excesses (up to x183 solar); 26Al/27Al ratios range up to 0.07. Type II supernovae have previously been proposed as stellar sources of low density graphite grains [1,2,3]. Grain KE3c-551 (14 micrometers in size) has the most extreme C-, N-, and O-isotopic ratios ever measured in a graphite grain (^12C/^13C=7223+/-111, 14N/15N=28+/-2, 16O/18O=2.72+/-0.08). Interestingly, the isotopic ratios of these elements changed during analysis, becoming more anomalous with time. This suggests that isotopically "normal" components had been absorbed onto the grain surface or that partial exchange of the indigenous component had occurred. The above ratios are therefore lower (for C) and upper (for N and O) limits. High ^12C/^13C and ^16O/^17O (4595+/-858) and low ^16O/^18O ratios as well as the Ti isotopic ratios of the grain (delta 46Ti/48Ti=12+/-10 permil, delta ^47Ti/^48Ti=-62+/-9 permil, delta ^49Ti/^48Ti=901+/-16 permil, delta ^50Ti/^48Ti=200+/-12 permil) show the signature of the He/C zone in presupernova stars [4]. Eleven grains were measured for their K, Ca, and Ti isotopic ratios. Four of them, including KE3c-551, have ^41K excesses (218+/-50 permil to 10610+/-326 permil), apparently due to the decay of ^41Ca (T(sub)1/2=1.03 x 10^5a). Inferred ^41Ca/^40Ca ratios range from (1.94+/-0.43) x 10^-3 to (1.65+/-0.38) x 10^-2. In supernovae, ^41Ca is produced by neutron capture in the He/C, the O/C, and the O/Ne zones, as well as by explosive nucleosynthesis in the Si/S zone [4,5]. The expected ^41Ca/^40Ca ratios in the neutron capture zones are 1.6-1.8 x 10^-2 and in the Si/S zone 8 x 10^-4. Two of the 4 grains with ^41K excesses have Ca isotopic

  15. Kinetics and stoichiometry of coupled Na efflux and Ca influx (Na/Ca exchange) in barnacle muscle cells.

    PubMed

    Rasgado-Flores, H; Santiago, E M; Blaustein, M P

    1989-06-01

    Coupled Na+ exit/Ca2+ entry (Na/Ca exchange operating in the Ca2+ influx mode) was studied in giant barnacle muscle cells by measuring 22Na+ efflux and 45Ca2+ influx in internally perfused, ATP-fueled cells in which the Na+ pump was poisoned by 0.1 mM ouabain. Internal free Ca2+, [Ca2+]i, was controlled with a Ca-EGTA buffering system containing 8 mM EGTA and varying amounts of Ca2+. Ca2+ sequestration in internal stores was inhibited with caffeine and a mitochondrial uncoupler (FCCP). To maximize conditions for Ca2+ influx mode Na/Ca exchange, and to eliminate tracer Na/Na exchange, all of the external Na+ in the standard Na+ sea water (NaSW) was replaced by Tris or Li+ (Tris-SW or LiSW, respectively). In both Na-free solutions an external Ca2+ (Cao)-dependent Na+ efflux was observed when [Ca2+]i was increased above 10(-8) M; this efflux was half-maximally activated by [Ca2+]i = 0.3 microM (LiSW) to 0.7 microM (Tris-SW). The Cao-dependent Na+ efflux was half-maximally activated by [Ca2+]o = 2.0 mM in LiSW and 7.2 mM in Tris-SW; at saturating [Ca2+]o, [Ca2+]i, and [Na+]i the maximal (calculated) Cao-dependent Na+ efflux was approximately 75 pmol#cm2.s. This efflux was inhibited by external Na+ and La3+ with IC50's of approximately 125 and 0.4 mM, respectively. A Nai-dependent Ca2+ influx was also observed in Tris-SW. This Ca2+ influx also required [Ca2+]i greater than 10(-8) M. Internal Ca2+ activated a Nai-independent Ca2+ influx from LiSW (tracer Ca/Ca exchange), but in Tris-SW virtually all of the Cai-activated Ca2+ influx was Nai-dependent (Na/Ca exchange). Half-maximal activation was observed with [Na+]i = 30 mM. The fact that internal Ca2+ activates both a Cao-dependent Na+ efflux and a Nai-dependent Ca2+ influx in Tris-SW implies that these two fluxes are coupled; the activating (intracellular) Ca2+ does not appear to be transported by the exchanger. The maximal (calculated) Nai-dependent Ca2+ influx was -25 pmol/cm2.s. At various [Na+]i between 6 and 106 m

  16. Enhanced heavy metal immobilization in soil by grinding with addition of nanometallic Ca/CaO dispersion mixture.

    PubMed

    Mallampati, Srinivasa Reddy; Mitoma, Yoshiharu; Okuda, Tetsuji; Sakita, Shogo; Kakeda, Mitsunori

    2012-10-01

    This study investigated the use of a nanometallic Ca and CaO dispersion mixture for the immobilization of heavy metals (As, Cd, Cr and Pb) in contaminated soil. Simple grinding achieved 85-90% heavy metal immobilization, but it can be enhanced further to 98-100% by addition of a nanometallic Ca/CaO dispersion mixture produced by grinding. Observations using SEM-EDS elemental maps and semi-quantitative analysis showed that the amounts of As, Cd, Cr, and Pb measurable on the soil particle surface decrease after nanometallic Ca/CaO treatment. The leachable heavy metal concentrations were reduced after nanometallic Ca/CaO treatment to concentrations lower than the Japan soil elution standard regulatory threshold: <0.01 mg L(-1) for As, Cd, and Pb; and 0.05 mg L(-1) for Cr. Effects of soil moisture and pH on heavy metal immobilization were not strongly influenced. The most probable mechanisms for the enhancement of heavy metal immobilization capacity with nanometallic Ca/CaO treatment might be due to adsorption and entrapment of heavy metals into newly formed aggregates, thereby prompting aggregation of soil particles and enclosure/binding with Ca/CaO-associated immobile salts. Results suggest that the nanometallic Ca/CaO mixture is suitable for use in immobilization of heavy-metal-contaminated soil under normal moisture conditions. PMID:22818089

  17. Luminal Ca2+ promoting spontaneous Ca2+ release from inositol trisphosphate-sensitive stores in rat hepatocytes.

    PubMed Central

    Missiaen, L; Taylor, C W; Berridge, M J

    1992-01-01

    1. Spontaneous Ca2+ release from the inositol 1,4,5-trisphosphate (InsP3)-sensitive stores in permeabilized hepatocytes was monitored using Fluo-3 to measure the free [Ca2+] of the medium bathing the cells. 2. Permeabilized cells rapidly sequestered Ca2+, reducing the [Ca2+] to 103 +/- 5 nM. Under conditions that depended critically upon cell density and the amount of Ca2+ in the medium, this was followed by a slow increase in [Ca2+] culminating in a substantial Ca2+ spike representing synchronous discharge from the InsP3-sensitive stores. 3. During the latency preceding the Ca2+ spike, the stores increased their sensitivity to InsP3. This sensitization seemed to be an all-or-none phenomenon. 4. Oxidized glutathione and thimerosal promoted the spontaneous release by sensitizing the InsP3 receptor. 5. An increase in the [Ca2+] within the stores was required for both the increased sensitivity to InsP3 and the subsequent spike. 6. Caffeine (6 mM) antagonized the effect of very low InsP3 concentrations and abolished the Ca2+ spike, without itself releasing Ca2+. 7. Our results suggesting that luminal Ca2+ may sensitive InsP3-sensitive stores leading to spontaneous Ca2+ mobilization will be discussed in the light of a modified version of the two-pool model for explaining cytosolic Ca2+ oscillations. PMID:1484365

  18. Activations of the Ca dependent K channel by Ca released from the sarcoplasmic reticulum of mammalian smooth muscles.

    PubMed

    Kitamura, K; Sakai, T; Kajioka, S; Kuriyama, H

    1989-01-01

    In mammalian smooth muscles, the outward K current recorded using the whole cell voltage clamp or patch clamp methods can be classified into the Ca-dependent and independent K currents. The former is sub-classified into the extra- and intra-cellular Ca dependent K current. The intra-cellular Ca dependent K current has a close relation to Ca released from the sarcoplasmic reticulum, i.e. Ca released by inositol 1,4,5-trisphosphate (InsP3), ryanodine or Ca ionophores (A23187 or ionomycin) modify the appearance of the K current. The transient (Ca dependent) outward current evoked by depolarization pulses, as measured using the whole cell voltage clamp method, is closely related with after-hyperpolarization of the action potential as recorded using the microelectrode method and is postulated to be due to activations of the Ca-induced Ca release mechanism in the sarcoplasmic reticulum. The oscillatory (Ca dependent) outward K current is closely related with the amount of Ca released from the sarcoplasmic reticulum during the long depolarization induced by electrical stimulation (command pulse) or applications of Ca releasers such as InsP3 or ryanodine. In this review, the Ca dependent K current recorded from smooth muscle cells is compared with the influx and release of Ca. PMID:2667516

  19. The Structure of Ca2+ Sensor Case16 Reveals the Mechanism of Reaction to Low Ca2+ Concentrations

    PubMed Central

    Leder, Lukas; Stark, Wilhelm; Freuler, Felix; Marsh, May; Meyerhofer, Marco; Stettler, Thomas; Mayr, Lorenz M.; Britanova, Olga V.; Strukova, Lydia A.; Chudakov, Dmitriy M.; Souslova, Ekaterina A.

    2010-01-01

    Here we report the first crystal structure of a high-contrast genetically encoded circularly permuted green fluorescent protein (cpGFP)-based Ca2+ sensor, Case16, in the presence of a low Ca2+ concentration. The structure reveals the positioning of the chromophore within Case16 at the first stage of the Ca2+-dependent response when only two out of four Ca2+-binding pockets of calmodulin (CaM) are occupied with Ca2+ ions. In such a “half Ca2+-bound state”, Case16 is characterized by an incomplete interaction between its CaM-/M13-domains. We also report the crystal structure of the related Ca2+ sensor Case12 at saturating Ca2+ concentration. Based on this structure, we postulate that cpGFP-based Ca2+ sensors can form non-functional homodimers where the CaM-domain of one sensor molecule binds symmetrically to the M13-peptide of the partner sensor molecule. Case12 and Case16 behavior upon addition of high concentrations of free CaM or M13-peptide reveals that the latter effectively blocks the fluorescent response of the sensor. We speculate that the demonstrated intermolecular interaction with endogenous substrates and homodimerization can impede proper functioning of this type of Ca2+ sensors in living cells. PMID:22163646

  20. Comparison of Ca and Ar Diffusion in Phlogopite: Implications for K-Ca and K-Ar Geochronology

    NASA Astrophysics Data System (ADS)

    Cruz, M. F.; Szilas, K.; Grove, M. J.

    2015-12-01

    Coupled geochronology based upon branched decay of 40K-40Ar and 40K-40Ca decay is rarely exploited because 40Ca is the major common isotope of calcium and 40Ca and 40K are difficult to resolve isotopically without resorting to isotope dilution wet chemistry. Recently developed ion microprobe methods based upon measurement of doubly ionized species partially overcome the latter problem and have been applied to high K/Ca micas. The ability to interpret K-Ar and K-Ca results is limited due to uncertainty in the relative diffusion properties of Ca and Ar. To address this problem, we are performing Ar and Ca diffusion experiments and fluid-crystal Ar partitioning experiments with anhydrous F-phlogopite that is stable to 1390°C. As an additional check, we are comparing K-Ca and K-Ar ages from natural mantle phlogopites from a variety of settings to assess the relative retentivity of Ar and Ca. South African xenoliths tend to yield 40Ar/39Ar ages that are much older than K-Ca ages from the same phologopites. Possible excess 40Ar and high common Ca render the comparisons inconclusive, but this suggests that Ca diffuses more readily than Ar in phlogopite. Our most definitive K-Ca phlogopite results (i.e., least affected by common Ca) come from the Archean Seqi dunite of SW Greenland. The K-Ca ages of Seqi phlogopites is 927 ± 26 Ma (2s). Incremental heating 40Ar/39Ar results from the same sample yields a much older result with a terminal age of 3.5 Ga. However, the first 5-10% of 39Ar release are consistent with transient heating at ca. 900 Ma. Considered together, the K-Ca and 40Ar/39Ar results from the Seqi dunite locality strongly suggest that Ca diffusion is more rapid than Ar diffusion in phlogopite.

  1. Oxidative Stress and Ca2+ Release Events in Mouse Cardiomyocytes

    PubMed Central

    Shirokova, Natalia; Kang, Chifei; Fernandez-Tenorio, Miguel; Wang, Wei; Wang, Qiongling; Wehrens, Xander H.T.; Niggli, Ernst

    2014-01-01

    Cellular oxidative stress, associated with a variety of common cardiac diseases, is well recognized to affect the function of several key proteins involved in Ca2+ signaling and excitation-contraction coupling, which are known to be exquisitely sensitive to reactive oxygen species. These include the Ca2+ release channels of the sarcoplasmic reticulum (ryanodine receptors or RyR2s) and the Ca2+/calmodulin-dependent protein kinase II (CaMKII). Oxidation of RyR2s was found to increase the open probability of the channel, whereas CaMKII can be activated independent of Ca2+ through oxidation. Here, we investigated how oxidative stress affects RyR2 function and SR Ca2+ signaling in situ, by analyzing Ca2+ sparks in permeabilized mouse cardiomyocytes under a broad range of oxidative conditions. The results show that with increasing oxidative stress Ca2+ spark duration is prolonged. In addition, long and very long-lasting (up to hundreds of milliseconds) localized Ca2+ release events started to appear, eventually leading to sarcoplasmic reticulum (SR) Ca2+ depletion. These changes of release duration could be prevented by the CaMKII inhibitor KN93 and did not occur in mice lacking the CaMKII-specific S2814 phosphorylation site on RyR2. The appearance of long-lasting Ca2+ release events was paralleled by an increase of RyR2 oxidation, but also by RyR-S2814 phosphorylation, and by CaMKII oxidation. Our results suggest that in a strongly oxidative environment oxidation-dependent activation of CaMKII leads to RyR2 phosphorylation and thereby contributes to the massive prolongation of SR Ca2+ release events. PMID:25517148

  2. Conserved properties of individual Ca2+-binding sites in calmodulin

    PubMed Central

    Halling, D. Brent; Liebeskind, Benjamin J.; Hall, Amelia W.; Aldrich, Richard W.

    2016-01-01

    Calmodulin (CaM) is a Ca2+-sensing protein that is highly conserved and ubiquitous in eukaryotes. In humans it is a locus of life-threatening cardiomyopathies. The primary function of CaM is to transduce Ca2+ concentration into cellular signals by binding to a wide range of target proteins in a Ca2+-dependent manner. We do not fully understand how CaM performs its role as a high-fidelity signal transducer for more than 300 target proteins, but diversity among its four Ca2+-binding sites, called EF-hands, may contribute to CaM’s functional versatility. We therefore looked at the conservation of CaM sequences over deep evolutionary time, focusing primarily on the four EF-hand motifs. Expanding on previous work, we found that CaM evolves slowly but that its evolutionary rate is substantially faster in fungi. We also found that the four EF-hands have distinguishing biophysical and structural properties that span eukaryotes. These results suggest that all eukaryotes require CaM to decode Ca2+ signals using four specialized EF-hands, each with specific, conserved traits. In addition, we provide an extensive map of sites associated with target proteins and with human disease and correlate these with evolutionary sequence diversity. Our comprehensive evolutionary analysis provides a basis for understanding the sequence space associated with CaM function and should help guide future work on the relationship between structure, function, and disease. PMID:26884197

  3. Ca cycling and isotopic fluxes in forested ecosystems in Hawaii

    USGS Publications Warehouse

    Wiegand, B.A.; Chadwick, O.A.; Vitousek, P.M.; Wooden, J.L.

    2005-01-01

    Biogeochemical processes fractionate Ca isotopes in plants and soils along a 4 million year developmental sequence in the Hawaiian Islands. We observed that plants preferentially take up 40Ca relative to 44Ca, and that biological fractionation and changes in the relative contributions from volcanic and marine sources produce a significant increase in 44Ca in soil exchangeable pools. Our results imply moderate fluxes enriched in 44Ca from strongly nutrient-depleted old soils, in contrast with high 40Ca fluxes in young and little weathered environments. In addition, biological fractionation controls divergent geochemical pathways of Ca and Sr in the plant-soil system. While Ca depletes progressively with increasing soil age, Sr/Ca ratios increase systematically. Sr isotope ratios provide a valuable tracer for provenance studies of alkaline earth elements in forested ecosystems, but its usefulness is limited when deciphering biogeochemical processes involved in the terrestrial Ca cycle. Ca isotopes in combination with Sr/ Ca ratios reveal more complex processes involved in the biogeochemistry of Ca and Sr. Copyright 2005 by the American Geophysical Union.

  4. Ca sup + emission in the sunlit ionosphere

    SciTech Connect

    Torr, M.R. ); Torr, D.G.; Bhatt, P.; Swift, W.; Dougani, H. )

    1990-03-01

    In the course of a program of twilight airglow observations from the McDonald Observatory in southwest Texas, the resonance fluorescence emissions from calcium ions were measured. In particular, twilight sequences were obtained during the period of December 19-22, 1987, which coincided with the Ursids meteorite shower. During this meteorite event the intensities of the Ca{sup +} emission lines at 3,934 {angstrom} increased to the point that the surface brightness profiles could be inverted to volume emission rate profiles. These profiles show evidence for strong spatial redistribution of the Ca{sup +} over the course of three days. Prior to the onset of the meteorite activity, emissions from the Ca{sup +} originate from below 100 km, on the occasions when the emissions are visible. By the evening of December 19 a peak is measurable at 108 km. On the morning of December 22, a high-altitude peak was observed above 250 km, with a larger peak down at approximately 85 km. By the evening of December 22, the emission had substantially intensified, with the peak of the layer being at 80 km or below, but with emission being produced all the way up to at least 160 km. Observations of these emissions during meteor shower periods could provide a valuable tracer for the processes responsible for the transport of ions in the D, E, and F region, allowing the full altitude and latitude extent of the distribution to be determined.

  5. TRP-Na(+)/Ca(2+) Exchanger Coupling.

    PubMed

    Harper, Alan G S; Sage, Stewart O

    2016-01-01

    Na(+)/Ca(2+) exchangers (NCXs) have traditionally been viewed principally as a means of Ca(2+) removal from non-excitable cells. However there has recently been increasing interest in the operation of NCXs in reverse mode acting as a means of eliciting Ca(2+) entry into these cells. Reverse mode exchange requires a significant change in the normal resting transmembrane ion gradients and membrane potential, which has been suggested to occur principally via the coupling of NCXs to localised Na(+) entry through non-selective cation channels such as canonical transient receptor potential (TRPC) channels. Here we review evidence for functional or physical coupling of NCXs to non-selective cation channels, and how this affects NCX activity in non-excitable cells. In particular we focus on the potential role of nanojunctions, where the close apposition of plasma and intracellular membranes may help create the conditions needed for the generation of localised rises in Na(+) concentration that would be required to trigger reverse mode exchange. PMID:27161225

  6. Superconductivity in Ca-doped graphene laminates

    NASA Astrophysics Data System (ADS)

    Chapman, J.; Su, Y.; Howard, C. A.; Kundys, D.; Grigorenko, A. N.; Guinea, F.; Geim, A. K.; Grigorieva, I. V.; Nair, R. R.

    2016-03-01

    Despite graphene’s long list of exceptional electronic properties and many theoretical predictions regarding the possibility of superconductivity in graphene, its direct and unambiguous experimental observation has not been achieved. We searched for superconductivity in weakly interacting, metal decorated graphene crystals assembled into so-called graphene laminates, consisting of well separated and electronically decoupled graphene crystallites. We report robust superconductivity in all Ca-doped graphene laminates. They become superconducting at temperatures (Tc) between ≈4 and ≈6 K, with Tc’s strongly dependent on the confinement of the Ca layer and the induced charge carrier concentration in graphene. We find that Ca is the only dopant that induces superconductivity in graphene laminates above 1.8 K among several dopants used in our experiments, such as potassium, caesium and lithium. By revealing the tunability of the superconducting response through doping and confinement of the metal layer, our work shows that achieving superconductivity in free-standing, metal decorated monolayer graphene is conditional on an optimum confinement of the metal layer and sufficient doping, thereby bringing its experimental realization within grasp.

  7. Superconductivity in CaBi2.

    PubMed

    Winiarski, M J; Wiendlocha, B; Gołąb, S; Kushwaha, S K; Wiśniewski, P; Kaczorowski, D; Thompson, J D; Cava, R J; Klimczuk, T

    2016-08-01

    Superconductivity is observed with critical temperature Tc = 2.0 K in self-flux-grown single crystals of CaBi2. This material adopts the ZrSi2 structure type with lattice parameters a = 4.696(1) Å, b = 17.081(2) Å and c = 4.611(1) Å. The crystals of CaBi2 were studied by means of magnetic susceptibility, specific heat and electrical resistivity measurements. The heat capacity jump at Tc is ΔC/γTc = 1.41, confirming bulk superconductivity; the Sommerfeld coefficient γ = 4.1 mJ mol(-1) K(-2) and the Debye temperature ΘD = 157 K. The electron-phonon coupling strength is λel-ph = 0.59, and the thermodynamic critical field Hc is low, between 111 and 124 Oe CaBi2 is a moderate coupling type-I superconductor. Results of electronic structure calculations are reported and charge densities, electronic bands, densities of states and Fermi surfaces are discussed, focusing on the effects of spin-orbit coupling and electronic property anisotropy. We find a mixed quasi-2D + 3D character in the electronic structure, which reflects the layered crystal structure of the material. PMID:27435423

  8. Superconductivity in Ca-doped graphene laminates.

    PubMed

    Chapman, J; Su, Y; Howard, C A; Kundys, D; Grigorenko, A N; Guinea, F; Geim, A K; Grigorieva, I V; Nair, R R

    2016-01-01

    Despite graphene's long list of exceptional electronic properties and many theoretical predictions regarding the possibility of superconductivity in graphene, its direct and unambiguous experimental observation has not been achieved. We searched for superconductivity in weakly interacting, metal decorated graphene crystals assembled into so-called graphene laminates, consisting of well separated and electronically decoupled graphene crystallites. We report robust superconductivity in all Ca-doped graphene laminates. They become superconducting at temperatures (Tc) between ≈4 and ≈6 K, with Tc's strongly dependent on the confinement of the Ca layer and the induced charge carrier concentration in graphene. We find that Ca is the only dopant that induces superconductivity in graphene laminates above 1.8 K among several dopants used in our experiments, such as potassium, caesium and lithium. By revealing the tunability of the superconducting response through doping and confinement of the metal layer, our work shows that achieving superconductivity in free-standing, metal decorated monolayer graphene is conditional on an optimum confinement of the metal layer and sufficient doping, thereby bringing its experimental realization within grasp. PMID:26979564

  9. Superconductivity in Ca-doped graphene laminates

    PubMed Central

    Chapman, J.; Su, Y.; Howard, C. A.; Kundys, D.; Grigorenko, A. N.; Guinea, F.; Geim, A. K.; Grigorieva, I. V.; Nair, R. R.

    2016-01-01

    Despite graphene’s long list of exceptional electronic properties and many theoretical predictions regarding the possibility of superconductivity in graphene, its direct and unambiguous experimental observation has not been achieved. We searched for superconductivity in weakly interacting, metal decorated graphene crystals assembled into so-called graphene laminates, consisting of well separated and electronically decoupled graphene crystallites. We report robust superconductivity in all Ca-doped graphene laminates. They become superconducting at temperatures (Tc) between ≈4 and ≈6 K, with Tc’s strongly dependent on the confinement of the Ca layer and the induced charge carrier concentration in graphene. We find that Ca is the only dopant that induces superconductivity in graphene laminates above 1.8 K among several dopants used in our experiments, such as potassium, caesium and lithium. By revealing the tunability of the superconducting response through doping and confinement of the metal layer, our work shows that achieving superconductivity in free-standing, metal decorated monolayer graphene is conditional on an optimum confinement of the metal layer and sufficient doping, thereby bringing its experimental realization within grasp. PMID:26979564

  10. Dissociation of Ca-bearing Molecules as a Source of Mercury's Ca Exosphere

    NASA Astrophysics Data System (ADS)

    Burger, Matthew H.; Killen, Rosemary M.

    2015-11-01

    Observations of Mercury's calcium exosphere by MESSENGER have revealed three key features: (1) The Ca is extremely energetic, with a temperature ~70,000 K if the source is thermal, (2) the source region is located in the dawn hemisphere, and (3) there is a strong annual variation in the Ca source rate (Burger et al. 2014). Killen and Hahn (2015) have shown that the source rate is consistent with impact vaporization by interplanetary dust and the intersection of Mercury with a cometary dust stream (likely associated with Comet Encke, Christou et al., submitted).Killen et al. (2005) suggested that energetic calcium could be produced by the dissociation of Ca-bearing molecules produced in impact vaporization plumes. We test this hypothesis with a Monte Carlo model that follows the evolution of atomic and molecular calcium produced in impact plumes. Ca-bearing molecules such as CaO, CaOH, and Ca(OH)2 are more likely to be are produced in vapor plumes than atomic Ca (Berezhnoy and Klumov 2008); these molecules quickly break apart either through vibrational dissociation or photodissociation. The excess energy associated with dissociation gives the atomic Ca an extra energy boost above the temperature of the impact plumes (~5000 K). We determine impact vaporization rates and excess energies required by the dissociation process to reproduce the scale height and spatial morphology of the Ca exosphere as observed by the MESSENGER Ultraviolet and Visible Spectrometer (UVVS).ReferencesBerezhnoy, A.A. and Klumov, B.A., Impacts as sources of the exosphere on Mercury, Icarus, 195, 511-522, 2008, doi:10.1016/j.icarus.2008.01.005.Burger, M.H., et al., Seasonal variations in Mercury's dayside calcium exosphere, Icarus, 238, 51-58, 2014, doi:10.1016/j.icarus.2014.04.049.Killen, R.M., et al., The calcium exosphere of Mercury, Icarus, 173, 300-311, 2005, doi:10.1016/j.icarus.2004.08.022.Killen, R.M. and Hahn, J.M., Impact vaporization as a possible source ofMercury's calcium exosphere

  11. Nitric oxide inhibits capacitative Ca2+ entry by suppression of mitochondrial Ca2+ handling

    PubMed Central

    Thyagarajan, Baskaran; Malli, Roland; Schmidt, Kurt; Graier, Wolfgang F; Groschner, Klaus

    2002-01-01

    Nitric oxide (NO) is a key modulator of cellular Ca2+ signalling and a determinant of mitochondrial function. Here, we demonstrate that NO governs capacitative Ca2+ entry (CCE) into HEK293 cells by impairment of mitochondrial Ca2+ handling. Authentic NO as well as the NO donors 1-[2-(carboxylato)pyrrolidin-1-yl]diazem-1-ium-1,2-diolate (ProliNO) and 2-(N,N-diethylamino)-diazenolate-2-oxide (DEANO) suppressed CCE activated by thapsigargin (TG)-induced store depletion. Threshold concentrations for inhibition of CCE by ProliNO and DEANO were 0.3 and 1 μM, respectively. NO-induced inhibition of CCE was not mimicked by peroxynitrite (100 μM), the peroxynitrite donor 3-morpholino-sydnonimine (SIN-1, 100 μM) or 8-bromoguanosine 3′,5′-cyclic monophosphate (8-BrcGMP, 1 mM). In addition, the guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazole[4,3-a] quinoxalin-1-one (ODQ, 30 μM) failed to antagonize the inhibitory action of NO on CCE. DEANO (1–10 μM) suppressed mitochondrial respiration as evident from inhibition of cellular oxygen consumption. Experiments using fluorescent dyes to monitor mitochondrial membrane potential and mitochondrial Ca2+ levels, respectively, indicated that DEANO (10 μM) depolarized mitochondria and suppressed mitochondrial Ca2+ sequestration. The inhibitory effect of DEANO on Ca2+ uptake into mitochondria was confirmed by recording mitochondrial Ca2+ during agonist stimulation in HEK293 cells expressing ratiometric-pericam in mitochondria. DEANO (10 μM) failed to inhibit Ba2+ entry into TG-stimulated cells when extracellular Ca2+ was buffered below 1 μM, while clear inhibition of Ba2+ entry into store depleted cells was observed when extracellular Ca2+ levels were above 10 μM. Moreover, buffering of intracellular Ca2+ by use of N,N′-[1,2-ethanediylbis(oxy-2,1-phenylene)] bis [N-[25-[(acetyloxy) methoxy]-2-oxoethyl

  12. Multimodality of Ca2+ signaling in rat atrial myocytes.

    PubMed

    Morad, Martin; Javaheri, Ashkan; Risius, Tim; Belmonte, Steve

    2005-06-01

    It has been suggested that the multiplicity of Ca(2+) signaling pathways in atrial myocytes may contribute to the variability of its function. This article reports on a novel Ca(2+) signaling cascade initiated by mechanical forces induced by "puffing" of solution onto the myocytes. Ca(i) transients were measured in fura-2 acetoxymethyl (AM) loaded cells using alternating 340- and 410-nm excitation waves at 1.2 kHz. Pressurized puffs of bathing solutions, applied by an electronically controlled micro-barrel system, activated slowly (approximately 300 ms) developing Ca(i) transients that lasted 1,693 +/- 68 ms at room temperature. Subsequent second and third puffs, applied at approximately 20 s intervals activated significantly smaller or no Ca(i) transients. Puff-triggered Ca(i) transients could be reactivated once again following caffeine (10 mM)-induced release of Ca(2+) from sarcoplasmic reticulum (SR). Puff-triggered Ca(i) transients were independent of [Ca(2+)](o), and activation of voltage-gated Ca(2+) or cationic stretch channels or influx of Ca(2+) on Na(+)/Ca(2+)exchanger, because puffing solution containing no Ca(2+), 10 microM diltiazem, 1 mM Cd(2+), 5 mM Ni(2+), or 100 microM Gd(3+) failed to suppress them. Puff-triggered Ca(i) transients were enhanced in paced compared to quiescent myocytes. Electrically activated Ca(i) transients triggered during the time course of puff-induced transients were unaltered, suggesting functionally separate Ca(2+) pools. Contribution of inositol 1,4,5-triphosphate (IP(3))-gated or mitochondrial Ca(2+) pools or modulation of SR stores by nitric oxide/nitric oxide synthase (NO/NOS) signaling were evaluated using 0.5 to 500 microM 2-aminoethoxydiphenyl borate (2-APB) and 0.1 to 1 microM carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), and 1 mM Nomega-Nitro-L-arginine methyl ester (L-NAME) and 7-nitroindizole, respectively. Only FCCP appeared to significantly suppress the puff-triggered Ca(i) transients. It was

  13. Ca Isotopic Ratios in Igneous Rocks: Some Preliminary Results

    NASA Astrophysics Data System (ADS)

    Huang, S.; Farkas, J.; Jacobsen, S. B.

    2009-12-01

    Calcium (Ca) is the 5th most abundant element on the Earth, and it is an important geochemical and cosmochemical tracer. It has six isotopes and only H and He have a larger percentage mass difference (Δm/m) between the heaviest and the lightest isotopes. Systematic Ca isotopic studies have mostly focused on low-temperature geochemical processes, and most Ca isotopic analyses have been applied on modern and ancient marine carbonates and sulphates, documenting large and systematic isotopic variations, which were used to infer the chemical evolution of seawater. Detailed work on igneous rocks is very limited. Here we show two examples of how stable Ca isotopic ratios can be a useful geochemical tool in understanding igneous processes. Ca isotopic fractionation between coexisting clinopyroxene and orthopyroxene from mantle peridotites: We report Ca isotopic ratios on co-existing clino- and ortho-pyroxenes from Kilbourne Hole and San Carlos mantle peridotites. The 44Ca/40Ca in orthopyroxenes is ~0.5 per mil heavier than that in co-existing clinopyroxenes. Combined with published Ca isotopic data on low-temperature Ca-bearing minerals (calcite, aragonite and barite), we show that the fractionation of Ca isotopes between Ca-bearing minerals (at both low-temperature and high-temperature) is primarily controlled by the strength of Ca-O bond in the minerals. The mineral with shorter (i.e., stronger) Ca-O bond yields heavier Ca isotopic ratio. Using our measured 44Ca/40Ca in mantle pyroxenes and the relative proportions of major Ca-bearing minerals in the upper mantle, the estimated 44Ca/40Ca of the upper mantle is 1.1 per mil heavier relative to the NIST 915a, ~0.1 to 0.2 per mil higher than basalts. Ca isotopic variation in Hawaiian shield lavas: Large geochemical and isotopic variations have been observed in lavas forming the large tholeiitic shields of Hawaiian volcanoes, with lavas from the surface of the Koolau volcano (Makapuu-stage) defining one compositional and

  14. Substantial depletion of the intracellular Ca2+ stores is required for macroscopic activation of the Ca2+ release-activated Ca2+ current in rat basophilic leukaemia cells.

    PubMed

    Fierro, L; Parekh, A B

    2000-01-15

    1. Tight-seal whole-cell patch clamp experiments were performed to examine the ability of different intracellular Ca2+ mobilising agents to activate the Ca2+ release-activated Ca2+ current (ICRAC) in rat basophilic leukaemia (RBL-1) cells under conditions of weak cytoplasmic Ca2+ buffering. 2. Dialysis with a maximal concentration of inositol 1,4,5-trisphosphate (IP3) routinely failed to activate macroscopic ICRAC in low buffer (0.mM EGTA, BAPTA or dimethyl BAPTA), whereas it activated the current to its maximal extent in high buffer (10 mM EGTA). Dialysis with a poorly metabolisable analogue of IP3, with ionomycin, or with IP3 and ionomycin all failed to generate macroscopic ICRAC in low Ca2+ buffering conditions. 3. Dialysis with the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump blocker thapsigargin was able to activate ICRAC even in the presence of low cytoplasmic Ca2+ buffering, albeit at a slow rate. Exposure to IP3 together with the SERCA blockers thapsigargin, thapsigargicin or cyclopiazonic acid rapidly activated ICRAC in low buffer. 4. Following activation of ICRAC by intracellular dialysis with IP3 and thapsigargin in low buffer, the current was very selective for Ca2+ (apparent KD of 1 mM) Sr2+ and Ba2+ were less effective charge carriers and Na+ was not conducted to any appreciable extent. The ionic selectivity of ICRAC was very similar in low or high intracellular Ca2+ buffer. 5. Fast Ca2+-dependent inactivation of ICRAC occurred at a similar rate and to a similar extent in low or high Ca2+ buffer. Ca2+-dependent inactivation is not the reason why macroscopic ICRAC cannot be seen under conditions of low cytoplasmic Ca2+ buffering. 6. ICRAC could be activated by combining IP3 with thapsigargin, even in the presence of 100 microM Ca2+ and the absence of any exogenous Ca2+ chelator, where ATP and glutamate represented the only Ca2+ buffers in the pipette solution. 7. Our results suggest that a threshold exists within the IP3-sensitive Ca2+ store

  15. Small event Ca2+ release: a probable precursor of Ca2+ sparks in frog skeletal muscle.

    PubMed Central

    Shirokova, N; Ríos, E

    1997-01-01

    1. Fluo-3 fluorescence associated with Ca2+ release was recorded with confocal microscopy in single muscle fibres. Clamp depolarization to -65 or -60 mV elicited Ca2+ sparks with amplitudes and spatial widths distributed approximately normally, with mean values of 0.79 of resting fluorescence and 0.8 micron (S.D., 0.17 and 0.2 micron; n = 193), respectively. Given these distributions, events of amplitude less than 0.45 or width less than 0.4 micron are unlikely to be sparks. 2. Low voltage depolarization (-72 mV) elicited only one spark per triad every 6 s, but generated a relative increase in fluorescence at triads of 0.05. This increase must therefore have been due to events smaller than sparks. 3. The variance/mean ratio of triadic fluorescence gradients averaged 0.11 at low voltages and increased severalfold at the higher voltages at which sparks appeared, indicating the existence of at least two event amplitudes. 4. Tetracaine (200 microM) reversibly abolished sparks and the early peak of Ca2+ release at all voltages. In its presence, discrete events were smaller than the spark criterion, and triadic gradients had a variance/mean ratio of 0.11. 5. The phenylalkylamine D600 (2 microM) reduced release at all voltages, abolishing sparks and the peak of Ca2+ release at low but not at high voltages. 6. The parallel abolition of all sparks and the peak of Ca2+ release indicates that both phenomena are activated by Ca2+. The restoration of sparks by voltage in D600 suggests that release in small events provides the trigger Ca2+ for activation of sparks. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9234193

  16. Pressure-induced structural transformation of CaC2.

    PubMed

    Wang, Lu; Huang, Xiaoli; Li, Da; Huang, Yanping; Bao, Kuo; Li, Fangfei; Wu, Gang; Liu, Bingbing; Cui, Tian

    2016-05-21

    The high pressure structural changes of calcium carbide CaC2 have been investigated with Raman spectroscopy and synchrotron X-ray diffraction (XRD) techniques in a diamond anvil cell at room temperature. At ambient conditions, two forms of CaC2 co-exist. Above 4.9 GPa, monoclinic CaC2-ii diminished indicating the structural phase transition from CaC2-ii to CaC2-i. At about 7.0 GPa, both XRD patterns and Raman spectra confirmed that CaC2-i transforms into a metallic Cmcm structure which contains polymeric carbon chains. Along with the phase transition, the isolated C2 dumbbells are polymerized into zigzag chains resulting in a large volume collapse with 22.4%. Above 30.0 GPa, the XRD patterns of CaC2 become featureless and remain featureless upon decompression, suggesting an irreversible amorphization of CaC2. PMID:27208957

  17. The emerging role of CaMKII in cancer

    PubMed Central

    Wang, Yan-yang; Zhao, Ren; Zhe, Hong

    2015-01-01

    Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional serine/threonine kinases best known for its critical role in learning and memory. Recent studies suggested that high levels of CaMKII also expressed in variety of malignant diseases. In this review, we focus on the structure and biology properties of CaMKII, including the role of CaMKII in the regulation of cancer progression and therapy response. We also describe the role of CaMKII in the diagnosis of different kinds of cancer and recent progress in the development of CaMKII inhibitors. These data establishes CaMKII as a novel target whose modulation presents new opportunities for cancer diagnosis and treatment. PMID:25961153

  18. Pressure-induced structural transformation of CaC2

    NASA Astrophysics Data System (ADS)

    Wang, Lu; Huang, Xiaoli; Li, Da; Huang, Yanping; Bao, Kuo; Li, Fangfei; Wu, Gang; Liu, Bingbing; Cui, Tian

    2016-05-01

    The high pressure structural changes of calcium carbide CaC2 have been investigated with Raman spectroscopy and synchrotron X-ray diffraction (XRD) techniques in a diamond anvil cell at room temperature. At ambient conditions, two forms of CaC2 co-exist. Above 4.9 GPa, monoclinic CaC2-ii diminished indicating the structural phase transition from CaC2-ii to CaC2-i. At about 7.0 GPa, both XRD patterns and Raman spectra confirmed that CaC2-i transforms into a metallic Cmcm structure which contains polymeric carbon chains. Along with the phase transition, the isolated C2 dumbbells are polymerized into zigzag chains resulting in a large volume collapse with 22.4%. Above 30.0 GPa, the XRD patterns of CaC2 become featureless and remain featureless upon decompression, suggesting an irreversible amorphization of CaC2.

  19. MicroRNA-145 suppresses ROS-induced Ca{sup 2+} overload of cardiomyocytes by targeting CaMKIIδ

    SciTech Connect

    Cha, Min-Ji; Jang, Jin-Kyung; Ham, Onju; Song, Byeong-Wook; Lee, Se-Yeon; Lee, Chang Yeon; Park, Jun-Hee; Lee, Jiyun; Seo, Hyang-Hee; Choi, Eunhyun; Jeon, Woo-min; Hwang, Hye Jin; Shin, Hyun-Taek; and others

    2013-06-14

    Highlights: •CaMKIIδ mediates H{sub 2}O{sub 2}-induced Ca{sup 2+} overload in cardiomyocytes. •miR-145 can inhibit Ca{sup 2+} overload. •A luciferase assay confirms that miR-145 functions as a CaMKIIδ-targeting miRNA. •Overexpression of miR-145 regulates CaMKIIδ-related genes and ameliorates apoptosis. -- Abstract: A change in intracellular free calcium (Ca{sup 2+}) is a common signaling mechanism of reperfusion-induced cardiomyocyte death. Calcium/calmodulin dependent protein kinase II (CaMKII) is a critical regulator of Ca{sup 2+} signaling and mediates signaling pathways responsible for functions in the heart including hypertrophy, apoptosis, arrhythmia, and heart disease. MicroRNAs (miRNA) are involved in the regulation of cell response, including survival, proliferation, apoptosis, and development. However, the roles of miRNAs in Ca{sup 2+}-mediated apoptosis of cardiomyocytes are uncertain. Here, we determined the potential role of miRNA in the regulation of CaMKII dependent apoptosis and explored its underlying mechanism. To determine the potential roles of miRNAs in H{sub 2}O{sub 2}-mediated Ca{sup 2+} overload, we selected and tested 6 putative miRNAs that targeted CaMKIIδ, and showed that miR-145 represses CaMKIIδ protein expression and Ca{sup 2+} overload. We confirmed CaMKIIδ as a direct downstream target of miR-145. Furthermore, miR-145 regulates Ca{sup 2+}-related signals and ameliorates apoptosis. This study demonstrates that miR-145 regulates reactive oxygen species (ROS)-induced Ca{sup 2+} overload in cardiomyocytes. Thus, miR-145 affects ROS-mediated gene regulation and cellular injury responses.

  20. Application of Ca stable isotopes to long-term changes in the Ca cycle of a Northern Hardwood forest

    NASA Astrophysics Data System (ADS)

    Kurtz, A. C.; Takagi, K.; Bailey, S. W.; Bullen, T. D.

    2015-12-01

    The Hubbard Brook Ecosystem Study (New Hampshire, USA) presents an unusual opportunity for the application of innovative isotope methods in forest biogeochemistry. Changes in biogeochemical cycling resulting from decades of acid deposition, subsequent reductions in acid deposition, and a series of experimental treatments (harvesting, Ca amendment) have been studied continuously for 60 years at this site. Importantly, researchers have archived soil, water, and vegetation samples for much of the site's history. Our work seeks to complement earlier mass balance studies of Ca cycling by measuring Ca isotope ratios on archived samples. In the first component of our study, we examined the Ca isotopic response to an experimental clearcut in the early 1980's. Earlier work showed that the clearcut promoted dramatic loss of Ca from the watershed, indicated by a 5-fold increase in streamwater Ca concentrations. The mechanism for this loss was unclear as no resolvable changes in soil Ca pools were observed. Our work shows that streamwater dissolved Ca becomes isotopically lighter as Ca concentrations increase. These data are best accounted for by an increase in Ca loss from the soil cation exchange complex. Soil exchangeable δ44Ca itself evolves towards lighter values in the years following the experimental harvest. We interpret this as replenishment of the soil exchange complex by release of isotopically light Ca from root biomass. In the second component of our study, we examine decadal-scale changes in streamwater and soil Ca in an un-manipulated biogeochemical reference watershed. Historical data from Hubbard Brook show that streamwater Ca concentrations began decreasing sharply in the early 1970's, attributed to decreased deposition of both acidity and Ca with the passage of the Clean Air Act. Preliminary data indicate no resolvable change in the average δ44Ca of streamwater, with variability mostly attributable to discharge (flowpath control). Preliminary data

  1. Sr/Ca and Ba/Ca variations in environmental and biological sources: A survey of marine and terrestrial systems

    NASA Astrophysics Data System (ADS)

    Peek, Stephanie; Clementz, Mark T.

    2012-10-01

    The relative concentrations of strontium to calcium (Sr/Ca) and barium to calcium (Ba/Ca) in mammalian bioapatite are common biogeochemical indicators for trophic level and/or dietary preferences in terrestrial foodwebs; however, similar research in marine foodwebs is lacking. This study combined environmental and biological Sr/Ca and Ba/Ca data from both terrestrial and marine settings from 62 published books, reports, and studies along with original data collected from 149 marine mammals (30 species) and 83 prey items (18 species) and found that variations in Sr/Ca and Ba/Ca ratios of biological and environmental samples are appreciably different in terrestrial and marine systems. In terrestrial systems, environmental sources account for most of the variations in Sr/Ca and Ba/Ca ratios. In contrast, environmental sources in marine systems (i.e., seawater) are comparatively invariant, meaning most of the variations in Sr/Ca and Ba/Ca ratios originate from biological processes. Marine consumers, particularly non-mammalian and mammalian vertebrates, show evidence of biopurification of Ca relative to Sr and Ba, similar to what is observed in terrestrial systems; however, unlike terrestrial systems, variations in Sr/Ca and Ba/Ca ratios of environmental sources are overprinted by bioaccumulation of Sr and Ba at the base of marine foodwebs. This demonstrates that in marine systems, spatial or temporal differences may have little to no effect on Sr/Ca and Ba/Ca ratios of marine vertebrates, making Sr/Ca, and to a lesser extent Ba/Ca, potentially useful global proxies for trophic level and dietary preferences of marine vertebrates.

  2. Graded Ca²⁺/calmodulin-dependent coupling of voltage-gated CaV1.2 channels.

    PubMed

    Dixon, Rose E; Moreno, Claudia M; Yuan, Can; Opitz-Araya, Ximena; Binder, Marc D; Navedo, Manuel F; Santana, Luis F

    2015-01-01

    In the heart, reliable activation of Ca(2+) release from the sarcoplasmic reticulum during the plateau of the ventricular action potential requires synchronous opening of multiple CaV1.2 channels. Yet the mechanisms that coordinate this simultaneous opening during every heartbeat are unclear. Here, we demonstrate that CaV1.2 channels form clusters that undergo dynamic, reciprocal, allosteric interactions. This 'functional coupling' facilitates Ca(2+) influx by increasing activation of adjoined channels and occurs through C-terminal-to-C-terminal interactions. These interactions are initiated by binding of incoming Ca(2+) to calmodulin (CaM) and proceed through Ca(2+)/CaM binding to the CaV1.2 pre-IQ domain. Coupling fades as [Ca(2+)]i decreases, but persists longer than the current that evoked it, providing evidence for 'molecular memory'. Our findings suggest a model for CaV1.2 channel gating and Ca(2+)-influx amplification that unifies diverse observations about Ca(2+) signaling in the heart, and challenges the long-held view that voltage-gated channels open and close independently. PMID:25714924

  3. Graded Ca2+/calmodulin-dependent coupling of voltage-gated CaV1.2 channels

    PubMed Central

    Dixon, Rose E; Moreno, Claudia M; Yuan, Can; Opitz-Araya, Ximena; Binder, Marc D; Navedo, Manuel F; Santana, Luis F

    2015-01-01

    In the heart, reliable activation of Ca2+ release from the sarcoplasmic reticulum during the plateau of the ventricular action potential requires synchronous opening of multiple CaV1.2 channels. Yet the mechanisms that coordinate this simultaneous opening during every heartbeat are unclear. Here, we demonstrate that CaV1.2 channels form clusters that undergo dynamic, reciprocal, allosteric interactions. This ‘functional coupling’ facilitates Ca2+ influx by increasing activation of adjoined channels and occurs through C-terminal-to-C-terminal interactions. These interactions are initiated by binding of incoming Ca2+ to calmodulin (CaM) and proceed through Ca2+/CaM binding to the CaV1.2 pre-IQ domain. Coupling fades as [Ca2+]i decreases, but persists longer than the current that evoked it, providing evidence for ‘molecular memory’. Our findings suggest a model for CaV1.2 channel gating and Ca2+-influx amplification that unifies diverse observations about Ca2+ signaling in the heart, and challenges the long-held view that voltage-gated channels open and close independently. DOI: http://dx.doi.org/10.7554/eLife.05608.001 PMID:25714924

  4. The EF-Hand Ca2+ Binding Protein MICU Choreographs Mitochondrial Ca2+ Dynamics in Arabidopsis[OPEN

    PubMed Central

    Carraretto, Luca; Teardo, Enrico; Cendron, Laura; Füßl, Magdalena; Doccula, Fabrizio G.; Szabò, Ildikò

    2015-01-01

    Plant organelle function must constantly adjust to environmental conditions, which requires dynamic coordination. Ca2+ signaling may play a central role in this process. Free Ca2+ dynamics are tightly regulated and differ markedly between the cytosol, plastid stroma, and mitochondrial matrix. The mechanistic basis of compartment-specific Ca2+ dynamics is poorly understood. Here, we studied the function of At-MICU, an EF-hand protein of Arabidopsis thaliana with homology to constituents of the mitochondrial Ca2+ uniporter machinery in mammals. MICU binds Ca2+ and localizes to the mitochondria in Arabidopsis. In vivo imaging of roots expressing a genetically encoded Ca2+ sensor in the mitochondrial matrix revealed that lack of MICU increased resting concentrations of free Ca2+ in the matrix. Furthermore, Ca2+ elevations triggered by auxin and extracellular ATP occurred more rapidly and reached higher maximal concentrations in the mitochondria of micu mutants, whereas cytosolic Ca2+ signatures remained unchanged. These findings support the idea that a conserved uniporter system, with composition and regulation distinct from the mammalian machinery, mediates mitochondrial Ca2+ uptake in plants under in vivo conditions. They further suggest that MICU acts as a throttle that controls Ca2+ uptake by moderating influx, thereby shaping Ca2+ signatures in the matrix and preserving mitochondrial homeostasis. Our results open the door to genetic dissection of mitochondrial Ca2+ signaling in plants. PMID:26530087

  5. Ca2+ transport capacity of sarcolemmal Na+-Ca2+ exchange. Extrapolation of vesicle data to in vivo conditions.

    PubMed

    Philipson, K D; Ward, R

    1986-09-01

    Na+-Ca2+ exchange activity is high in cardiac sarcolemmal vesicles suggesting an important physiologic role. Vesicular Na+-Ca2+ exchange, however, is usually measured under conditions which are far from physiologic. Using sarcolemmal vesicles, we have estimated the possible significance of both Ca2+ influx and efflux mediated by Na+-Ca2+ exchange under approximate in vivo ionic conditions. In this situation, Na+-Ca2+ exchange activity is far from maximal with intracellular Mg2+ causing significant inhibition. The capacity of the Na+-Ca2+ exchange system to extrude intracellular Ca2+ (at [Ca2+] = 6.0 microM) is about 1.2 mumol Ca2+/kg wet weight/s and approximately equals the capacity of the sarcolemmal ATP-dependent Ca2+ pump. The capacity of the sarcoplasmic reticular Ca2+ pump to remove cytoplasmic Ca2+ is much larger. Significant Ca2+ influx through the exchanger is unlikely to occur in normal mammalian myocardium and would require reduced extracellular Na+ or elevated intracellular Na+. PMID:3783729

  6. Role of sarcomere mechanics and Ca2+ overload in Ca2+ waves and arrhythmias in rat cardiac muscle.

    PubMed

    ter Keurs, Henk E D J; Wakayama, Yuji; Sugai, Yoshinao; Price, Guy; Kagaya, Yutaka; Boyden, Penelope A; Miura, Masahito; Stuyvers, Bruno D M

    2006-10-01

    Ca(2+) release from the sarcoplasmic reticulum (SR) depends on the sarcoplasmic reticulum (SR) Ca(2+) load and the cytosolic Ca(2+) level. Arrhythmogenic Ca(2+) waves underlying triggered propagated contractions arise from Ca(2+) overloaded regions near damaged areas in the cardiac muscle. Ca(2+) waves can also be induced in undamaged muscle, in regions with nonuniform excitation-contraction (EC) coupling by the cycle of stretch and release in the border zone between the damaged and intact regions. We hypothesize that rapid shortening of sarcomeres in the border zone during relaxation causes Ca(2+) release from troponin C (TnC) on thin filaments and initiates Ca(2+) waves. Elimination of this shortening will inhibit the initiation of Ca(2+) waves, while SR Ca(2+) overload will enhance the waves. Force, sarcomere length (SL), and [Ca(2+)](i) were measured and muscle length was controlled. A small jet of Hepes solution with an extracellular [Ca(2+)] 10 mM (HC), or HC containing BDM, was used to weaken a 300 mum long muscle segment. Trains of electrical stimuli were used to induce Ca(2+) waves. The effects of small exponential stretches on triggered propagatory contraction (TPC) amplitude and propagation velocity of Ca(2+) waves (V(prop)) were studied. Sarcomere shortening was uniform prior to activation. HC induced spontaneous diastolic sarcomere contractions in the jet region and attenuated twitch sarcomere shortening; HC+ butanedione monoxime (BDM) caused stretch only in the jet region. Stimulus trains induced Ca(2+) waves, which started inside the HC jet region during twitch relaxation. Ca(2+) waves started in the border zone of the BDM jet. The initial local [Ca(2+)](i) rise of the waves by HC was twice that by BDM. The waves propagated at a V(prop) of 2.0 +/- 0.2 mm/sec. Arrhythmias occurred frequently in trabeculae following exposure to the HC jet. Stretch early during relaxation, which reduced sarcomere shortening in the weakened regions, substantially

  7. Control of IP3-mediated Ca2+ puffs in Xenopus laevis oocytes by the Ca2+-binding protein parvalbumin

    PubMed Central

    John, Linu M; Mosquera-Caro, Monica; Camacho, Patricia; Lechleiter, James D

    2001-01-01

    Elementary events of Ca2+ release (Ca2+ puffs) can be elicited from discrete clusters of inositol 1,4,5 trisphosphate receptors (IP3Rs) at low concentrations of IP3. Ca2+ puffs have rarely been observed unless elicited by either hormone treatment or introduction of IP3 into the cell. However, cells appear to have sufficient concentrations of IP3 (0.1-3.0 μM) to induce Ca2+ release under resting conditions. Here, we investigated Ca2+ puff activity in non-stimulated Xenopus oocytes using confocal microscopy. The fluorescent Ca2+ dye indicators Calcium Green 1 and Oregon Green 488 BAPTA-2 were injected into oocytes to monitor basal Ca2+ activity. In this preparation, injection or overexpression of parvalbumin, an EF-hand Ca2+-binding protein (CaBP), induced Ca2+ puffs in resting Xenopus oocytes. This activity was inhibited by heparin, an IP3R channel blocker, and by mutation of the Ca2+-binding sites in parvalbumin. Ca2+ puff activity was also evoked by injection of low concentrations of the Ca2+ chelator EGTA, but not by calbindin D28k, another member of the EF-hand CaBP superfamily. BAPTA and the Ca2+ indicator dye Oregon Green 488 BAPTA-1 evoked Ca2+ puff activity, while the dextran conjugate of Oregon Green 488 BAPTA-1 did not. These data indicate that a Ca2+ buffer must be mobile in order to increase Ca2+ puff activity. Together, the data indicate that some IP3Rs spontaneously release Ca2+ under resting concentrations of IP3. These elementary Ca2+ events appear to be below the level of detection of current imaging techniques. We suggest that parvalbumin evokes Ca2+ puffs by coordinating the activity of elementary IP3R channel openings. We conclude that Ca2+ release can be evoked not only by hormone-induced increases in IP3, but also by expression of mobile cytosolic CaBPs under resting concentrations of IP3. PMID:11507154

  8. Ca++ induced hypothermia in a hibernator /Citellus beechyi/

    NASA Technical Reports Server (NTRS)

    Hanegan, J. L.; Williams, B. A.

    1975-01-01

    Results of perfusion of excess Ca++ and Na+ into the hypothalamus of the hibernating ground squirrel Citellus beechyi are presented. The significant finding is that perfused excess Ca++ causes a reduction in core temperature when ambient temperature is low (12 C). Ca++ also causes a rise in rectal temperature at high ambient temperature (33 C). Thus hypothalamic Ca++ perfusion apparently causes a nonspecific depression of thermoregulatory control.

  9. T-type Ca2+ channel modulation by otilonium bromide

    PubMed Central

    Strege, Peter R.; Sha, Lei; Beyder, Arthur; Bernard, Cheryl E.; Perez-Reyes, Edward; Evangelista, Stefano; Gibbons, Simon J.; Szurszewski, Joseph H.

    2010-01-01

    Antispasmodics are used clinically to treat a variety of gastrointestinal disorders by inhibition of smooth muscle contraction. The main pathway for smooth muscle Ca2+ entry is through L-type channels; however, there is increasing evidence that T-type Ca2+ channels also play a role in regulating contractility. Otilonium bromide, an antispasmodic, has previously been shown to inhibit L-type Ca2+ channels and colonic contractile activity. The objective of this study was to determine whether otilonium bromide also inhibits T-type Ca2+ channels. Whole cell currents were recorded by patch-clamp technique from HEK293 cells transfected with cDNAs encoding the T-type Ca2+ channels, CaV3.1 (α1G), CaV3.2 (α1H), or CaV3.3 (α1I) alpha subunits. Extracellular solution was exchanged with otilonium bromide (10−8 to 10−5 M). Otilonium bromide reversibly blocked all T-type Ca2+ channels with a significantly greater affinity for CaV3.3 than CaV3.1 or CaV3.2. Additionally, the drug slowed inactivation in CaV3.1 and CaV3.3. Inhibition of T-type Ca2+ channels may contribute to inhibition of contractility by otilonium bromide. This may represent a new mechanism of action for antispasmodics and may contribute to the observed increased clinical effectiveness of antispasmodics compared with selective L-type Ca2+ channel blockers. PMID:20203058

  10. High precision calcium isotope analysis using 42Ca-48Ca double-spike TIMS technique

    NASA Astrophysics Data System (ADS)

    Feng, L.; Zhou, L.; Gao, S.; Tong, S. Y.; Zhou, M. L.

    2014-12-01

    Double spike techniques are widely used for determining calcium isotopic compositions of natural samples. The most important factor controlling precision of the double spike technique is the choice of appropriate spike isotope pair, the composition of double spikes and the ratio of spike to sample(CSp/CN). We propose an optimal 42Ca-48Ca double spike protocol which yields the best internal precision for calcium isotopic composition determinations among all kinds of spike pairs and various spike compositions and ratios of spike to sample, as predicted by linear error propagation method. It is suggested to use spike composition of 42Ca/(42Ca+48Ca) = 0.44 mol/mol and CSp/(CN+ CSp)= 0.12mol/mol because it takes both advantages of the largest mass dispersion between 42Ca and 48Ca (14%) and lowest spike cost. Spiked samples were purified by pass through homemade micro-column filled with Ca special resin. K, Ti and other interference elements were completely separated, while 100% calcium was recovered with negligible blank. Data collection includes integration time, idle time, focus and peakcenter frequency, which were all carefully designed for the highest internal precision and lowest analysis time. All beams were automatically measured in a sequence by Triton TIMS so as to eliminate difference of analytical conditions between samples and standards, and also to increase the analytical throughputs. The typical internal precision of 100 duty cycles for one beam is 0.012‒0.015 ‰ (2δSEM), which agrees well with the predicted internal precision of 0.0124 ‰ (2δSEM). Our methods improve internal precisions by a factor of 2‒10 compared to previous methods of determination of calcium isotopic compositions by double spike TIMS. We analyzed NIST SRM 915a, NIST SRM 915b and Pacific Seawater as well as interspersed geological samples during two months. The obtained average δ44/40Ca (all relative to NIST SRM 915a) is 0.02 ± 0.02 ‰ (n=28), 0.72±0.04 ‰ (n=10) and 1

  11. Nature of the individual Ca2+ binding sites in Ca2+-regenerated bacteriorhodopsin

    PubMed Central

    Zhang, Y. N.; Sweetman, L. L.; Awad, E. S.; El-Sayed, M. A.

    1992-01-01

    The binding constants, K1 and K2, and the number of Ca2+ ions in each of the two high affinity sites of Ca2+-regenerated bacteriorhodopsin (bR) are determined potentiometrically at different pH values in the range of pH 3.5-4.5 by using the Scatchard plot method. From the pH dependence of K1 and K2, it was found that two hydrogen ions are released for each Ca2+ bound to each of the two high affinity sites. Furthermore, we have measured by a direct spectroscopic method the association constant, Ks, for the binding of Ca2+ to deionized bR, which is responsible for producing the blue to purple color change. Comparing the value of Ks and its pH dependence with those of K1 and K2 showed that the site corresponding to Ks is to be identified with that of K2. This is in agreement with the conclusion reached previously, using a different approach, which showed that it is the second Ca2+ that causes the blue to purple color change. Our studies also show that in addition to the two distinct high affinity sites, there are about four to six sites with lower binding constants. These are attributed to the nonspecific binding in bR. PMID:19431830

  12. Electronic structure of Ca, Sr, and Ba under pressure.

    NASA Technical Reports Server (NTRS)

    Animalu, A. O. E.; Heine, V.; Vasvari, B.

    1967-01-01

    Electronic band structure calculations phase of Ca, Sr and Ba over wide range of atomic volumes under pressure electronic band structure calculations for fcc phase of Ca, Sr and Ba over wide range of atomic volumes under pressure electronic band structure calculations for fcc phase of Ca, Sr and Ba over wide range of atomic volumes under pressure

  13. Memory retrieval along the proximodistal axis of CA1.

    PubMed

    Nakazawa, Yuki; Pevzner, Aleksandr; Tanaka, Kazumasa Z; Wiltgen, Brian J

    2016-09-01

    The proximal and distal segments of CA1 are thought to perform distinct computations. Neurons in proximal CA1 are reciprocally connected with the medial entorhinal cortex (MEC) and exhibit precise spatial firing. In contrast, cells in distal CA1 communicate with the lateral entorhinal cortex (LEC), exhibit more diffuse spatial firing and are affected by the presence of objects in the environment. To determine if these segments make unique contributions to memory retrieval, we examined cellular activity along the proximodistal axis of CA1 using transgenic reporter mice. Neurons tagged during context learning in proximal CA1 were more likely to be reactivated during testing than those in distal CA1. This was true following context fear conditioning and after exposure to a novel environment. Reactivation was also higher in brain regions connected to proximal CA1 (MEC, distal CA3) than those connected to the distal segment (LEC, proximal CA3). To examine contributions to memory retrieval, we performed neurotoxic lesions of proximal or distal CA1 after training. Lesions of the proximal segment significantly impaired memory retrieval while damage to distal CA1 had no effect. These data suggest that context memories are retrieved by a hippocampal microcircuit that involves the proximal but not distal segment of CA1. © 2016 Wiley Periodicals, Inc. PMID:27068122

  14. 78 FR 36655 - Drawbridge Operation Regulation; Carquinez Strait, Martinez, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-19

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Carquinez Strait, Martinez, CA AGENCY... Drawbridge across the Carquinez Strait, mile 7.0 at Martinez, CA. The deviation is necessary to perform a..., at Martinez, CA. The drawbridge navigation span provides 135 feet vertical clearance above Mean...

  15. Registration of CA0469C025C chickpea germplasm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chickpea (Cicer arientinum L.) germplasm CA0469C025C (Reg. No. XXX; PI XXX), was released by the USDA-ARS in 2010. CA0469C025C was released based on its improved yield and reaction to Ascochyta blight relative to the popular commercial cultivars ‘Dwelley’, ‘Sierra’, and ‘Sawyer’. CA0490C025C is deri...

  16. 77 FR 10371 - Drawbridge Operation Regulation; Sacramento River, Sacramento, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-22

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Sacramento River, Sacramento, CA... of the Tower Drawbridge across the Sacramento River, mile 59.0, at Sacramento, CA. The deviation is... Drawbridge, mile 59.0, Sacramento River, at Sacramento, CA. The Tower Drawbridge navigation span provides...

  17. 77 FR 22216 - Drawbridge Operation Regulation; Sacramento River, Sacramento, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-13

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Sacramento River, Sacramento, CA... across the Sacramento River, mile 59.0, at Sacramento, CA. The deviation is necessary to allow the... Tower Drawbridge, mile 59.0, Sacramento River, at Sacramento, CA. The Tower Drawbridge navigation...

  18. 78 FR 42452 - Drawbridge Operation Regulation; Sacramento River, Sacramento, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-16

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Sacramento River, Sacramento, CA... across the Sacramento River, mile 59.4 at Sacramento, CA. The deviation is necessary to allow the bridge... Sacramento River, at Sacramento, CA. The drawbridge navigation span provides 109 feet vertical...

  19. 76 FR 79067 - Drawbridge Operation Regulation; Sacramento River, Sacramento, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-21

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Sacramento River, Sacramento, CA... of the Tower Drawbridge across the Sacramento River, mile 59.0, at Sacramento, CA. The deviation is... change to the operation of the Tower Drawbridge, mile 59.0, Sacramento River, at Sacramento, CA....

  20. 78 FR 15878 - Drawbridge Operation Regulations; Sacramento River, Sacramento, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-13

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulations; Sacramento River, Sacramento, CA... across Sacramento River, mile 59.0, at Sacramento, CA. The deviation is necessary to allow the community... Sacramento River, at Sacramento, CA. The Tower Drawbridge navigation span provides a vertical clearance of...

  1. 77 FR 44139 - Drawbridge Operation Regulation; Sacramento River, Sacramento, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-27

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Sacramento River, Sacramento, CA... across the Sacramento River, mile 59.0, at Sacramento, CA. The deviation is necessary to allow the... operation of the Tower Drawbridge, mile 59.0, Sacramento River, at Sacramento, CA. The Tower...

  2. 77 FR 419 - Drawbridge Operation Regulation; Sacramento River, Paintersville, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-05

    ... CFR Part 117 Drawbridge Operation Regulation; Sacramento River, Paintersville, CA AGENCY: Coast Guard... Paintersville Drawbridge across Sacramento River, mile 33.4, at Paintersville, CA. The deviation is necessary to... Paintersville Drawbridge, mile 33.4, over Sacramento River, at Paintersville, CA. The drawbridge navigation...

  3. Dual effect of spermine on mitochondrial Ca2+ transport.

    PubMed Central

    Lenzen, S; Münster, W; Rustenbeck, I

    1992-01-01

    1. A dual effect of the polyamine spermine on Ca2+ uptake by isolated rat liver, brain and heart mitochondria could be demonstrated by using a high-resolution system for studying mitochondrial Ca2+ transport. Depending on the experimental situation, spermine had an inhibiting or accelerating effects on mitochondrial Ca(2+)-uptake rate, but invariably increased the mitochondrial Ca2+ accumulation. 2. Both effects were concentration-dependent and clearly discernible on the basis of their different kinetic characteristics. For mitochondria from all three tissues the half-maximally effective concentration for inhibition of the initial rate of Ca2+ uptake was approx. 180 microM, whereas that for the subsequent stimulation of Ca2+ accumulation was approx. 50 microM. 3. Acceleration of the initial uptake rate could be seen when the mitochondria were preloaded with spermine during a 2 min preincubation period and thereafter incubated in a medium without spermine. 4. When such spermine-preloaded mitochondria were incubated in a spermine-containing medium, the increase in Ca(2+)-accumulation capacity was maintained in spite of an unchanged rate of Ca2+ uptake. 5. Mg2+ interacted with the effects of spermine in a differential manner, enhancing the initial inhibition of the rate of mitochondrial Ca2+ uptake and diminishing the subsequent stimulation of mitochondrial Ca2+ accumulation. 6. This dual effect of spermine on mitochondrial Ca2+ transport resolves the apparent paradox that a polycationic compound can act as a stimulator of Ca2+ uptake. PMID:1530590

  4. Research on urban sprawl based on GIS and CA

    NASA Astrophysics Data System (ADS)

    Qin, Fen; Yan, Lijie

    2008-10-01

    The complex urban system can't be simulated directly by the traditional and static models. Cellular automata (CA) is a kind of dynamically modeling framework from bottom to top, which possesses the capability of modeling spatialtemporal evolvement process of a complicated geographical system. The peculiarities of CA are apt for simulating urban sprawl, urban expansion and land use evolution, which make the application of CA become very popular. The environment of CA simulation can be improved by using the CA model integrated with GIS to simulate the urban sprawl, and new parameters and transition rules can be found out by establishing classical urban CA. The paper summarizes the status and the application of urban CA in the world, develops a CA model named GIS-CA on the basis of the principle of CA, integrated with GIS and RS, adds urban plan as controlling factor into GIS-CA model, and uses GIS-CA model to simulate and forecast urban sprawl, and takes Luoyang City as the case study. The simulation and forecast results are acceptable for that the precision and Lee-Sallee shape index are rational.

  5. Characteristics (Delta44/40Ca, Mg/Ca and Sr/Ca) of Mytilus edulis and Arctica islandica Shells formed in a Temperature-Salinity Matrix

    NASA Astrophysics Data System (ADS)

    Hiebenthal, C.; Eisenhauer, A.; Wahl, M.

    2008-12-01

    We investigated the influence of temperature (5°C to 15°C (A. islandica) resp. 25°C (M. edulis)) and salinity (15 to 35 psu) regimes on the calcium (Ca) isotope fractionation (Δ44/40Ca) and on Mg/Ca and Sr/Ca in cultured bivalves (Mytilus edulis and Arctica islandica). In an orthogonal 2-factorial (temperature vs. salinity) experiment, the bivalves were allowed to grow for 15 weeks under tightly controlled conditions and then probed and analysed by thermal ionisation mass spectrometry (TIMS) and optical emission spectrometry (ICP-OES). Several interactions between the factors temperature and salinity with respect to their influence on bivalve shell parameters could be found. However, with the exception of Sr/Ca data, the variation of measured shell characteristics between individual bivalves was high. The Sr/Ca - salinity proxy seems to be the most reliable (linear. regression, M. edulis: Sr/Ca = -0.0283*sal + 1.7967, R2 = 0.81, p < 0.001), even though, in A. islandica shells, it can be blurred by temperature effects at low salinities (lin. regr. at 5°C: p > 0.05, at 10°C: Sr/Ca = - 0.061*sal + 3.13, R2 = 0.93, p < 0.001, at 15°C: Sr/Ca = -0.066*sal + 3.34, R2 = 0.92, p < 0.001). In M. edulis shells Mg/Ca ratios related well with seawater temperature (lin. regr.: Mg/Ca = 0.642*t - 0.107, R2 = 0.81, p < 0.001). Ca isotope ratios only in A. islandica related significantly with temperature (lin. regr.: Δ44/40Ca = 0.016*t - 1.26, R2 = 0.29, p < 0.01) but due to an interacting salinity effect at 10°C (lin. regr.: Δ44/40Ca = -0.0148*sal - 0.738, R2 = 0.62, p = 0.002) the temperature model can only explain a limited part of the variation. Overall, the calcitic shells of M. edulis appear to provide the better element ratio proxies (Mg/Ca for temperature and Sr/Ca for salinity) and the aragonitic shells of A. islandica have the better Ca isotope - temperature proxy.

  6. Intracellular Na+ overload causes oxidation of CaMKII and leads to Ca2+ mishandling in isolated ventricular myocytes.

    PubMed

    Viatchenko-Karpinski, Serge; Kornyeyev, Dmytro; El-Bizri, Nesrine; Budas, Grant; Fan, Peidong; Jiang, Zhan; Yang, Jin; Anderson, Mark E; Shryock, John C; Chang, Ching-Pin; Belardinelli, Luiz; Yao, Lina

    2014-11-01

    An increase of late Na(+) current (INaL) in cardiac myocytes can raise the cytosolic Na(+) concentration and is associated with activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and alterations of mitochondrial metabolism and Ca(2+) handling by sarcoplasmic reticulum (SR). We tested the hypothesis that augmentation of INaL can increase mitochondrial reactive oxygen species (ROS) production and oxidation of CaMKII, resulting in spontaneous SR Ca(2+) release and increased diastolic Ca(2+) in myocytes. Increases of INaL and/or of the cytosolic Na(+) concentration led to mitochondrial ROS production and oxidation of CaMKII to cause dysregulation of Ca(2+) handling in rabbit cardiac myocytes. PMID:25252177

  7. Using Ca isotopes to constrain source of streamwater Ca following clear-cutting of a New England watershed

    NASA Astrophysics Data System (ADS)

    Takagi, K.; Kurtz, A. C.; Bailey, S. W.

    2011-12-01

    Stable Ca isotopes have been used in applications ranging from use as a paleooceanographic temperature proxy to tracing continental weathering fluxes to the oceans. One of the most important applications has been in understanding Ca cycling in terrestrial ecosystems. Major land use disturbance such as forest harvesting results in increased hydrologic export of cations but the mechanisms that lead to increased Ca export and the sources of streamwater Ca following disturbance remain uncertain. Ca isotope ratios may allow us to determine the internal Ca pools that contribute to increased export. We measured stable Ca isotopes on archived streamwater samples from Hubbard Brook Watershed 5 before and after a 1983 whole-watershed harvest experiment to test the following hypothesis: following harvest, the Ca isotopic value of streamwater will shift towards an isotopically light composition reflecting loss of biologically cycled Ca from soil pools. Ca concentrations measured on archived samples correspond exactly to values measured at the time of collection indicating adequate sample preservation over several decades of storage. Preliminary stable Ca isotopic results on these streamwater samples indicate a robust shift in δ40Ca from a pre-harvest value of -0.95% (vs. seawater) to a post-harvest value of -1.45%. We developed a box model of Ca cycling in forested ecosystems that includes Ca isotopes as tracer in order to model the δ40Ca of the various soil and vegetation pools. Steady-state model results indicate that vegetation is isotopically light relative to the B-horizon and forest floor soil pools and the forest floor soil pool is isotopically light relative to the B-horizon soil pool. We used modeled δ40Ca values of B-horizon and forest floor soil pools in a two end-member mixing analysis to evaluate changes in streamwater δ40Ca following harvesting. Our mixing analysis indicates that the observed decrease in the δ40Ca of streamwater following harvest requires an

  8. Late INa increases diastolic SR-Ca2+-leak in atrial myocardium by activating PKA and CaMKII

    PubMed Central

    Fischer, Thomas H.; Herting, Jonas; Mason, Fleur E.; Hartmann, Nico; Watanabe, Saera; Nikolaev, Viacheslav O.; Sprenger, Julia U.; Fan, Peidong; Yao, Lina; Popov, Aron-Frederik; Danner, Bernhard C.; Schöndube, Friedrich; Belardinelli, Luiz; Hasenfuss, Gerd; Maier, Lars S.; Sossalla, Samuel

    2015-01-01

    Aims Enhanced cardiac late Na current (late INa) and increased sarcoplasmic reticulum (SR)-Ca2+-leak are both highly arrhythmogenic. This study seeks to identify signalling pathways interconnecting late INa and SR-Ca2+-leak in atrial cardiomyocytes (CMs). Methods and results In murine atrial CMs, SR-Ca2+-leak was increased by the late INa enhancer Anemonia sulcata toxin II (ATX-II). An inhibition of Ca2+/calmodulin-dependent protein kinase II (Autocamide-2-related inhibitory peptide), protein kinase A (H89), or late INa (Ranolazine or Tetrodotoxin) all prevented ATX-II-dependent SR-Ca2+-leak. The SR-Ca2+-leak induction by ATX-II was not detected when either the Na+/Ca2+ exchanger was inhibited (KBR) or in CaMKIIδc-knockout mice. FRET measurements revealed increased cAMP levels upon ATX-II stimulation, which could be prevented by inhibition of adenylyl cyclases (ACs) 5 and 6 (NKY 80) but not by inhibition of phosphodiesterases (IBMX), suggesting PKA activation via an AC-dependent increase of cAMP levels. Western blots showed late INa-dependent hyperphosphorylation of CaMKII as well as PKA target sites at ryanodine receptor type-2 (-S2814 and -S2808) and phospholamban (-Thr17, -S16). Enhancement of late INa did not alter Ca2+-transient amplitude or SR-Ca2+-load. However, upon late INa activation and simultaneous CaMKII inhibition, Ca2+-transient amplitude and SR-Ca2+-load were increased, whereas PKA inhibition reduced Ca2+-transient amplitude and load and additionally slowed Ca2+ elimination. In atrial CMs from patients with atrial fibrillation, inhibition of late INa, CaMKII, or PKA reduced the SR-Ca2+-leak. Conclusion Late INa exerts distinct effects on Ca2+ homeostasis in atrial myocardium through activation of CaMKII and PKA. Inhibition of late INa represents a potential approach to attenuate CaMKII activation and decreases SR-Ca2+-leak in atrial rhythm disorders. The interconnection with the cAMP/PKA system further increases the antiarrhythmic potential of late

  9. CaV1.2/CaV3.x channels mediate divergent vasomotor responses in human cerebral arteries.

    PubMed

    Harraz, Osama F; Visser, Frank; Brett, Suzanne E; Goldman, Daniel; Zechariah, Anil; Hashad, Ahmed M; Menon, Bijoy K; Watson, Tim; Starreveld, Yves; Welsh, Donald G

    2015-05-01

    The regulation of arterial tone is critical in the spatial and temporal control of cerebral blood flow. Voltage-gated Ca(2+) (CaV) channels are key regulators of excitation-contraction coupling in arterial smooth muscle, and thereby of arterial tone. Although L- and T-type CaV channels have been identified in rodent smooth muscle, little is known about the expression and function of specific CaV subtypes in human arteries. Here, we determined which CaV subtypes are present in human cerebral arteries and defined their roles in determining arterial tone. Quantitative polymerase chain reaction and Western blot analysis, respectively, identified mRNA and protein for L- and T-type channels in smooth muscle of cerebral arteries harvested from patients undergoing resection surgery. Analogous to rodents, CaV1.2 (L-type) and CaV3.2 (T-type) α1 subunits were expressed in human cerebral arterial smooth muscle; intriguingly, the CaV3.1 (T-type) subtype present in rodents was replaced with a different T-type isoform, CaV3.3, in humans. Using established pharmacological and electrophysiological tools, we separated and characterized the unique profiles of Ca(2+) channel subtypes. Pressurized vessel myography identified a key role for CaV1.2 and CaV3.3 channels in mediating cerebral arterial constriction, with the former and latter predominating at higher and lower intraluminal pressures, respectively. In contrast, CaV3.2 antagonized arterial tone through downstream regulation of the large-conductance Ca(2+)-activated K(+) channel. Computational analysis indicated that each Ca(2+) channel subtype will uniquely contribute to the dynamic regulation of cerebral blood flow. In conclusion, this study documents the expression of three distinct Ca(2+) channel subtypes in human cerebral arteries and further shows how they act together to orchestrate arterial tone. PMID:25918359

  10. Reorientable dipolar CuCa antisite and anomalous screening in CaCu3Ti4O12

    NASA Astrophysics Data System (ADS)

    Delugas, Pietro; Alippi, Paola; Fiorentini, Vincenzo; Raineri, Vito

    2010-02-01

    Based on first-principles calculations, we show that the abundant CuCa antisite defect contributes sizably to dielectric screening in single-crystal CaCu3Ti4O12 . CuCa has a multi-minimum off-center equilibrium configuration, whereby it possesses a large and easily reorientable dipole moment. The low-temperature and frequency cut-off behavior of CuCa -induced response is consistent with experiment.

  11. Mg/Ca, Sr/Ca and Ca isotope ratios in benthonic foraminifers related to test structure, mineralogy and environmental controls

    NASA Astrophysics Data System (ADS)

    Gussone, Nikolaus; Filipsson, Helena L.; Kuhnert, Henning

    2016-01-01

    We analysed Mg/Ca, Sr/Ca and Ca isotope ratios of benthonic foraminifers from sediment core tops retrieved during several research cruises in the Atlantic Ocean, in order to improve the understanding of isotope fractionation and element partitioning resulting from biomineralisation processes and changes in ambient conditions. Species include foraminifers secreting tests composed of hyaline low magnesium calcite, porcelaneous high magnesium calcite as well as aragonite. Our results demonstrate systematic isotope fractionation and element partitioning patterns specific for these foraminiferal groups. Calcium isotope fractionation is similar in porcelaneous and hyaline calcite tests and both groups demonstrate the previously described anomaly with enrichment of heavy isotopes around 3-4 °C (Gussone and Filipsson, 2010). Calcium isotope ratios of the aragonitic species Hoeglundina elegans, on the other hand, are about 0.4‰ lighter compared to the calcitic species, which is in general agreement with stronger fractionation in inorganic aragonite compared to calcite. However, the low and strongly variable Sr content suggests additional processes during test formation, and we propose that transmembrane ion transport or a precursor phase to aragonite may be involved. Porcelaneous tests, composed of high Mg calcite, incorporate higher amounts of Sr compared to hyaline low Mg calcite, in agreement with inorganic calcite systematics, but also porcelaneous tests with reduced Mg/Ca show high Sr/Ca. While calcium isotopes, Sr/Ca and Mg/Ca in benthonic foraminifers primarily appear to fractionate and partition with a dominant inorganic control, δ44/40Ca temperature and growth rate dependencies of benthonic foraminifer tests favour a dominant contribution of light Ca by transmembrane transport relative to unfractionated seawater Ca to the calcifying fluid, thus controlling the formation of foraminiferal δ44/40Ca and Sr/Ca proxy signals.

  12. Association of serum levels of CEA, CA199, CA125, CYFRA21-1 and CA72-4 and disease characteristics in colorectal cancer.

    PubMed

    Zhong, Wa; Yu, Zhong; Zhan, Jun; Yu, Tao; Lin, Ying; Xia, Zhong-Sheng; Yuan, Yu-Hong; Chen, Qi-Kui

    2015-01-01

    Identifying predictive biomarkers for colorectal cancer would facilitate diagnosis and treatment of the disease. This study aimed to investigate the association of the serological biomarkers CEA, CA19-9, CA125, CYFRA21-1 and CA72-4 with patient characteristics and disease outcomes in colorectal cancer. Patients (N = 373) with colorectal cancer were evaluated for the association of CEA, CA19-9, CA125, CYFRA21-1, and CA72-4 pre and post-surgery and at disease recurrence with demographics, disease characteristics including pathological types, degree of differentiation, invasion depth, abdominal lymph node metastasis, TMN stage, Dukes stage, location of cancer and metastasis, and disease outcomes. It was more common for a patient to express these markers prior to surgery and at disease recurrence than following surgery. Overall, the serum levels of CEA, CA19-9, CA125, CYFRA21-1, and CA72-4 were not associated with age, gender, pathological type and location of cancer (all P-values >0.05), but were associated with the poor tumor differentiation, higher tumor invasion, greater degree of abdominal lymph node metastasis, and higher TNM and Duke stage tumors (all P-values < 0.01). CEA expression was associated with older ages (median age 65 years). Multivariate analysis indicated that CEA was correlated with overall survival and none of the markers correlated with disease recurrence. The expression of CEA, CA19-9, CA125, CYFRA21-1, and CA72-4 was associated with specific disease characteristics which tended to indicated more advanced disease and disease recurrence consistent with these biomarkers being useful for detecting colorectal cancer. PMID:24875250

  13. Ca(2+)-mobilizing hormones induce sequentially ordered Ca2+ signals in multicellular systems of rat hepatocytes.

    PubMed Central

    Combettes, L; Tran, D; Tordjmann, T; Laurent, M; Berthon, B; Claret, M

    1994-01-01

    The development of hormone-mediated Ca2+ signals was analysed in polarized doublets, triplets and quadruplets of rat hepatocytes by video imaging of fura2 fluorescence. These multicellular models showed dilated bile canaliculi, and gap junctions were observed by using an anti-connexin-32 antibody. They also showed highly organized Ca2+ signals in response to vasopressin or noradrenaline. Surprisingly, the primary rises in intracellular Ca2+ concentration ([Ca2+]i) did not start randomly from any cell of the multiplet. It originated invariably in the same hepatocyte (first-responding cell), and then was propagated in a sequential manner to the nearest connected cells (cell 2, then 3, in triplets; cell 2, 3, then 4 in quadruplets). The sequential activation of the cells appeared to be an intrinsic property of multiplets of rat hepatocytes. (1) In the continued presence of hormones, the same sequential order was observed up to six times, i.e. at each train of oscillations occurring between the cells. (2) The order of [Ca2+]i responses was modified neither by the repeated addition of hormones nor by the hormonal dose. (3) The mechanical disruption of an intermediate cell slowed down the speed of the propagation, suggesting a role of gap junctions in the rapidity of the sequential activation of cells. (4) The same multiplet could have a different first-responding cell for vasopressin or noradrenaline, suggesting a role of the hormonal receptors in the sequentiality of cell responses. It is postulated that a functional heterogeneity of hormonal receptors, and the presence of functional gap junctions, are involved in the existence of sequentially ordered hormone-mediated [Ca2+]i rises in the multiplets of rat hepatocytes. Images Figure 1 Figure 2 Figure 3 PMID:7998996

  14. Superdeformed and Triaxial States in 42Ca

    NASA Astrophysics Data System (ADS)

    Hadyńska-KlÈ©k, K.; Napiorkowski, P. J.; Zielińska, M.; Srebrny, J.; Maj, A.; Azaiez, F.; Valiente Dobón, J. J.; Kicińska-Habior, M.; Nowacki, F.; Naïdja, H.; Bounthong, B.; Rodríguez, T. R.; de Angelis, G.; Abraham, T.; Anil Kumar, G.; Bazzacco, D.; Bellato, M.; Bortolato, D.; Bednarczyk, P.; Benzoni, G.; Berti, L.; Birkenbach, B.; Bruyneel, B.; Brambilla, S.; Camera, F.; Chavas, J.; Cederwall, B.; Charles, L.; Ciemała, M.; Cocconi, P.; Coleman-Smith, P.; Colombo, A.; Corsi, A.; Crespi, F. C. L.; Cullen, D. M.; Czermak, A.; Désesquelles, P.; Doherty, D. T.; Dulny, B.; Eberth, J.; Farnea, E.; Fornal, B.; Franchoo, S.; Gadea, A.; Giaz, A.; Gottardo, A.; Grave, X.; GrÈ©bosz, J.; Görgen, A.; Gulmini, M.; Habermann, T.; Hess, H.; Isocrate, R.; Iwanicki, J.; Jaworski, G.; Judson, D. S.; Jungclaus, A.; Karkour, N.; Kmiecik, M.; Karpiński, D.; Kisieliński, M.; Kondratyev, N.; Korichi, A.; Komorowska, M.; Kowalczyk, M.; Korten, W.; Krzysiek, M.; Lehaut, G.; Leoni, S.; Ljungvall, J.; Lopez-Martens, A.; Lunardi, S.; Maron, G.; Mazurek, K.; Menegazzo, R.; Mengoni, D.; Merchán, E.; MÈ©czyński, W.; Michelagnoli, C.; Mierzejewski, J.; Million, B.; Myalski, S.; Napoli, D. R.; Nicolini, R.; Niikura, M.; Obertelli, A.; Özmen, S. F.; Palacz, M.; Próchniak, L.; Pullia, A.; Quintana, B.; Rampazzo, G.; Recchia, F.; Redon, N.; Reiter, P.; Rosso, D.; Rusek, K.; Sahin, E.; Salsac, M.-D.; Söderström, P.-A.; Stefan, I.; Stézowski, O.; Styczeń, J.; Theisen, Ch.; Toniolo, N.; Ur, C. A.; Vandone, V.; Wadsworth, R.; Wasilewska, B.; Wiens, A.; Wood, J. L.; Wrzosek-Lipska, K.; ZiÈ©bliński, M.

    2016-08-01

    Shape parameters of a weakly deformed ground-state band and highly deformed slightly triaxial sideband in 42Ca were determined from E 2 matrix elements measured in the first low-energy Coulomb excitation experiment performed with AGATA. The picture of two coexisting structures is well reproduced by new state-of-the-art large-scale shell model and beyond-mean-field calculations. Experimental evidence for superdeformation of the band built on 02+ has been obtained and the role of triaxiality in the A ˜40 mass region is discussed. Furthermore, the potential of Coulomb excitation as a tool to study superdeformation has been demonstrated for the first time.

  15. Ca2+-Regulated Photoproteins: Effective Immunoassay Reporters

    PubMed Central

    Frank, Ludmila A.

    2010-01-01

    Ca2+-regulated photoproteins of luminous marine coelenterates are of interest and a challenge for researchers as a unique bioluminescent system and as a promising analytical instrument for both in vivo and in vitro applications. The proteins are comprehensively studied as to biochemical properties, tertiary structures, bioluminescence mechanism, etc. This knowledge, along with available recombinant proteins serves the basis for development of unique bioluminescent detection systems that are “self-contained”, triggerable, fast, highly sensitive, and non-hazardous. In the paper, we focus on the use of photoproteins as reporters in binding assays based on immunological recognition element—bioluminescent immunoassay and hybridization immunoassay, their advantages and prospects. PMID:22163526

  16. San Francisco and Bay Area, CA, USA

    NASA Technical Reports Server (NTRS)

    1991-01-01

    This cloud free color infrared view of San Francisco and Bay Area, CA (38.0N, 122.5W) is unusual because the city is normally concealed from view by clouds and fog. Gray tones represent urban areas and the red toned areas are vegetated. Within the city, parks easily stand out from the well-developed parts of the city as enclaves of color. The trace of the San Andreas fault shows as a straight valley running across the San Francisco peninsula.

  17. Mechanics of Old Faithful Geyser, Calistoga, CA

    USGS Publications Warehouse

    Rudolph, M.L.; Manga, M.; Hurwitz, Shaul; Johnston, Malcolm J.; Karlstrom, L.; Wang, Chun-Yong

    2012-01-01

    In order to probe the subsurface dynamics associated with geyser eruptions, we measured ground deformation at Old Faithful Geyser of Calistoga, CA. We present a physical model in which recharge during the period preceding an eruption is driven by pressure differences relative to the aquifer supplying the geyser. The model predicts that pressure and ground deformation are characterized by an exponential function of time, consistent with our observations. The geyser's conduit is connected to a reservoir at a depth of at least 42 m, and pressure changes in the reservoir can produce the observed ground deformations through either a poroelastic or elastic mechanical model.

  18. Influx of na, k, and ca into roots of salt-stressed cotton seedlings : effects of supplemental ca.

    PubMed

    Cramer, G R; Lynch, J; Läuchli, A; Epstein, E

    1987-03-01

    High Na(+) concentrations may disrupt K(+) and Ca(2+) transport and interfere with growth of many plant species, cotton (Gossypium hirsutum L.) included. Elevated Ca(2+) levels often counteract these consequences of salinity. The effect of supplemental Ca(2+) on influx of Ca(2+), K(+), and Na(+) in roots of intact, salt-stressed cotton seedlings was therefore investigated. Eight-day-old seedlings were exposed to treatments ranging from 0 to 250 millimolar NaCl in the presence of nutrient solutions containing 0.4 or 10 millimolar Ca(2+). Sodium influx increased proportionally to increasing salinity. At high external Ca(2+), Na(+) influx was less than at low Ca(2+). Calcium influx was complex and exhibited two different responses to salinity. At low salt concentrations, influx decreased curvilinearly with increasing salt concentration. At 150 to 250 millimolar NaCl, (45)Ca(2+) influx increased in proportion to salt concentrations, especially with high Ca(2+). Potassium influx declined significantly with increasing salinity, but was unaffected by external Ca(2+). The rate of K(+) uptake was dependent upon root weight, although influx was normalized for root weight. We conclude that the protection of root growth from salt stress by supplemental Ca(2+) is related to improved Ca-status and maintenance of K(+)/Na(+) selectivity. PMID:16665280

  19. Ca2+ entry into neurons is facilitated by cooperative gating of clustered CaV1.3 channels

    PubMed Central

    Moreno, Claudia M; Dixon, Rose E; Tajada, Sendoa; Yuan, Can; Opitz-Araya, Ximena; Binder, Marc D; Santana, Luis F

    2016-01-01

    CaV1.3 channels regulate excitability in many neurons. As is the case for all voltage-gated channels, it is widely assumed that individual CaV1.3 channels behave independently with respect to voltage-activation, open probability, and facilitation. Here, we report the results of super-resolution imaging, optogenetic, and electrophysiological measurements that refute this long-held view. We found that the short channel isoform (CaV1.3S), but not the long (CaV1.3L), associates in functional clusters of two or more channels that open cooperatively, facilitating Ca2+ influx. CaV1.3S channels are coupled via a C-terminus-to-C-terminus interaction that requires binding of the incoming Ca2+ to calmodulin (CaM) and subsequent binding of CaM to the pre-IQ domain of the channels. Physically-coupled channels facilitate Ca2+ currents as a consequence of their higher open probabilities, leading to increased firing rates in rat hippocampal neurons. We propose that cooperative gating of CaV1.3S channels represents a mechanism for the regulation of Ca2+ signaling and electrical activity. DOI: http://dx.doi.org/10.7554/eLife.15744.001 PMID:27187148

  20. Ca2+/calmodulin kinase II increases ryanodine binding and Ca2+-induced sarcoplasmic reticulum Ca2+ release kinetics during β-adrenergic stimulation

    PubMed Central

    Ferrero, Paola; Said, Matilde; Sánchez, Gina; Vittone, Leticia; Valverde, Carlos; Donoso, Paulina; Mattiazzi, Alicia; Mundiña-Weilenmann, Cecilia

    2007-01-01

    We aimed to define the relative contribution of both PKA and Ca2+/calmodulin-dependent protein kinase II (CaMKII) cascades to the phosphorylation of RyR2 and the activity of the channel during β-adrenergic receptor (βAR) stimulation. Rat hearts were perfused with increasing concentrations of the β-agonist isoproterenol in the absence and the presence of CaMKII inhibition. CaMKII was inhibited either by preventing the Ca2+ influx to the cell by low [Ca]o plus nifedipine or by the specific inhibitor KN-93. We immunodetected RyR2 phosphorylated at Ser2809 (PKA and putative CaMKII site) and at Ser2815 (CaMKII site) and measured [3H]-ryanodine binding and fast Ca2+ release kinetics in sarcoplasmic reticulum (SR) vesicles. SR vesicles were isolated in conditions that preserved the phosphorylation levels achieved in the intact heart and were actively and equally loaded with Ca2+. Our results demonstrated that Ser2809 and Ser2815 of RyR2 were dose-dependently phosphorylated under βAR stimulation by PKA and CaMKII, respectively. The isoproterenol-induced increase in the phosphorylation of Ser2815 site was prevented by the PKA inhibitor H-89 and mimicked by forskolin. CaMKII-dependent phosphorylation of RyR2 (but not PKA-dependent phosphorylation) was responsible for the β-induced increase in the channel activity as indicated by the enhancement of the [3H]-ryanodine binding and the velocity of fast SR Ca2+ release. The present results show for the first time a dose-dependent increase in the phosphorylation of Ser2815 of RyR2 through the PKA-dependent activation of CaMKII and a predominant role of CaMKII-dependent phosphorylation of RyR2, over that of PKA-dependent phosphorylation, on SR-Ca2+ release during βAR stimulation. PMID:17643448

  1. Ca2+ Sparks and Ca2+ Waves are the subcellular events underlying Ca2+ overload during ischemia and reperfusion in perfused intact hearts

    PubMed Central

    Alicia, Mattiazzi; Mariana, Argenziano; Yuriana, Aguilar-Sanchez; Gabriela, Mazzocchi; Escobar Ariel, L.

    2014-01-01

    Abnormal intracellular Ca2+ cycling plays a key role in cardiac dysfunction, particularly during the setting of ischemia/reperfusion (I/R). During ischemia there is an increase in cytosolic and sarcoplasmic reticulum (SR) Ca2+. At the onset of reperfusion there is a transient and abrupt increase in cytosolic Ca2+ which occurs timely associated with reperfusion arrhythmias. However, little is known about the subcellular dynamics of Ca2+ increase during I/R and a possible role of the SR as a mechanism underlying this increase has been previously overlooked. The aim of the present work is to test two main hypotheses: 1. An increase in the frequency of diastolic Ca2+ sparks (cspf) constitutes a mayor substrate for the ischemia-induced diastolic Ca2+ increase; 2. An increase in cytosolic Ca2+ pro-arrhythmogenic events (Ca2+ waves), mediates the abrupt diastolic Ca2+ rise at the onset of reperfusion. We used confocal microscopy on mouse intact hearts loaded with Fluo-4. Hearts were submitted to global I/R (12/30 min) to assess epicardial Ca2+ sparks in the whole heart. Intact heart sparks were faster than in isolated myocytes whereas cspf was not different. During ischemia, cspf significantly increased relative to preischemia (2.07±0.33 vs. 1.13±0.20 sp/sec/100μm, n=29/34, 7 hearts). Reperfusion significantly changed Ca2+ sparks kinetics, by prolonging Ca2+ sparks rise time and decreased cspf. However it significantly increased Ca2+ wave frequency relative to ischemia (0.71±0.14 vs. 0.38±0.06 w/sec/100μm, n=32/33, 7 hearts). The results show for the first time the assessment of intact perfused heart Ca2+ sparks and provides direct evidence of increased Ca2+ sparks in ischemia that transform into Ca2+ waves during reperfusion. These waves may constitute a main trigger of reperfusion arrhythmias. PMID:25451173

  2. An integrated mechanism of cardiomyocyte nuclear Ca2+ signaling

    PubMed Central

    Ibarra, Cristián; Vicencio, Jose Miguel; Varas-Godoy, Manuel; Jaimovich, Enrique; Rothermel, Beverly A.; Uhlén, Per; Hill, Joseph A.; Lavandero, Sergio

    2015-01-01

    In cardiomyocytes, Ca2+ plays a central role in governing both contraction and signaling events that regulate gene expression. Current evidence indicates that discrimination between these two critical functions is achieved by segregating Ca2+ within subcellular microdomains: transcription is regulated by Ca2+ release within nuclear microdomains, and excitation–contraction coupling is regulated by cytosolic Ca2+. Accordingly, a variety of agonists that control cardiomyocyte gene expression, such as endothelin-1, angiotensin-II or insulin-like growth factor-1, share the feature of triggering nuclear Ca2+ signals. However, signaling pathways coupling surface receptor activation to nuclear Ca2+ release, and the phenotypic responses to such signals, differ between agonists. According to earlier hypotheses, the selective control of nuclear Ca2+ signals by activation of plasma membrane receptors relies on the strategic localization of inositol trisphosphate receptors at the nuclear envelope. There, they mediate Ca2+ release from perinuclear Ca2+ stores upon binding of inositol trisphosphate generated in the cytosol, which diffuses into the nucleus. More recently, identification of such receptors at nuclear membranes or perinuclear sarcolemmal invaginations has uncovered novel mechanisms whereby agonists control nuclear Ca2+ release. In this review, we discuss mechanisms for the selective control of nuclear Ca2+ signals with special focus on emerging models of agonist receptor activation. PMID:24997440

  3. An integrated mechanism of cardiomyocyte nuclear Ca(2+) signaling.

    PubMed

    Ibarra, Cristián; Vicencio, Jose Miguel; Varas-Godoy, Manuel; Jaimovich, Enrique; Rothermel, Beverly A; Uhlén, Per; Hill, Joseph A; Lavandero, Sergio

    2014-10-01

    In cardiomyocytes, Ca(2+) plays a central role in governing both contraction and signaling events that regulate gene expression. Current evidence indicates that discrimination between these two critical functions is achieved by segregating Ca(2+) within subcellular microdomains: transcription is regulated by Ca(2+) release within nuclear microdomains, and excitation-contraction coupling is regulated by cytosolic Ca(2+). Accordingly, a variety of agonists that control cardiomyocyte gene expression, such as endothelin-1, angiotensin-II or insulin-like growth factor-1, share the feature of triggering nuclear Ca(2+) signals. However, signaling pathways coupling surface receptor activation to nuclear Ca(2+) release, and the phenotypic responses to such signals, differ between agonists. According to earlier hypotheses, the selective control of nuclear Ca(2+) signals by activation of plasma membrane receptors relies on the strategic localization of inositol trisphosphate receptors at the nuclear envelope. There, they mediate Ca(2+) release from perinuclear Ca(2+) stores upon binding of inositol trisphosphate generated in the cytosol, which diffuses into the nucleus. More recently, identification of such receptors at nuclear membranes or perinuclear sarcolemmal invaginations has uncovered novel mechanisms whereby agonists control nuclear Ca(2+) release. In this review, we discuss mechanisms for the selective control of nuclear Ca(2+) signals with special focus on emerging models of agonist receptor activation. PMID:24997440

  4. Neurogranin regulates CaM dynamics at dendritic spines

    PubMed Central

    Petersen, Amber; Gerges, Nashaat Z.

    2015-01-01

    Calmodulin (CaM) plays a key role in synaptic function and plasticity due to its ability to mediate Ca2+ signaling. Therefore, it is essential to understand the dynamics of CaM at dendritic spines. In this study we have explored CaM dynamics using live-cell confocal microscopy and fluorescence recovery after photobleaching (FRAP) to study CaM diffusion. We find that only a small fraction of CaM in dendritic spines is immobile. Furthermore, the diffusion rate of CaM was regulated by neurogranin (Ng), a CaM-binding protein enriched at dendritic spines. Interestingly, Ng did not influence the immobile fraction of CaM at recovery plateau. We have previously shown that Ng enhances synaptic strength in a CaM-dependent manner. Taken together, these data indicate that Ng-mediated enhancement of synaptic strength is due to its ability to target, rather than sequester, CaM within dendritic spines. PMID:26084473

  5. Influence of Ca2+ on tetracycline adsorption on montmorillonite.

    PubMed

    Parolo, M Eugenia; Avena, Marcelo J; Pettinari, Gisela R; Baschini, Miria T

    2012-02-15

    The adsorption of tetracycline (TC) on montmorillonite was studied as a function of pH and Ca(2+) concentration using a batch technique complemented with X-ray diffraction and transmission electron microscopy. In the absence of Ca(2+), TC adsorption was high at low pH and decreased as the pH increased. In the presence of Ca(2+), at least two different adsorption processes took place in the studied systems, i.e., cation exchange and Ca-bridging. Cation exchange was the prevailing process at pH<5, and thus, TC adsorption decreased by increasing total Ca(2+) concentration. On the contrary, Ca-bridging was the prevailing process at pH>5, and thus, TC adsorption increased by increasing Ca(2+) concentration. The pH 5 represents an isoadsorption pH where both adsorption processes compensate each other. TC adsorption became independent of Ca(2+) concentration at this pH. For TC adsorption on Ca(2+)-montmorillonite in 0.01 M NaCl experiments, the ratio adsorbed TC/retained Ca(2+) was close to 1 in the pH range of 5-9, indicating an important participation of Ca(2+) in the binding of TC to montmorillonite. X-ray diffraction and transmission electron microscopy showed that TC adsorption induced intercalation between montmorillonite layers forming a multiphase system with stacking of layers with and without intercalated TC. PMID:22189389

  6. The hippocampal CA2 region is essential for social memory

    PubMed Central

    Hitti, Frederick L.; Siegelbaum, Steven A.

    2014-01-01

    Summary The hippocampus is critical for encoding declarative memory, our repository of knowledge of who, what, where, and when1. Mnemonic information is processed in the hippocampus through several parallel routes involving distinct subregions. In the classic trisynaptic pathway, information proceeds from entorhinal cortex (EC) to dentate gyrus (DG) to CA3 and then to CA1, the main hippocampal output2. Genetic lesions of EC3 and hippocampal DG4, CA35, and CA16 regions have revealed their distinct functions in learning and memory. In contrast, little is known about the role of CA2, a relatively small area interposed between CA3 and CA1 that forms the nexus of a powerful disynaptic circuit linking EC input with CA1 output7. Here, we report a novel transgenic mouse line that enabled us to selectively examine the synaptic connections and behavioral role of the CA2 region in adult mice. Genetically targeted inactivation of CA2 pyramidal neurons caused a pronounced loss of social memory, the ability of an animal to remember a conspecific, with no change in sociability or several other hippocampal-dependent behaviors, including spatial and contextual memory. These behavioral and anatomical results thus reveal CA2 as a critical hub of sociocognitive memory processing. PMID:24572357

  7. Nicotinic acid adenine dinucleotide phosphate (NAADP) and Ca2+ mobilization.

    PubMed

    Mándi, Miklós; Bak, Judit

    2008-01-01

    Many physiological processes are controlled by a great diversity of Ca2+ signals that depend on Ca2+ entry into the cell and/or Ca2+ release from internal Ca2+ stores. Ca2+ mobilization from intracellular stores is gated by a family of messengers including inositol-1,4,5-trisphosphate (InsP3), cyclic ADP-ribose (cADPR), and nicotinic acid adenine dinucleotide phosphate (NAADP). There is increasing evidence for a novel intracellular Ca2+ release channel that may be targeted by NAADP and that displays properties distinctly different from the well-characterized InsP3 and ryanodine receptors. These channels appear to localize on a wider range of intracellular organelles, including the acidic Ca2+ stores. Activation of the NAADP-sensitive Ca2+ channels evokes complex changes in cytoplasmic Ca2+ levels by means of channel chatter with other intracellular Ca2+ channels. The recent demonstration of changes in intracellular NAADP levels in response to physiologically relevant extracellular stimuli highlights the significance of NAADP as an important regulator of intracellular Ca2+ signaling. PMID:18569524

  8. Accretion rate of extraterrestrial 41Ca in Antarctic snow samples

    NASA Astrophysics Data System (ADS)

    Gómez-Guzmán, J. M.; Bishop, S.; Faestermann, T.; Famulok, N.; Fimiani, L.; Hain, K.; Jahn, S.; Korschinek, G.; Ludwig, P.; Rodrigues, D.

    2015-10-01

    Interplanetary Dust Particles (IDPs) are small grains, generally less than a few hundred micrometers in size. Their main source is the Asteroid Belt, located at 3 AU from the Sun, between Mars and Jupiter. During their flight from the Asteroid Belt to the Earth they are irradiated by galactic and solar cosmic rays (GCR and SCR), thus radionuclides are formed, like 41Ca and 53Mn. Therefore, 41Ca (T1/2 = 1.03 × 105 yr) can be used as a key tracer to determine the accretion rate of IDPs onto the Earth because there are no significant terrestrial sources for this radionuclide. The first step of this study consisted to calculate the production rate of 41Ca in IDPs accreted by the Earth during their travel from the Asteroid Belt. This production rate, used in accordance with the 41Ca/40Ca ratios that will be measured in snow samples from the Antarctica will be used to calculate the amount of extraterrestrial material accreted by the Earth per year. There challenges for this project are, at first, the much longer time for the flight needed by the IDPs to travel from the Asteroid Belt to the Earth in comparison with the 41Ca half-life yields an early saturation for the 41Ca/40Ca ratio, and second, the importance of selecting the correct sampling site to avoid a high influx of natural 40Ca, preventing dilution of the 41Ca/40Ca ratio, the quantity measured by AMS.

  9. caB2B hosting update —

    Cancer.gov

    cancer Bench-to-Beside - caB2B - is an open-source query tool that permits translational research scientists to search and combine data from virtually any caGrid data service. The caB2B suite is composed of three core components: the Web application, the Client Application and the Administrative Module. The caB2B Web Application provides query templates that allow easy search and retrieval of microarray data (from caArray), imaging data (from the National Biomedical Imaging Archive (NBIA)), specimen data (from caTissue) and nanoparticle data (from caNanoLab) across the grid. Searches can be performed on selected locations using either form-based or keyword searches and data can be exported in the CSV format.

  10. Influence of isolation media on synaptosomal properties: Intracellular pH, pCa, and Ca sup 2+ uptake

    SciTech Connect

    Bandeira-Duarte, C.; Carvalho, C.A.; Cragoe Junior, E.J.; Carvalho, A.P. )

    1990-03-01

    Preparations of synaptosomes isolated in sucrose or in Na(+)-rich media were compared with respect to internal pH (pHi), internal Ca{sup 2+} concentration ((Ca{sup 2+})i), membrane potential and {sup 45}Ca{sup 2+} uptake due to K+ depolarization and Na{sup +}/Ca{sup 2+} exchange. We found that synaptosomes isolated in sucrose media have a pHi of 6.77 +/- 0.04 and a (Ca{sup 2+})i of about 260 nM, whereas synaptosomes isolated in Na(+)-rich ionic media have a pHi of 6.96 +/- 0.07 and a (Ca{sup 2+})i of 463 nM, but both types of preparations have similar membrane potentials of about -50 mV when placed in choline media. The sucrose preparation takes up Ca{sup 2+} only by voltage sensitive calcium channels (VSCC'S) when K(+)-depolarized, while the Na(+)-rich synaptosomes take up {sup 45}Ca{sup 2+} both by VSCC'S and by Na{sup +}/Ca{sup 2+} exchange. The amiloride derivative 2',4'-dimethylbenzamil (DMB), at 30 microM, inhibits both mechanisms of Ca{sup 2+} influx, but 5-(N-4-chlorobenzyl)-2',4' dimethylbenzamil (CBZ-DMB), at 30 microM, inhibits the Ca{sup 2+} uptake by VSCC'S, but not by Na+/Ca2+ exchange. Thus, DMB and CBZ-DMB permit distinguishing between Ca{sup 2+} flux through channels and through Na{sup +}/Ca{sup 2+} exchange. We point out that the different properties of the two types of synaptosomes studied account for some of the discrepancies in results reported in the literature for studies of Ca{sup 2+} fluxes and neurotransmitter release by different types of preparations of synaptosomes.

  11. Mechanisms of enhanced taurine release under Ca2+ depletion.

    PubMed

    Molchanova, Svetlana M; Oja, Simo S; Saransaari, Pirjo

    2005-10-01

    The sulfur-containing amino acid taurine is an inhibitory neuromodulator in the brain of mammals, as well as a key substance in the regulation of cell volumes. The effect of Ca(2+) on extracellular taurine concentrations is of special interest in the context of the regulatory mechanisms of taurine release. The aim of this study was to characterize the basal release of taurine in Ca(2+)-free medium using in vivo microdialysis of the striatum of anesthetized rats. Perfusion of Ca(2+)-free medium via a microdialysis probe evoked a sustained release of taurine (up to 180 % compared to the basal levels). The Ca(2+) chelator EGTA (1mM) potentiated Ca(2+) depletion-evoked taurine release. The substitution of CaCl(2) by choline chloride did not alter the observed effect. Ca(2+)-free solution did not significantly evoke release of taurine from tissue loaded with the competitive inhibitor of taurine transporter guanidinoethanesulfonate (1mM), suggesting that in Ca(2+) depletion taurine is released by the transporter operating in the outward direction. The volume-sensitive chloride channel blocker diisothiocyanostilbene-2,2'-disulfonate (1mM) did not attenuate the taurine release evoked by Ca(2+) depletion. The non-specific blocker of voltage-sensitive Ca(2+) channels NiCl(2) (0.65 mM) enhanced taurine release in the presence of Ca(2+). CdCl(2) (0.25 mM) had no effect under these conditions. However, both CdCl(2) and NiCl(2) attenuated the effect of Ca(2+)-free medium on the release of taurine. The data obtained imply the involvement of both decreased influx of Ca(2+) and increased non-specific influx of Na(+) through voltage-sensitive calcium channels in the regulation of transporter-mediated taurine release in Ca(2+) depletion. PMID:15982785

  12. The Ca2+ release-activated Ca2+ current (I(CRAC)) mediates store-operated Ca2+ entry in rat microglia.

    PubMed

    Ohana, Lily; Newell, Evan W; Stanley, Elise F; Schlichter, Lyanne C

    2009-01-01

    Ca2+ signaling plays a central role in microglial activation, and several studies have demonstrated a store-operated Ca2+ entry (SOCE) pathway to supply this ion. Due to the rapid pace of discovery of novel Ca2+ permeable channels, and limited electrophysiological analyses of Ca2+ currents in microglia, characterization of the SOCE channels remains incomplete. At present, the prime candidates are 'transient receptor potential' (TRP) channels and the recently cloned Orai1, which produces a Ca2+-release-activated Ca2+ (CRAC) current. We used cultured rat microglia and real-time RT-PCR to compare expression levels of Orai1, Orai2, Orai3, TRPM2, TRPM7, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6 and TRPC7 channel genes. Next, we used Fura-2 imaging to identify a store-operated Ca2+ entry pathway that was reduced by depolarization and blocked by Gd3+, SKF-96365, diethylstilbestrol (DES), and a high concentration of 2-aminoethoxydiphenyl borate (50 microM 2-APB). The Fura-2 signal was increased by hyperpolarization, and by a low concentration of 2-APB (5 microM), and exhibited Ca(2+)-dependent potentiation. These properties are entirely consistent with Orai1/CRAC, rather than any known TRP channel and this conclusion was supported by patch-clamp electrophysiological analysis. We identified a store-operated Ca2+ current with the same properties, including high selectivity for Ca2+ over monovalent cations, pronounced inward rectification and a very positive reversal potential, Ca(2+)-dependent current potentiation, and block by SKF-96365, DES and 50 microM 2-APB. Determining the contribution of Orai1/CRAC in different cell types is crucial to future mechanistic and therapeutic studies; this comprehensive multi-strategy analysis demonstrates that Orai1/CRAC channels are responsible for SOCE in primary microglia. PMID:19411837

  13. Effects of Na+ and Ca2+ gradients on intracellular free Ca2+ in voltage-clamped Aplysia neurons.

    PubMed

    Levy, S; Tillotson, D

    1988-12-01

    Selected neurons of the abdominal ganglion of Aplysia californica were voltage-clamped and intracellular free Ca [( Ca2+]i) and Na [( Na+]i) concentrations were monitored with ion selective microelectrodes. Reducing [Na+]o from 500 mM (normal seawater, NSW) to 5 mM resulted in a decrease of the potential measured by the Ca electrode (VCa). Increasing [Ca2+]o from 10 to 50 mM increased [Ca2+]i two-fold, keeping [Ca2+]o at 50 mM and decreasing [Na+]o to 5 mM still led to a decrease in VCa. With 100 mM [Ca2+]o, which also increased [Ca2+]i, decreasing [Na+]o increased VCa in two of the eight cells tested. This indicates that in normal or moderately high resting [Ca2+]i, Ca2+ extrusion by Na/Ca exchange (forward mode) is not essential for [Ca2+]i buffering. [Na+]i was 12.9 +/- 3.6 mM (S.E.M., n = 7) in NSW; reducing [Na+]o to 5 mM decreased [Na+]i to 2.0 +/- 1.1 mM (S.E.M.). Keeping [Na+]o at 5 mM and increasing [Ca2+]o from 10 to 20 mM further decreased [Na+]i to about 1.0 mM, evidence of Na/Ca exchange operating in the reverse mode. Attempts to increase [Ca2+]i by bath application of the Ca ionophores A23187, X537A, ionomycin or ETH 1001 resulted in no measurable change of the resting [Ca2+]i. Application of Ouabain caused an apparent increase in [Ca2+]i in two of the six cells tested. In cells injected with the metallochromic indicator arsenazo III (AIII), the rate of the falling phase of the AIII absorbance increase, following a voltage-clamp pulse, was significantly slower in 5 mM [Na+]o. This indicates that in its forward mode Na-Ca exchange is active in clearing large submembrane increases in [Ca2+]i. PMID:3208137

  14. The influence of the 2-neutron elastic transfer on the fusion of 42Ca + 40Ca

    NASA Astrophysics Data System (ADS)

    Stefanini, A. M.; Montagnoli, G.; Corradi, L.; Fioretto, E.; Goasduff, A.; Grebosz, J.; Haas, F.; Mazzocco, M.; Scarlassara, F.; Strano, E.

    2016-05-01

    Strong coupling to a single channel with zero Q-value is predicted to produce a characteristic fusion barrier distribution with two peaks, one on each side of the original uncoupled Coulomb barrier. In practical cases, only coupling to an elastic transfer channel may produce such a distribution which, however, has never been observed sofar, probably because low-lying surface vibrations usually have a dominant role, and this may obscure the two-peak structure. The case of the two-neutron (2n) elastic transfer in 42Ca + 40Ca is particularly attractive, because of the relatively rigid nature of the two nuclei. We have measured the fusion excitation function of this system using the 42Ca beam of the XTU Tandem of LNL on a thin 40Ca target enriched to 99.96% in mass 40. Cross sections have been measured down to ≤1 mb. The extracted barrier distribution shows clearly two main peaks. We have performed preliminary CC calculations where the 2+ coupling strengths have been taken from the literature and the schematic 2n pair transfer form factor has been used, with a deformation length σt= 0.39 fm. The excitation function is well reproduced by the calculation including the 2n transfer channel. However, including the octupole excitations destroys the agreement.

  15. Expression of an "Arabidopsis" Ca(2+)/H(+) transporter increases bioavailable Ca(2+) in edible carrot roots

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our long range goal is to make vegetables a better source of dietary calcium. We demonstrate that carrots expressing the Arabidopsis H(+)/Ca(2+) transporter sCAX1 contain up to 50% more calcium compared to plants transformed with the vector only. These modified carrots were fertile and robust, wit...

  16. Pycnogenol protects CA3-CA1 synaptic function in a rat model of traumatic brain injury.

    PubMed

    Norris, Christopher M; Sompol, Pradoldej; Roberts, Kelly N; Ansari, Mubeen; Scheff, Stephen W

    2016-02-01

    Pycnogenol (PYC) is a patented mix of bioflavonoids with potent anti-oxidant and anti-inflammatory properties. Previously, we showed that PYC administration to rats within hours after a controlled cortical impact (CCI) injury significantly protects against the loss of several synaptic proteins in the hippocampus. Here, we investigated the effects of PYC on CA3-CA1 synaptic function following CCI. Adult Sprague-Dawley rats received an ipsilateral CCI injury followed 15 min later by intravenous injection of saline vehicle or PYC (10 mg/kg). Hippocampal slices from the injured (ipsilateral) and uninjured (contralateral) hemispheres were prepared at seven and fourteen days post-CCI for electrophysiological analyses of CA3-CA1 synaptic function and induction of long-term depression (LTD). Basal synaptic strength was impaired in slices from the ipsilateral, relative to the contralateral, hemisphere at seven days post-CCI and susceptibility to LTD was enhanced in the ipsilateral hemisphere at both post-injury timepoints. No interhemispheric differences in basal synaptic strength or LTD induction were observed in rats treated with PYC. The results show that PYC preserves synaptic function after CCI and provides further rationale for investigating the use of PYC as a therapeutic in humans suffering from neurotrauma. PMID:26607913

  17. Expression of CEA, CA19-9, CA125, and EpCAM in pseudomyxoma peritonei.

    PubMed

    Nummela, Pirjo; Leinonen, Hannele; Järvinen, Petrus; Thiel, Alexandra; Järvinen, Heikki; Lepistö, Anna; Ristimäki, Ari

    2016-08-01

    Pseudomyxoma peritonei is a fatal clinical syndrome with mucinous tumor cells disseminated into peritoneal cavity and secreting abundant mucinous ascites. The serum tumor markers CEA, CA19-9, and CA125 are used to monitor pseudomyxoma peritonei remission, but their expression at tissue level has not been well characterized. Herein, we analyzed expression of these proteins and the adenocarcinoma marker EpCAM in 92 appendix-derived pseudomyxoma peritonei tumors by immunohistochemistry. All tumors were found to ubiquitously express CEA and EpCAM. In the majority of the tumors (94.6%), CEA showed polarized immunostaining, but in 5 aggressive high-grade tumors containing numerous signet ring cells, a nonpolarized staining was detected. We found preoperative CEA serum values to correlate with peritoneal cancer index. However, the serum values of the advanced cases with nonpolarized staining pattern were normal, and the patients died within 5 years after diagnosis. Thus, serum CEA measurements did not reflect aggressiveness of these tumors. CA19-9 showed strong immunopositivity in most of the tumors (91.3%), and mutated enzyme FUT3 was demonstrated from the cases showing negative or weak staining. CA125 was infrequently expressed by tumor cells (focal staining in 6.5% of the cases), but in most of the cases (79.3%), adjacent nonneoplastic mesothelial cells showed immunopositivity. As a conclusion, CEA and EpCAM are invariably expressed by pseudomyxoma peritonei tumor cells and could be exploited to targeted therapies against this malignancy. PMID:27038681

  18. EXPRESSION OF AN ARABIDOPSIS CA2+/H+ TRANSPORTER INCREASES BIOAVAILABLE CA2+ IN EDIBLE CARROT ROOTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our long range goal is to make vegetables a better source of dietary calcium. We demonstrate that carrots expressing the Arabidopsis H+/Ca2+ transporter sCAX1 contain up to 50% more calcium compared to plants transformed with the vector only. These modified carrots were fertile and robust, with no d...

  19. Design and application of a class of sensors to monitor Ca2+ dynamics in high Ca2+ concentration cellular compartments

    PubMed Central

    Tang, Shen; Wong, Hing-Cheung; Wang, Zhong-Min; Huang, Yun; Zou, Jin; Zhuo, You; Pennati, Andrea; Gadda, Giovanni; Delbono, Osvaldo; Yang, Jenny J.

    2011-01-01

    Quantitative analysis of Ca2+ fluctuations in the endoplasmic/sarcoplasmic reticulum (ER/SR) is essential to defining the mechanisms of Ca2+-dependent signaling under physiological and pathological conditions. Here, we developed a unique class of genetically encoded indicators by designing a Ca2+ binding site in the EGFP. One of them, calcium sensor for detecting high concentration in the ER, exhibits unprecedented Ca2+ release kinetics with an off-rate estimated at around 700 s−1 and appropriate Ca2+ binding affinity, likely attributable to local Ca2+-induced conformational changes around the designed Ca2+ binding site and reduced chemical exchange between two chromophore states. Calcium sensor for detecting high concentration in the ER reported considerable differences in ER Ca2+ dynamics and concentration among human epithelial carcinoma cells (HeLa), human embryonic kidney 293 cells (HEK-293), and mouse myoblast cells (C2C12), enabling us to monitor SR luminal Ca2+ in flexor digitorum brevis muscle fibers to determine the mechanism of diminished SR Ca2+ release in aging mice. This sensor will be invaluable in examining pathogenesis characterized by alterations in Ca2+ homeostasis. PMID:21914846

  20. Thermodynamics of Reducing Refining of Phosphorus from Si-Mn Alloy Using CaO-CaF2 Slag

    NASA Astrophysics Data System (ADS)

    Shin, Jae Hong; Park, Joo Hyun

    2012-12-01

    The thermodynamic behavior of phosphide ions in the CaO-CaF2 flux in equilibrium with a SiMn(-Fe) alloy melt was investigated under a strongly reducing atmosphere at 1823 K (1550 °C). The phosphide capacity increased with increasing CaO concentration in the flux before reaching a constant value. The composition for the saturating capacity is in good agreement with the saturation content of CaO in the CaO-CaF2 flux at 1823 K (1550 °C). The relationship between the phosphide capacity and the activity of CaO in the flux exhibited a linear relationship on the logarithmic scale, indicating that phosphorus was removed from the SiMn(-Fe) melt by the reducing refining mechanism.

  1. Aluminian Low-Ca Pyroxene in a Ca-Al-rich Chondrule from the Semarkona Meteorite

    NASA Technical Reports Server (NTRS)

    Rubin, Alan E.

    2006-01-01

    A Ca-AI-rich chondrule (labeled G7) from the Semarkona LL3.0 ordinary chondrite (OC) consists of 73 vol% glassy mesostasis, 22 vol% skeletal forsterite. 3 vol% fassaite (i.e., Al-Ti diopside), and 2 vol% Al-rich, low-Ca pyroxene. The latter phase, which contains up to 16.3 wt% A1203, is among the most AI-rich, low-Ca pyroxene grains ever reported. It is inferred that 20% of the tetrahedral sites and 13% of the octahedral sites in this grain are occupied by Al. Approximately parallel optical extinction implies that the Al-rich, low-Ca pyroxene grains are probably orthorhombic, consistent with literature data that show that A1203 stabilizes the orthoenstatite structure relative to protoenstatite at low pressure. The order of crystallization in the chondrule was forsterite, AI-rich low-Ca pyroxene, and fassaite; the residual liquid vitrified during chondrule quenching. Phase relationships indicate that, for a G7-composition liquid at equilibrium, spinel and anorthite should crystallize early and orthopyroxene should not crystallize at all. The presence of AI-rich orthopyroxene in G7 is due mainly to the kinetic failure of anorthite to crystallize; this failure was caused by quenching of the G7 precursor droplet. Aluminum preferentially enters the relatively large B tetrahedra of orthopyroxene; because only one tetrahedral size occurs in fassaite, this phase contains higher mean concentrations of Al2O3 than the Al-rich orthopyroxene (17.8 and 14.7 wt%, respectively). Chondrule G7 may have formed by remelting an amoeboid olivine inclusion that entered the OC region of the solar nebula during an episode of chondrule formation.

  2. CHEMILUMINESCENT CHEMI-IONIZATION: Ar* + Ca AND THE CaAr+ EMISSION SPECTRUM

    SciTech Connect

    Hartman, Dennis C.; Winn, John S.

    1980-09-01

    A flowing afterglow chemiluminescence apparatus has been used to analyze visible fluorescence in the Ar* ({sup 3}P{sub 2}{sup o}) + Ca ({sup 1}S{sub 0}) reaction. The rate constants for production of Ca{sup +} ({sup 2}P{sub 3/2}{sup o}) and Ca{sup +} ({sup 2}P{sub 1/2}{sup o}) were measured to be 1.6 x 10{sup -10} cm{sup 3}-molecule{sup -1} sec{sup -1} and 3.2 x 10{sup -11} cm{sup 3} molecule{sup -1} sec{sup -1}, respectively. These results demonstrate a transfer of the total electronic angular momentum polarization in Ar* tothe excited ion levels. The molecular band spectrum of the associative ionization product CaAr{sup +} (A{sup 2}{Pi}) was observed. Molecular fluorescence constituted 14% of the total fluorescence from all ion products. This spectrum was analyzed with a model (exp-Z4) potential, yielding, for the ground state, {Chi}{sup 2}{Sigma}{sup +}, R{sub e} = 2.8 {angstrom}, {omega}''{sub e} = 87 cm{sup -1}, and D''{sub e} = 1000 cm{sup -1}, and, for the A{sup 2}{Pi} state, R{sub e} = 2.6 {angstrom}, {omega}'{sub e} = 200 cm{sup -1}, and D'{sub e} = 4900 cm{sup -1}. The nascent internal state distribution in CaAr{sup +} is found to consist of a fairly narrow range of high vibrational levels. The analysis of spectra from chemiluminescent reaction is a well established technique for elucidating the product state distributions of elementary processes. In this paper, they use the analysis of the chemiluminescent chemi-ionization reactions between metastable argon atoms and calcium atoms to expose the dynamics of associative ionization (AI) and to measure the branching ratios for chemi-ionization into more than one product channel.

  3. PGC-1{alpha} accelerates cytosolic Ca{sup 2+} clearance without disturbing Ca{sup 2+} homeostasis in cardiac myocytes

    SciTech Connect

    Chen, Min; Wang, Yanru; Qu, Aijuan

    2010-06-11

    Energy metabolism and Ca{sup 2+} handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1{alpha}) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1{alpha} in cardiac Ca{sup 2+} signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1{alpha} via adenoviral transduction. Our data shows that overexpressing PGC-1{alpha} improved myocyte contractility without increasing the amplitude of Ca{sup 2+} transients, suggesting that myofilament sensitivity to Ca{sup 2+} increased. Interestingly, the decay kinetics of global Ca{sup 2+} transients and Ca{sup 2+} waves accelerated in PGC-1{alpha}-expressing cells, but the decay rate of caffeine-elicited Ca{sup 2+} transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca{sup 2+}-ATPase (SERCA2a), but not Na{sup +}/Ca{sup 2+} exchange (NCX) contribute to PGC-1{alpha}-induced cytosolic Ca{sup 2+} clearance. Furthermore, PGC-1{alpha} induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1{alpha} did not disturb cardiac Ca{sup 2+} homeostasis, because SR Ca{sup 2+} load and the propensity for Ca{sup 2+} waves remained unchanged. These data suggest that PGC-1{alpha} can ameliorate cardiac Ca{sup 2+} cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1{alpha}-calcium handing pathway sheds new light on the role of PGC-1{alpha} in the therapy of cardiac diseases.

  4. Ca2+ influx via the Na+/Ca2+ exchanger is enhanced in malignant hyperthermia skeletal muscle.

    PubMed

    Altamirano, Francisco; Eltit, José M; Robin, Gaëlle; Linares, Nancy; Ding, Xudong; Pessah, Isaac N; Allen, Paul D; López, José R

    2014-07-01

    Malignant hyperthermia (MH) is potentially fatal pharmacogenetic disorder of skeletal muscle caused by intracellular Ca(2+) dysregulation. NCX is a bidirectional transporter that effluxes (forward mode) or influxes (reverse mode) Ca(2+) depending on cellular activity. Resting intracellular calcium ([Ca(2+)]r) and sodium ([Na(+)]r) concentrations are elevated in MH susceptible (MHS) swine and murine muscles compared with their normal (MHN) counterparts, although the contribution of NCX is unclear. Lowering [Na(+)]e elevates [Ca(2+)]r in both MHN and MHS swine muscle fibers and it is prevented by removal of extracellular Ca(2+) or reduced by t-tubule disruption, in both genotypes. KB-R7943, a nonselective NCX3 blocker, reduced [Ca(2+)]r in both swine and murine MHN and MHS muscle fibers at rest and decreased the magnitude of the elevation of [Ca(2+)]r observed in MHS fibers after exposure to halothane. YM-244769, a high affinity reverse mode NCX3 blocker, reduces [Ca(2+)]r in MHS muscle fibers and decreases the amplitude of [Ca(2+)]r rise triggered by halothane, but had no effect on [Ca(2+)]r in MHN muscle. In addition, YM-244769 reduced the peak and area under the curve of the Ca(2+) transient elicited by high [K(+)]e and increased its rate of decay in MHS muscle fibers. siRNA knockdown of NCX3 in MHS myotubes reduced [Ca(2+)]r and the Ca(2+) transient area induced by high [K(+)]e. These results demonstrate a functional NCX3 in skeletal muscle whose activity is enhanced in MHS. Moreover reverse mode NCX3 contributes to the Ca(2+) transients associated with K(+)-induced depolarization and the halothane-triggered MH episode in MHS muscle fibers. PMID:24847052

  5. Ca2+ Influx via the Na+/Ca2+ Exchanger Is Enhanced in Malignant Hyperthermia Skeletal Muscle*

    PubMed Central

    Altamirano, Francisco; Eltit, José M.; Robin, Gaëlle; Linares, Nancy; Ding, Xudong; Pessah, Isaac N.; Allen, Paul D.; López, José R.

    2014-01-01

    Malignant hyperthermia (MH) is potentially fatal pharmacogenetic disorder of skeletal muscle caused by intracellular Ca2+ dysregulation. NCX is a bidirectional transporter that effluxes (forward mode) or influxes (reverse mode) Ca2+ depending on cellular activity. Resting intracellular calcium ([Ca2+]r) and sodium ([Na+]r) concentrations are elevated in MH susceptible (MHS) swine and murine muscles compared with their normal (MHN) counterparts, although the contribution of NCX is unclear. Lowering [Na+]e elevates [Ca2+]r in both MHN and MHS swine muscle fibers and it is prevented by removal of extracellular Ca2+ or reduced by t-tubule disruption, in both genotypes. KB-R7943, a nonselective NCX3 blocker, reduced [Ca2+]r in both swine and murine MHN and MHS muscle fibers at rest and decreased the magnitude of the elevation of [Ca2+]r observed in MHS fibers after exposure to halothane. YM-244769, a high affinity reverse mode NCX3 blocker, reduces [Ca2+]r in MHS muscle fibers and decreases the amplitude of [Ca2+]r rise triggered by halothane, but had no effect on [Ca2+]r in MHN muscle. In addition, YM-244769 reduced the peak and area under the curve of the Ca2+ transient elicited by high [K+]e and increased its rate of decay in MHS muscle fibers. siRNA knockdown of NCX3 in MHS myotubes reduced [Ca2+]r and the Ca2+ transient area induced by high [K+]e. These results demonstrate a functional NCX3 in skeletal muscle whose activity is enhanced in MHS. Moreover reverse mode NCX3 contributes to the Ca2+ transients associated with K+-induced depolarization and the halothane-triggered MH episode in MHS muscle fibers. PMID:24847052

  6. Cytosolic Ca2+ and Ca2+-activated Cl− current dynamics: insights from two functionally distinct mouse exocrine cells

    PubMed Central

    Giovannucci, David R; Bruce, Jason I. E; Straub, Stephen V; Arreola, Jorge; Sneyd, James; Shuttleworth, Trevor J; Yule, David I

    2002-01-01

    The dynamics of Ca2+ release and Ca2+-activated Cl− currents in two related, but functionally distinct exocrine cells, were studied to gain insight into how the molecular specialization of Ca2+ signalling machinery are utilized to produce different physiological endpoints: in this case, fluid or exocytotic secretion. Digital imaging and patch-clamp methods were used to monitor the temporal and spatial properties of changes in cytosolic Ca2+ concentration ([Ca2+]c) and Cl− currents following the controlled photolytic release of caged-InsP3 or caged-Ca2+. In parotid and pancreatic acinar cells, changes in [Ca2+]c and activation of a Ca2+-activated Cl− current occurred with close temporal coincidence. In parotid, a rapid global Ca2+ signal was invariably induced, even with low-level photolytic release of threshold amounts of InsP3. In pancreas, threshold stimulation generated an apically delimited [Ca2+]c signal, while a stronger stimulus induced a global [Ca2+]c signal which exhibited characteristics of a propagating wave. InsP3 was more effective in parotid, where [Ca2+]c signals initiated with shorter latency and exhibited a faster time-to-peak than in pancreas. The increased potency of InsP3 in parotid probably results from a four-fold higher number of InsP3 receptors as measured by radiolabelled InsP3 binding and western blot analysis. The Ca2+ sensitivity of the Cl− channels in parotid and pancreas was determined from the [Ca2+]-current relationship measured during a dynamic ‘Ca2+ ramp’ produced by the continuous, low-level photolysis of caged-Ca2+. In addition to a greater number of InsP3 receptors, the Cl− current density of parotid acinar cells was more than four-fold greater than that of pancreatic cells. Whereas activation of the current was tightly coupled to increases in Ca2+ in both cell types, local Ca2+ clearance was found to contribute substantially to the deactivation of the current in parotid. These data reveal specializations of

  7. Effects of spermine on mitochondrial Ca2+ transport and the ranges of extramitochondrial Ca2+ to which the matrix Ca2+-sensitive dehydrogenases respond.

    PubMed Central

    McCormack, J G

    1989-01-01

    1. Spermine has previously been reported to be an activator of mitochondrial Ca2+ uptake [Nicchitta & Williamson (1984) J. Biol. Chem. 259, 12978-12983]. This is confirmed in the present studies on rat heart, liver and kidney mitochondria by using the activities of the Ca2+-sensitive intramitochondrial dehydrogenases (pyruvate, NAD+-isocitrate and 2-oxoglutarate dehydrogenases) as probes for matrix Ca2+, and also, for the heart mitochondria, by using entrapped fura-2. 2. As also found previously [Damuni, Humphreys & Reed (1984) Biochem. Biophys. Res. Commun. 124, 95-99], spermine activated extracted pyruvate dehydrogenase phosphate phosphatase. However, it was found to have no effects at all on the extracted NAD+-isocitrate or 2-oxoglutarate dehydrogenases. It also had no effects on activities of the enzymes in mitochondria incubated in the absence of Ca2+, or on the Ca2+-sensitivity of the enzymes in uncoupled mitochondria. 3. Spermine clearly activated 45Ca uptake by coupled mitochondria, but had no effect on Ca2+ egress from mitochondria previously loaded with 45Ca. 4. Spermine (with effective Km values of around 0.2-0.4 mM) caused an approx. 2-3-fold decrease in the effective ranges of extramitochondrial Ca2+ in the activation of the Ca2+-sensitive matrix enzymes in coupled mitochondria from all of the tissues. The effects of spermine appeared to be largely independent of the other effectors of mitochondrial Ca2+ transport, such as Mg2+ (inhibitor of uptake) and Na+ (promoter of egrees). 5. In the most physiological circumstance, coupled mitochondria incubated with Na+ and Mg2+, the presence of saturating spermine (2 mM) resulted in an effective extramitochondrial Ca2+ range for matrix enzyme activation of from about 30-50 nM up to about 800-1200 nM, with half-maximal effects around 250-400 nM-Ca2+. The implications of these findings for the regulation of matrix and extramitochondrial Ca2+ are discussed. PMID:2604711

  8. U-Pb Dating of CA/non-CA Treated Zircons Obtained by LA-ICP-MS and CA-TIMS Techniques: Impact for their Geological Interpretation

    NASA Astrophysics Data System (ADS)

    Von Quadt, A.; Gallhofer, D.; Guillong, M.; Peytcheva, I.

    2014-12-01

    Chemical Abrasion Isotope-Dilution Thermal Ionization Mass Spectrometry (CA-ID-TIMS) is known as a high precision technique for resolving lead loss and improving the interpretation of U-Pb zircon age data. We argue that combining CA with the widely applied Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) improves the precision and accuracy of zircon dates, while removing the substantial parts with lead loss, reducing data scatter, and providing meaningful geological interpretations. The samples are magmatic rocks chosen from different geological time periods (Paleozoic, Mesozoic and Cenozoic time). All zircon separates are analysed by LA-ICP-MS before and after CA, and all age data are compared with CA-ID-TIMS 206Pb/238U dates that are considered as the most accurately age. All CA-treated zircon crystals show up to 50% less data scatter compared to the non-CA treated zircon grains and thus a reduction of the calculated uncertainties is apparent. The obtained wt average LA-ICP-MS 206Pb/238U ages of the CA-treated zircon grains are up to 4-6% higher than those of the non-CA treated crystals, exceeding the analytical uncertainties of the LA-ICP-MS dating technique of 1-2%. The damaged crystal parts, caused by U-decay, with lead loss are removed, so that we can exclude younging from the possible geological scenarios. CA-LA-ICP-MS age data are in good agreement with the CA-ID-TIMS dates and suggest advantages of using CA-LA-ICP-MS in order to define accurate ages. The use of the CA technique for very young zircons (~0.2 Ma, Kos rhyolitic tuff, Greece) seems optional; as the obtained mean 206Pb/238U ages of non-CA and CA treated zircons coincide within the uncertainty. The negligible time to produce the lattice damage (based on alpha decay or spontaneous fission) makes lead loss less important for age dating and data interpretation of very young zircons (<1 Ma). Von Quadt, A. et al., 2014, JAAS, doi: 10.1039/c4ja00102h.

  9. Luminal Ca(2+) dynamics during IP3R mediated signals.

    PubMed

    Lopez, Lucia F; Dawson, Silvina Ponce

    2016-01-01

    The role of cytosolic Ca(2+) on the kinetics of Inositol 1,4,5-triphosphate receptors (IP3Rs) and on the dynamics of IP3R-mediated Ca(2+) signals has been studied at large both experimentally and by modeling. The role of luminal Ca(2+) has not been investigated with that much detail although it has been found that it is relevant for signal termination in the case of Ca(2+) release through ryanodine receptors. In this work we present the results of observing the dynamics of luminal and cytosolic Ca(2+) simultaneously in Xenopus laevis oocytes. Combining observations and modeling we conclude that there is a rapid mechanism that guarantees the availability of free Ca(2+) in the lumen even when a relatively large Ca(2+) release is evoked. Comparing the dynamics of cytosolic and luminal Ca(2+) during a release, we estimate that they are consistent with a 80% of luminal Ca(2+) being buffered. The rapid availability of free luminal Ca(2+) correlates with the observation that the lumen occupies a considerable volume in several regions across the images. PMID:27232767

  10. The Effect of OPA1 on Mitochondrial Ca2+ Signaling

    PubMed Central

    Enyedi, Balázs; Várnai, Péter; Spät, András

    2011-01-01

    The dynamin-related GTPase protein OPA1, localized in the intermembrane space and tethered to the inner membrane of mitochondria, participates in the fusion of these organelles. Its mutation is the most prevalent cause of Autosomal Dominant Optic Atrophy. OPA1 controls the diameter of the junctions between the boundary part of the inner membrane and the membrane of cristae and reduces the diffusibility of cytochrome c through these junctions. We postulated that if significant Ca2+ uptake into the matrix occurs from the lumen of the cristae, reduced expression of OPA1 would increase the access of Ca2+ to the transporters in the crista membrane and thus would enhance Ca2+ uptake. In intact H295R adrenocortical and HeLa cells cytosolic Ca2+ signals evoked with K+ and histamine, respectively, were transferred into the mitochondria. The rate and amplitude of mitochondrial [Ca2+] rise (followed with confocal laser scanning microscopy and FRET measurements with fluorescent wide-field microscopy) were increased after knockdown of OPA1, as compared with cells transfected with control RNA or mitofusin1 siRNA. Ca2+ uptake was enhanced despite reduced mitochondrial membrane potential. In permeabilized cells the rate of Ca2+ uptake by depolarized mitochondria was also increased in OPA1-silenced cells. The participation of Na+/Ca2+ and Ca2+/H+ antiporters in this transport process is indicated by pharmacological data. Altogether, our observations reveal the significance of OPA1 in the control of mitochondrial Ca2+ metabolism. PMID:21980395

  11. Ca2+ dynamics in oocytes from naturally-aged mice

    PubMed Central

    Haverfield, Jenna; Nakagawa, Shoma; Love, Daniel; Tsichlaki, Elina; Nomikos, Michail; Lai, F. Anthony; Swann, Karl; FitzHarris, Greg

    2016-01-01

    The ability of human metaphase-II arrested eggs to activate following fertilisation declines with advancing maternal age. Egg activation is triggered by repetitive increases in intracellular Ca2+ concentration ([Ca2+]i) in the ooplasm as a result of sperm-egg fusion. We therefore hypothesised that eggs from older females feature a reduced ability to mount appropriate Ca2+ responses at fertilisation. To test this hypothesis we performed the first examination of Ca2+ dynamics in eggs from young and naturally-aged mice. Strikingly, we find that Ca2+ stores and resting [Ca2+]i are unchanged with age. Although eggs from aged mice feature a reduced ability to replenish intracellular Ca2+ stores following depletion, this difference had no effect on the duration, number, or amplitude of Ca2+ oscillations following intracytoplasmic sperm injection or expression of phospholipase C zeta. In contrast, we describe a substantial reduction in the frequency and duration of oscillations in aged eggs upon parthenogenetic activation with SrCl2. We conclude that the ability to mount and respond to an appropriate Ca2+ signal at fertilisation is largely unchanged by advancing maternal age, but subtle changes in Ca2+ handling occur that may have more substantial impacts upon commonly used means of parthenogenetic activation. PMID:26785810

  12. Ca2+/H+ exchange in acidic vacuoles of Trypanosoma brucei.

    PubMed Central

    Vercesi, A E; Moreno, S N; Docampo, R

    1994-01-01

    The use of digitonin to permeabilize the plasma membrane of Trypanosoma brucei procyclic and bloodstream trypomastigotes allowed the identification of a non-mitochondrial nigericin-sensitive Ca2+ compartment. The proton ionophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) was able to cause Ca2+ release from this compartment, which was also sensitive to sodium orthovanadate. Preincubation of the cells with the vacuolar H(+)-ATPase inhibitor bafilomycin A1 greatly reduced the nigericin-sensitive Ca2+ compartment. Bafilomycin A1 inhibited the initial rate of ATP-dependent non-mitochondrial Ca2+ uptake and stimulated the initial rate of nigericin-induced Ca2+ release by permeabilized procyclic trypomastigotes. ATP-dependent and bafilomycin A1- and 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD-Cl)-sensitive Acridine Orange uptake was demonstrated in permeabilized cells. Under these conditions Acridine Orange was concentrated in abundant cytoplasmic round vacuoles by a process inhibited by bafilomycin A1, NBD-Cl, nigericin, and Ca2+. Vanadate or EGTA significantly increased Acridine Orange uptake, while Ca2+ released Acridine Orange from these preparations, thus suggesting that the dye and Ca2+ were being accumulated in the same acidic vacuole. Acridine Orange uptake was reversed by nigericin, bafilomycin A1 and NH4Cl. The results are consistent with the presence of a Ca2+/H(+)-ATPase system pumping Ca2+ into an acidic vacuole, that we tentatively named the acidocalcisome. Images Figure 5 PMID:7998937

  13. Characteristics and Possible Functions of Mitochondrial Ca2+ Transport Mechanisms

    PubMed Central

    Gunter, Thomas E.; Sheu, Shey-Shing

    2009-01-01

    Mitochondria produce around 92% of the ATP used in the typical animal cell by oxidative phosphorylation using energy from their electrochemical proton gradient. Intramitochondrial free Ca2+ concentration ([Ca2+]m) has been found to be an important component of control of the rate of this ATP production. In addition, [Ca2+]m also controls the opening of a large pore in the inner mitochondrial membrane, the permeability transition pore (PTP), which plays a role in mitochondrial control of programmed cell death or apoptosis. Therefore, [Ca2+]m can control whether the cell has sufficient ATP to fulfill its functions and survive or is condemned to death. Ca2+ is also one of the most important second messengers within the cytosol, signaling changes in cellular response through Ca2+ pulses or transients. Mitochondria can also sequester Ca2+ from these transients so as to modify the shape of Ca2+ signaling transients or control their location within the cell. All of this is controlled by the action of four or five mitochondrial Ca2+ transport mechanisms and the PTP. The characteristics of these mechanisms of Ca2+ transport and a discussion of how they might function are described in this paper. PMID:19161975

  14. Osmotically induced cytosolic free Ca(2+) changes in human neutrophils.

    PubMed

    Morris, M R; Doull, I J; Hallett, M B

    2001-02-01

    Cytosolic free Ca(2+) concentration in neutrophils was measured by ratiometric fluorometry of intracellular fura2. Increasing the extracellular osmolarity, by either NaCl (300-600 mM) or sucrose (600-1200 mM), caused a rise in cytosolic free Ca(2+) (Delta(max) approximately equal to 600 nM). This was not due to cell lysis as the cytosolic free Ca(2+) concentration was reversed by restoration of isotonicity and a second rise in cytosolic free Ca(2+) could be provoked by repeating the change in extracellular osmolarity. Furthermore, the rise in cytosolic free Ca(2+) concentration occurred in the absence of extracellular Ca(2+), demonstrating that release of intracellular fura2 into the external medium did not occur. The osmotically-induced rise in cytosolic free Ca(2+) was not inhibited by either the phospholipase C-inhibitor U73122, or the microfilament inhibitor cytochalasin B, suggesting that neither signalling via inositol tris-phosphate or the cytoskeletal system were involved. However, the rise in cytosolic free Ca(2+) may have resulted from a reduction in neutrophil water volume in hyperosmotic conditions. As these rises in cytosolic Ca(2+) (Delta(max) approximately equal to 600 nM) were large enough to provoke changes in neutrophil activity, we propose that conditions which removes cell water may similarly elevate cytosolic free Ca(2+) to physiologically important levels. PMID:11341979

  15. Ca2+-Dependent Enhancement of Release by Subthreshold Somatic Depolarization

    PubMed Central

    Christie, Jason M.; Chiu, Delia N.; Jahr, Craig E.

    2010-01-01

    Summary In many neurons, subthreshold somatic depolarization can spread electrotonically into the axon and modulate subsequent spike-evoked transmission. Although release probability is regulated by intracellular Ca2+, the Ca2+-dependence of this modulatory mechanism has been debated. Using paired recordings from synaptically connected molecular-layer interneurons (MLIs) of the rat cerebellum, we observed Ca2+-mediated strengthening of release following brief subthreshold depolarization of the soma. Two-photon microscopy revealed that, at the axon, somatic depolarization evoked Ca2+ influx through voltage-sensitive Ca2+ channels (VSCCs) and facilitated spike-evoked Ca2+ entry. Exogenous Ca2+ buffering diminished these Ca2+ transients and eliminated the strengthening of release. Axonal Ca2+ entry elicited by subthreshold somatic depolarization also triggered asynchronous transmission that may deplete vesicle availability and thereby temper release strengthening. In this cerebellar circuit, activity-dependent presynaptic plasticity depends on Ca2+ elevations resulting from both sub- and suprathreshold electrical activity initiated at the soma. PMID:21170054

  16. Luminal Ca2+ dynamics during IP3R mediated signals

    NASA Astrophysics Data System (ADS)

    Lopez, Lucia F.; Ponce Dawson, Silvina

    2016-06-01

    The role of cytosolic Ca2+ on the kinetics of Inositol 1,4,5-triphosphate receptors (IP3Rs) and on the dynamics of IP3R-mediated Ca2+ signals has been studied at large both experimentally and by modeling. The role of luminal Ca2+ has not been investigated with that much detail although it has been found that it is relevant for signal termination in the case of Ca2+ release through ryanodine receptors. In this work we present the results of observing the dynamics of luminal and cytosolic Ca2+ simultaneously in Xenopus laevis oocytes. Combining observations and modeling we conclude that there is a rapid mechanism that guarantees the availability of free Ca2+ in the lumen even when a relatively large Ca2+ release is evoked. Comparing the dynamics of cytosolic and luminal Ca2+ during a release, we estimate that they are consistent with a 80% of luminal Ca2+ being buffered. The rapid availability of free luminal Ca2+ correlates with the observation that the lumen occupies a considerable volume in several regions across the images.

  17. The 3R polymorph of CaSi{sub 2}

    SciTech Connect

    Nedumkandathil, Reji; Benson, Daryn E.; Grins, Jekabs; Spektor, Kristina; Häussermann, Ulrich

    2015-02-15

    The Zintl phase CaSi{sub 2} commonly occurs in the 6R structure where puckered hexagon layers of Si atoms are stacked in an AA′BB′CC′ fashion. In this study we show that sintering of CaSi{sub 2} in a hydrogen atmosphere (30 bar) at temperatures between 200 and 700 °C transforms 6R-CaSi{sub 2} quantitatively into 3R-CaSi{sub 2}. In the 3R polymorph (space group R-3m (no. 166), a=3.8284(1), c=15.8966(4), Z=3) puckered hexagon layers are stacked in an ABC fashion. The volume per formula unit is about 3% larger compared to 6R-CaSi{sub 2}. First principles density functional calculations reveal that 6R and 3R-CaSi{sub 2} are energetically degenerate at zero Kelvin. With increasing temperature 6R-CaSi{sub 2} stabilizes over 3R because of its higher entropy. This suggests that 3R-CaSi{sub 2} should revert to 6R at elevated temperatures, which however is not observed up to 800 °C. 3R-CaSi{sub 2} may be stabilized by small amounts of incorporated hydrogen and/or defects. - Graphical abstract: The common 6R form of CaSi{sub 2} can be transformed quantitatively into 3R-CaSi{sub 2} upon sintering in a hydrogen atmosphere. - Highlights: • Quantitative and reproducible bulk synthesis of the rare 3R polymorph of CaSi{sub 2}. • Clarification of the energetic relation between 3R and conventional 6R form. • 3R-CaSi{sub 2} is presumably stabilized by small amounts of incorporated hydrogen and/or defects.

  18. Fractionation of stable Ca isotopes in a shallow groundwater aquifer

    NASA Astrophysics Data System (ADS)

    Wiegand, B. A.

    2006-12-01

    Calcium has six stable isotopes, which fractionate during biological and inorganic processes, and thus may provide an important tracer in hydrological studies. To evaluate the potential use of Ca isotopes in determining sources and biogeochemical processes, groundwater from a shallow aquifer in NW Germany was investigated. 44Ca/40Ca ratios (expressed as Δ44Ca) of dissolved Ca2+ in water were analyzed by thermal ionization mass spectrometry using a ^{42}Ca-^{48}Ca double spike to correct for fractionation during the analytical procedure. 44Ca/40Ca ratios were normalized to seawater (Δ44Ca = 0), which was used as a standard. Groundwater samples were collected from monitoring wells in depths between 1.5 and 50 meters below surface. The aquifer is composed of Quaternary unconsolidated sediments. pH values increase from 4.5 in shallow wells to 7.6 at deeper levels, indicating low buffering capacities due to long-term decalcification processes in near-surface horizons. Near-surface groundwater is strongly undersaturated with respect to calcite whereas deep groundwater is close to saturation with calcite. Deep groundwater and several shallow wells are characterized by anoxic conditions while in parts of the aquifer oxic conditions prevail. Δ44Ca values of groundwater range between 0.2 and -1.4 ‰, indicating changes in the sources that are contributing to the dissolved Ca2+ loads, and biogeochemical fractionation processes. The main sources of calcium in the groundwater include mineral weathering and atmospheric deposition. Ca isotopes may be fractionated by secondary minerals precipitation, ion-exchange processes, and biological processes. In this presentation, possible scenarios will be discussed. Acknowledgements: Thanks to Dr. P. Groth, Dr. A. Mehling and the personnel of the Harzwasserwerke GmbH, Germany.

  19. Synchrony of Cardiomyocyte Ca2+ Release is Controlled by t-tubule Organization, SR Ca2+ Content, and Ryanodine Receptor Ca2+ Sensitivity

    PubMed Central

    Øyehaug, Leiv; Loose, Kristian Ø.; Jølle, Guro F.; Røe, Åsmund T.; Sjaastad, Ivar; Christensen, Geir; Sejersted, Ole M.; Louch, William E.

    2013-01-01

    Recent work has demonstrated that cardiomyocyte Ca2+release is desynchronized in several pathological conditions. Loss of Ca2+ release synchrony has been attributed to t-tubule disruption, but it is unknown if other factors also contribute. We investigated this issue in normal and failing myocytes by integrating experimental data with a mathematical model describing spatiotemporal dynamics of Ca2+ in the cytosol and sarcoplasmic reticulum (SR). Heart failure development in postinfarction mice was associated with progressive t-tubule disorganization, as quantified by fast-Fourier transforms. Data from fast-Fourier transforms were then incorporated in the model as a dyadic organization index, reflecting the proportion of ryanodine receptors located in dyads. With decreasing dyadic-organization index, the model predicted greater dyssynchrony of Ca2+ release, which exceeded that observed in experimental line-scan images. Model and experiment were reconciled by reducing the threshold for Ca2+ release in the model, suggesting that increased RyR sensitivity partially offsets the desynchronizing effects of t-tubule disruption in heart failure. Reducing the magnitude of SR Ca2+ content and release, whether experimentally by thapsigargin treatment, or in the model, desynchronized the Ca2+ transient. However, in cardiomyocytes isolated from SERCA2 knockout mice, RyR sensitization offset such effects. A similar interplay between RyR sensitivity and SR content was observed during treatment of myocytes with low-dose caffeine. Initial synchronization of Ca2+ release during caffeine was reversed as SR content declined due to enhanced RyR leak. Thus, synchrony of cardiomyocyte Ca2+ release is not only determined by t-tubule organization but also by the interplay between RyR sensitivity and SR Ca2+ content. PMID:23601316

  20. Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free solution

    PubMed Central

    LV, XINTONG; GUO, FENG; XU, XIAOXUE; CHEN, ZAIXING; SUN, XUEFEI; MIN, DONGYU; CAO, YONGGANG; SHI, XIANBAO; WANG, LEI; CHEN, TIANBAO; SHAW, CHRIS; GAO, HUILING; HAO, LIYING; CAI, JIQUN

    2015-01-01

    Voltage-dependent calcium channels (VDCCs) are key elements in epileptogenesis. There are several binding-sites linked to calmodulin (CaM) and several potential CaM-dependent protein kinase II (CaMKII)-mediated phosphorylation sites in CaV1.2. The tremor rat model (TRM) exhibits absence-like seizures from 8 weeks of age. The present study was performed to detect changes in the Ca2+/CaV1.2/CaM/CaMKII pathway in TRMs and in cultured hippocampal neurons exposed to Mg2+-free solution. The expression levels of CaV1.2, CaM and phosphorylated CaMKII (p-CaMKII; Thr-286) in these two models were examined using immunofluorescence and western blotting. Compared with Wistar rats, the expression levels of CaV1.2 and CaM were increased, and the expression of p-CaMKII was decreased in the TRM hippocampus. However, the expression of the targeted proteins was reversed in the TRM temporal cortex. A significant increase in the expression of CaM and decrease in the expression of CaV1.2 were observed in the TRM cerebellum. In the cultured neuron model, p-CaMKII and CaV1.2 were markedly decreased. In addition, neurons exhibiting co-localized expression of CaV1.2 and CaM immunoreactivities were detected. Furthermore, intracellular calcium concentrations were increased in these two models. For the first time, o the best of our knowledge, the data of the present study suggested that abnormal alterations in the Ca2+/CaV1.2/CaM/CaMKII pathway may be involved in epileptogenesis and in the phenotypes of TRMs and cultured hippocampal neurons exposed to Mg2+-free solution. PMID:26299765

  1. Superdeformed and Triaxial States in ^{42}Ca.

    PubMed

    Hadyńska-Klȩk, K; Napiorkowski, P J; Zielińska, M; Srebrny, J; Maj, A; Azaiez, F; Valiente Dobón, J J; Kicińska-Habior, M; Nowacki, F; Naïdja, H; Bounthong, B; Rodríguez, T R; de Angelis, G; Abraham, T; Anil Kumar, G; Bazzacco, D; Bellato, M; Bortolato, D; Bednarczyk, P; Benzoni, G; Berti, L; Birkenbach, B; Bruyneel, B; Brambilla, S; Camera, F; Chavas, J; Cederwall, B; Charles, L; Ciemała, M; Cocconi, P; Coleman-Smith, P; Colombo, A; Corsi, A; Crespi, F C L; Cullen, D M; Czermak, A; Désesquelles, P; Doherty, D T; Dulny, B; Eberth, J; Farnea, E; Fornal, B; Franchoo, S; Gadea, A; Giaz, A; Gottardo, A; Grave, X; Grȩbosz, J; Görgen, A; Gulmini, M; Habermann, T; Hess, H; Isocrate, R; Iwanicki, J; Jaworski, G; Judson, D S; Jungclaus, A; Karkour, N; Kmiecik, M; Karpiński, D; Kisieliński, M; Kondratyev, N; Korichi, A; Komorowska, M; Kowalczyk, M; Korten, W; Krzysiek, M; Lehaut, G; Leoni, S; Ljungvall, J; Lopez-Martens, A; Lunardi, S; Maron, G; Mazurek, K; Menegazzo, R; Mengoni, D; Merchán, E; Mȩczyński, W; Michelagnoli, C; Mierzejewski, J; Million, B; Myalski, S; Napoli, D R; Nicolini, R; Niikura, M; Obertelli, A; Özmen, S F; Palacz, M; Próchniak, L; Pullia, A; Quintana, B; Rampazzo, G; Recchia, F; Redon, N; Reiter, P; Rosso, D; Rusek, K; Sahin, E; Salsac, M-D; Söderström, P-A; Stefan, I; Stézowski, O; Styczeń, J; Theisen, Ch; Toniolo, N; Ur, C A; Vandone, V; Wadsworth, R; Wasilewska, B; Wiens, A; Wood, J L; Wrzosek-Lipska, K; Ziȩbliński, M

    2016-08-01

    Shape parameters of a weakly deformed ground-state band and highly deformed slightly triaxial sideband in ^{42}Ca were determined from E2 matrix elements measured in the first low-energy Coulomb excitation experiment performed with AGATA. The picture of two coexisting structures is well reproduced by new state-of-the-art large-scale shell model and beyond-mean-field calculations. Experimental evidence for superdeformation of the band built on 0_{2}^{+} has been obtained and the role of triaxiality in the A∼40 mass region is discussed. Furthermore, the potential of Coulomb excitation as a tool to study superdeformation has been demonstrated for the first time. PMID:27541463

  2. Fast Inversion of Solar Ca II Spectra

    NASA Astrophysics Data System (ADS)

    Beck, C.; Choudhary, D. P.; Rezaei, R.; Louis, R. E.

    2015-01-01

    We present a fast (Lt1 s per profile) inversion code for solar Ca II lines. The code uses an archive of spectra that are synthesized prior to the inversion under the assumption of local thermodynamic equilibrium (LTE). We show that it can be successfully applied to spectrograph data or more sparsely sampled spectra from two-dimensional spectrometers. From a comparison to a non-LTE inversion of the same set of spectra, we derive a first-order non-LTE correction to the temperature stratifications derived in the LTE approach. The correction factor is close to unity up to log τ ~ -3 and increases to values of 2.5 and 4 at log τ = -6 in the quiet Sun and the umbra, respectively.

  3. FAST INVERSION OF SOLAR Ca II SPECTRA

    SciTech Connect

    Beck, C.; Choudhary, D. P.; Rezaei, R.; Louis, R. E.

    2015-01-10

    We present a fast (<<1 s per profile) inversion code for solar Ca II lines. The code uses an archive of spectra that are synthesized prior to the inversion under the assumption of local thermodynamic equilibrium (LTE). We show that it can be successfully applied to spectrograph data or more sparsely sampled spectra from two-dimensional spectrometers. From a comparison to a non-LTE inversion of the same set of spectra, we derive a first-order non-LTE correction to the temperature stratifications derived in the LTE approach. The correction factor is close to unity up to log τ ∼ –3 and increases to values of 2.5 and 4 at log τ = –6 in the quiet Sun and the umbra, respectively.

  4. The CaV2.3 R-Type Voltage-Gated Ca2+ Channel in Mouse Sleep Architecture

    PubMed Central

    Siwek, Magdalena Elisabeth; Müller, Ralf; Henseler, Christina; Broich, Karl; Papazoglou, Anna; Weiergräber, Marco

    2014-01-01

    Study Objectives: Voltage-gated Ca2+ channels (VGCCs) are key elements in mediating thalamocortical rhythmicity. Low-voltage activated (LVA) CaV 3 T-type Ca2+ channels have been related to thalamic rebound burst firing and to generation of non-rapid eye movement (NREM) sleep. High-voltage activated (HVA) CaV 1 L-type Ca2+ channels, on the opposite, favor the tonic mode of action associated with higher levels of vigilance. However, the role of the HVA Non-L-type CaV2.3 Ca2+ channels, which are predominantly expressed in the reticular thalamic nucleus (RTN), still remains unclear. Recently, CaV2.3−/− mice were reported to exhibit altered spike-wave discharge (SWD)/absence seizure susceptibility supported by the observation that CaV2.3 mediated Ca2+ influx into RTN neurons can trigger small-conductance Ca2+-activated K+-channel type 2 (SK2) currents capable of maintaining thalamic burst activity. Based on these studies we investigated the role of CaV2.3 R-type Ca2+ channels in rodent sleep. Methods: The role of CaV2.3 Ca2+ channels was analyzed in CaV2.3−/− mice and controls in both spontaneous and artificial urethane-induced sleep, using implantable video-EEG radiotelemetry. Data were analyzed for alterations in sleep architecture using sleep staging software and time-frequency analysis. Results: CaV2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS). Whereas mean sleep stage durations remained unchanged, the total number of SWS epochs was increased in CaV2.3−/− mice. Additional changes were observed for sleep stage transitions and EEG amplitudes. Furthermore, urethane-induced SWS mimicked spontaneous sleep results obtained from CaV2.3 deficient mice. Quantitative Real-time PCR did not reveal changes in thalamic CaV3 T-type Ca2+ channel expression. The detailed mechanisms of SWS increase in CaV2.3−/− mice remain to be determined. Conclusions: Low-voltage activated CaV2.3 R-type Ca2+ channels in the thalamocortical

  5. Ca(2+)-handling proteins and heart failure: novel molecular targets?

    PubMed

    Prestle, J; Quinn, F R; Smith, G L

    2003-06-01

    Calcium (Ca(2+)) ions are the currency of heart muscle activity. During excitation-contraction coupling Ca(2+) is rapidly cycled between the cytosol (where it activates the myofilaments) and the sarcoplasmic reticulum (SR), the Ca(2+) store. These fluxes occur by the transient activity of Ca(2+)-pumps and -channels. In the failing human heart, changes in activity and expression profile of Ca(2+)-handling proteins, in particular the SR Ca(2+)-ATPase (SERCA2a), are thought to cause an overall reduction in the amount of SR-Ca(2+) available for contraction. In the steady state, the Ca(2+)-content of the SR is essentially a balance between Ca(2+)-uptake via SERCA2a pump and Ca(2+)-release via the cardiac SR Ca(2+)-release channel complex (Ryanodine receptor, RyR2). This review discusses current pharmacological options available to enhance cardiac SR Ca(2+) content and the implications of this approach as an inotropic therapy in heart failure. Two options are considered: (i) activation of the SERCA2a pump to increase SR Ca(2+)-uptake, and (ii) reduction of SR Ca(2+)-leakage through RyR2. RyR2 forms a macromolecular complex with a number of regulatory proteins that either remain permanently bound or that interact in a time- and/or Ca(2+)-dependant manner. These regulatory proteins can dramatically affect RyR2 function, e.g. over-expression of the accessory protein FK 506-binding protein 12.6 (FKBP12.6) has recently been shown to reduce SR Ca(2+)-leak. Recent attempts to design positive inotropes for chronic administrations have focussed on the use of phosphodiesterase III inhibitors (PDE III inhibitors). These compounds, which increase intracellular cAMP-levels, have failed in clinical trials. Therefore medical researchers are seeking new drugs that act through alternative pathways. Novel cardiac inotropes targeting SR Ca(2+)-cycling proteins may have the potential to fill this gap. PMID:12678683

  6. Experimental identification of Ca isotopic fractionations in higher plants

    NASA Astrophysics Data System (ADS)

    Cobert, Florian; Schmitt, Anne-Désirée; Bourgeade, Pascale; Labolle, François; Badot, Pierre-Marie; Chabaux, François; Stille, Peter

    2011-10-01

    Hydroponic experiments have been performed in order to identify the co-occurring geochemical and biological processes affecting the Ca isotopic compositions within plants. To test the influence of the Ca concentration and pH of the nutritive solution on the Ca isotopic composition of the different plant organs, four experimental conditions were chosen combining two different Ca concentrations (5 and 60 ppm) and two pHs (4 and 6). The study was performed on rapid growing bean plants in order to have a complete growth cycle. Several organs (root, stem, leaf, reproductive) were sampled at two different growth stages (10 days and 6 weeks of culture) and prepared for Ca isotopic measurements. The results allow to identify three Ca isotopic fractionation levels. The first one takes place when Ca enters the lateral roots, during Ca adsorption on cation-exchange binding sites in the apoplasm. The second one takes place when Ca is bound to the polygalacturonic acids (pectins) of the middle lamella of the xylem cell wall. Finally, the last fractionation occurs in the reproductive organs, also caused by cation-exchange processes with pectins. However, the cell wall structures of these organs and/or number of available exchange sites seem to be different to those of the xylem wall. These three physico-chemical fractionation mechanisms allow to enrich the organs in the light 40Ca isotope. The amplitude of the Ca isotopic fractionation within plant organs is highly dependent on the composition of the nutritive solution: low pH (4) and Ca concentrations (5 ppm) have no effect on the biomass increase of the plants but induce smaller fractionation amplitudes compared to those obtained from other experimental conditions. Thus, Ca isotopic signatures of bean plants are controlled by the external nutritive medium. This study highlights the potential of Ca isotopes to be applied in plant physiology (to identify Ca uptake, circulation and storage mechanisms within plants) and in

  7. Modelling Changes of the Paleogene Ca Budget Using Benthic Foraminifera

    NASA Astrophysics Data System (ADS)

    Pabich, S.; Gussone, N. C.; Vollmer, C.; Palike, H.; Rabe, K.; Teichert, B. M.

    2014-12-01

    Understanding the earth's climate as well as the oceanic chemical and isotopic evolution in the past is one of the main aims in earth science. Ca as one of the major elements in the ocean is especially important. Its variation in concentration are controlled by different factors including the CO2 concentration of the atmosphere, continental weathering and Ca carbonate sedimentation. We used samples from IODP Exp. 320/321 to establish a δ44/40Ca paleo-seawater record between 45 and 25 Ma and model changes in the Ca budget through time. Our results show differences in the Eocene and Oligocene Ca isotope record of benthic foraminifers. The δ44/40Ca values during the Eocene are relatively constant with no significant fluctuations during phases of large short term CCD fluctuations[1]. The Oligocene is characterized by sediments with uniformly high carbonate content and increasing δ44/40Ca towards the late Oligocene. Past seawater δ44/40Ca values (Fig. 1) were calculated from the measured benthic foraminifer record applying the calibration for Gyroidinoides spp.[2]. The Ca budget during the Eocene is relatively constant and not affected by short term CCD fluctuations, indicating that they are too small to alter the isotopic Ca budget. The Oligocene, in contrast is characterized by a general increase in δ44/40Ca seawater values and a continuously deep CCD[1]. This is consistent with a massive long term (>1Ma) CaCO3 deposition and decreasing Ca concentration in the ocean water. To examine the preservation (dissolution and recrystallization) of the foraminifer test through time, we studied additionally the changes in the crystallographic orientations trough time by Electron Backscatter Diffraction (EBSD) analysis and Raman spectroscopy. As a final step we use our δ44/40Ca seawater record to run a combined Ca and C model showing the effect of Ca weathering input, carbonate remobilization and dolomitization on the Ca and carbonate system of seawater [1]. [1]Pälike H

  8. The many phases of CaC2

    NASA Astrophysics Data System (ADS)

    Konar, Sumit; Nylén, Johanna; Svensson, Gunnar; Bernin, Diana; Edén, Mattias; Ruschewitz, Uwe; Häussermann, Ulrich

    2016-07-01

    Polymorphic CaC2 was prepared by reacting mixtures of CaH2 and graphite with molar ratios between 1:1.8 and 1:2.2 at temperatures between 700 and 1400 °C under dynamic vacuum. These conditions provided a well controlled, homogeneous, chemical environment and afforded products with high purity. The products, which were characterized by powder X-ray diffraction, solid state NMR and Raman spectroscopy, represented mixtures of the three known polymorphs, tetragonal CaC2-I and monoclinic CaC2-II and -III. Their proportion is dependent on the nominal C/CaH2 ratio of the reaction mixture and temperature. Reactions with excess carbon produced a mixture virtually free from CaC2-I, whereas high temperatures (above 1100 °C) and C-deficiency favored the formation of CaC2-I. From first principles calculations it is shown that CaC2-I is dynamically unstable within the harmonic approximation. This indicates that existing CaC2-I is structurally/dynamically disordered and may possibly even occur as slightly carbon-deficient phase CaC2-δ. It is proposed that monoclinic II is the ground state of CaC2 and polymorph III is stable at temperatures above 200 °C. Tetragonal I represents a metastable, heterogeneous, phase of CaC2. It is argued that a complete understanding of the occurrence of three room temperature modifications of CaC2 will require a detailed characterization of compositional and structural heterogeneities within the high temperature form CaC2-IV, which is stable above 450 °C. The effect of high pressure on the stability of the monoclinic forms of CaC2 was studied in a diamond anvil cell using Raman spectroscopy. CaC2-II and -III transform into tetragonal CaC2-I at about 4 and 1GPa, respectively.

  9. Effects of Ca2+ on phosphoinositide breakdown in exocrine pancreas.

    PubMed Central

    Taylor, C W; Merritt, J E; Putney, J W; Rubin, R P

    1986-01-01

    Recent studies have established that inositol 1,4,5-trisphosphate [I(1,4,5)P3] provides the link between receptor-regulated polyphosphoinositide hydrolysis and mobilization of intracellular Ca2+. Here, we report the effects of Ca2+ on inositol trisphosphate (IP3) formation from phosphatidylinositol bisphosphate (PIP2) catalysed by phospholipase C in intact and electrically permeabilized rat pancreatic acinar cells. In permeabilized cells, the Ca2+-mobilizing agonist caerulein stimulated [3H]IP3 formation when the free [Ca2+] was buffered at 140 nM, the cytosolic free [Ca2+] of unstimulated pancreatic acinar cells. When the free [Ca2+] was reduced to less than 10 nM, caerulein did not stimulate [3H]IP3 formation. Ca2+ in the physiological range stimulated [3H]IP3 formation and reduced the amount of [3H]PIP2 in permeabilized cells. The effects of Ca2+ and the receptor agonist caerulein were additive, but we have not established whether this reflects independent effects on the same or different enzymes. The effect of Ca2+ on [3H]IP3 formation by permeabilized cells was unaffected by inhibitors of the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism; nor were the effects of Ca2+ mimicked by addition of arachidonic acid. These results suggest that the effects of Ca2+ on phospholipase C activity are not a secondary consequence of Ca2+ activation of phospholipase A2. Changes in free [Ca2+] (less than 10 nM-1.2 mM) did not affect the metabolism of exogenous [3H]I(1,4,5)P3 by permeabilized cells. In permeabilized cells, breakdown of exogenous [3H]IP3 to [3H]IP2 (inositol bisphosphate), and formation of [3H]IP3 in response to receptor agonists were equally inhibited by 2,3-bisphosphoglyceric acid. This suggests that the [3H]IP2 formed in response to receptor agonists is entirely derived from [3H]IP3. In intact cells, [3H]IP3 formation was stimulated when ionomycin was used to increase the cytosolic free [Ca2+]. However, a maximal concentration of

  10. T-type Ca2+ channels mediate propagation of odor-induced Ca2+ transients in rat olfactory receptor neurons.

    PubMed

    Gautam, S H; Otsuguro, K-I; Ito, S; Saito, T; Habara, Y

    2007-01-19

    Propagation of odor-induced Ca(2+) transients from the cilia/knob to the soma in mammalian olfactory receptor neurons (ORNs) is thought to be mediated exclusively by high-voltage-activated Ca(2+) channels. However, using confocal Ca(2+) imaging and immunocytochemistry we identified functional T-type Ca(2+) channels in rat ORNs. Here we show that T-type Ca(2+) channels in ORNs also mediate propagation of odor-induced Ca(2+) transients from the knob to the soma. In the presence of the selective inhibitor of T-type Ca(2+) channels mibefradil (10-15 microM) or Ni(2+) (100 microM), odor- and forskolin/3-isobutyl-1-methyl-xanthine (IBMX)-induced Ca(2+) transients in the soma and dendrite were either strongly inhibited or abolished. The percentage of inhibition of the Ca(2+) transients in the knob, however, was 40-50% less than that in the soma. Ca(2+) transients induced by 30 mM K(+) were partially inhibited by mibefradil, but without a significant difference in the extent of inhibition between the knob and soma. Furthermore, an increase of as little as 2.5 mM in the extracellular K(+) concentration (7.5 mM K(+)) was found to induce Ca(2+) transients in ORNs, and such responses were completely inhibited by mibefradil or Ni(2+). Total replacement of extracellular Na(+) with N-methyl-d-glutamate inhibited none of the odor-, forskolin/IBMX- or 7.5 mM K(+)-induced Ca(2+) transients. Positive immunoreactivity to the Ca(v)3.1, Ca(v)3.2 and Ca(v)3.3 subunits of the T-type Ca(2+) channel was observed throughout the soma, dendrite and knob. These data suggest that involvement of T-type Ca(2+) channels in the propagation of odor-induced Ca(2+) transients in ORNs may contribute to signal transduction and odor sensitivity. PMID:17110049

  11. Apocalmodulin and Ca2+ calmodulin bind to the same region on the skeletal muscle Ca2+ release channel

    NASA Technical Reports Server (NTRS)

    Moore, C. P.; Rodney, G.; Zhang, J. Z.; Santacruz-Toloza, L.; Strasburg, G.; Hamilton, S. L.

    1999-01-01

    The skeletal muscle Ca2+ release channel (RYR1) is regulated by calmodulin in both its Ca2+-free (apocalmodulin) and Ca2+-bound (Ca2+ calmodulin) states. Apocalmodulin is an activator of the channel, and Ca2+ calmodulin is an inhibitor of the channel. Both apocalmodulin and Ca2+ calmodulin binding sites on RYR1 are destroyed by a mild tryptic digestion of the sarcoplasmic reticulum membranes, but calmodulin (either form), bound to RYR1 prior to tryptic digestion, protects both the apocalmodulin and Ca2+ calmodulin sites from tryptic destruction. The protected sites are after arginines 3630 and 3637 on RYR1. These studies suggest that both Ca2+ calmodulin and apocalmodulin bind to the same or overlapping regions on RYR1 and block access of trypsin to sites at amino acids 3630 and 3637. This sequence is part of a predicted Ca2+ CaM binding site of amino acids 3614-3642 [Takeshima, H., et al. (1989) Nature 339, 439-445].

  12. Na+-Ca2+ exchanger contributes to Ca2+ extrusion in ATP-stimulated endothelium of intact rat aorta.

    PubMed

    Berra-Romani, Roberto; Raqeeb, Abdul; Guzman-Silva, Alejandro; Torres-Jácome, Julián; Tanzi, Franco; Moccia, Francesco

    2010-04-23

    The role of Na(+)-Ca(2+) exchanger (NCX) in vascular endothelium is still matter of debate. Depending on both the endothelial cell (EC) type and the extracellular ligand, NCX has been shown to operate in either the forward (Ca(2+) out)- or the reverse (Ca(2+) in)-mode. In particular, acetylcholine (Ach) has been shown to promote Ca(2+) inflow in the intact endothelium of excised rat aorta. Herein, we assessed the involvement of NCX into the Ca(2+) signals elicited by ATP in such preparation. Removal of extracellular Na(+) (0Na(+)) causes the NCX to switch into the reverse-mode and induced an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)), which disappeared in the absence of extracellular Ca(2+), and in the presence of benzamil, which blocks both modes of NCX, and KB-R 7943, a selective inhibitor of the reverse-mode. ATP induced a transient Ca(2+) signal, whose decay was significantly prolonged by 0Na(+), benzamil, DCB, and monensin while it was unaffected by KB-R 7943. Notably, lowering extracellular Na(+) concentration increased the sensibility to lower doses of ATP. These date suggest that, unlike Ach-stimulated ECs, NCX promotes Ca(2+) extrusion when the stimulus is provided by ATP in intact endothelium of rat aorta. These data show that, within the same preparation, NCX operates in both modes, depending on the chemical nature of the extracellular stimulus. PMID:20353753

  13. Cytosolic and mitochondrial [Ca2+] in whole hearts using indo-1 acetoxymethyl ester: effects of high extracellular Ca2+.

    PubMed Central

    Schreur, J H; Figueredo, V M; Miyamae, M; Shames, D M; Baker, A J; Camacho, S A

    1996-01-01

    Assessment of free cytosolic [Ca2+] ([Ca2+]c) using the acetoxymethyl ester (AM) form of indo-1 may be compromised by loading of indo-1 into noncytosolic compartments, primarily mitochondria. To determine the fraction of noncytosolic fluorescence in whole hearts loaded with indo-1 AM, Mn2+ was used to quench cytosolic fluorescence. Residual (i.e., noncytosolic) fluorescence was subtracted from the total fluorescence before calculating [Ca2+]c. Noncytosolic fluorescence was used to estimate mitochondrial [Ca2+]. In hearts paced at 5 Hz (N = 17), noncytosolic fluorescence was 0.61 +/- 0.06 and 0.56 +/- 0.07 of total fluorescence at lambda 385 and lambda 456, respectively. After taking into account noncytosolic fluorescence, systolic and diastolic [Ca2+]c was 673 +/- 72 and 132 +/- 9 nM, respectively, noncytosolic [Ca2+] was 183 +/- 36 nM and increased to 272 +/- 12 when extracellular Ca2+ was increased from 2 to 6 mM. This increase in noncytosolic [Ca2+] was inhibited by ruthenium red, a blocker of Ca2+ uptake by mitochondria. We conclude that cytosolic and mitochondrial [Ca2+] can be determined in whole hearts loaded with indo-1 AM by using Mn2+ to quench cytosolic fluorescence. PMID:8744296

  14. Genetical and Comparative Genomics of Brassica under Altered Ca Supply Identifies Arabidopsis Ca-Transporter Orthologs[W][OPEN

    PubMed Central

    Graham, Neil S.; Hammond, John P.; Lysenko, Artem; Mayes, Sean; Ó Lochlainn, Seosamh; Blasco, Bego; Bowen, Helen C.; Rawlings, Chris J.; Rios, Juan J.; Welham, Susan; Carion, Pierre W.C.; Dupuy, Lionel X.; King, Graham J.; White, Philip J.; Broadley, Martin R.

    2014-01-01

    Although Ca transport in plants is highly complex, the overexpression of vacuolar Ca2+ transporters in crops is a promising new technology to improve dietary Ca supplies through biofortification. Here, we sought to identify novel targets for increasing plant Ca accumulation using genetical and comparative genomics. Expression quantitative trait locus (eQTL) mapping to 1895 cis- and 8015 trans-loci were identified in shoots of an inbred mapping population of Brassica rapa (IMB211 × R500); 23 cis- and 948 trans-eQTLs responded specifically to altered Ca supply. eQTLs were screened for functional significance using a large database of shoot Ca concentration phenotypes of Arabidopsis thaliana. From 31 Arabidopsis gene identifiers tagged to robust shoot Ca concentration phenotypes, 21 mapped to 27 B. rapa eQTLs, including orthologs of the Ca2+ transporters At-CAX1 and At-ACA8. Two of three independent missense mutants of BraA.cax1a, isolated previously by targeting induced local lesions in genomes, have allele-specific shoot Ca concentration phenotypes compared with their segregating wild types. BraA.CAX1a is a promising target for altering the Ca composition of Brassica, consistent with prior knowledge from Arabidopsis. We conclude that multiple-environment eQTL analysis of complex crop genomes combined with comparative genomics is a powerful technique for novel gene identification/prioritization. PMID:25082855

  15. Improving transesterification acitvity of CaO with hydration technique.

    PubMed

    Yoosuk, Boonyawan; Udomsap, Parncheewa; Puttasawat, Buppa; Krasae, Pawnprapa

    2010-05-01

    An efficient technique for increasing the transesterification activity of CaO obtained from calcination of CaCO(3) was proposed in order to make them highly suitable for use as heterogeneous catalysts for biodiesel production. CaO was refluxed in water followed by the synthesis of the oxide from hydroxide species. The characterization results indicate that this procedure substantially increases both the specific surface area and the amount of basic site. Hydration and subsequent calcination also generates a new calcium oxide with less crystalline. Transesterification of palm olein was used to determine the activity of catalysts to show that the decomposed-hydrated CaO exhibits higher catalytic activity than CaO generated from calcination of CaCO(3). The methyl ester content was enhanced 18.4 wt.%. PMID:20089395

  16. Ca(2+) influx through L-type Ca(2+) channels and transient receptor potential channels activates pathological hypertrophy signaling.

    PubMed

    Gao, Hui; Wang, Fang; Wang, Wei; Makarewich, Catherine A; Zhang, Hongyu; Kubo, Hajime; Berretta, Remus M; Barr, Larry A; Molkentin, Jeffery D; Houser, Steven R

    2012-11-01

    Common cardiovascular diseases such as hypertension and myocardial infarction require that myocytes develop greater than normal force to maintain cardiac pump function. This requires increases in [Ca(2+)]. These diseases induce cardiac hypertrophy and increases in [Ca(2+)] are known to be an essential proximal signal for activation of hypertrophic genes. However, the source of "hypertrophic" [Ca(2+)] is not known and is the topic of this study. The role of Ca(2+) influx through L-type Ca(2+) channels (LTCC), T-type Ca(2+) channels (TTCC) and transient receptor potential (TRP) channels on the activation of calcineurin (Cn)-nuclear factor of activated T cells (NFAT) signaling and myocyte hypertrophy was studied. Neonatal rat ventricular myocytes (NRVMs) and adult feline ventricular myocytes (AFVMs) were infected with an adenovirus containing NFAT-GFP, to determine factors that could induce NFAT nuclear translocation. Four millimolar Ca(2+) or pacing induced NFAT nuclear translocation. This effect was blocked by Cn inhibitors. In NRVMs Nifedipine (Nif, LTCC antagonist) blocked high Ca(2+)-induced NFAT nuclear translocation while SKF-96365 (TRP channel antagonist) and Nickel (Ni, TTCC antagonist) were less effective. The relative potency of these antagonists against Ca(2+) induced NFAT nuclear translocation (Nif>SKF-96365>Ni) was similar to their effects on Ca(2+) transients and the LTCC current. Infection of NRVM with viruses containing TRP channels also activated NFAT-GFP nuclear translocation and caused myocyte hypertrophy. TRP effects were reduced by SKF-96365, but were more effectively antagonized by Nif. These experiments suggest that Ca(2+) influx through LTCCs is the primary source of Ca(2+) to activate Cn-NFAT signaling in NRVMs and AFVMs. While TRP channels cause hypertrophy, they appear to do so through a mechanism involving Ca(2+) entry via LTCCs. PMID:22921230

  17. Apparent Ca2+ dissociation constant of Ca2+ chelators incorporated non-disruptively into intact human red cells.

    PubMed Central

    Tiffert, T; Lew, V L

    1997-01-01

    1. A recently developed method of measuring cytoplasmic Ca2+ buffering in intact red cells was applied to re-evaluate the intracellular Ca2+ binding properties of the Ca2+ chelators benz2 and BAPTA. Incorporation of the free chelators was accomplished by incubating the cells with the acetoxymethyl ester forms (benz2 AM or BAPTA AM). The divalent cation ionophore A23187 was used to induce equilibrium distribution of Ca2+ between cells and medium. 45Ca2+ was added stepwise to cell suspensions in the presence and absence of external BAPTA. To induce full Ca2+ equilibration, the plasma membrane Ca2+ pump was inhibited either by depleting the cells of ATP or by adding vanadate to the cell suspension. 2. The properties of the incorporated chelators were assessed from the difference in cytoplasmic Ca2+ buffering between chelator-free and chelator-loaded cells, over a wide range of intracellular ionized calcium concentrations ([Ca2+]i), from nanomolar to millimolar. 3. Under the experimental conditions applied, incorporation of benz2 and BAPTA into the red cells increased their Ca2+ buffering capacity by 300-600 mumol (340 g Hb)-1. The intracellular apparent Ca2+ dissociation constants (KDi) were about 500 nM for benz2 and 800 nM for BAPTA, values much higher than those reported for standard salt solutions (KD) of about 40 and 130 nM, respectively. These results suggest that, contrary to earlier observations, the intracellular red cell environment may cause large shifts in the apparent Ca2+ binding behaviour of incorporated chelators. 4. The possibility that the observed KD shifts are due to reversible binding of the chelators to haemoglobin is considered, and the implications of the present results for early estimates of physiological [Ca2+]i levels is discussed. PMID:9423182

  18. Calcineurin inhibits VCX1-dependent H+/Ca2+ exchange and induces Ca2+ ATPases in Saccharomyces cerevisiae.

    PubMed Central

    Cunningham, K W; Fink, G R

    1996-01-01

    The PMC1 gene in Saccharomyces cerevisiae encodes a vacuolar Ca2+ ATPase required for growth in high-Ca2+ conditions. Previous work showed that Ca2+ tolerance can be restored to pmc1 mutants by inactivation of calcineurin, a Ca2+/calmodulin-dependent protein phosphatase sensitive to the immunosuppressive drug FK506. We now report that calcineurin decreases Ca2+ tolerance of pmc1 mutants by inhibiting the function of VCX1, which encodes a vacuolar H+/Ca2+ exchanger related to vertebrate Na+/Ca2+ exchangers. The contribution of VCX1 in Ca2+ tolerance is low in strains with a functional calcineurin and is high in strains which lack calcineurin activity. In contrast, the contribution of PMC1 to Ca2+ tolerance is augmented by calcineurin activation. Consistent with these positive and negative roles of calcineurin, expression of a vcx1::lacZ reporter was slightly diminished and a pmc1::lacZ reporter was induced up to 500-fold by processes dependent on calcineurin, calmodulin, and Ca2+. It is likely that calcineurin inhibits VCX1 function mainly by posttranslational mechanisms. Activities of VCX1 and PMC1 help to control cytosolic free Ca2+ concentrations because their function can decrease pmc1::lacZ induction by calcineurin. Additional studies with reporter genes and mutants indicate that PMR1 and PMR2A, encoding P-type ion pumps required for Mn2+ and Na+ tolerance, may also be induced physiologically in response to high-Mn2+ and -Na+ conditions through calcineurin-dependent mechanisms. In these situations, inhibition of VCX1 function may be important for the production of Ca2+ signals. We propose that elevated cytosolic free Ca2+ concentrations, calmodulin, and calcineurin regulate at least four ion transporters in S. cerevisiae in response to several environmental conditions. PMID:8628289

  19. Citrus bergamia Risso Elevates Intracellular Ca (2+) in Human Vascular Endothelial Cells due to Release of Ca (2+) from Primary Intracellular Stores.

    PubMed

    Kang, Purum; Han, Seung Ho; Moon, Hea Kyung; Lee, Jeong-Min; Kim, Hyo-Keun; Min, Sun Seek; Seol, Geun Hee

    2013-01-01

    The purpose of the present study is to examine the effects of essential oil of Citrus bergamia Risso (bergamot, BEO) on intracellular Ca(2+) in human umbilical vein endothelial cells. Fura-2 fluorescence was used to examine changes in intracellular Ca(2+) concentration [Ca(2+)]i . In the presence of extracellular Ca(2+), BEO increased [Ca(2+)]i , which was partially inhibited by a nonselective Ca(2+) channel blocker La(3+). In Ca(2+)-free extracellular solutions, BEO increased [Ca(2+)]i in a concentration-dependent manner, suggesting that BEO mobilizes intracellular Ca(2+). BEO-induced [Ca(2+)]i increase was partially inhibited by a Ca(2+)-induced Ca(2+) release inhibitor dantrolene, a phospholipase C inhibitor U73122, and an inositol 1,4,5-triphosphate (IP3)-gated Ca(2+) channel blocker, 2-aminoethoxydiphenyl borane (2-APB). BEO also increased [Ca(2+)]i in the presence of carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of mitochondrial Ca(2+) uptake. In addition, store-operated Ca(2+) entry (SOC) was potentiated by BEO. These results suggest that BEO mobilizes Ca(2+) from primary intracellular stores via Ca(2+)-induced and IP3-mediated Ca(2+) release and affect promotion of Ca(2+) influx, likely via an SOC mechanism. PMID:24348719

  20. Structural basis for the differential effects of CaBP1 and calmodulin on CaV1.2 calcium-dependent inactivation

    PubMed Central

    Findeisen, Felix; Minor, Daniel L.

    2010-01-01

    Calcium-binding protein 1 (CaBP1), a calmodulin (CaM) homolog, endows certain voltage-gated calcium channels (CaVs) with unusual properties. CaBP1 inhibits CaV1.2 calcium-dependent inactivation (CDI) and introduces calcium-dependent facilitation (CDF). Here, we show that the ability of CaBP1 to inhibit CaV1.2 CDI and induce CDF arises from interaction between the CaBP1 N-lobe and interlobe linker residue Glu94. Unlike CaM, where functional EF hands are essential for channel modulation, CDI inhibition does not require functional CaBP1 EF-hands. Furthermore, CaBP1-mediated CDF has different molecular requirements than CaM-mediated CDF. Overall, the data show that CaBP1 comprises two structural modules having separate functions: similar to CaM, the CaBP1 C-lobe serves as a high-affinity anchor that binds the CaV1.2 IQ domain at a site that overlaps with the Ca2+/CaM C-lobe site, whereas the N-lobe/linker module houses the elements required for channel modulation. Discovery of this division provides the framework for understanding how CaBP1 regulates CaVs. PMID:21134641

  1. Evaporated CaS thin films for AC electroluminescence devices

    NASA Astrophysics Data System (ADS)

    Kobayashi, H.; Tanaka, S.; Shanker, V.; Shiiki, M.; Deguchi, H.

    1985-08-01

    The growth behavior of evaporated CaS thin films has been investigated to achieve bright electroluminescence. The crystallinity of CaS films is improved with substrate temperature and for temperatures higher than 300°C, the films orient to the (200) plane. Sulfur coevaporation further helps to form a more perfect film even at lower temperatures. A CaS: Ce,Cl electroluminescent thin film device has been fabricated with a brightness of 650 cd/m 2.

  2. SNL/CA Environmental Management System Program Manual.

    SciTech Connect

    Larsen, Barbara L.

    2007-04-01

    The Sandia National Laboratories, California (SNL/CA) Environmental Management System (EMS) Program Manual documents the elements of the site EMS Program. The SNL/CA EMS Program conforms to the International Standard on Environmental Management Systems, ISO 14001:2004. Elements of the ISO standard overlap with those of Department of Energy (DOE) Order 450.1, thus SNL/CA's EMS program also meets the DOE requirements.

  3. Ca-Al-rich chondrules and inclusions in ordinary chondrites

    NASA Technical Reports Server (NTRS)

    Bischoff, A.; Keil, K.

    1983-01-01

    Ca-Al-rich objects, hitherto mostly found in carbonaceous chondrites, are shown to be widespread, albeit rare, constituents of type 3 ordinary chondrites. Widespread occurrence and textural similarities of Ca-Al-rich chondrules to common, Mg-Fe-rich chondrules suggest that they formed by related processes. It is suggested in this article that Ca-Al-rich chondrules were formed by total melting and crystallization of heterogeneous, submillimeter- to submillimeter-sized dustballs made up of mixtures of high-temperature, Ca-Al-rich and lower-temperature, Na-K-rich components.

  4. Semantic web data warehousing for caGrid

    PubMed Central

    McCusker, James P; Phillips, Joshua A; Beltrán, Alejandra González; Finkelstein, Anthony; Krauthammer, Michael

    2009-01-01

    The National Cancer Institute (NCI) is developing caGrid as a means for sharing cancer-related data and services. As more data sets become available on caGrid, we need effective ways of accessing and integrating this information. Although the data models exposed on caGrid are semantically well annotated, it is currently up to the caGrid client to infer relationships between the different models and their classes. In this paper, we present a Semantic Web-based data warehouse (Corvus) for creating relationships among caGrid models. This is accomplished through the transformation of semantically-annotated caBIG® Unified Modeling Language (UML) information models into Web Ontology Language (OWL) ontologies that preserve those semantics. We demonstrate the validity of the approach by Semantic Extraction, Transformation and Loading (SETL) of data from two caGrid data sources, caTissue and caArray, as well as alignment and query of those sources in Corvus. We argue that semantic integration is necessary for integration of data from distributed web services and that Corvus is a useful way of accomplishing this. Our approach is generalizable and of broad utility to researchers facing similar integration challenges. PMID:19796399

  5. Toward a predictive model of Ca2+ puffs

    NASA Astrophysics Data System (ADS)

    Thul, R.; Thurley, K.; Falcke, M.

    2009-09-01

    We investigate the key characteristics of Ca2+ puffs in deterministic and stochastic frameworks that all incorporate the cellular morphology of IP3 receptor channel clusters. In the first step, we numerically study the Ca2+ liberation in a three-dimensional representation of a cluster environment with reaction-diffusion dynamics in both the cytosol and the lumen. These simulations reveal that Ca2+ concentrations at a releasing cluster range from 80 to 170 μM and equilibrate almost instantaneously on the time scale of the release duration. These highly elevated Ca2+ concentrations eliminate Ca2+ oscillations in a deterministic model of an IP3R channel cluster at physiological parameter values as revealed by a linear stability analysis. The reason lies in the saturation of all feedback processes in the IP3R gating dynamics, so that only fluctuations can restore experimentally observed Ca2+ oscillations. In this spirit, we derive master equations that allow us to analytically quantify the onset of Ca2+ puffs and hence the stochastic time scale of intracellular Ca2+ dynamics. Moving up the spatial scale, we suggest to formulate cellular dynamics in terms of waiting time distribution functions. This approach prevents the state space explosion that is typical for the description of cellular dynamics based on channel states and still contains information on molecular fluctuations. We illustrate this method by studying global Ca2+ oscillations.

  6. Study of OSL in NaF: Ca,Cu

    NASA Astrophysics Data System (ADS)

    More, Y. K.; Wankhede, S. P.; Moharil, S. V.

    2013-06-01

    Sodium Fluoride containing Cu+ ions was prepared by R.A.P. followed by melt-quenching technique. Results on photo, thermo and optically stimulated luminescence in NaF:Ca,Cu are reported. OSL sensitivity of NaF:Ca,Cu is approximately 2 times than that of standard phosphor LMP. The rate of OSL depletion for 90% decay for NaF:Ca,Cu is 0.3 times as that of OSL phosphor LMP. NaF:Ca,Cu thus deserves much more attention than it has received up till now.

  7. TRPV5-mediated Ca2+ Reabsorption and Hypercalciuria

    NASA Astrophysics Data System (ADS)

    Renkema, Kirsten Y.; Hoenderop, Joost G. J.; Bindels, René J. M.

    2007-04-01

    The concerted action of the intestine, kidney and bone results in the maintenance of a normal Ca2+ balance, a mechanism that is tightly controlled by the calciotropic hormones vitamin D, parathyroid hormone and calcitonin. Disturbances in the Ca2+ balance have been linked to diverse pathophysiological disorders like urolithiasis, hypertension, electroencephalogram abnormalities and rickets. Importantly, the final amount of Ca2+ that is released from the body is determined in the distal part of the nephron, where active Ca2+ reabsorption occurs. Here, Transient Receptor Potential Vanilloid member 5 (TRPV5), a highly Ca2+-selective channel, has been recognized as the gatekeeper of active Ca2+ reabsorption. The in vivo relevance of TRPV5 has been further investigated by the characterization of TRPV5 knockout (TRPV5-/-) mice, which exhibit severe disturbances in renal Ca2+ handling, such as profound hypercalciuria, intestinal Ca2+ hyperabsorption and reduced bone thickness. Hypercalciuria increases the risk of kidney stone formation in these mice. This review highlights our current knowledge about TRPV5-mediated Ca2+ reabsorption and emphasizes the physiological relevance and the clinical implications related to the TRPV5-/- mice model.

  8. Semantic web data warehousing for caGrid.

    PubMed

    McCusker, James P; Phillips, Joshua A; González Beltrán, Alejandra; Finkelstein, Anthony; Krauthammer, Michael

    2009-01-01

    The National Cancer Institute (NCI) is developing caGrid as a means for sharing cancer-related data and services. As more data sets become available on caGrid, we need effective ways of accessing and integrating this information. Although the data models exposed on caGrid are semantically well annotated, it is currently up to the caGrid client to infer relationships between the different models and their classes. In this paper, we present a Semantic Web-based data warehouse (Corvus) for creating relationships among caGrid models. This is accomplished through the transformation of semantically-annotated caBIG Unified Modeling Language (UML) information models into Web Ontology Language (OWL) ontologies that preserve those semantics. We demonstrate the validity of the approach by Semantic Extraction, Transformation and Loading (SETL) of data from two caGrid data sources, caTissue and caArray, as well as alignment and query of those sources in Corvus. We argue that semantic integration is necessary for integration of data from distributed web services and that Corvus is a useful way of accomplishing this. Our approach is generalizable and of broad utility to researchers facing similar integration challenges. PMID:19796399

  9. 2. Photocopy of photograph Photographer unknown, ca. 1893 Train shed ...

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

    2. Photocopy of photograph Photographer unknown, ca. 1893 Train shed under construction - Pennsylvania Railroad Station, Broad Street Station, Broad & Market Streets, Philadelphia, Philadelphia County, PA

  10. Study of dielectric properties of Ca doped barium titanate ceramics

    NASA Astrophysics Data System (ADS)

    Pradhan, S. K.; Kumar, Amit; Sinha, A. N.; Kour, P.

    2016-05-01

    Ba1-xCax Zr0.52Ti0.48 O3 ceramics was prepared by sol gel method. The crystallite size was in nano scale range. The dielectric constant was increased with increase in Ca2+ concentration in the sample. The dielectric loss was decreased with increase in ca concentration in the sample. The ac conductivity of the sample was increased with increase in Ca2+ concentration in the sample. The ac conductivity of the sample follows Johnscher power law. AC conductivity analysis shows that the interactions between neighbouring dipoles were decreased with the increase in Ca2+ concentration in the sample.

  11. Hot Tearing Susceptibility of Mg-Ca Binary Alloys

    NASA Astrophysics Data System (ADS)

    Song, Jiangfeng; Wang, Zhi; Huang, Yuanding; Srinivasan, Amirthalingam; Beckmann, Felix; Kainer, Karl Ulrich; Hort, Norbert

    2015-12-01

    Hot tearing is known as one of the most critical solidification defects commonly encountered during casting practice. As most Mg alloys are initially prepared by casting, ingots must have superior quality with no casting defects for the further processing. Due to the extensive potential biodegradable applications of binary Mg-Ca alloys, it is of great importance to investigate their hot tearing behavior. In the present study, the influence of Ca content (0.1, 0.2, 0.5, 1.0, and 2.0 wt pct) on hot tearing susceptibility (HTS) of Mg-Ca binary alloys was investigated using a constrained rod casting apparatus equipped with a load cell and data acquisition system. Tear volumes were quantified with 3D X-ray tomography. Results showed that the influence of Ca content on HTS followed a "Λ" shape: the HTS increased with increase in Ca content, reached a maximum at 0.5 to 1 wt pct Ca, and then decreased with further increasing the Ca content to 2.0 wt pct. The wide solidification range and reasonably high volume of intermetallic in the Mg-0.5 wt pct Ca and Mg-1 wt pct Ca alloys resulted in high HTS. Microstructure analysis suggested that the hot tear initiated at grain boundaries and propagated along them through thin film rupture or across the eutectic.

  12. 41Ca - a possible neutron specific biomarker in tooth enamel

    NASA Astrophysics Data System (ADS)

    Wallner, A.; Arazi, A.; Faestermann, T.; Knie, K.; Korschinek, G.; Maier, H. J.; Nakamura, N.; Rühm, W.; Rugel, G.

    2004-08-01

    The measurement of long-lived radionuclides, produced by neutrons originating from the atomic-bomb explosions, offers the possibility to reconstruct neutron fluences to which survivors in Hiroshima and Nagasaki were exposed. The long-lived radionuclide, 41Ca (T1/2=103 000 years), is suggested here as a means for a retrospective determination of thermal neutron fluences, directly within the human body of a survivor. As proper material tooth enamel is proposed. The 41Ca signal in tooth enamel may be correlated with the exposure to A-bomb induced thermal neutron fluences, provided the natural background level of 41Ca/Ca is significantly lower. Therefore, tooth samples of unexposed survivors of the A-bomb explosions have been examined by means of accelerator mass spectrometry, in order to quantify the natural background level of 41Ca/Ca. Measured 41Ca/Ca ratios were confirmed to be as low as about 2 × 10-15. Thus, the A-bomb induced additional signal should be detectable for survivors at epidemiological relevant distances. Since tooth enamel had already been used as a dosemeter for gamma radiation from the A-bomb explosion, the detection of 41Ca in tooth enamel would allow, for the first time, an assessment of both, γ-ray and neutron exposures in the same biological material.

  13. A new tumor marker: CA125 for ovarian carcinomas

    SciTech Connect

    Sakahara, H.; Endo, K.; Nakajima, K.; Nakashima, T.; Koizumi, M.; Ohta, H.; Torizuka, K.; Konishi, I.; Fujii, S.; Mori, T.

    1985-05-01

    To evaluate CA125 as a tumor marker for ovarian carcinomas, CA125 concentrations were measured by the simultaneous immunoradiometric assay. The binding of I-125 labeled monoclonal antibody to the bead-bound antigen was greatly influenced by many factors, such as the incubation time, pH, IgG concentrations of samples, the sequence of addition of the tracer and samples and so on. By applying the forward two-step assay, diminished binding was observed than in the simultaneous assay, probably due to the relatively low affinity of the antibody. This simultaneous immunoradiometric assay resulted in the ''prozone'' or ''hook'' effect at high CA125 samples and proper dilution was necessary to determine the accurate CA125 values. All 72 normal control subjects had low concentrations of under 35 U/ml. Elevated serum CA125 was observed in 43% (9/21) cases with malignant ovarian tumors, depending on the stage and the histopathological findings. All 4 serous cystadenocarcinomas and 2 of 3 endometrioid carcinomas were positive and the measurement of serum CA125 was useful in the sequential monitoring of these cases. In contrast, 51 benign gynecological diseases, none had elevated serum CA125 except one with follicular cyst. Among 75 cases with non-gynecological benign and malignant diseases, only 1 of 12 gastric carcinomas and 2 of 13 pancreatic carcinomas had elevated CA125 levels. In summary, CA125 is a promising and relatively specific marker for ovarian carcinomas.

  14. Pathways for energization of Ca in Mercury's exosphere

    NASA Astrophysics Data System (ADS)

    Killen, Rosemary M.

    2016-04-01

    We investigate the possible pathways to produce the extreme energy observed in the calcium exosphere of Mercury. Any mechanism must explain the facts that Ca in Mercury's exosphere is extremely hot, that it is seen almost exclusively on the dawnside of the planet, and that its content varies seasonally, not sporadically. Simple diatomic molecules or their clusters are considered, focusing on calcium oxides while acknowledging that Ca sulfides may also be the precursor molecules. We first discuss impact vaporization to justify the assumption that CaO and Ca-oxide clusters are expected from impacts on Mercury. Then we discuss processes by which the atomic Ca is energized to a 70,000 K gas. The processes considered are (1) electron-impact dissociation of CaO molecules, (2) spontaneous dissociation of Ca-bearing molecules following impact vaporization, (3) shock-induced dissociative ionization, (4) photodissociation and (5) sputtering. We conclude that electron-impact dissociation cannot produce the required abundance of Ca, and sputtering cannot reproduce the observed spatial and temporal variation that is measured. Spontaneous dissociation is unlikely to result in the high energy that is seen. Of the two remaining processes, shock-induced dissociative ionization produces the required energy and comes close to producing the required abundance, but rates are highly dependent on the incoming velocity distribution of the impactors. Photodissociation probably can produce the required abundance of Ca, but simulations show that photodissociation cannot reproduce the observed spatial distribution.

  15. CA1 Long-Term Potentiation Is Diminished but Present in Hippocampal Slices from α-CaMKII Mutant Mice

    PubMed Central

    Hinds, Heather L.; Tonegawa, Susumu; Malinow, Roberto

    1998-01-01

    Previous work has shown that mice missing the α-isoform of calcium–calmodulin-dependent protein kinase II (α-CaMKII) have a deficiency in CA1 hippocampal long-term potentiation (LTP). Follow-up studies on subsequent generations of these mutant mice in a novel inbred background by our laboratories have shown that whereas a deficiency in CA1 LTP is still present in α-CaMKII mutant mice, it is different both quantitatively and qualitatively from the deficiency first described. Mice of a mixed 129SvOla/SvJ;BALB/c;C57Bl/6 background derived from brother/sister mating of the α-CaMKII mutant line through multiple generations (>10) were produced by use of in vitro fertilization. Although LTP at 60 min post-tetanus was clearly deficient in these (−/−) α-CaMKII mice (42.6%, n = 33) compared with (+/+) α-CaMKII control animals (81.7%, n = 17), α-CaMKII mutant mice did show a significant level of LTP. The amount of LTP observed in α-CaMKII mutants was normally distributed, blocked by APV (2.7%, n = 8), and did not correlate with age. Although this supports a role for α-CaMKII in CA1 LTP, it also suggests that a form of α-CaMKII-independent LTP is present in mice that could be dependent on another kinase, such as the β-isoform of CaMKII. A significant difference in input/output curves was also observed between (−/−) α-CaMKII and (+/+) α-CaMKII animals, suggesting that differences in synaptic transmission may be contributing to the LTP deficit in mutant mice. However, tetani of increasing frequency (50, 100, and 200 Hz) did not reveal a higher threshold for potentiation in (−/−) α-CaMKII mice compared with (+/+) α-CaMKII controls. PMID:10454359

  16. Studies of Ca{sup 2+} binding in spinach photosytem II using {sup 45}Ca{sup 2+}

    SciTech Connect

    Aedelroth, P.; Lindberg, K.; Andreasson, L.E.

    1995-07-18

    The Ca{sup 2+}-binding properties of photosystem II were investigated with radioactive {sup 45}Ca{sup 2+}. PS II membranes, isolated from spinach grown on a medium containing {sup 45}Ca{sup 2+}, contained 1.5 Ca{sup 2+} per PS II unit. Approximately half of the incorporated radioactivity was lost after incubation for 30 h in nonradioactive buffer. About 1 Ca{sup 2+}/PS II bound slowly to Ca{sup 2+}-depleted membranes in the presence of the extrinsic 16- and 23-kDa polypeptides in parallel with restoration of oxygen-evolving activity. The binding was heterogeneous with dissociation constants of 60 {mu}M (0.7 Ca{sup 2+}/PS II) and 1.7 mM (0.3 Ca{sup 2+}/ PS II), respectively, which could reflect different affinities of the dark-stable S-states for Ca{sup 2+}. The reactivation of oxygen-evolving activity closely followed the binding of Ca{sup 2+}, showing that a single exchangeable Ca{sup 2+} per PS II is sufficient for the water-splitting reaction to function. In PS II, depleted of the 16- and 23-kDa polypeptides, about 0.7 exchangeable Ca{sup 2+}/PS II binds with a dissociation constant of 26 {mu}M, while 0.3 Ca{sup 2+} binds with a much weaker affinity (K{sub d} > 0.5 mM). The rate of binding of Ca{sup 2+} in the absence of the two extrinsic polypeptides was significantly higher than with the polypeptides bound. The rate of dissociation of bound Ca{sup 2+} in the dark, which had a half-time of about 80 h in intact PS H, increased in the absence of the 16-and 23-kDa polypeptides and showed a further increase after the additional removal of the 33-kDa protein and manganese. The rate of dissociation was also significantly faster in weak light than in the dark. Removal of the 33-kDa donor-side polypeptide together with the two lighter ones led to a reduction in the amount of bound Ca{sup 2+}, while practically no Ca{sup 2+} bound after treatments to dissociate also the manganese of the water-oxidizing site. 34 refs., 9 figs., 2 tabs.

  17. OLM interneurons differentially modulate CA3 and entorhinal inputs to hippocampal CA1 neurons

    PubMed Central

    Leão, Richardson N; Mikulovic, Sanja; Leão, Katarina E; Munguba, Hermany; Gezelius, Henrik; Enjin, Anders; Patra, Kalicharan; Eriksson, Anders; Loew, Leslie M.; Tort, Adriano BL; Kullander, Klas

    2012-01-01

    The vast diversity of GABAergic interneurons is believed to endow hippocampal microcircuits with the required flexibility for memory encoding and retrieval. However, dissection of the functional roles of defined interneuron types have been hampered by the lack of cell specific tools. Here we report a precise molecular marker for a population of hippocampal GABAergic interneurons known as oriens lacunosum-moleculare (OLM) cells. By combining novel transgenic mice and optogenetic tools, we demonstrate that OLM cells have a key role in gating the information flow in CA1, facilitating the transmission of intrahippocampal information (from CA3) while reducing the influence of extrahippocampal inputs (from the entorhinal cortex). We further demonstrate that OLM cells are interconnected by gap junctions, receive direct cholinergic inputs from subcortical afferents, and account for the effect of nicotine on synaptic plasticity of the Schaffer collateral pathway. Our results suggest that acetylcholine acting through OLM cells can control the mnemonic processes executed by the hippocampus. PMID:23042082

  18. Hindrance in the fusion of {sup 48}Ca+{sup 48}Ca

    SciTech Connect

    Esbensen, H.; Jiang, C. L.; Stefanini, A. M.

    2010-11-15

    The coupled-channels technique is applied to analyze recent fusion data for {sup 48}Ca+{sup 48}Ca. The calculations include the excitations of the low-lying 2{sup +}, 3{sup -}, and 5{sup -} states in projectile and target, and the influence of mutual excitations as well as the two-phonon quadrupole excitations is also investigated. The ion-ion potential is obtained by double-folding the nuclear densities of the reacting nuclei with the M3Y+repulsion effective interaction but a standard Woods-Saxon potential is also applied. The data exhibit a strong hindrance at low energy compared to calculations that are based on a standard Woods-Saxon potential but they can be reproduced quite well by applying the M3Y+repulsion potential with an adjusted radius of the nuclear density. The influence of the polarization of high-lying states on the extracted radius is discussed.

  19. Electron pair production in p + Be and Ca + Ca collisions at the Bevalac

    SciTech Connect

    Naudet, C.; Carroll, J.; Gordon, J.; Hallman, T.; Igo, G.; Kirk, P.; Krebs, G.F.; Lallier, E.; Landaud, G.; Letessier, A.

    1988-07-01

    We report on the measurements of direct electron pair production in p-Be interactions at 1.0, 2.1 and 4.9 GeV and Ca + Ca at 1.0 and 2.0 GeV/A. The distributions of invariant mass and p/sub t/ are presented along with the total cross section. We observe a structure in the invariant mass spectra at approximately 275 MeV for 2.0 and 4.9 GeV p + Be data. A rapid decrease in the p + Be total cross-section is observed between 2.1 and 1.0 GeV. Both observations are consistent with the interpretation that pion-pion annihilations dominate production mechanism. 10 refs., 3 figs., 1 tab.

  20. Sr2+/Ca2+ and 44Ca/40Ca fractionation during inorganic calcite formation: III. Impact of salinity/ionic strength

    PubMed Central

    Tang, Jianwu; Niedermayr, Andrea; Köhler, Stephan J.; Böhm, Florian; Kısakürek, Basak; Eisenhauer, Anton; Dietzel, Martin

    2012-01-01

    In order to apply Sr/Ca and 44Ca/40Ca fractionation during calcium carbonate (CaCO3) formation as a proxy to reconstruct paleo-environments, it is essential to evaluate the impact of various environmental factors. In this study, a CO2 diffusion technique was used to crystallize inorganic calcite from aqueous solutions at different ionic strength/salinity by the addition of NaCl at 25 °C. Results show that the discrimination of Sr2+ versus Ca2+ during calcite formation is mainly controlled by precipitation rate (R in μmol/m2/h) and is weakly influenced by ionic strength/salinity. In analogy to Sr incorporation, 44Ca/40Ca fractionation during precipitation of calcite is weakly influenced by ionic strength/salinity too. At 25 °C the calcium isotope fractionation between calcite and aqueous calcium ions (Δ44/40Cacalcite-aq = δ44/40Cacalcite − δ44/40Caaq) correlates inversely to log R values for all experiments. In addition, an inverse relationship between Δ44/40Cacalcite-aq and log DSr, which is independent of temperature, precipitation rate, and aqueous (Sr/Ca)aq ratio, is not affected by ionic strength/salinity either. Considering the log DSr and Δ44/40Cacalcite-aq relationship, Sr/Ca and δ44/40Cacalcite values of precipitated calcite can be used as an excellent multi-proxy approach to reconstruct environmental conditions (e.g., temperature, precipitation rate) of calcite growth and diagenetic alteration. PMID:22347722

  1. Estimation Model for Electrical Conductivity of CaF2-CaO-Al2O3 Slags

    NASA Astrophysics Data System (ADS)

    Shi, Guan-yong; Zhang, Ting-an; Dou, Zhi-he; Niu, Li-ping

    2016-04-01

    Electrical conductivity is one of the most important properties of molten slags. It has an important influence on process parameter selection of the electroslag remelting process. In the present work, a new model for estimating electrical conductivity of high-temperature slags has been proposed via calculating the conductivity by electrical conductivity of pure substances and interaction parameters between the different components in the slag has been proposed. In this model, the Arrhenius law is used to describe the relationship between electrical conductivity and temperature of slags. This model has been successfully applied to the CaF2-Al2O3, CaF2-CaO, and CaO-Al2O3, as well as CaF2-CaO-Al2O3 systems, and the calculated results are in good agreement with the measured values.

  2. Reconstructing past seawater Mg/Ca and Sr/Ca from mid-ocean ridge flank calcium carbonate veins.

    PubMed

    Coggon, Rosalind M; Teagle, Damon A H; Smith-Duque, Christopher E; Alt, Jeffrey C; Cooper, Matthew J

    2010-02-26

    Proxies for past seawater chemistry, such as Mg/Ca and Sr/Ca ratios, provide a record of the dynamic exchanges of elements between the solid Earth, the atmosphere, and the hydrosphere and the evolving influence of life. We estimated past oceanic Mg/Ca and Sr/Ca ratios from suites of 1.6- to 170-million-year-old calcium carbonate veins that had precipitated from seawater-derived fluids in ocean ridge flank basalts. Our data indicate that before the Neogene, oceanic Mg/Ca and Sr/Ca ratios were lower than in the modern ocean. Decreased ocean spreading since the Cretaceous and the resulting slow reduction in ocean crustal hydrothermal exchange throughout the early Tertiary may explain the recent rise in these ratios. PMID:20133522

  3. Activity-dependent upregulation of presynaptic kainate receptors at immature CA3-CA1 synapses.

    PubMed

    Clarke, Vernon R J; Molchanova, Svetlana M; Hirvonen, Teemu; Taira, Tomi; Lauri, Sari E

    2014-12-10

    Presynaptic kainate-type glutamate receptors (KARs) regulate glutamate release probability and short-term plasticity in various areas of the brain. Here we show that long-term depression (LTD) in the area CA1 of neonatal rodent hippocampus is associated with an upregulation of tonic inhibitory KAR activity, which contributes to synaptic depression and causes a pronounced increase in short-term facilitation of transmission. This increased KAR function was mediated by high-affinity receptors and required activation of NMDA receptors, nitric oxide (NO) synthetase, and postsynaptic calcium signaling. In contrast, KAR activity was irreversibly downregulated in response to induction of long-term potentiation in a manner that depended on activation of the TrkB-receptor of BDNF. Both tonic KAR activity and its plasticity were restricted to early stages of synapse development and were lost in parallel with maturation of the network due to ongoing BDNF-TrkB signaling. These data show that presynaptic KARs are targets for activity-dependent modulation via diffusible messengers NO and BDNF, which enhance and depress tonic KAR activity at immature synapses, respectively. The plasticity of presynaptic KARs in the developing network allows nascent synapses to shape their response to incoming activity. In particular, upregulation of KAR function after LTD allows the synapse to preferentially pass high-frequency afferent activity. This can provide a potential rescue from synapse elimination by uncorrelated activity and also increase the computational dynamics of the developing CA3-CA1 circuitry. PMID:25505341

  4. Vibrational spectroscopic study of poldervaartite CaCa[SiO3(OH)(OH)].

    PubMed

    Frost, Ray L; López, Andrés; Scholz, Ricardo; Lima, Rosa Malena Fernandes

    2015-02-25

    We have studied the mineral poldervaartite CaCa[SiO3(OH)(OH)] which forms a series with its manganese analogue olmiite CaMn[SiO3(OH)](OH) using a range of techniques including scanning electron microscopy, thermogravimetric analysis, Raman and infrared spectroscopy. Chemical analysis shows the mineral is reasonably pure and contains only calcium and manganese with low amounts of Al and F. Thermogravimetric analysis proves the mineral decomposes at 485°C with a mass loss of 7.6% compared with the theoretical mass loss of 7.7%. A strong Raman band at 852 cm(-1) is assigned to the SiO stretching vibration of the SiO3(OH) units. Two Raman bands at 914 and 953 cm(-1) are attributed to the antisymmetric vibrations. Intense prominent peaks observed at 3487, 3502, 3509, 3521 and 3547 cm(-1) are assigned to the OH stretching vibration of the SiO3(OH) units. The observation of multiple OH bands supports the concept of the non-equivalence of the OH units. Vibrational spectroscopy enables a detailed assessment of the molecular structure of poldervaartite. PMID:25280331

  5. Model-Based Assessment of an In-Vivo Predictive Relationship from CA1 to CA3 in the Rodent Hippocampus

    PubMed Central

    Sandler, Roman A.; Song, Dong; Hampson, Robert E.; Deadwyler, Sam A.; Berger, Theodore W.; Marmarelis, Vasilis Z.

    2014-01-01

    Although an anatomical connection from CA1 to CA3 via the Entorhinal Cortex (EC) and through backprojecting interneurons has long been known it exist, it has never been examined quantitatively on the single neuron level, in the in-vivo nonpatholgical, nonperturbed brain. Here, single spike activity was recorded using a multi-electrode array from the CA3 and CA1 areas of the rodent hippocampus (N=7) during a behavioral task. The predictive power from CA3→CA1 and CA1→CA3 was examined by constructing Multivariate Autoregressive (MVAR) models from recorded neurons in both directions. All nonsignificant inputs and models were identified and removed by means of Monte Carlo simulation methods. It was found that 121/166 (73%) CA3→CA1 models and 96/145 (66%) CA1→CA3 models had significant predictive power, thus confirming a predictive ‘Granger’ causal relationship from CA1 to CA3. This relationship is thought to be caused by a combination of truly causal connections such as the CA1→EC→CA3 pathway and common inputs such as those from the Septum. All MVAR models were then examined in the frequency domain and it was found that CA3 kernels had significantly more power in the theta and beta range than those of CA1, confirming CA3’s role as an endogenous hippocampal pacemaker. PMID:25260381

  6. Altered Ca2+ concentration, permeability and buffering in the myofibre Ca2+ store of a mouse model of malignant hyperthermia

    PubMed Central

    Manno, Carlo; Figueroa, Lourdes; Royer, Leandro; Pouvreau, Sandrine; Lee, Chang Seok; Volpe, Pompeo; Nori, Alessandra; Zhou, Jingsong; Meissner, Gerhard; Hamilton, Susan L; Ríos, Eduardo

    2013-01-01

    Malignant hyperthermia (MH) is linked to mutations in the type 1 ryanodine receptor, RyR1, the Ca2+ channel of the sarcoplasmic reticulum (SR) of skeletal muscle. The Y522S MH mutation was studied for its complex presentation, which includes structurally and functionally altered cell ‘cores’. Imaging cytosolic and intra-SR [Ca2+] in muscle cells of heterozygous YS mice we determined Ca2+ release flux activated by clamp depolarization, permeability (P) of the SR membrane (ratio of flux and [Ca2+] gradient) and SR Ca2+ buffering power (B). In YS cells resting [Ca2+]SR was 45% of the value in normal littermates (WT). P was more than doubled, so that initial flux was normal. Measuring [Ca2+]SR(t) revealed dynamic changes in B(t). The alterations were similar to those caused by cytosolic BAPTA, which promotes release by hampering Ca2+-dependent inactivation (CDI). The [Ca2+] transients showed abnormal ‘breaks’, decaying phases after an initial rise, traced to a collapse in flux and P. Similar breaks occurred in WT myofibres with calsequestrin reduced by siRNA; calsequestrin content, however, was normal in YS muscle. Thus, the Y522S mutation causes greater openness of the RyR1, lowers resting [Ca2+]SR and alters SR Ca2+ buffering in a way that copies the functional instability observed upon reduction of calsequestrin content. The similarities with the effects of BAPTA suggest that the mutation, occurring near the cytosolic vestibule of the channel, reduces CDI as one of its primary effects. The unstable SR buffering, mimicked by silencing of calsequestrin, may help precipitate the loss of Ca2+ control that defines a fulminant MH event. PMID:23798496

  7. Different Levels of CEA, CA153 and CA125 in Milk and Benign and Malignant Nipple Discharge

    PubMed Central

    Zhao, Song; Mei, Yu; Wang, Jianli; Zhang, Kai; Ma, Rong

    2016-01-01

    Background The aim of this study was to assess the diagnostic values of three breast tumor markers (i.e., CEA, CA153 and CA125) in milk and nipple discharge in the prediction of different breast diseases diagnoses. Methods Three hundred thirty-six patients (96 breast cancer and 240 benign disease patients) with nipple discharge and a control group of 56 healthy parturient participants were enrolled in the present study. Nipple discharge samples were preoperatively collected from the patients, and milk was collected from the colostrum of the parturient participants. The samples were assayed for the CEA, CA153 and CA125 levels. Cutoff values were determined for the detection of breast diseases using ROC curves. Results The levels of CEA, CA153 and CA125 were significantly different between the nipple discharge and the milk (all ps < 0.001). In the nipple discharge, the CEA and CA153 levels in the breast cancer group were significantly greater than those in the benign group (all ps < 0.001), and cutoff values of 263.3 ng/mL and 1235.3 U/mL, respectively, were established. However, the expression of CA125 did not differ significantly between the breast cancer and benign groups. Conclusion Differences in the apparent expression levels of CEA, CA153 and CA125 in patients with nipple discharge and healthy persons were validated. The present data suggest that CEA and CA153 might potentially be useful in the differential diagnoses of benign tumors and breast cancer. CA125 did not seem to be useful for breast cancer detection. PMID:27327081

  8. Nonspatial Sequence Coding in CA1 Neurons

    PubMed Central

    Allen, Timothy A.; Salz, Daniel M.; McKenzie, Sam

    2016-01-01

    The hippocampus is critical to the memory for sequences of events, a defining feature of episodic memory. However, the fundamental neuronal mechanisms underlying this capacity remain elusive. While considerable research indicates hippocampal neurons can represent sequences of locations, direct evidence of coding for the memory of sequential relationships among nonspatial events remains lacking. To address this important issue, we recorded neural activity in CA1 as rats performed a hippocampus-dependent sequence-memory task. Briefly, the task involves the presentation of repeated sequences of odors at a single port and requires rats to identify each item as “in sequence” or “out of sequence”. We report that, while the animals' location and behavior remained constant, hippocampal activity differed depending on the temporal context of items—in this case, whether they were presented in or out of sequence. Some neurons showed this effect across items or sequence positions (general sequence cells), while others exhibited selectivity for specific conjunctions of item and sequence position information (conjunctive sequence cells) or for specific probe types (probe-specific sequence cells). We also found that the temporal context of individual trials could be accurately decoded from the activity of neuronal ensembles, that sequence coding at the single-cell and ensemble level was linked to sequence memory performance, and that slow-gamma oscillations (20–40 Hz) were more strongly modulated by temporal context and performance than theta oscillations (4–12 Hz). These findings provide compelling evidence that sequence coding extends beyond the domain of spatial trajectories and is thus a fundamental function of the hippocampus. SIGNIFICANCE STATEMENT The ability to remember the order of life events depends on the hippocampus, but the underlying neural mechanisms remain poorly understood. Here we addressed this issue by recording neural activity in hippocampal

  9. Homer proteins accelerate Ca2+ clearance mediated by the plasma membrane Ca2+ pump in hippocampal neurons.

    PubMed

    Salm, Elizabeth J; Thayer, Stanley A

    2012-07-20

    The plasma membrane Ca(2+) ATPase (PMCA) is responsible for maintaining basal intracellular Ca(2+) concentration ([Ca(2+)](i)) and returning small increases in [Ca(2+)](i) back to resting levels. The carboxyl terminus of some PMCA splice variants bind Homer proteins; how binding affects PMCA function is unknown. Here, we examined the effects of altered expression of Homer proteins on PMCA-mediated Ca(2+) clearance from rat hippocampal neurons in culture. The kinetics of PMCA-mediated recovery from the [Ca(2+)](i) increase evoked by a brief train of action potentials was determined in the soma of single neurons using indo-1-based photometry. Exogenous expression of Homer 1a, Homer 1c or Homer 2a did not affect PMCA function. However, shRNA mediated knockdown of Homer 1 slowed PMCA mediated Ca(2+) clearance by 28% relative to cells expressing non-silencing shRNA. The slowed recovery rate in cells expressing Homer 1 shRNA was reversed by expression of a short Homer 2 truncation mutant. These results indicate that constitutively expressed Homer proteins tonically stimulate PMCA function in hippocampal neurons. We propose a model in which binding of short or long Homer proteins to the carboxyl terminus of the PMCA stimulates Ca(2+) clearance rate. PMCA-mediated Ca(2+) clearance may be stimulated following incorporation of the pump into Homer organized signaling domains and following induction of the Homer 1a immediate early gene. PMID:22732411

  10. Open Structure of the Ca2+ Gating Ring in the High-Conductance Ca2+-Activated K+ Channel

    PubMed Central

    Yuan, Peng; Leonetti, Manuel D.; Hsiung, Yichun; MacKinnon, Roderick

    2012-01-01

    High conductance voltage-and Ca2+-activated K+ channels (Slo1 or BK channels) function in many physiological processes that link cell membrane voltage and intracellular Ca2+, including neuronal electrical activity, skeletal and smooth muscle contraction, and hair cell tuning1–8. Like other voltage-dependent K+ (Kv) channels, BK channels open when the cell membrane depolarizes, but in contrast to other Kv channels they also open when intracellular Ca2+ levels rise. Channel opening by Ca2+ is conferred by a structure called the gating ring, located in the cytoplasm. Recent structural studies have defined the Ca2+-free, closed conformation of the gating ring, but the open conformation is not yet known9. Here we present the Ca2+-bound, open conformation of the gating ring. This structure shows how one layer of the gating ring, in response to the binding of Ca2+, opens like the petals of a flower. The magnitude of opening explains how Ca2+ binding can open the pore. These findings present amolecular basis of Ca2+ activation and suggest new possibilities for targeting the gating ring to treat diseases such as asthma and hypertension. PMID:22139424

  11. Genetic and Pharmacological Inhibition of the Ca2+ Influx Channel TRPC3 Protects Secretory Epithelia from Ca2+-Dependent Toxicity

    PubMed Central

    Kim, Min Seuk; Lee, Kyu Pil; Yang, Dongki; Shin, Dong Min; Abramowitz, Joel; Kiyonaka, Shigeki; Birnbaumer, Lutz; Mori, Yasuo; Muallem, Shmuel

    2011-01-01

    Background & Aims Excessive Ca2+ influx mediates many cytotoxic processes, including those associated with autoimmune inflammatory diseases such as acute pancreatitis and Sjögren's syndrome. TRPC3 is a major Ca2+ influx channel in pancreatic and salivary gland cells. We investigated whether genetic or pharmacological inhibition of TRPC3 protects pancreas and salivary glands from Ca2+-dependent damage. Methods We developed a Ca2+-dependent model of cell damage for salivary gland acini. Acute pancreatitis was induced by injection of cerulein into wild-type and Trpc3−/− mice. Mice were also given the Trpc3-selective inhibitor pyrazole 3 (Pyr3). Results Salivary glands and pancreas of Trpc3−/− mice were protected from Ca2+-mediated cell toxicity. Analysis of Ca2+ signaling in wild-type and Trpc3−/− acini showed that Pyr3 is highly specific inhibitor of Tprc3; it protected salivary glands and pancreas cells from Ca2+-mediated toxicity by inhibiting the Trpc3-mediated component of Ca2+ influx. Conclusions TRPC3-mediated Ca2+ influx mediates damage to pancreas and salivary glands. Pharmacological inhibition of TRPC3 with the highly selective TRPC3 inhibitor Pyr3 might be developed for treatment of patients with acute pancreatitis and Sjögren's syndrome. PMID:21354153

  12. Ca-intercalated graphite as a hydrogen storage material: Stability against decomposition into CaH{sub 2} and graphite

    SciTech Connect

    Wood, C.R.; Skipper, N.T.; Gillan, M.J.

    2011-06-15

    We have used calculations based on density functional theory to investigate the energetics of hydrogen absorption in calcium-intercalated graphites. We focus particularly on the absorption energy and the stability of the hydrogenated material with respect to decomposition into graphite and calcium hydride, which is essential if this material is to be used for practical H{sub 2} storage. The calculations are performed with two commonly used approximations for the exchange-correlation energies. Our calculations confirm earlier predictions that the absorption energy is approximately -0.2 to -0.4 eV, which is favourable for practical use of Ca-intercalated graphite as a hydrogen storage medium. However, we find that the hydrogenated material is strongly unstable against decomposition. Our results therefore explain recent experiments which show that H{sub 2} does not remain stable in CaC{sub 6} but instead forms a hydride plus graphite. - Graphical abstract: The hydrogenation of Ca-graphite (left) results in its decomposition into pure graphite (middle) and CaH{sub 2} (right). Highlights: > We investigate the stability of hydrogenated Ca-intercalated graphite with DFT. > Dissociated H absorption in CaC{sub 6} is most favourable, with reasonable binding energies. > Molecular H{sub 2} absorption is most favourable in CaC{sub 8} and CaC{sub 14}. > We find all scenarios are unstable against decomposition into CaH{sub 2} and graphite. > The decomposition will be strongly exothermic in agreement with experiments.

  13. Effects of cytosolic ATP on spontaneous and triggered Ca2+-induced Ca2+ release in permeabilised rat ventricular myocytes.

    PubMed

    Yang, Z; Steele, D S

    2000-02-15

    1. The effects of cytosolic ATP on sarcoplasmic reticulum (SR) Ca2+ regulation were investigated in saponin-permeabilised rat ventricular myocytes. [Ca2+] within the cells was monitored using Fura-2 or Fluo-3 fluorescence. Spontaneous cyclic Ca2+ release from the SR was induced by increasing the bathing [Ca2+] to 200-300 nM, in solutions weakly Ca2+ buffered with 0.05 mM EGTA. Alternatively, Ca2+-induced Ca2+ release (CICR) was triggered by a rapid increase in [Ca2+] induced by flash photolysis of Nitr-5 (0.08 mM), replacing EGTA in the solution. 2. Stepwise reductions in [ATP] were associated with corresponding decreases in the frequency and increases in the amplitude of spontaneous Ca2+ transients. A decrease from 5 mM to 0. 1 mM ATP, reduced the release frequency by 48.6 +/- 7 % (n = 7) and almost doubled the amplitude of the Ca2+ transient. Marked prolongation of the spontaneous Ca2+ transient occurred when [ATP] was further reduced to 10 microM, consistent with inhibition of the SR Ca2+ pump. 3. These effects of ATP were compared with other interventions that inhibit Ca2+ uptake or reduce the sensitivity of the SR Ca2+ release mechanism. Inhibition of the SR Ca2+ pump with cyclopiazonic acid (CPA) markedly reduced the spontaneous Ca2+ release frequency, without changing the amplitude. The descending phase of the Ca2+ transient was prolonged in the presence of CPA, while the rising phase was unaffected. In contrast, desensitisation of the SR Ca2+ release mechanism with tetracaine decreased the frequency of spontaneous release, but markedly increased the amplitude. 4. CICR triggered by flash photolysis of Nitr-5 appeared to be more sensitive to cytosolic [ATP] than spontaneous release and was generally delayed by a decrease to 2.5 mM ATP. In the presence of 0.1-0.2 mM ATP, release often failed completely or was not consistently triggered. Some preparations exhibited Ca2+ release 'alternans', whereby every alternate trigger induced a response. 5. These results

  14. Ca(2+) Signalling in Endothelial Progenitor Cells: Friend or Foe?

    PubMed

    Moccia, Francesco; Guerra, Germano

    2016-02-01

    Endothelial progenitor cells (EPCs) are mobilized either from the bone marrow and/or the arterial to replace dysfunctional endothelial cells and rescue blood perfusion in ischemic tissues. In addition, they may contribute to the angiogenic switch, thereby sustaining tumour growth and metastatization. Understanding the molecular mechanisms utilized by vascular endothelial growth factor (VEGF) to stimulate EPCs might unveil novel targets to enhance their clinical outcome in regenerative medicine and to adverse tumour vascularisation. VEGF stimulates peripheral blood-derived EPCs to undergo repetitive Ca(2+) oscillations shaped by the interaction between inositol-1,4,5-trisphosphate (InsP3 )-dependent Ca(2+) release and store-operated Ca(2+) entry (SOCE). However, the Ca(2+) machinery underlying VEGF-induced Ca(2+) spikes changes in umbilical cord blood-derived EPCs, which require TRPC3-mediated Ca(2+) entry to trigger the interplay between InsP3 and SOCE. Surprisingly, VEGF fails to elicit pro-angiogenic Ca(2+) signals when EPCs derive from renal cellular carcinoma patients, thus questioning the suitability of VEGFR-2 as a target for anti-angiogenic treatments in these individuals. The lack of response to VEGF is likely due to the dramatic rearrangement of the Ca(2+) toolkit occurring in RCC-derived EPCs. Finally, primary myelofibrosis-derived EPCs display a further pattern of reorganization of the Ca(2+) machinery and proliferate independently of SOCE. Thus, the Ca(2+) machinery in human ECFCs is extremely plastic and may change depending on the physio-pathological background of the donor. As a consequence, the Ca(2+) toolkit could properly be used to enhance the regenerative outcome of cell-based therapy or adverse tumor vascularisation. PMID:26247172

  15. Ca2+-activated Cl− current in rabbit sinoatrial node cells

    PubMed Central

    Verkerk, Arie O; Wilders, Ronald; Zegers, Jan G; van Borren, Marcel M G J; Ravesloot, Jan H; Verheijck, E Etienne

    2002-01-01

    The Ca2+-activated Cl− current (ICl(Ca)) has been identified in atrial, Purkinje and ventricular cells, where it plays a substantial role in phase-1 repolarization and delayed after-depolarizations. In sinoatrial (SA) node cells, however, the presence and functional role of ICl(Ca) is unknown. In the present study we address this issue using perforated patch-clamp methodology and computer simulations. Single SA node cells were enzymatically isolated from rabbit hearts. ICl(Ca) was measured, using the perforated patch-clamp technique, as the current sensitive to the anion blocker 4,4′-diisothiocyanostilbene-2,2′-disulphonic acid (DIDS). Voltage clamp experiments demonstrate the presence of ICl(Ca) in one third of the spontaneously active SA node cells. The current was transient outward with a bell-shaped current-voltage relationship. Adrenoceptor stimulation with 1 μm noradrenaline doubled the ICl(Ca) density. Action potential clamp measurements demonstrate that ICl(Ca) is activate late during the action potential upstroke. Current clamp experiments show, both in the absence and presence of 1 μm noradrenaline, that blockade of ICl(Ca) increases the action potential overshoot and duration, measured at 20 % repolarization. However, intrinsic interbeat interval, upstroke velocity, diastolic depolarization rate and the action potential duration measured at 50 and 90 % repolarization were not affected. Our experimental data are supported by computer simulations, which additionally demonstrate that ICl(Ca) has a limited role in pacemaker synchronization or action potential conduction. In conclusion, ICl(Ca) is present in one third of SA node cells and is activated during the pacemaker cycle. However, ICl(Ca) does not modulate intrinsic interbeat interval, pacemaker synchronization or action potential conduction. PMID:11927673

  16. Heterogeneities in ICC Ca2+ activity within canine large intestine

    PubMed Central

    Lee, Hyun-Tai; Hennig, Grant W.; Park, Kyu Joo; Bayguinov, Peter O.; Ward, Sean M.; Sanders, Kenton M.; Smith, Terence K.

    2016-01-01

    Background & Aims In human and canine colon, both slow (slow waves, 2–8/min) and fast (myenteric potential oscillations; MPOs, 16–20/min) electrical rhythms in the smooth muscle originate at the submucosal and myenteric borders, respectively. We used Ca2+ imaging to investigate whether ICC at these borders generated distinct rhythms. Methods Segments of canine colon were pinned submucosal or myenteric surface uppermost, or cut in cross-section. Tissues were loaded with a Ca2+ indicator (fluo-4) and activity was monitored at 36.5±0.5°C using a CCD camera. Results Rhythmic, biphasic Ca2+ transients (5–8/min), similar in waveform to electrical slow waves, propagated without decrement as a wave front through the ICC-SM network (2–5mm/s), decaying exponentially through the thickness of the CM. In contrast, rhythmic intracellular Ca2+ waves (~16/min) and spontaneous reductions in Ca2+ were observed in ICC-MY. Normally, intracellular Ca2+ waves were unsynchronized between adjacent ICC-MY, although excitatory nerve activity synchronized activity. In addition, spontaneous reductions in Ca2+ were observed that inhibited Ca2+ waves. L-NA (100µM; NO antagonist) blocked the reductions in Ca2+ and increased the frequency (~19/min) of intracellular Ca2+ waves within ICC-MY. Conclusions ICC-SM form a tightly coupled network that is able to generate and propagate slow waves. In contrast, Ca2+ transients in ICC-MY, which are normally not synchronized, have a similar duration and frequency as MPOs. Like MPOs, their activity is inhibited by nitrergic nerves and synchronized by excitatory nerves. PMID:19268670

  17. {sup 48}Ca HETEROGENEITY IN DIFFERENTIATED METEORITES

    SciTech Connect

    Chen, Hsin-Wei; Lee, Typhoon; Lee, Der-Chuen; Shen, Jason Jiun-San; Chen, Jiang-Chang

    2011-12-10

    Isotopic heterogeneities of {sup 48}Ca have been found in numerous bulk meteorites that are correlated with {sup 50}Ti and {sup 54}Cr anomalies among differentiated planetary bodies, and the results suggest that a rare subset of neutron-rich Type Ia supernova (nSN Ia) was responsible for contributing these neutron-rich iron-group isotopes into the solar system (SS). The heterogeneity of these isotopes found in differentiated meteorites indicates that the isotopic compositions of the bulk SS are not uniform, and there are significant amounts of nSNe Ia dust incompletely mixed with the rest of SS materials during planetary formation. Combined with the data of now-extinct short-lived nuclide {sup 60}Fe, which can be produced more efficiently from an nSN Ia than a Type II supernova ejecta, the observed planetary-scale isotopic heterogeneity probably reflects a late input of stellar dust grains with neutron-rich nuclear statistical equilibrium nuclides into the early SS.

  18. TRP channels and Ca2+ signaling

    PubMed Central

    Minke, Baruch

    2007-01-01

    There is a rapidly growing interest in the family of transient receptor potential (TRP) channels because TRP channels are not only important for many sensory systems, but they are crucial components of the function of neurons, epithelial, blood and smooth muscle cells. These facts make TRP channels important targets for treatment of diseases arising from the malfunction of these channels in the above cells and for treatment of inflammatory pain. TRP channels are also important for a growing number of genetic diseases arising from mutations in various types of TRP channels. The Minerva-Gentner Symposium on TRP channels and Ca2+ signaling, which took place in Eilat, Israel (February 24–28, 2006) has clearly demonstrated that the study of TRP channels is a newly emerging field of biomedicine with prime importance. In the Eilat symposium, investigators who have contributed seminal publications and insight into the TRP field presented their most recent, and in many cases still unpublished, studies. The excellent presentations and excitement generated by them demonstrated that much progress has been achieved. Nevertheless, it was also evident that the field of TRP channels is still in its infancy in comparison to other fields of ion channels, and even the fundamental knowledge of the gating mechanism of TRP channels is still unsolved. The beautiful location of the symposium, together with informal intensive discussions among the participants, contributed to the success of this meeting. PMID:16806461

  19. Diversity of atrial local Ca2+ signalling: evidence from 2-D confocal imaging in Ca2+-buffered rat atrial myocytes.

    PubMed

    Woo, Sun-Hee; Cleemann, Lars; Morad, Martin

    2005-09-15

    Atrial myocytes, lacking t-tubules, have two functionally separate groups of ryanodine receptors (RyRs): those at the periphery colocalized with dihydropyridine receptors (DHPRs), and those at the cell interior not associated with DHPRs. We have previously shown that the Ca(2+) current (I(Ca))-gated central Ca(2+) release has a fast component that is followed by a slower and delayed rising phase. The mechanisms that regulate the central Ca(2+) releases remain poorly understood. The fast central release component is highly resistant to dialysed Ca(2+) buffers, while the slower, delayed component is completely suppressed by such exogenous buffers. Here we used dialysis of Ca(2+) buffers (EGTA) into voltage-clamped rat atrial myocytes to isolate the fast component of central Ca(2+) release and examine its properties using rapid (240 Hz) two-dimensional confocal Ca(2+) imaging. We found two populations of rat atrial myocytes with respect to the ratio of central to peripheral Ca(2+) release (R(c/p)). In one population ('group 1', approximately 60% of cells), R(c/p) converged on 0.2, while in another population ('group 2', approximately 40%), R(c/p) had a Gaussian distribution with a mean value of 0.625. The fast central release component of group 2 cells appeared to result from in-focus Ca(2+) sparks on activation of I(Ca). In group 1 cells intracellular membranes associated with t-tubular structures were never seen using short exposures to membrane dyes. In most of the group 2 cells, a faint intracellular membrane staining was observed. Quantification of caffeine-releasable Ca(2+) pools consistently showed larger central Ca(2+) stores in group 2 and larger peripheral stores in group 1 cells. The R(c/p) was larger at more positive and negative voltages in group 1 cells. In contrast, in group 2 cells, the R(c/p) was constant at all voltages. In group 1 cells the gain of peripheral Ca(2+) release sites (Delta[Ca(2+)]/I(Ca)) was larger at -30 than at +20 mV, but

  20. SNL/CA Environmental Management System Program Manual.

    SciTech Connect

    Larsen, Barbara L.

    2005-09-01

    The Sandia National Laboratories, California (SNL/CA) Environmental Management System (EMS) Program Manual documents the elements of the site EMS Program. The SNL/CA EMS Program was developed in accordance with Department of Energy (DOE) Order 450.1 and incorporates the elements of the International Standard on Environmental Management Systems, ISO 14001.

  1. 33 CFR 80.1152 - Crescent City Harbor, CA.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Crescent City Harbor, CA. 80.1152... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1152 Crescent City Harbor, CA. A line drawn from Crescent City Entrance Light to the southeasternmost extremity of Whaler Island....

  2. 33 CFR 80.1152 - Crescent City Harbor, CA.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Crescent City Harbor, CA. 80.1152... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1152 Crescent City Harbor, CA. A line drawn from Crescent City Entrance Light to the southeasternmost extremity of Whaler Island....

  3. 33 CFR 80.1152 - Crescent City Harbor, CA.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Crescent City Harbor, CA. 80.1152... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1152 Crescent City Harbor, CA. A line drawn from Crescent City Entrance Light to the southeasternmost extremity of Whaler Island....

  4. 33 CFR 80.1152 - Crescent City Harbor, CA.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Crescent City Harbor, CA. 80.1152... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1152 Crescent City Harbor, CA. A line drawn from Crescent City Entrance Light to the southeasternmost extremity of Whaler Island....

  5. CA Condensates as a Retrospective Search Tool. A Commentary

    ERIC Educational Resources Information Center

    Hansen, Inge Berg

    1973-01-01

    A retrospective test search on one year of CA Condensates was carried out in order to calculate the costs per profile and to get an impression of how CA Condensates would suffice as a database for retrospective use. (11 references) (Author)

  6. Intracellular Ca-carbonate biomineralization is widespread in cyanobacteria.

    PubMed

    Benzerara, Karim; Skouri-Panet, Feriel; Li, Jinhua; Férard, Céline; Gugger, Muriel; Laurent, Thierry; Couradeau, Estelle; Ragon, Marie; Cosmidis, Julie; Menguy, Nicolas; Margaret-Oliver, Isabel; Tavera, Rosaluz; López-García, Purificación; Moreira, David

    2014-07-29

    Cyanobacteria have played a significant role in the formation of past and modern carbonate deposits at the surface of the Earth using a biomineralization process that has been almost systematically considered induced and extracellular. Recently, a deep-branching cyanobacterial species, Candidatus Gloeomargarita lithophora, was reported to form intracellular amorphous Ca-rich carbonates. However, the significance and diversity of the cyanobacteria in which intracellular biomineralization occurs remain unknown. Here, we searched for intracellular Ca-carbonate inclusions in 68 cyanobacterial strains distributed throughout the phylogenetic tree of cyanobacteria. We discovered that diverse unicellular cyanobacterial taxa form intracellular amorphous Ca-carbonates with at least two different distribution patterns, suggesting the existence of at least two distinct mechanisms of biomineralization: (i) one with Ca-carbonate inclusions scattered within the cell cytoplasm such as in Ca. G. lithophora, and (ii) another one observed in strains belonging to the Thermosynechococcus elongatus BP-1 lineage, in which Ca-carbonate inclusions lie at the cell poles. This pattern seems to be linked with the nucleation of the inclusions at the septum of the cells, showing an intricate and original connection between cell division and biomineralization. These findings indicate that intracellular Ca-carbonate biomineralization by cyanobacteria has been overlooked by past studies and open new perspectives on the mechanisms and the evolutionary history of intra- and extracellular Ca-carbonate biomineralization by cyanobacteria. PMID:25009182

  7. 46 CFR 7.115 - Santa Catalina Island, CA.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Santa Catalina Island, CA. 7.115 Section 7.115 Shipping... Coast § 7.115 Santa Catalina Island, CA. (a) A line drawn from the northernmost point of Lion Head to the north tangent of Bird Rock Island; thence to the northernmost point of Blue Cavern Point. (b)...

  8. 46 CFR 7.115 - Santa Catalina Island, CA.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 1 2014-10-01 2014-10-01 false Santa Catalina Island, CA. 7.115 Section 7.115 Shipping... Coast § 7.115 Santa Catalina Island, CA. (a) A line drawn from the northernmost point of Lion Head to the north tangent of Bird Rock Island; thence to the northernmost point of Blue Cavern Point. (b)...

  9. 33 CFR 80.1122 - Channel Islands Harbor, CA.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Channel Islands Harbor, CA. 80... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1122 Channel Islands Harbor, CA. (a) A line drawn from Channel Islands Harbor South Jetty Light 2 to Channel Islands Harbor...

  10. 33 CFR 80.1102 - Santa Catalina Island, CA.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Santa Catalina Island, CA. 80... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1102 Santa Catalina Island, CA. The 72 COLREGS shall apply to the harbors on Santa Catalina Island....

  11. 33 CFR 80.1122 - Channel Islands Harbor, CA.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Channel Islands Harbor, CA. 80... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1122 Channel Islands Harbor, CA. (a) A line drawn from Channel Islands Harbor South Jetty Light 2 to Channel Islands Harbor...

  12. 33 CFR 80.1102 - Santa Catalina Island, CA.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Santa Catalina Island, CA. 80... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1102 Santa Catalina Island, CA. The 72 COLREGS shall apply to the harbors on Santa Catalina Island....

  13. 33 CFR 80.1102 - Santa Catalina Island, CA.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Santa Catalina Island, CA. 80... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1102 Santa Catalina Island, CA. The 72 COLREGS shall apply to the harbors on Santa Catalina Island....

  14. 33 CFR 80.1122 - Channel Islands Harbor, CA.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Channel Islands Harbor, CA. 80... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1122 Channel Islands Harbor, CA. (a) A line drawn from Channel Islands Harbor South Jetty Light 2 to Channel Islands Harbor...

  15. 46 CFR 7.115 - Santa Catalina Island, CA.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 1 2013-10-01 2013-10-01 false Santa Catalina Island, CA. 7.115 Section 7.115 Shipping... Coast § 7.115 Santa Catalina Island, CA. (a) A line drawn from the northernmost point of Lion Head to the north tangent of Bird Rock Island; thence to the northernmost point of Blue Cavern Point. (b)...

  16. 33 CFR 80.1102 - Santa Catalina Island, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Santa Catalina Island, CA. 80... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1102 Santa Catalina Island, CA. The 72 COLREGS shall apply to the harbors on Santa Catalina Island....

  17. 33 CFR 80.1102 - Santa Catalina Island, CA.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Santa Catalina Island, CA. 80... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1102 Santa Catalina Island, CA. The 72 COLREGS shall apply to the harbors on Santa Catalina Island....

  18. 33 CFR 80.1122 - Channel Islands Harbor, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Channel Islands Harbor, CA. 80... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1122 Channel Islands Harbor, CA. (a) A line drawn from Channel Islands Harbor South Jetty Light 2 to Channel Islands Harbor...

  19. 46 CFR 7.115 - Santa Catalina Island, CA.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Santa Catalina Island, CA. 7.115 Section 7.115 Shipping... Coast § 7.115 Santa Catalina Island, CA. (a) A line drawn from the northernmost point of Lion Head to the north tangent of Bird Rock Island; thence to the northernmost point of Blue Cavern Point. (b)...

  20. 33 CFR 80.1122 - Channel Islands Harbor, CA.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Channel Islands Harbor, CA. 80... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1122 Channel Islands Harbor, CA. (a) A line drawn from Channel Islands Harbor South Jetty Light 2 to Channel Islands Harbor...

  1. Ca2+ Signaling During Mammalian Fertilization: Requirements, Players, and Adaptations

    PubMed Central

    Wakai, Takuya; Vanderheyden, Veerle; Fissore, Rafael A.

    2011-01-01

    Changes in the intracellular concentration of calcium ([Ca2+]i) represent a vital signaling mechanism enabling communication among cells and between cells and the environment. The initiation of embryo development depends on a [Ca2+]i increase(s) in the egg, which is generally induced during fertilization. The [Ca2+]i increase signals egg activation, which is the first stage in embryo development, and that consist of biochemical and structural changes that transform eggs into zygotes. The spatiotemporal patterns of [Ca2+]i at fertilization show variability, most likely reflecting adaptations to fertilizing conditions and to the duration of embryonic cell cycles. In mammals, the focus of this review, the fertilization [Ca2+]i signal displays unique properties in that it is initiated after gamete fusion by release of a sperm-derived factor and by periodic and extended [Ca2+]i responses. Here, we will discuss the events of egg activation regulated by increases in [Ca2+]i, the possible downstream targets that effect these egg activation events, and the property and identity of molecules both in sperm and eggs that underpin the initiation and persistence of the [Ca2+]i responses in these species. PMID:21441584

  2. 75 FR 16006 - Drawbridge Operation Regulation; Sacramento River, Sacramento, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-31

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Sacramento River, Sacramento, CA... of the I Street Drawbridge across the Sacramento River, mile 59.4, at Sacramento, CA. The deviation... change to the operation of the I Street Drawbridge, mile 59.4, over Sacramento River, at Sacramento,...

  3. 76 FR 11960 - Drawbridge Operation Regulation; Sacramento River, Sacramento, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-04

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Sacramento River, Sacramento, CA... of the Tower Drawbridge across the Sacramento River, mile 59.0, at Sacramento, CA. The deviation is... a temporary change to the operation of the Tower Drawbridge, mile 59.0, Sacramento River,...

  4. 76 FR 26181 - Drawbridge Operation Regulation; Sacramento River, Sacramento, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-06

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Sacramento River, Sacramento, CA... of the Tower Drawbridge across Sacramento River, mile 59.0, at Sacramento, CA. The deviation is... a temporary change to the operation of the Tower Drawbridge, mile 59.0, over Sacramento River,...

  5. Intracellular Ca-carbonate biomineralization is widespread in cyanobacteria

    PubMed Central

    Benzerara, Karim; Skouri-Panet, Feriel; Li, Jinhua; Férard, Céline; Gugger, Muriel; Laurent, Thierry; Couradeau, Estelle; Ragon, Marie; Cosmidis, Julie; Menguy, Nicolas; Margaret-Oliver, Isabel; Tavera, Rosaluz; López-García, Purificación; Moreira, David

    2014-01-01

    Cyanobacteria have played a significant role in the formation of past and modern carbonate deposits at the surface of the Earth using a biomineralization process that has been almost systematically considered induced and extracellular. Recently, a deep-branching cyanobacterial species, Candidatus Gloeomargarita lithophora, was reported to form intracellular amorphous Ca-rich carbonates. However, the significance and diversity of the cyanobacteria in which intracellular biomineralization occurs remain unknown. Here, we searched for intracellular Ca-carbonate inclusions in 68 cyanobacterial strains distributed throughout the phylogenetic tree of cyanobacteria. We discovered that diverse unicellular cyanobacterial taxa form intracellular amorphous Ca-carbonates with at least two different distribution patterns, suggesting the existence of at least two distinct mechanisms of biomineralization: (i) one with Ca-carbonate inclusions scattered within the cell cytoplasm such as in Ca. G. lithophora, and (ii) another one observed in strains belonging to the Thermosynechococcus elongatus BP-1 lineage, in which Ca-carbonate inclusions lie at the cell poles. This pattern seems to be linked with the nucleation of the inclusions at the septum of the cells, showing an intricate and original connection between cell division and biomineralization. These findings indicate that intracellular Ca-carbonate biomineralization by cyanobacteria has been overlooked by past studies and open new perspectives on the mechanisms and the evolutionary history of intra- and extracellular Ca-carbonate biomineralization by cyanobacteria. PMID:25009182

  6. 33 CFR 80.1152 - Crescent City Harbor, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Crescent City Harbor, CA. 80.1152... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1152 Crescent City Harbor, CA. A line drawn from Crescent City Entrance Light to the southeasternmost extremity of Whaler Island....

  7. Kinetics of Ca2+ carrier in rat liver mitochondria.

    PubMed

    Bragadin, M; Pozzan, T; Azzone, G F

    1979-12-25

    The rate of aerobic Ca2+ transport is limited by the rate of the H+ pump rather than by the Ca2+ carrier. The kinetics of the Ca2+ carrier has therefore been studied by using the K+ diffusion potential as the driving force. The apparent Vmax of the Ca2+ carrier is, at 20 degrees C, about 900 nmol (mg of protein)-1 min-1, more than twice the rate of the H+ pump. The apparent Vmax is depressed by Mg2+ and Li+. This supports the view that the electrolytes act as noncompetitive inhibitors of the Ca2+ carrier. The degree of sigmoidicity of the kinetics of Ca2+ transport increases with the lowering of the temperature and proportionally with the concentration of impermeant electrolytes such as Mg2+ and Li+ but not choline. The effects of temperature and of electrolyte do not support the view that the sigmoidicity is due to modifications of the surface potential. Rather, they suggest that Ca2+ transport occurs through a multisubunit carrier, where cooperative phenomena are the result of ligand-induced conformational changes due to the interaction of several allosteric effectors with the carrier subunits. In contrast with La3+ which acts as a competitive inhibitor, Ruthenium Red affects the kinetics by inducing phenomena both of positive and of negative cooperativity. The Ruthenium Red induced kinetics has been reproduced through curve-fitting procedures by applying the Koshland sequential interaction hypothesis to a four-subunit Ca2+ carrier model. PMID:42437

  8. 35. Ca. 1930 historic view facing northeast, showing Yellow Mill ...

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

    35. Ca. 1930 historic view facing northeast, showing Yellow Mill Bridge and inset showing former ca. 1901 Yellow Mill Bridge. Photo located at the Bridgeport Public Library, Bridgeport, CT. - Yellow Mill Bridge, Spanning Yellow Mill Channel at Stratford Avenue, Bridgeport, Fairfield County, CT

  9. 33 CFR 80.1144 - Bodega and Tomales Bay, CA.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Bodega and Tomales Bay, CA. 80... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1144 Bodega and Tomales Bay, CA. (a... of Bodega Harbor North Breakwater to Bodega Harbor Entrance Light 1....

  10. 33 CFR 80.1144 - Bodega and Tomales Bay, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Bodega and Tomales Bay, CA. 80... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1144 Bodega and Tomales Bay, CA. (a... of Bodega Harbor North Breakwater to Bodega Harbor Entrance Light 1....

  11. 33 CFR 80.1110 - Dana Point Harbor, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Dana Point Harbor, CA. 80.1110... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1110 Dana Point Harbor, CA. A line drawn from Dana Point Jetty Light 6 to Dana Point Breakwater Light 5....

  12. 33 CFR 80.1120 - Port Hueneme, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Port Hueneme, CA. 80.1120 Section... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1120 Port Hueneme, CA. (a) A line drawn from Port Hueneme East Jetty Light 4 to Port Hueneme West Jetty Light 3....

  13. 4. Historic photograph (from Illinois Central Railroad), photographer unknown, ca. ...

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

    4. Historic photograph (from Illinois Central Railroad), photographer unknown, ca. 1915 SECOND PASSENGER DEPOT, CA. 1915, DURING REMODELING OF DEPOT - Illinois Central Railroad, Passenger Depot No. 2, North of First Street, east of Union Street, La Salle, La Salle County, IL

  14. 46 CFR 7.115 - Santa Catalina Island, CA.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 1 2012-10-01 2012-10-01 false Santa Catalina Island, CA. 7.115 Section 7.115 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Pacific Coast § 7.115 Santa Catalina Island, CA. (a) A line drawn from the northernmost point of Lion Head...

  15. Synthesis and characterisation of copper doped Ca-Li hydroxyapatite

    NASA Astrophysics Data System (ADS)

    Pogosova, M. A.; Kazin, P. E.; Tretyakov, Y. D.

    2012-08-01

    Hydroxyapapites M10(PO4)6(OH)2 (MHAP), where M is an alkaline earth metal, colored by incorporation of copper ions substituting protons, were discovered recently [1]. Now this kind of apatite-type materials can be used as inorganic pigments. Until now blue (BaHAP), violet (SrHAP) and wine-red (CaHAP) colors were achieved by the copper ions introduction [2]. The task of the present work was to study possibility of further M-ion substitution to affect the color and shift it toward the red-orange tint. Polycrystalline hydroxyapatites Ca10-xLix+yCuz(PO4)6O2H2-y-z-σ (Ca-LiHAP) were synthesized by solid state reaction at 1150 °C (ceramic method) and studied by X-ray powder diffraction (XRD), infrared absorption and diffuse-reflectance spectroscopy. Refinement of the X-ray diffraction patterns by the Rietveld method shows that CaHAP unit cell parameters are a little bigger, than Ca-LiHAP ones. Small difference between unit cell parameters could be caused by two ways of the Li+ ions introduction: (1) at the Ca2+ sites (Ca-Li substitution); (2) into hexagonal channels (H-Li substitution). The Li ions doping changes the color of the copper doped CaHAP from wine-red to pink and red.

  16. 10. "TEST STAND 15, AIR FORCE FLIGHT TEST CENTER." ca. ...

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

    10. "TEST STAND 1-5, AIR FORCE FLIGHT TEST CENTER." ca. 1958. Test Area 1-115. Original is a color print, showing Test Stand 1-5 from below, also showing the superstructure of TS1-4 at left. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Leuhman Ridge near Highways 58 & 395, Boron, Kern County, CA

  17. 76 FR 69608 - Modification of Class E Airspace; Blythe, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-09

    ... follows: Authority: 49 U.S.C. 106(g), 40103, 40113, 40120; E. O. 10854, 24 FR 9565, 3 CFR, 1959-1963 Comp... Modification of Class E Airspace; Blythe, CA AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action modifies Class E airspace at Blythe, CA, to accommodate aircraft using...

  18. 75 FR 41076 - Establishment of Class E Airspace; Monterey, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-15

    ... follows: Authority: 49 U.S.C. 106(g), 40103, 40113, 40120; E. O. 10854, 24 FR 9565, 3 CFR, 1959-1963 Comp... Federal Aviation Administration 14 CFR Part 71 Establishment of Class E Airspace; Monterey, CA AGENCY... E airspace at Monterey, CA, to accommodate aircraft using a new Area Navigation (RNAV)...

  19. 33 CFR 80.1136 - Moss Landing Harbor, CA.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Moss Landing Harbor, CA. 80.1136... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1136 Moss Landing Harbor, CA. A line drawn from the seaward extremity of the pier located 0.3 mile south of Moss Landing Harbor Entrance to...

  20. 33 CFR 80.1136 - Moss Landing Harbor, CA.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Moss Landing Harbor, CA. 80.1136... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1136 Moss Landing Harbor, CA. A line drawn from the seaward extremity of the pier located 0.3 mile south of Moss Landing Harbor Entrance to...

  1. 33 CFR 80.1136 - Moss Landing Harbor, CA.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Moss Landing Harbor, CA. 80.1136... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1136 Moss Landing Harbor, CA. A line drawn from the seaward extremity of the pier located 0.3 mile south of Moss Landing Harbor Entrance to...

  2. 33 CFR 80.1136 - Moss Landing Harbor, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Moss Landing Harbor, CA. 80.1136... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1136 Moss Landing Harbor, CA. A line drawn from the seaward extremity of the pier located 0.3 mile south of Moss Landing Harbor Entrance to...

  3. 33 CFR 80.1136 - Moss Landing Harbor, CA.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Moss Landing Harbor, CA. 80.1136... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1136 Moss Landing Harbor, CA. A line drawn from the seaward extremity of the pier located 0.3 mile south of Moss Landing Harbor Entrance to...

  4. Knockin of mutant PIK3CA activates multiple oncogenic pathways

    PubMed Central

    Gustin, John P.; Karakas, Bedri; Weiss, Michele B.; Abukhdeir, Abde M.; Lauring, Josh; Garay, Joseph P.; Cosgrove, David; Tamaki, Akina; Konishi, Hiroyuki; Konishi, Yuko; Mohseni, Morassa; Wang, Grace; Rosen, D. Marc; Denmeade, Samuel R.; Higgins, Michaela J.; Vitolo, Michele I.; Bachman, Kurtis E.; Park, Ben Ho

    2009-01-01

    The phosphatidylinositol 3-kinase subunit PIK3CA is frequently mutated in human cancers. Here we used gene targeting to “knock in” PIK3CA mutations into human breast epithelial cells to identify new therapeutic targets associated with oncogenic PIK3CA. Mutant PIK3CA knockin cells were capable of epidermal growth factor and mTOR-independent cell proliferation that was associated with AKT, ERK, and GSK3β phosphorylation. Paradoxically, the GSK3β inhibitors lithium chloride and SB216763 selectively decreased the proliferation of human breast and colorectal cancer cell lines with oncogenic PIK3CA mutations and led to a decrease in the GSK3β target gene CYCLIN D1. Oral treatment with lithium preferentially inhibited the growth of nude mouse xenografts of HCT-116 colon cancer cells with mutant PIK3CA compared with isogenic HCT-116 knockout cells containing only wild-type PIK3CA. Our findings suggest GSK3β is an important effector of mutant PIK3CA, and that lithium, an FDA-approved therapy for bipolar disorders, has selective antineoplastic properties against cancers that harbor these mutations. PMID:19196980

  5. CaMKII inhibitors: from research tools to therapeutic agents

    PubMed Central

    Pellicena, Patricia; Schulman, Howard

    2014-01-01

    The cardiac field has benefited from the availability of several CaMKII inhibitors serving as research tools to test putative CaMKII pathways associated with cardiovascular physiology and pathophysiology. Successful demonstrations of its critical pathophysiological roles have elevated CaMKII as a key target in heart failure, arrhythmia, and other forms of heart disease. This has caught the attention of the pharmaceutical industry, which is now racing to develop CaMKII inhibitors as safe and effective therapeutic agents. While the first generation of CaMKII inhibitor development is focused on blocking its activity based on ATP binding to its catalytic site, future inhibitors can also target sites affecting its regulation by Ca2+/CaM or translocation to some of its protein substrates. The recent availability of crystal structures of the kinase in the autoinhibited and activated state, and of the dodecameric holoenzyme, provides insights into the mechanism of action of existing inhibitors. It is also accelerating the design and development of better pharmacological inhibitors. This review examines the structure of the kinase and suggests possible sites for its inhibition. It also analyzes the uses and limitations of current research tools. Development of new inhibitors will enable preclinical proof of concept tests and clinical development of successful lead compounds, as well as improved research tools to more accurately examine and extend knowledge of the role of CaMKII in cardiac health and disease. PMID:24600394

  6. 33 CFR 80.1150 - Arcata-Humboldt Bay, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Arcata-Humboldt Bay, CA. 80.1150... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1150 Arcata-Humboldt Bay, CA. A line drawn from Humboldt Bay Entrance Light 4 to Humboldt Bay Entrance Light 3....

  7. 77 FR 63725 - Drawbridge Operation Regulations; Old River, Orwood, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-17

    ... deviation entitled ``Drawbridge Operation Regulation; Old River, Orwood CA'' in the Federal Register (77 FR... navigation. DATES: The temporary deviation published on September 21, 2012 (77 FR 58491) is cancelled as of... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulations; Old River, Orwood, CA AGENCY:...

  8. Credit USAF, ca. 1945. Original housed in the Photograph Files, ...

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

    Credit USAF, ca. 1945. Original housed in the Photograph Files, AFFTC/HO, Edwards AFB, California. Early view of the Control Tower (designated T-65, Building 4500) fitted out with radio antennae. Structure at base of tower was T42 (later Building 4503), Flight Operations - Edwards Air Force Base, North Base, Radio & Control Tower T-65, Northeast of A Street, Boron, Kern County, CA

  9. 73. MISSISSIPPI, MONROE CO. MAP OF MONROE CO., ca. 1925 ...

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

    73. MISSISSIPPI, MONROE CO. MAP OF MONROE CO., ca. 1925 Broadside map of Monroe Co., published by the Examiner Printing Co., Aberdeen, Ms. Original scale: ca. 1 in. to 2 mi. No date. Property of Helen (Mrs. Sam L.) Crawford, Hamilton, Ms. Sarcone Photograpy, Columbus, Ms., Sep 1978. - Bridges of the Upper Tombigbee River Valley, Columbus, Lowndes County, MS

  10. 68. MISSISSIPPI, LOWNDES CO. COLUMBUS MAP OF COLUMBUS ca. 1875 ...

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

    68. MISSISSIPPI, LOWNDES CO. COLUMBUS MAP OF COLUMBUS ca. 1875 BIRD'S EYE VIEW OF COLUMBUS MISSISSIPPI by Camille Drie ca. 1875. Copy of snapshot in Lowndes Co. Public Library, Columbus, Ms. Snow status in early 1870s: includes M&O RR bridge, but no highway bridge. Sarcone Photography, Columbus, Ms., Sept 1978. - Bridges of the Upper Tombigbee River Valley, Columbus, Lowndes County, MS

  11. 72. MISSISSIPPI, MONROE CO. MAP OF MONROE COUNTY, ca. 1925 ...

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

    72. MISSISSIPPI, MONROE CO. MAP OF MONROE COUNTY, ca. 1925 Broad side of map of Monroe Co., 'Compliments of Home Mortgage & Realty Co., Amory, Miss.' Orig. scale: ca. 1 in. to 2 mi. No date. Property of Helen (Mrs. Sam L.) Crawford, Hamilton, Ms. Sarcone Photography, Columbus, Ms., Sep 1978. - Bridges of the Upper Tombigbee River Valley, Columbus, Lowndes County, MS

  12. Credit USAF, ca. 1943. Original housed in the Photograph Files, ...

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

    Credit USAF, ca. 1943. Original housed in the Photograph Files, AFFTC/HO, Edwards AFB, California. Historic view of finished swimming pool, with fence and lifeguard station. View looks west - Edwards Air Force Base, North Base, Swimming Pool, Second Street, Boron, Kern County, CA

  13. 33 CFR 80.1138 - Santa Cruz Harbor, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Santa Cruz Harbor, CA. 80.1138 Section 80.1138 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1138 Santa Cruz Harbor, CA. A line drawn...

  14. 33 CFR 80.1126 - Santa Barbara Harbor, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Santa Barbara Harbor, CA. 80.1126 Section 80.1126 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1126 Santa Barbara Harbor, CA. A line...

  15. 33 CFR 80.1116 - Redondo Harbor, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Redondo Harbor, CA. 80.1116 Section 80.1116 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1116 Redondo Harbor, CA. A line drawn...

  16. 33 CFR 80.1104 - San Diego Harbor, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false San Diego Harbor, CA. 80.1104 Section 80.1104 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1104 San Diego Harbor, CA. A line drawn...

  17. 33 CFR 80.1112 - Newport Bay, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Newport Bay, CA. 80.1112 Section 80.1112 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1112 Newport Bay, CA. A line drawn from...

  18. 33 CFR 80.1148 - Noyo River, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Noyo River, CA. 80.1148 Section 80.1148 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1148 Noyo River, CA. A line drawn from...

  19. 33 CFR 80.1134 - Monterey Harbor, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Monterey Harbor, CA. 80.1134 Section 80.1134 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1134 Monterey Harbor, CA. A line drawn...

  20. 33 CFR 80.1106 - Mission Bay, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Mission Bay, CA. 80.1106 Section 80.1106 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1106 Mission Bay, CA. A line drawn from...

  1. 33 CFR 80.1108 - Oceanside Harbor, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Oceanside Harbor, CA. 80.1108 Section 80.1108 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1108 Oceanside Harbor, CA. A line drawn...

  2. 33 CFR 80.1130 - San Luis Obispo Bay, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false San Luis Obispo Bay, CA. 80.1130 Section 80.1130 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1130 San Luis Obispo Bay, CA. A line drawn...

  3. 33 CFR 80.1142 - San Francisco Harbor, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false San Francisco Harbor, CA. 80.1142 Section 80.1142 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1142 San Francisco Harbor, CA. A straight...

  4. 33 CFR 80.1124 - Ventura Marina, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Ventura Marina, CA. 80.1124 Section 80.1124 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1124 Ventura Marina, CA. A line drawn...

  5. 33 CFR 80.1146 - Albion River, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Albion River, CA. 80.1146 Section 80.1146 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1146 Albion River, CA. A line drawn on an...

  6. 33 CFR 80.1118 - Marina Del Rey, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Marina Del Rey, CA. 80.1118 Section 80.1118 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1118 Marina Del Rey, CA. (a) A line drawn...

  7. 33 CFR 80.1132 - Estero-Morro Bay, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Estero-Morro Bay, CA. 80.1132 Section 80.1132 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1132 Estero-Morro Bay, CA. A line drawn...

  8. PVP-CA composite preparation and its characteristics

    NASA Astrophysics Data System (ADS)

    Cui, Ruiyao

    Polyvinylpyrrolidone (PVP) is a commonly used polymer that has some excellent properties, such as great strength and biocompatibility. Cellulose Acetate (CA) is another excellent polymer that has been employed in many applications, including drug. PVP-CA composite has both strength and flexible properties that can be used as ultrafiltration membranes or the drug release system. PVP-CA composites comprise a new class of materials that have been the scope of this work. In this research, the electrospun PVP-CA composites were prepared under different concentrations. Then, the impact of different electrospinning parameters on fiber diameters was investigated. Moreover, acetic acid and acetone were used as solvents for dissolving PVP, CA respectively. For comparison, PVP in water and CA in acetone was each deposited on the aluminum foil by electrospinning, forming a two-layer structure. Scanning electron microscopy(SEM) and Raman spectroscopy test were carried out. From the test results, fibers with 200nm to 1um diameter were prepared and the interaction between PVP and CA were proved. Then the oil absorption testing was carried out. The membrane structure of the electrospun composite fibers showed good oil absorption capacity, that was twice higher than the 2-layer PVP-CA fibers.

  9. 33 CFR 80.1140 - Pillar Point Harbor, CA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Pillar Point Harbor, CA. 80.1140... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1140 Pillar Point Harbor, CA. A line drawn from Pillar Point Harbor Light 6 to Pillar Point Harbor Entrance Light....

  10. 33 CFR 80.1140 - Pillar Point Harbor, CA.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Pillar Point Harbor, CA. 80.1140... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1140 Pillar Point Harbor, CA. A line drawn from Pillar Point Harbor Light 6 to Pillar Point Harbor Entrance Light....

  11. 33 CFR 80.1110 - Dana Point Harbor, CA.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Dana Point Harbor, CA. 80.1110... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1110 Dana Point Harbor, CA. A line drawn from Dana Point Jetty Light 6 to Dana Point Breakwater Light 5....

  12. Intracellular Ca(2+) release as irreversible Markov process.

    PubMed Central

    Rengifo, Juliana; Rosales, Rafael; González, Adom; Cheng, Heping; Stern, Michael D; Ríos, Eduardo

    2002-01-01

    In striated muscles, intracellular Ca(2+) release is tightly controlled by the membrane voltage sensor. Ca(2+) ions are necessary mediators of this control in cardiac but not in skeletal muscle, where their role is ill-understood. An intrinsic gating oscillation of Ca(2+) release-not involving the voltage sensor-is demonstrated in frog skeletal muscle fibers under voltage clamp. A Markov model of the Ca(2+) release units is shown to reproduce the oscillations, and it is demonstrated that for Markov processes to have oscillatory transients, its transition rates must violate thermodynamic reversibility. Such irreversibility results in permanent cycling of the units through a ring of states, which requires a source of free energy. Inhibition of the oscillation by 20 to 40 mM EGTA or partial depletion of Ca(2+) in the sarcoplasmic reticulum (SR) identifies the SR [Ca(2+)] gradient as the energy source, and indicates a location of the critical Ca(2+)-sensing site at distances greater than 35 nm from the open channel. These results, which are consistent with a recent demonstration of irreversibility in gating of cardiac Ca(2+) sparks, (Wang, S.-Q., L.-S. Song, L. Xu, G. Meissner, E. G. Lakatta, E. Ríos, M. D. Stern, and H. Cheng. 2002. Biophys. J. 83:242-251) exemplify a cell-wide oscillation caused by coupling between ion permeation and channel gating. PMID:12414685

  13. Store-Operated Ca2+ Release-Activated Ca2+ Channels Regulate PAR2-Activated Ca2+ Signaling and Cytokine Production in Airway Epithelial Cells.

    PubMed

    Jairaman, Amit; Yamashita, Megumi; Schleimer, Robert P; Prakriya, Murali

    2015-09-01

    The G-protein-coupled protease-activated receptor 2 (PAR2) plays an important role in the pathogenesis of various inflammatory and auto-immune disorders. In airway epithelial cells (AECs), stimulation of PAR2 by allergens and proteases triggers the release of a host of inflammatory mediators to regulate bronchomotor tone and immune cell recruitment. Activation of PAR2 turns on several cell signaling pathways of which the mobilization of cytosolic Ca(2+) is likely a critical but poorly understood event. In this study, we show that Ca(2+) release-activated Ca(2+) (CRAC) channels encoded by stromal interaction molecule 1 and Orai1 are a major route of Ca(2+) entry in primary human AECs and drive the Ca(2+) elevations seen in response to PAR2 activation. Activation of CRAC channels induces the production of several key inflammatory mediators from AECs including thymic stromal lymphopoietin, IL-6, and PGE2, in part through stimulation of gene expression via nuclear factor of activated T cells (NFAT). Furthermore, PAR2 stimulation induces the production of many key inflammatory mediators including PGE2, IL-6, IL-8, and GM-CSF in a CRAC channel-dependent manner. These findings indicate that CRAC channels are the primary mechanism for Ca(2+) influx in AECs and a vital checkpoint for the induction of PAR2-induced proinflammatory cytokines. PMID:26238490

  14. Identification of the site on calcineurin phosphorylated by Ca sup + /CaM-dependent kinase II: Modification of the CaM-binding domain

    SciTech Connect

    Martensen, T.M.; Kincaid, R.L. ); Martin, B.M. )

    1989-11-28

    The catalytic subunit of the Ca{sup 2+}/calmodulin- (CaM) dependent phosphoprotein phosphatase calcineurin (CN) was phosphorylated by an activated form of Ca{sup 2+}/CaM-dependent protein kinase II (CaM-kinase II) incorporating approximately 1 mol of phosphoryl group/mol of catalytic subunit, in agreement with a value previously reported. Cyanogen bromide cleavage of radiolabeled CN followed by peptide fractionation using reverse-phase high-performance liquid chromatography yielded a single labeled peptide that contained a phosphoserine residue. Microsequencing of the peptide allowed both the determination of the cleavage cycle that released ({sup 32}P)phosphoserine and the identity of amino acids adjacent to it. Comparison of this sequence with the sequences of methionyl peptides deduced from the cDNA structure of CN allowed the phosphorylated serine to be uniquely identified. Interestingly, the phosphoserine exists in the sequence Met-Ala-Arg-Val-Phe-Ser(P)-Val-Leu-Arg-Glu, part of which lies within the putative CaM-binding sites. The phosphorylated serine residue was resistant to autocatalytic dephosphorylation, yet the slow rate of hydrolysis could be powerfully stimulated by effectors of CN phosphatase activity. The mechanism of dephosphorylation may be intramolecular since the initial rate was the same at phosphoCN concentrations of 2.5-250 nM.

  15. Roles of cytosolic Ca2+ concentration and myofilament Ca2+ sensitization in age-dependent cerebrovascular myogenic tone.

    PubMed

    Charles, Shelton M; Zhang, Lubo; Cipolla, Marilyn J; Buchholz, John N; Pearce, William J

    2010-10-01

    In light of evidence that immature arteries contain a higher proportion of noncontractile smooth muscle cells than found in fully differentiated mature arteries, the present study explored the hypothesis that age-related differences in the smooth muscle phenotype contribute to age-related differences in contractility. Because Ca(2+) handling differs markedly between contractile and noncontractile smooth muscle, the present study specifically tested the hypothesis that the relative contributions of Ca(2+) influx and myofilament sensitization to myogenic tone are upregulated, whereas Ca(2+) release is downregulated, in immature [14 days postnatal (P14)] compared with mature (6 mo old) rat middle cerebral arteries (MCAs). Myofilament Ca(2+) sensitivity measured in β-escin-permeabilized arteries increased with pressure in P14 but not adult MCAs. Cyclopiazonic acid (an inhibitor of Ca(2+) release from the sarcoplasmic reticulum) increased diameter and reduced Ca(2+) in adult MCAs but increased diameter with no apparent change in Ca(2+) in P14 MCAs. La(3+) (Ca(2+) influx inhibitor) increased diameter and decreased Ca(2+) in adult MCAs, but in P14 MCAs, La(3+) increased diameter with no apparent change in Ca(2+). After treatment with both La(3+) and CPA, diameters were passive in both adult and P14 MCAs, but Ca(2+) was decreased only in adult MCAs. To quantify the fraction of smooth muscle cells in the fully differentiated contractile phenotype, extents of colocalization between smooth muscle α-actin and SM2 myosin heavy chain were determined and found to be at least twofold greater in adult than pup MCAs. These data suggest that compared with adult MCAs, pup MCAs contain a greater proportion of noncontractile smooth muscle and, as a consequence, rely more on myofilament Ca(2+) sensitization and Ca(2+) influx to maintain myogenic reactivity. The inability of La(3+) to reduce cytosolic Ca(2+) in the pup MCA appears due to La(3+)-insensitive noncontractile smooth muscle

  16. Cytoplasmic Na+-dependent modulation of mitochondrial Ca2+ via electrogenic mitochondrial Na+–Ca2+ exchange

    PubMed Central

    Kim, Bongju; Matsuoka, Satoshi

    2008-01-01

    To clarify the role of mitochondrial Na+–Ca2+ exchange (NCXmito) in regulating mitochondrial Ca2+ (Ca2+mito) concentration at intact and depolarized mitochondrial membrane potential (ΔΨmito), we measured Ca2+mito and ΔΨmito using fluorescence probes Rhod-2 and TMRE, respectively, in the permeabilized rat ventricular cells. Applying 300 nm cytoplasmic Ca2+ (Ca2+c) increased Ca2+mito and this increase was attenuated by cytoplasmic Na+ (Na+c) with an IC50 of 2.4 mm. To the contrary, when ΔΨmito was depolarized by FCCP, a mitochondrial uncoupler, Na+c enhanced the Ca2+c-induced increase in Ca2+mito with an EC50 of about 4 mm. This increase was not significantly affected by ruthenium red or cyclosporin A. The inhibition of NCXmito by CGP-37157 further increased Ca2+mito when ΔΨmito was intact, while it suppressed the Ca2+mito increase when ΔΨmito was depolarized, suggesting that ΔΨmito depolarization changed the exchange mode from forward to reverse. Furthermore, ΔΨmito depolarization significantly reduced the Ca2+mito decrease via forward mode, and augmented the Ca2+mito increase via reverse mode. When the respiratory chain was attenuated, the induction of the reverse mode of NCXmito hyperpolarized ΔΨmito, while ΔΨmito depolarized upon inducing the forward mode of NCXmito. Both changes in ΔΨmito were remarkably inhibited by CGP-37157. The above experimental data indicated that NCXmito is voltage dependent and electrogenic. This notion was supported theoretically by computer simulation studies with an NCXmito model constructed based on present and previous studies, presuming a consecutive and electrogenic Na+–Ca2+ exchange and a depolarization-induced increase in Na+ flux. It is concluded that Ca2+mito concentration is dynamically modulated by Na+c and ΔΨmito via electrogenic NCXmito. PMID:18218682

  17. Rapid heparin-sensitive Ca2+ release following Ca(2+)-ATPase inhibition in intact HL-60 granulocytes. Evidence for Ins(1,4,5)P3-dependent Ca2+ cycling across the membrane of Ca2+ stores.

    PubMed Central

    Favre, C J; Lew, D P; Krause, K H

    1994-01-01

    In many cell types, emptying of intracellular Ca2+ stores after application of inhibitors of the intracellular Ca(2+)-ATPase (e.g. thapsigargin) is astonishingly rapid. It was the aim of this study to elucidate the underlying mechanism. We first compared thapsigargin-induced emptying of intracellular Ca2+ stores in intact and homogenized HL-60 granulocytes. Thapsigargin-induced Ca2+ release was rapid in intact cells (33.9 +/- 4.9% of store content/min), but it was slow in permeabilized or homogenized cells (7.7 +/- 3.9 and 12 +/- 3.8% of store content/min respectively). To study whether the Ins(1,4,5)P3 receptor might be involved in thapsigargin-induced Ca2+ release, we tested the effect of heparin, a competitive Ins(1,4,5)P3 antagonist. In homogenized and permeabilized preparations, heparin did not interfere with thapsigargin-induced Ca2+ release. In contrast, when introduced into intact cells by an endocytosis/osmotic-shock procedure, heparin, but not the inactive de-N-sulphated heparin, decreased the rate of Ca2+ release by approx. 70%. Heparin inhibited Ca2+ release in response to the Ins(1,4,5)P3-generating receptor agonist N-formylmethionyl-leucyl-phenylalanine (f-MLP) (50 nM) and to thapsigargin (50 nM) at comparable concentrations. Heparin inhibition was competitive for f-MLP-induced, but not for thapsigargin-induced, Ca2+ release. In permeabilized cells, the addition of low Ins(1,4,5)P3 concentrations before thapsigargin increased the rate of thapsigargin-induced Ca2+ release 4-fold. Taken together, our results suggest that the rapid Ca(2+)-ATPase-inhibitor-induced Ca2+ release is due to a partial activation of the Ins(1,4,5)P3 receptor in resting cells. This implies Ca2+ cycling across the membrane of Ins(1,4,5)P3-sensitive Ca2+ stores in resting cells. Images Figure 7 PMID:8068001

  18. Ca(2+) regulation of mitochondrial function in neurons.

    PubMed

    Rueda, Carlos B; Llorente-Folch, Irene; Amigo, Ignacio; Contreras, Laura; González-Sánchez, Paloma; Martínez-Valero, Paula; Juaristi, Inés; Pardo, Beatriz; del Arco, Araceli; Satrústegui, Jorgina

    2014-10-01

    Calcium is thought to regulate respiration but it is unclear whether this is dependent on the increase in ATP demand caused by any Ca(2+) signal or to Ca(2+) itself. [Na(+)]i, [Ca(2+)]i and [ATP]i dynamics in intact neurons exposed to different workloads in the absence and presence of Ca(2+) clearly showed that Ca(2+)-stimulation of coupled respiration is required to maintain [ATP]i levels. Ca(2+) may regulate respiration by activating metabolite transport in mitochondria from outer face of the inner mitochondrial membrane, or after Ca(2+) entry in mitochondria through the calcium uniporter (MCU). Two Ca(2+)-regulated mitochondrial metabolite transporters are expressed in neurons, the aspartate-glutamate exchanger ARALAR/AGC1/Slc25a12, a component of the malate-aspartate shuttle, and the ATP-Mg/Pi exchanger SCaMC-3/APC2/Slc25a23, with S0.5 for Ca(2+) of 300nM and 3.4μM, respectively. The lack of SCaMC-3 results in a smaller Ca(2+)-dependent stimulation of respiration only at high workloads, as caused by veratridine, whereas the lack of ARALAR reduced by 46% basal OCR in intact neurons using glucose as energy source and the Ca(2+)-dependent responses to all workloads: a reduction of about 65-70% in the response to the high workload imposed by veratridine, and completely suppression of the OCR responses to moderate (K(+)-depolarization) and small (carbachol) workloads, effects reverted by pyruvate supply. For K(+)-depolarization, this occurs in spite of the presence of large [Ca(2+)]mit signals and increased formation of mitochondrial NAD(P)H. These results show that ARALAR-MAS is a major contributor of Ca(2+)-stimulated respiration in neurons by providing increased pyruvate supply to mitochondria. In its absence and under moderate workloads, matrix Ca(2+) is unable to stimulate pyruvate metabolism and entry in mitochondria suggesting a limited role of MCU in these conditions. This article was invited for a Special Issue entitled: 18th European Bioenergetic

  19. [Effect of vanadate on Ca++-activation in skeletal muscle].

    PubMed

    Son'kin, B Ia; Bukatina, A E

    1983-01-01

    Vanadate (0.1 mM) reduces tension of glycerinated rabbit psoas muscle fibers, shifts tension--pCa curve to lower pCa, increases the rate constant of delayed tension development and changes dependence of this rate constant on the level of Ca2+-activation. Vanadate influence stops the increase of the rate constant with the rise of Ca++-activated tension. Since actin-myosin-ADP complex is dissociated by vanadate, the muscle performance at low activation levels is supposed to be conditioned largely by the cross-bridges interacting with actin of the actin blocks switched on by myosin-ADP. Kinetics of such cross-bridges differs from that of the cross bridges interacting with actin activated by Ca++ binding to troponin C. PMID:6556917

  20. Modulation of the matrix redox signaling by mitochondrial Ca2+

    PubMed Central

    Santo-Domingo, Jaime; Wiederkehr, Andreas; De Marchi, Umberto

    2015-01-01

    Mitochondria sense, shape and integrate signals, and thus function as central players in cellular signal transduction. Ca2+ waves and redox reactions are two such intracellular signals modulated by mitochondria. Mitochondrial Ca2+ transport is of utmost physio-pathological relevance with a strong impact on metabolism and cell fate. Despite its importance, the molecular nature of the proteins involved in mitochondrial Ca2+ transport has been revealed only recently. Mitochondrial Ca2+ promotes energy metabolism through the activation of matrix dehydrogenases and down-stream stimulation of the respiratory chain. These changes also alter the mitochondrial NAD(P)H/NAD(P)+ ratio, but at the same time will increase reactive oxygen species (ROS) production. Reducing equivalents and ROS are having opposite effects on the mitochondrial redox state, which are hard to dissect. With the recent development of genetically encoded mitochondrial-targeted redox-sensitive sensors, real-time monitoring of matrix thiol redox dynamics has become possible. The discoveries of the molecular nature of mitochondrial transporters of Ca2+ combined with the utilization of the novel redox sensors is shedding light on the complex relation between mitochondrial Ca2+ and redox signals and their impact on cell function. In this review, we describe mitochondrial Ca2+ handling, focusing on a number of newly identified proteins involved in mitochondrial Ca2+ uptake and release. We further discuss our recent findings, revealing how mitochondrial Ca2+ influences the matrix redox state. As a result, mitochondrial Ca2+ is able to modulate the many mitochondrial redox-regulated processes linked to normal physiology and disease. PMID:26629314

  1. A sodium calcium arsenate, NaCa(AsO(4)).

    PubMed

    Lin, Jinru; Sun, Wei; Mi, Jin-Xiao; Pan, Yuanming

    2011-12-01

    The title compound, NaCa(AsO(4)), was synthesized using a hydro-thermal method at 633-643 K. It has a dense structure composed of alternating layers of distorted [CaO(6)] octa-hedra and layers of [AsO(4)] tetra-hedra and distorted [NaO(6)] octa-hedra, stacked along the a axis. The As, Ca and two O atoms lie on the mirror plane at y = 1/4 (i.e. 4c), while the Na atom lies on an inversion centre (1/2, 1/2, 0) (i.e. 4b). Each distorted [CaO(6)] octa-hedron shares four equatorial common O vertices with four neighboring octa-hedra, forming a layer parallel to (100), whereas each distorted [NaO(6)] octa-hedron shares two opposite edges with two neighboring ones, forming a chain running along [010]. Each isolated [AsO(4)] tetra-hedron shares two edges with two different [NaO(6)] octa-hedra in one [NaO(6)] chain and a vertex with another chain. Simultaneously the above [AsO(4)] tetra-hedron located in a four-membered [CaO(6)] ring shares one edge of its base facet with one [CaO(6)] octa-hedron and three corners with three other [CaO(6)] octa-hedra of one [CaO(6)] layer, and the remaining apex is shared with another [CaO(6)] layer. [NaO(6)] octa-hedra and [CaO(6)] octa-hedra are linked to each other by sharing edges and vertices. PMID:22199467

  2. CaO interaction in the staged combustion of coal

    SciTech Connect

    Levy, A.; Merryman, E.L.; Rising, B.W.

    1983-12-19

    The LIMB (limestone injection multi-stage burner) process offers special potential for reducing NO/sub x/ and SO/sub x/ by at least 50 percent in coal combustion. This is to be accomplished by adding limestone with fuel and/or air in a low NO/sub x/ burner. This program has been directed to defining the chemistry and kinetics necessary to optimize sulfur capture in LIMB combustion. More specifically, this program has attempted to clarify the role of calcium sulfide in LIMB chemistry. When limestone is added in a staged burner, there is a strong possibility that under certain circumstances CaS is produced in the reducing (fuel-rich) zone of the burner. Since CaS is more stable than CaSO/sub 4/, this affords the opportunity to (1) operate the burner at a higher temperature, 2200 to 2500 F, (2) pass the CaS rapidly through the high temperature zone (before dissociation), and (3) complete the combustion in a lean (air-rich) region where the sulfur is finally retained in CaSO/sub 4/. For these reasons this program has concentrated on the high temperature chemistry and kinetics of CaS. To achieve the program objective, the program was divided into three tasks. These involved (1) a study of CaS formation, (2) a brief examination of CaS oxidation, and (3) a laboratory examination of the combustion of coal in the presence of CaO under first stage, fuel-rich conditions. In the most general sense, the study has shown that the formation of CaS in the reducing zones of the burner may be restricted by competing kinetics and thermodynamics. The addition of lime in LIMB will require special care to optimize the ability to capture sulfur. 36 references, 44 figures, 10 tables.

  3. Ca2+-calmodulin regulates fesselin-induced actin polymerization.

    PubMed

    Schroeter, Mechthild; Chalovich, Joseph M

    2004-11-01

    Fesselin is a proline-rich actin-binding protein that was isolated from avian smooth muscle. Fesselin bundles actin and accelerates actin polymerization by facilitating nucleation. We now show that this polymerization of actin can be regulated by Ca(2+)-calmodulin. Fesselin was shown to bind to immobilized calmodulin in the presence of Ca(2+). The fesselin-calmodulin interaction was confirmed by a Ca(2+)-dependent increase in 2-(4-maleimidoanilino)naphthalene-6-sulfonic acid (MIANS) fluorescence upon addition of fesselin to MIANS-labeled wheat germ calmodulin. The affinity was estimated to be approximately 10(9) M(-1). The affinity of Ca(2+)-calmodulin to the fesselin F-actin complex was approximately 10(8) M(-1). Calmodulin binding to fesselin appeared to be functionally significant. In the presence of fesselin and calmodulin, the polymerization of actin was Ca(2+)-dependent. Ca(2+)-free calmodulin either had no effect or enhanced the ability of fesselin to accelerate actin polymerization. Ca(2+)-calmodulin not only reversed the stimulatory effect of fesselin but reduced the rate of polymerization below that observed in the absence of fesselin. While Ca(2+)-calmodulin had a large effect on the interaction of fesselin with G-actin, the effect on F-actin was small. Neither the binding of fesselin to F-actin nor the subsequent bundling of F-actin was greatly affected by Ca(2+)-calmodulin. Fesselin may function as an actin-polymerizing factor that is regulated by Ca(2+) levels. PMID:15504050

  4. Modulation of the matrix redox signaling by mitochondrial Ca(2.).

    PubMed

    Santo-Domingo, Jaime; Wiederkehr, Andreas; De Marchi, Umberto

    2015-11-26

    Mitochondria sense, shape and integrate signals, and thus function as central players in cellular signal transduction. Ca(2+) waves and redox reactions are two such intracellular signals modulated by mitochondria. Mitochondrial Ca(2+) transport is of utmost physio-pathological relevance with a strong impact on metabolism and cell fate. Despite its importance, the molecular nature of the proteins involved in mitochondrial Ca(2+) transport has been revealed only recently. Mitochondrial Ca(2+) promotes energy metabolism through the activation of matrix dehydrogenases and down-stream stimulation of the respiratory chain. These changes also alter the mitochondrial NAD(P)H/NAD(P)(+) ratio, but at the same time will increase reactive oxygen species (ROS) production. Reducing equivalents and ROS are having opposite effects on the mitochondrial redox state, which are hard to dissect. With the recent development of genetically encoded mitochondrial-targeted redox-sensitive sensors, real-time monitoring of matrix thiol redox dynamics has become possible. The discoveries of the molecular nature of mitochondrial transporters of Ca(2+) combined with the utilization of the novel redox sensors is shedding light on the complex relation between mitochondrial Ca(2+) and redox signals and their impact on cell function. In this review, we describe mitochondrial Ca(2+) handling, focusing on a number of newly identified proteins involved in mitochondrial Ca(2+) uptake and release. We further discuss our recent findings, revealing how mitochondrial Ca(2+) influences the matrix redox state. As a result, mitochondrial Ca(2+) is able to modulate the many mitochondrial redox-regulated processes linked to normal physiology and disease. PMID:26629314

  5. Ca cofactor of the water-oxidation complex: Evidence for a Mn/Ca heteronuclear cluster

    SciTech Connect

    Cinco, Roehl M.; Robblee, John H.; Messinger, Johannes; Fernandez, Carmen; McFarlane, Karen L.; Pizarro, Shelly A.; Sauer, Ken; Yachandra, Vittal K.

    2001-07-25

    Calcium and chloride are necessary cofactors for the proper function of the oxygen-evolving complex (OEC) of Photosystem II (PS II). Located in the thylakoid membranes of green plants, cyanobacteria and algae, PS II and the OEC catalyze the light-driven oxidation of water into dioxygen (released into the biosphere), protons and electrons for carbon fixation. The actual chemistry of water oxidation is performed by a cluster of four manganese atoms, along with the requisite cofactors Ca{sup 2+} and Cl{sup -}. While the Mn complex has been extensively studied by X-ray absorption techniques, comparatively less is known about the Ca{sup 2+} cofactor. The fewer number of studies on the Ca{sup 2+} cofactor have sometimes relied on substituting the native cofactor with strontium or other metals, and have stirred some debate about the structure of the binding site. past efforts using Mn EXAFS on Sr-substituted PSII are suggestive of a close link between the Mn cluster and Sr, within 3.5 {angstrom}. The most recent published study using Sr EXAFS on similar samples confirms this finding of a 3.5 {angstrom} distance between Mn and Sr. This finding was base3d on a second Fourier peak (R {approx} 3 {angstrom}) in the Sr EXAFS from functional samples, but is absent from inactive, hydroxylamine-treated PS II. This Fourier peak II was found to fit best to two Mn at 3.5 {angstrom} rather than lighter atoms (carbon). Nevertheless, other experiments have given contrary results. They wanted to extend the technique by using polarized Sr EXAFS on layered Sr-substituted samples, to provide important angle information. Polarized EXAFS involves collecting spectra for different incident angles ({theta}) between the membrane normal of the layered sample and the X-ray electric field vector. Dichroism in the EXAFS can occur, depending on how the particular absorber-backscatterer (A-B) vector is aligned with the electric field. Through analysis of the dichroism, they extract the average number

  6. Ca2+/Calmodulin-Dependent Protein Kinase Kinases (CaMKKs) Effects on AMP-Activated Protein Kinase (AMPK) Regulation of Chicken Sperm Functions

    PubMed Central

    Nguyen, Thi Mong Diep; Combarnous, Yves; Praud, Christophe; Duittoz, Anne; Blesbois, Elisabeth

    2016-01-01

    Sperm require high levels of energy to ensure motility and acrosome reaction (AR) accomplishment. The AMP-activated protein kinase (AMPK) has been demonstrated to be strongly involved in the control of these properties. We address here the question of the potential role of calcium mobilization on AMPK activation and function in chicken sperm through the Ca2+/calmodulin-dependent protein kinase kinases (CaMKKs) mediated pathway. The presence of CaMKKs and their substrates CaMKI and CaMKIV was evaluated by western-blotting and indirect immunofluorescence. Sperm were incubated in presence or absence of extracellular Ca2+, or of CaMKKs inhibitor (STO-609). Phosphorylations of AMPK, CaMKI, and CaMKIV, as well as sperm functions were evaluated. We demonstrate the presence of both CaMKKs (α and β), CaMKI and CaMKIV in chicken sperm. CaMKKα and CaMKI were localized in the acrosome, the midpiece, and at much lower fluorescence in the flagellum, whereas CaMKKβ was mostly localized in the flagellum and much less in the midpiece and the acrosome. CaMKIV was only present in the flagellum. The presence of extracellular calcium induced an increase in kinases phosphorylation and sperm activity. STO-609 reduced AMPK phosphorylation in the presence of extracellular Ca2+ but not in its absence. STO-609 did not affect CaMKIV phosphorylation but decreased CaMKI phosphorylation and this inhibition was quicker in the presence of extracellular Ca2+ than in its absence. STO-609 efficiently inhibited sperm motility and AR, both in the presence and absence of extracellular Ca2+. Our results show for the first time the presence of CaMKKs (α and β) and one of its substrate, CaMKI in different subcellular compartments in germ cells, as well as the changes in the AMPK regulation pathway, sperm motility and AR related to Ca2+ entry in sperm through the Ca2+/CaM/CaMKKs/CaMKI pathway. The Ca2+/CaMKKs/AMPK pathway is activated only under conditions of extracellular Ca2+ entry in the cells

  7. CA_OPPUSST - Cantera OPUS Steady State

    Energy Science and Technology Software Center (ESTSC)

    2005-03-01

    The Cantera Opus Steady State (ca-opusst) applications solves steady reacting flow problems in opposed-flow geometries. It is a 1-0 application that represents axisymmetnc 3-0 physical systems that can be reduced via a similarity transformation to a 1-0 mathematical representation. The code contain solutions of the general dynamic equations for the particle distribution functions using a sectional model to describe the particle distribution function. Operators for particle nucleation, coagulation, condensation (i.e., growth/etching via reactions with themore » gas ambient), internal particle reactions. particle transport due to convection and due to molecular transport, are included in the particle general dynamics equation. Heat transport due to radiation exchange of the environment with particles in local thermal equilibrium to the surrounding gas will be included in the enthalpy conservation equation that is solved for the coupled gas! particle system in an upcoming version of the code due in June 2005. The codes use Cantera , a C++ Cal Tech code, for determination of gas phase species transport, reaction, and thermodynamics physical properties and source terms. The Codes use the Cantera Aerosol Dynamics Simulator (CADS) package, a general library for aerosol modeling, to calculate properties and source terms for the aerosol general dynamics equation, including particle formation from gas phase reactions, particle surface chemistry (growth and oxidation), bulk particle chemistry, particle transport by Brownian diffusion, thermophoresis, and diffusiophoresis, and thermal radiative transport involving particles. Also included are post-processing programs, cajost and cajrof, to extract ascii data from binary output files to produce plots.« less

  8. Improved thermoelectric performance of n-type Ca and Ca-Ce filled skutterudites

    SciTech Connect

    Thompson, Daniel R.; Liu, Chang; Ellison, Nicole D.; Salvador, James R.; Meyer, Martin S.; Haddad, Daad B.; Wang, Hsin; Cai, W.

    2014-12-28

    Thermoelectric (TE) technology for use in automotive waste heat recovery is being advanced by General Motors with support from the US Department of Energy. Skutterudites are a very promising material for this application of TE technology due to their superior mechanical properties and good TE performance. Double-filled YbxBayCo4Sb12 with ZT values around 1.1 at 750K are the best performing n-type skutterudites produced on a large scale using an economically viable approach of melt spinning (MS) in conjunction with spark plasma sintering (SPS). Another economical production method on the tons scale, the melt quench annealing (MQA) technique, has been recently claimed by Treibacher Industrie AG, further information is available [G. Rogl et al., Acta Mater. 76, 434-448 (2014)]. A possible hurdle to commercial implementation of these materials is the use of rare earths as the fillers to reduce thermal conductivity and improve the electrical transport properties. It will be shown herein that skutterudites double-filled with Ca and Ce, both of which are lower-cost fillers, display markedly different TE properties depending on whether they are produced by MQA or MS + SPS synthesis techniques. Finally, Ca and Ce double-filled skutterudites prepared by MS + SPS have TE properties that are superior to the same compositions prepared by MQA and that are comparable to the best performing Yb and Ba filled materials. Furthermore, the results of this study suggest that the unusually poor transport properties of MQA Ca-filled skutterudites can be ascribed to deleterious secondary phases, which is contrary to reports in the literature attempting to explain these irregularities via band structure features.

  9. Improved thermoelectric performance of n-type Ca and Ca-Ce filled skutterudites

    DOE PAGESBeta

    Thompson, Daniel R.; Liu, Chang; Ellison, Nicole D.; Salvador, James R.; Meyer, Martin S.; Haddad, Daad B.; Wang, Hsin; Cai, W.

    2014-12-28

    Thermoelectric (TE) technology for use in automotive waste heat recovery is being advanced by General Motors with support from the US Department of Energy. Skutterudites are a very promising material for this application of TE technology due to their superior mechanical properties and good TE performance. Double-filled YbxBayCo4Sb12 with ZT values around 1.1 at 750K are the best performing n-type skutterudites produced on a large scale using an economically viable approach of melt spinning (MS) in conjunction with spark plasma sintering (SPS). Another economical production method on the tons scale, the melt quench annealing (MQA) technique, has been recently claimedmore » by Treibacher Industrie AG, further information is available [G. Rogl et al., Acta Mater. 76, 434-448 (2014)]. A possible hurdle to commercial implementation of these materials is the use of rare earths as the fillers to reduce thermal conductivity and improve the electrical transport properties. It will be shown herein that skutterudites double-filled with Ca and Ce, both of which are lower-cost fillers, display markedly different TE properties depending on whether they are produced by MQA or MS + SPS synthesis techniques. Finally, Ca and Ce double-filled skutterudites prepared by MS + SPS have TE properties that are superior to the same compositions prepared by MQA and that are comparable to the best performing Yb and Ba filled materials. Furthermore, the results of this study suggest that the unusually poor transport properties of MQA Ca-filled skutterudites can be ascribed to deleterious secondary phases, which is contrary to reports in the literature attempting to explain these irregularities via band structure features.« less

  10. Improved thermoelectric performance of n-type Ca and Ca-Ce filled skutterudites

    NASA Astrophysics Data System (ADS)

    Thompson, Daniel R.; Liu, Chang; Ellison, Nicole D.; Salvador, James R.; Meyer, Martin S.; Haddad, Daad B.; Wang, Hsin; Cai, W.

    2014-12-01

    Thermoelectric (TE) technology for use in automotive waste heat recovery is being advanced by General Motors with support from the US Department of Energy. Skutterudites are a very promising material for this application of TE technology due to their superior mechanical properties and good TE performance. Double-filled YbxBayCo4Sb12 with ZT values around 1.1 at 750 K are the best performing n-type skutterudites produced on a large scale using an economically viable approach of melt spinning (MS) in conjunction with spark plasma sintering (SPS). Another economical production method on the tons scale, the melt quench annealing (MQA) technique, has been recently claimed by Treibacher Industrie AG, further information is available [G. Rogl et al., Acta Mater. 76, 434-448 (2014)]. A possible hurdle to commercial implementation of these materials is the use of rare earths as the fillers to reduce thermal conductivity and improve the electrical transport properties. It will be shown herein that skutterudites double-filled with Ca and Ce, both of which are lower-cost fillers, display markedly different TE properties depending on whether they are produced by MQA or MS + SPS synthesis techniques. Ca and Ce double-filled skutterudites prepared by MS + SPS have TE properties that are superior to the same compositions prepared by MQA and that are comparable to the best performing Yb and Ba filled materials. Furthermore, the results of this study suggest that the unusually poor transport properties of MQA Ca-filled skutterudites can be ascribed to deleterious secondary phases, which is contrary to reports in the literature attempting to explain these irregularities via band structure features.

  11. Improved thermoelectric performance of n-type Ca and Ca-Ce filled skutterudites

    SciTech Connect

    Thompson, Daniel R.; Liu, Chang; Ellison, Nicole D.; Salvador, James R.; Meyer, Martin S.; Haddad, Daad B.; Wang, Hsin; Cai, W.

    2014-12-28

    Thermoelectric (TE) technology for use in automotive waste heat recovery is being advanced by General Motors with support from the US Department of Energy. Skutterudites are a very promising material for this application of TE technology due to their superior mechanical properties and good TE performance. Double-filled Yb{sub x}Ba{sub y}Co{sub 4}Sb{sub 12} with ZT values around 1.1 at 750 K are the best performing n-type skutterudites produced on a large scale using an economically viable approach of melt spinning (MS) in conjunction with spark plasma sintering (SPS). Another economical production method on the tons scale, the melt quench annealing (MQA) technique, has been recently claimed by Treibacher Industrie AG, further information is available [G. Rogl et al., Acta Mater. 76, 434–448 (2014)]. A possible hurdle to commercial implementation of these materials is the use of rare earths as the fillers to reduce thermal conductivity and improve the electrical transport properties. It will be shown herein that skutterudites double-filled with Ca and Ce, both of which are lower-cost fillers, display markedly different TE properties depending on whether they are produced by MQA or MS + SPS synthesis techniques. Ca and Ce double-filled skutterudites prepared by MS + SPS have TE properties that are superior to the same compositions prepared by MQA and that are comparable to the best performing Yb and Ba filled materials. Furthermore, the results of this study suggest that the unusually poor transport properties of MQA Ca-filled skutterudites can be ascribed to deleterious secondary phases, which is contrary to reports in the literature attempting to explain these irregularities via band structure features.

  12. Plasma membrane Ca2+-ATPase 4: interaction with constitutive nitric oxide synthases in human sperm and prostasomes which carry Ca2+/CaM-dependent serine kinase.

    PubMed

    Andrews, Rachel E; Galileo, Deni S; Martin-DeLeon, Patricia A

    2015-11-01

    Deletion of the gene encoding the widely conserved plasma membrane calcium ATPase 4 (PMCA4), a major Ca(2+) efflux pump, leads to loss of sperm motility and male infertility in mice. PMCA4's partners in sperm and how its absence exerts its effect on fertility are unknown. We hypothesize that in sperm PMCA4 interacts with endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) which are rapidly activated by Ca(2+), and that these fertility-modulating proteins are present in prostasomes, which deliver them to sperm. We show that in human sperm PMCA4 is present on the acrosome, inner acrosomal membrane, posterior head, neck, midpiece and the proximal principal piece. PMCA4 localization showed inter- and intra-individual variation and was most abundant at the posterior head/neck junction, co-localizing with NOSs. Co-immunoprecipitations (Co-IP) revealed a close association of PMCA4 and the NOSs in Ca(2+) ionophore-treated sperm but much less so in uncapacitated untreated sperm. Fluorescence resonance energy transfer (FRET) showed a similar Ca(2+)-related association: PMCA4 and the NOSs are within 10 nm apart, and preferentially so in capacitated, compared with uncapacitated, sperm. FRET efficiencies varied, being significantly (P < 0.001) higher at high cytosolic Ca(2+) concentration ([Ca(2+)]c) in capacitated sperm than at low [Ca(2+)]c in uncapacitated sperm for the PMCA4-eNOS complex. These dynamic interactions were not seen for PMCA4-nNOS complexes, which had the highest FRET efficiencies. Further, along with Ca(2+)/CaM-dependent serine kinase (CASK), PMCA4 and the NOSs are present in the seminal plasma, specifically in prostasomes where Co-IP showed complexes similar to those in sperm. Finally, flow cytometry demonstrated that following co-incubation of sperm and seminal plasma, PMCA4 and the NOSs can be delivered in vitro to sperm via prostasomes. Our findings indicate that PMCA4 interacts simultaneously with the NOSs preferentially at

  13. The Ca II triplet in red giant spectra: [Fe/H] determinations and the role of [Ca/Fe

    NASA Astrophysics Data System (ADS)

    Da Costa, G. S.

    2016-01-01

    Measurements are presented and analysed of the strength of the Ca II triplet lines in red giants in Galactic globular and open clusters, and in a sample of red giants in the LMC disc that have significantly different [Ca/Fe] abundance ratios to the Galactic objects. The Galactic objects are used to generate a calibration between Ca II triplet line strength and [Fe/H], which is then used to estimate [Fe/H]CaT for the LMC stars. The values are then compared with the [Fe/H]spec determinations from high-dispersion spectroscopy. After allowance for a small systematic offset, the two abundance determinations are in excellent agreement. Further, as found in earlier studies, the difference is only a very weak function of the [Ca/Fe] ratio. For example, changing [Ca/Fe] from +0.3 to -0.2 causes the Ca II-based abundance to underestimate [Fe/H]spec by only ˜0.15 dex, assuming a Galactic calibration. Consequently, the Ca II triplet approach to metallicity determinations can be used without significant bias to study stellar systems that have substantially different chemical evolution histories.

  14. Na+ /Ca2+ exchanger contributes to asterosap-induced elevation of intracellular Ca2+ concentration in starfish spermatozoa.

    PubMed

    Islam, M Sadiqul; Kawase, Osamu; Hase, Sumitaka; Minakata, Hiroyuki; Hoshi, Motonori; Matsumoto, Midori

    2006-05-01

    Asterosap, a group of equally active isoforms of sperm-activating peptides from the egg jelly of the starfish Asterias amurensis, functions as a chemotactic factor for sperm. It transiently increases the intracellular cGMP level of sperm, which in turn induces a transient elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)). Using a fluorescent Ca(2+)-sensitive dye, Fluo-4 AM, we measured the changes in sperm [Ca(2+)](i) in response to asterosap. KB-R7943 (KB), a selective inhibitor of Na(+)/Ca(2+) exchanger (NCX), significantly inhibited the asterosap-induced transient elevation of [Ca(2+)](i), suggesting that asterosap influences [Ca(2+)](i) through activation of a K+-dependent NCX (NCKX). An NCKX activity of starfish sperm also shows K(+) dependency like other NCKXs. Therefore, we cloned an NCKX from the starfish testes and predicted that it codes for a 616 amino acid protein that is a member of the NCKX family. Pharmacological evidence suggests that this exchanger participates in the asterosap-induced Ca(2+) entry into sperm. PMID:16719949

  15. Thermoelectric properties of antiperovskite calcium oxides Ca3PbO and Ca3SnO

    NASA Astrophysics Data System (ADS)

    Okamoto, Y.; Sakamaki, A.; Takenaka, K.

    2016-05-01

    We report the thermoelectric properties of polycrystalline samples of Ca3Pb1-xBixO (x = 0, 0.1, 0.2) and Ca3SnO, both crystallizing in a cubic antiperovskite-type structure. The Ca3SnO sample shows metallic resistivity and its thermoelectric power approaches 100 μV K-1 at room temperature, resulting in the thermoelectric power factor of Ca3SnO being larger than that of Ca3Pb1-xBixO. On the basis of Hall and Sommerfeld coefficients, the Ca3SnO sample is found to be a p-type metal with a carrier density of ˜1019 cm-3, a mobility of ˜80 cm2 V-1 s-1, both comparable to those in degenerated semiconductors, and a moderately large hole carrier effective mass. The coexistence of moderately high mobility and large effective mass observed in Ca3SnO, as well as possible emergence of a multivalley electronic structure with a small band gap at low-symmetry points in k-space, suggests that the antiperovskite Ca oxides have strong potential as a thermoelectric material.

  16. In vivo degradation behavior of Ca-deficient hydroxyapatite coated Mg-Zn-Ca alloy for bone implant application.

    PubMed

    Wang, Huanxin; Guan, Shaokang; Wang, Yisheng; Liu, Hongjian; Wang, Haitao; Wang, Liguo; Ren, Chenxing; Zhu, Shijie; Chen, Kuisheng

    2011-11-01

    In present paper, an in vivo study was carried out on uncoated and calcium-deficient hydroxyapatite (Ca-def HA) coated Mg-Zn-Ca alloy to investigate the effect of Ca-def HA coating on the degradation behavior and bone response of magnesium substrate. Magnesium alloy rods were implanted into rabbit femora and evaluated during 24 weeks implantation. The characterization of both implants indicates that in vivo degradation of the Ca-def HA coating and magnesium substrate occurs almost simultaneously, and in vivo valid life of the coating is about 8 weeks, after that the degradation rate of the coated implants increases obviously. The main reasons for the Ca-def HA coating degradation can be attributed to its reaction with body fluid and the substitution of Mg(2+) ions in Ca-def HA. Histopathological examinations show that the Ca-def HA coating has good osteoconductivity and is in favor of the formation of more new bone on the surface of magnesium alloy. So the Ca-def HA coating could not only slow down in vivo degradation of magnesium alloy but also improve its bone response. PMID:21783346

  17. A SIMS Calibration of Benthic Foraminiferal Mg/Ca

    NASA Astrophysics Data System (ADS)

    Curry, W. B.; Marchitto, T. M.

    2005-12-01

    Using a suite of multi-core tops, we have produced a calibration of C. pachyderma Mg/Ca versus temperature spanning the temperature range of 5 to 18 °C. The core tops are located along the Florida margin south of Dry Tortugas (KNR166), along the Bahamas west of Andros Island and Great Bahama Bank (KNR166), and along the southeastern margin of Brazil (KNR159). Water depths range from about 200 to 800 m for the Florida Straits multi-cores and 400 to 800 m for the Brazil margin multi-cores. Five of the KNR166 core tops contain post-1950 bomb radiocarbon with Fmodern> 1; several others have bomb radiocarbon mixed in with pre-bomb sediments to give ages less than 0 BP. Core top ages are generally older for the KNR159 multi-cores, but each is from a location with a well documented Holocene section. Sedimentation rates for KNR166 multi-cores vary from 10 to 100 cm kyr-1; for KNR159 multi-cores, sedimentation rates vary from 5 to 10 cm kyr-1. Elemental ratios were determined by Secondary Ionization Mass Spectrometry (SIMS) using a Cameca IMS 3f ion probe calibrated for Mg/Ca and Sr/Ca using two standards which were independently measured using ICP-MS. Using SIMS, the external precision of the calibration standards averages ±3.5% (1σ RSD) for Mg/Ca and ± 1.7% (1σ RSD) for Sr/Ca. SIMS elemental measurements were performed on one to three individual C. pachyderma tests in each core top; more than 30 tests have been measured from 18 multi-core tops. Mg/Ca variability within C. pachyderma tests averages ± 20% (1σ RSD) with a small but significant trend toward higher variability at higher Mg/Ca. Higher Mg/Ca is observed in warmer waters, but the Mg/Ca values are generally lower (at comparable warm temperatures) than observed in previous calibration studies. At temperatures below 8 °C, C. pachyderma Mg/Ca values are less than 2 mmole/mole. At temperatures warmer than 15 °C, C. pachyderma Mg/Ca values exceed 3 mmole/mole. The slope of Mg/Ca versus temperature (~0.14 mmole

  18. Regional and interspecific variation in Sr, Ca, and Sr/Ca ratios in avian eggshells from the USA.

    PubMed

    Mora, Miguel A; Brattin, Bryan; Baxter, Catherine; Rivers, James W

    2011-08-01

    To examine regional variation in strontium (Sr), which at high concentrations may reduce eggshell quality, increase egg breakage and reproductive failure, we analyzed Sr, and calcium (Ca) concentrations and Sr/Ca ratios in eggshells from 20 avian species from California, Texas, Idaho, Kansas, and Michigan. In addition, we included data previously reported from Arizona to expand the regional comparisons and to better establish patterns of Sr, and Sr/Ca ratios in bird species across the United States. We found Sr concentrations varied significantly among regions, among species, and among foraging guilds; this variability is strongly influenced by the Sr/Ca ratios in surface water from locations close to the region where the eggshells were collected. Sr concentrations and Sr/Ca ratios were significantly higher in bird eggshells from the Volta wildlife region in the San Joaquin Valley, California and in various locales from Arizona. Sr concentrations and Sr/Ca ratios in bird eggshells from other locations in the USA were lower than those detected in these two regions. Among foraging guilds, invertivores had the highest Sr concentrations and Sr/Ca ratios and carnivores had the lowest. In general, the Sr/Ca ratio increased strongly with increasing Sr concentrations (R(2) = 0.99, P < 0.0001). There was a significant correlation (R(2) = 0.58, P < 0.0001) between Sr/Ca ratios in water and the average Sr/Ca ratios in eggshells suggesting that these values could be determined from Sr/Ca ratios in water. Eggshell thickness was poorly correlated with Sr (R(2) = 0.03) but had a significant and positive correlation with Ca and was more properly correlated by a quadratic equation (R(2) = 0.50, Thickness = 2.13 - 0.02Ca - 3.07 * 10(-5)Ca(2)). Our study provides further evidence that Sr accumulates significantly in the avian eggshell, in some regions at concentrations which could be of concern for potential negative effects on reproduction. We suggest that when assessing the effects

  19. Na(+)-Ca sup 2+ exchange in cultured rat hepatocytes: Evidence against a role in cytosolic Ca sup 2+ regulation or signaling

    SciTech Connect

    Lidofsky, S.D.; Xie, M.H.; Scharschmidt, B.F. )

    1990-07-01

    Plasma membrane Na(+)-Ca2+ exchange contributes importantly to the regulation of cytosolic Ca2+ concentration ((Ca2+)i) in excitable cells. Despite extensive study in excitable tissues, the role of this transporter in the regulation of (Ca2+)i in hepatocytes is unknown, and conflicting information has been reported regarding the presence of Na(+)-Ca2+ exchange in hepatocyte plasma membrane vesicles. We have therefore assessed the role of Na(+)-dependent Ca2+ transport in the regulation of (Ca2+)i in rat hepatocytes in primary culture under basal conditions and after exposure to vasopressin, a hormone that elevates (Ca2+)i. Ca2+ efflux, measured using 45Ca, did not differ in the presence or absence of extracellular Na+, either under basal conditions or in response to vasopressin. (Ca2+)i, measured using the Ca2(+)-sensitive dye fura-2, was not altered by transient or prolonged exposure to Na(+)-free media or by exposure to ouabain in concentrations sufficient to produce a five-fold elevation in intracellular Na+ concentration. The (Ca2+)i response to vasopressin was also unaffected by Na+ removal or ouabain. By contrast, in cultured rat cardiac myocytes, cells that possess Na(+)-Ca2+ exchange, transient or prolonged Na+ removal as well as ouabain exposure produced greater than fivefold increases in (Ca2+)i compared with controls. We conclude that Na(+)-Ca2+ exchange does not contribute to the regulation of (Ca2+)i in hepatocytes.

  20. Echinacea-induced cytosolic Ca2+ elevation in HEK293

    PubMed Central

    2010-01-01

    Background With a traditional medical use for treatment of various ailments, herbal preparations of Echinacea are now popularly used to improve immune responses. One likely mode of action is that alkamides from Echinacea bind to cannabinoid type 2 (CB2) receptors and induce a transient increase in intracellular Ca2+. Here, we show that unidentified compounds from Echinacea purpurea induce cytosolic Ca2+ elevation in non-immune-related cells, which lack CB2 receptors and that the Ca2+ elevation is not influenced by alkamides. Methods A non-immune human cell line, HEK293, was chosen to evaluate E. purpurea root extracts and constituents as potential regulators of intracellular Ca2+ levels. Changes in cytosolic Ca2+ levels were monitored and visualized by intracellular calcium imaging. U73122, a phospholipase C inhibitor, and 2-aminoethoxydiphenyl borate (2-APB), an antagonist of inositol-1,4,5-trisphosphate (IP3) receptor, were tested to determine the mechanism of this Ca2+ signaling pathway. E. purpurea root ethanol extracts were fractionated by preparative HPLC, screened for bioactivity on HEK293 cells and by GC-MS for potential constituent(s) responsible for this bioactivity. Results A rapid transient increase in cytosolic Ca2+ levels occurs when E. purpurea extracts are applied to HEK293 cells. These stimulatory effects are phospholipase C and IP3 receptor dependent. Echinacea-evoked responses could not be blocked by SR 144528, a specific CB2 receptor antagonist, indicating that CB2 is not involved. Ca2+ elevation is sustained after the Echinacea-induced Ca2+ release from intracellular Ca2+ stores; this longer-term effect is abolished by 2-APB, indicating a possible store operated calcium entry involvement. Of 28 HPLC fractions from E. purpurea root extracts, six induce cytosolic Ca2+ increase. Interestingly, GC-MS analysis of these fractions, as well as treatment of HEK293 cells with known individual and combined chemicals, indicates the components thought to be

  1. Ca²⁺ channel and Na⁺/Ca²⁺ exchange localization in cardiac myocytes.

    PubMed

    Scriven, David R L; Moore, Edwin D W

    2013-05-01

    L-type Ca(2+) channels and the Na(+)/Ca(2+) exchanger are the main pathways for Ca(2+) influx and efflux across the sarcolemma. The majority of Ca(2+) channels are found in couplons adjacent to ryanodine receptors, but there are at least two smaller, physically and functionally distinct, extradyadic populations. NCX is more widely dispersed in the membrane although a subpopulation is closely associated with the alpha-2 isoform of the Na(+)/K(+) ATPase and has a direct effect on ECC. In addition to Ca(2+) channels and ryanodine receptors, couplons in adult animals contain a variety of other occupants that modulate their function. These modulators can vary from one couplon to another creating a variety of molecular architectures. In this review we examine our current understanding of the molecular composition, binding partners and determinants of the localization of these proteins. PMID:23220152

  2. Electron radiation damages to dicalcium (Ca2SiO4) and tricalcium (Ca3SiO5) orthosilicates

    NASA Astrophysics Data System (ADS)

    de Noirfontaine, Marie-Noëlle; Dunstetter, Frédéric; Courtial, Mireille; Signes-Frehel, Marcel; Wang, Guillaume; Gorse-Pomonti, Dominique

    2016-05-01

    Electron radiation damages to dicalcium silicate (Ca2SiO4) and tricalcium silicate (Ca3SiO5) are reported for the first time in this paper. With increasing flux, between 2.7 × 1017 and 2.2 × 1022 e- cm-2 s-1, decomposition into nanodomains of crystalline CaO plus an amorphous silica rich phase is first observed for both silicates, then amorphization at higher flux always for both silicates, and finally hole drilling but only for Ca3SiO5. These structural modifications are accompanied by a net reduction of Ca content under the electron beam depending on the silicate species. These radiation effects occur for values of flux and dose larger than in previously studied orthosilicates (like olivines), and much larger than in all tectosilicates.

  3. Ca(2+)-dependent and Ca(2+)-independent calmodulin binding sites in erythrocyte protein 4.1. Implications for regulation of protein 4.1 interactions with transmembrane proteins.

    PubMed

    Nunomura, W; Takakuwa, Y; Parra, M; Conboy, J G; Mohandas, N

    2000-03-01

    In vitro protein binding assays identified two distinct calmodulin (CaM) binding sites within the NH(2)-terminal 30-kDa domain of erythrocyte protein 4.1 (4.1R): a Ca(2+)-independent binding site (A(264)KKLWKVCVEHHTFFRL) and a Ca(2+)-dependent binding site (A(181)KKLSMYGVDLHKAKDL). Synthetic peptides corresponding to these sequences bound CaM in vitro; conversely, deletion of these peptides from a 30-kDa construct reduced binding to CaM. Thus, 4.1R is a unique CaM-binding protein in that it has distinct Ca(2+)-dependent and Ca(2+)-independent high affinity CaM binding sites. CaM bound to 4.1R at a stoichiometry of 1:1 both in the presence and absence of Ca(2+), implying that one CaM molecule binds to two distinct sites in the same molecule of 4.1R. Interactions of 4.1R with membrane proteins such as band 3 is regulated by Ca(2+) and CaM. While the intrinsic affinity of the 30-kDa domain for the cytoplasmic tail of erythrocyte membrane band 3 was not altered by elimination of one or both CaM binding sites, the ability of Ca(2+)/CaM to down-regulate 4. 1R-band 3 interaction was abrogated by such deletions. Thus, regulation of protein 4.1 binding to membrane proteins by Ca(2+) and CaM requires binding of CaM to both Ca(2+)-independent and Ca(2+)-dependent sites in protein 4.1. PMID:10692436

  4. Characterization of Ca2+-Dependent Protein-Protein Interactions within the Ca2+ Release Units of Cardiac Sarcoplasmic Reticulum

    PubMed Central

    Rani, Shilpa; Park, Chang Sik; Sreenivasaiah, Pradeep Kumar; Kim, Do Han

    2016-01-01

    In the heart, excitation-contraction (E-C) coupling is mediated by Ca2+ release from sarcoplasmic reticulum (SR) through the interactions of proteins forming the Ca2+ release unit (CRU). Among them, calsequestrin (CSQ) and histidine-rich Ca2+ binding protein (HRC) are known to bind the charged luminal region of triadin (TRN) and thus directly or indirectly regulate ryanodine receptor 2 (RyR2) activity. However, the mechanisms of CSQ and HRC mediated regulation of RyR2 activity through TRN have remained unclear. We first examined the minimal KEKE motif of TRN involved in the interactions with CSQ2, HRC and RyR2 using TRN deletion mutants and in vitro binding assays. The results showed that CSQ2, HRC and RyR2 share the same KEKE motif region on the distal part of TRN (aa 202–231). Second, in vitro binding assays were conducted to examine the Ca2+ dependence of protein-protein interactions (PPI). The results showed that TRN-HRC interaction had a bell-shaped Ca2+ dependence, which peaked at pCa4, whereas TRN-CSQ2 or TRN-RyR2 interaction did not show such Ca2+ dependence pattern. Third, competitive binding was conducted to examine whether CSQ2, HRC, or RyR2 affects the TRN-HRC or TRN-CSQ2 binding at pCa4. Among them, only CSQ2 or RyR2 competitively inhibited TRN-HRC binding, suggesting that HRC can confer functional refractoriness to CRU, which could be beneficial for reloading of Ca2+ into SR at intermediate Ca2+ concentrations. PMID:26674963

  5. MicroRNA-30 inhibits neointimal hyperplasia by targeting Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ)

    PubMed Central

    Liu, Yong Feng; Spinelli, Amy; Sun, Li-Yan; Jiang, Miao; Singer, Diane V.; Ginnan, Roman; Saddouk, Fatima Z.; Van Riper, Dee; Singer, Harold A.

    2016-01-01

    The multifunctional Ca2+/calmodulin-dependent protein kinase II δ-isoform (CaMKIIδ) promotes vascular smooth muscle (VSM) proliferation, migration, and injury-induced vascular wall neointima formation. The objective of this study was to test if microRNA-30 (miR-30) family members are endogenous regulators of CaMKIIδ expression following vascular injury and whether ectopic expression of miR-30 can inhibit CaMKIIδ-dependent VSM cell function and neointimal VSM hyperplasia induced by vascular injury. The CaMKIIδ 3′UTR contains a consensus miR-30 binding sequence that is highly conserved across species. A significant decrease in miR-30 family members and increase in CaMKIIδ2 protein expression, with no change in CaMKIIδ mRNA expression, was observed in medial layers of VSM 7 days post-injury. In vitro, overexpression of miR-30c or miR-30e inhibited CaMKIIδ2 protein expression by ~50% in cultured rat aortic VSM cells, and inhibited VSM cell proliferation and migration. In vivo, lenti-viral delivery of miR-30c into injured rat carotid arteries prevented the injury-induced increase in CaMKIIδ2. Furthermore, neointima formation was dramatically inhibited by lenti-viral delivery of miR-30c in the injured medial smooth muscle. These studies define a novel mechanism for regulating CaMKIIδ expression in VSM and provide a new potential therapeutic strategy to reduce progression of vascular proliferative diseases, including atherosclerosis and restenosis. PMID:27199283

  6. Development and evaluation of materials for thermochemical heat storage based on the CaO/CaCO3 reaction couple

    NASA Astrophysics Data System (ADS)

    Sakellariou, Kyriaki G.; Tsongidis, Nikolaos I.; Karagiannakis, George; Konstandopoulos, Athanasios G.; Baciu, Diana; Charalambopoulou, Georgia; Steriotis, Theodore; Stubos, Athanasios; Arlt, Wolfgang

    2016-05-01

    The current work relates to the development of synthetic calcium oxide (CaO) based compositions as candidate materials for energy storage under a cyclic carbonation/decarbonation reaction scheme. Although under such a cyclic scheme the energy density of natural lime based CaO is high (˜ 3MJ/kg), the particular materials suffer from notable cycle-to-cycle deactivation. To this direction, pure CaO and CaO/Al2O3 composites have been prepared and preliminarily evaluated under the suggested cyclic carbonation/decarbonation scheme in the temperature range of 600-800°C. For the composite materials, Ca/Al molar ratios were in the range between 95/5 and 52/48 and upon calcination the formation of mixed Ca/Al phases was verified. The preliminary evaluation of materials studied was conducted under 3 carbonation/decarbonation cycles and the loss of activity for the case of natural CaO was obvious. Synthetic materials with superior stability/capture c.f. natural CaO were further subjected to multi-cyclic carbonation/decarbonation, via which the positive effect of alumina addition was made evident. Selected compositions exhibited adequately high CO2 capture capacity and stable performance during multi-cyclic operation. Moreover, this study contains preliminary experiments referring to proof-of-principle validation of a concept based on the utilization of a CaO-based honeycomb reactor/heat exchanger preliminary design. In particular, cordierite monolithic structures were coated with natural CaO and in total 11 cycles were conducted. Upon operation, clear signs of heat dissipation by the imposed flow in the duration of the exothermic reaction step were identified.

  7. HIF-1α-mediated upregulation of SERCA2b: The endogenous mechanism for alleviating the ischemia-induced intracellular Ca(2+) store dysfunction in CA1 and CA3 hippocampal neurons.

    PubMed

    Kopach, Olga; Maistrenko, Anastasiia; Lushnikova, Iryna; Belan, Pavel; Skibo, Galina; Voitenko, Nana

    2016-05-01

    Pyramidal neurons of the hippocampus possess differential susceptibility to the ischemia-induced damage with the highest vulnerability of CA1 and the lower sensitivity of CA3 neurons. This damage is triggered by Ca(2+)-dependent excitotoxicity and can result in a delayed cell death that might be potentially suspended through activation of endogenous neuroprotection with the hypoxia-inducible transcription factors (HIF). However, the molecular mechanisms of this neuroprotection remain poorly understood. Here we show that prolonged (30min) oxygen and glucose deprivation (OGD) in situ impairs intracellular Ca(2+) regulation in CA1 rather than in CA3 neurons with the differently altered expression of genes coding Ca(2+)-ATPases: the mRNA level of plasmalemmal Ca(2+)-ATPases (PMCA1 and PMCA2 subtypes) was downregulated in CA1 neurons, whereas the mRNA level of the endoplasmic reticulum Ca(2+)-ATPases (SERCA2b subtype) was increased in CA3 neurons at 4h of re-oxygenation after prolonged OGD. These demonstrate distinct susceptibility of CA1 and CA3 neurons to the ischemic impairments in intracellular Ca(2+) regulation and Ca(2+)-ATPase expression. Stabilization of HIF-1α by inhibiting HIF-1α hydroxylation prevented the ischemic decrease in both PMCA1 and PMCA2 mRNAs in CA1 neurons, upregulated the SERCA2b mRNA level and eliminated the OGD-induced Ca(2+) store dysfunction in these neurons. Cumulatively, these findings reveal the previously unknown HIF-1α-driven upregulation of Ca(2+)-ATPases as a mechanism opposing the ischemic impairments in intracellular Ca(2+) regulation in hippocampal neurons. The ability of HIF-1α to modulate expression of genes coding Ca(2+)-ATPases suggests SERCA2b as a novel target for HIF-1 and may provide potential implications for HIF-1α-stabilizing strategy in activating endogenous neuroprotection. PMID:26969192

  8. Rice-like hollow nano-CaCO3 synthesis

    NASA Astrophysics Data System (ADS)

    Ulkeryildiz, Eda; Kilic, Sevgi; Ozdemir, Ekrem

    2016-09-01

    We have shown that Ca(OH)2 solution is a natural stabilizer for CaCO3 particles. We designed a CO2 bubbling crystallization reactor to produce nano-CaCO3 particles in homogenous size distribution without aggregation. In the experimental set-up, the crystallization region was separated from the stabilization region. The produced nanoparticles were removed from the crystallization region into the stabilization region before aggregation or crystal growth. It was shown that rice-like hollow nano-CaCO3 particles in about 250 nm in size were produced with almost monodispersed size distribution. The particles started to dissolve through their edges as CO2 bubbles were injected, which opened-up the pores inside the particles. At the late stages of crystallization, the open pores were closed as a result of dissolution-recrystallization of the newly synthesized CaCO3 particles. These particles were stable in Ca(OH)2 solution and no aggregation was detected. The present methodology can be used in drug encapsulation into inorganic CaCO3 particles for cancer treatment with some modifications.

  9. Decoding dynamic Ca2+ signaling in the vascular endothelium

    PubMed Central

    Taylor, Mark S.; Francis, Michael

    2014-01-01

    Although acute and chronic vasoregulation is inherently driven by endothelial Ca2+, control and targeting of Ca2+-dependent signals are poorly understood. Recent studies have revealed localized and dynamic endothelial Ca2+ events comprising an intricate signaling network along the vascular intima. Discrete Ca2+ transients emerging from both internal stores and plasmalemmal cation channels couple to specific membrane K+ channels, promoting endothelial hyperpolarization and vasodilation. The spatiotemporal tuning of these signals, rather than global Ca2+ elevation, appear to direct endothelial functions under physiologic conditions. In fact, altered patterns of dynamic Ca2+ signaling may underlie essential endothelial dysfunction in a variety of cardiovascular diseases. Advances in imaging approaches and analyses in recent years have allowed for detailed detection, quantification, and evaluation of Ca2+ dynamics in intact endothelium. Here, we discuss recent insights into these signals, including their sources of origination and their functional encoding. We also address key aspects of data acquisition and interpretation, including broad applications of automated high-content analysis. PMID:25452732

  10. Aerobic Hydrogen Production via Nitrogenase in Azotobacter vinelandii CA6

    PubMed Central

    Noar, Jesse; Loveless, Telisa; Navarro-Herrero, José Luis; Olson, Jonathan W.

    2015-01-01

    The diazotroph Azotobacter vinelandii possesses three distinct nitrogenase isoenzymes, all of which produce molecular hydrogen as a by-product. In batch cultures, A. vinelandii strain CA6, a mutant of strain CA, displays multiple phenotypes distinct from its parent: tolerance to tungstate, impaired growth and molybdate transport, and increased hydrogen evolution. Determining and comparing the genomic sequences of strains CA and CA6 revealed a large deletion in CA6's genome, encompassing genes related to molybdate and iron transport and hydrogen reoxidation. A series of iron uptake analyses and chemostat culture experiments confirmed iron transport impairment and showed that the addition of fixed nitrogen (ammonia) resulted in cessation of hydrogen production. Additional chemostat experiments compared the hydrogen-producing parameters of different strains: in iron-sufficient, tungstate-free conditions, strain CA6's yields were identical to those of a strain lacking only a single hydrogenase gene. However, in the presence of tungstate, CA6 produced several times more hydrogen. A. vinelandii may hold promise for developing a novel strategy for production of hydrogen as an energy compound. PMID:25911479

  11. CaMK4 Gene Deletion Induces Hypertension

    PubMed Central

    Santulli, Gaetano; Cipolletta, Ersilia; Sorriento, Daniela; Del Giudice, Carmine; Anastasio, Antonio; Monaco, Sara; Maione, Angela Serena; Condorelli, Gianluigi; Puca, Annibale; Trimarco, Bruno; Illario, Maddalena; Iaccarino, Guido

    2012-01-01

    Background The expression of calcium/calmodulin-dependent kinase IV (CaMKIV) was hitherto thought to be confined to the nervous system. However, a recent genome-wide analysis indicated an association between hypertension and a single-nucleotide polymorphism (rs10491334) of the human CaMKIV gene (CaMK4), which suggests a role for this kinase in the regulation of vascular tone. Methods and Results To directly assess the role of CaMKIV in hypertension, we characterized the cardiovascular phenotype of CaMK4−/− mice. They displayed a typical hypertensive phenotype, including high blood pressure levels, cardiac hypertrophy, vascular and kidney damage, and reduced tolerance to chronic ischemia and myocardial infarction compared with wild-type littermates. Interestingly, in vitro experiments showed the ability of this kinase to activate endothelial nitric oxide synthase. Eventually, in a population study, we found that the rs10491334 variant associates with a reduction in the expression levels of CaMKIV in lymphocytes from hypertensive patients. Conclusions Taken together, our results provide evidence that CaMKIV plays a pivotal role in blood pressure regulation through the control of endothelial nitric oxide synthase activity. (J Am Heart Assoc. 2012;1:e001081 doi: 10.1161/JAHA.112.001081.) PMID:23130158

  12. Ca intercalated bilayer graphene as a thinnest limit of superconducting C6Ca

    PubMed Central

    Kanetani, Kohei; Sugawara, Katsuaki; Sato, Takafumi; Shimizu, Ryota; Iwaya, Katsuya; Hitosugi, Taro; Takahashi, Takashi

    2012-01-01

    Success in isolating a 2D graphene sheet from bulky graphite has triggered intensive studies of its physical properties as well as its application in devices. Graphite intercalation compounds (GICs) have provided a platform of exotic quantum phenomena such as superconductivity, but it is unclear whether such intercalation is feasible in the thinnest 2D limit (i.e., bilayer graphene). Here we report a unique experimental realization of 2D GIC, by fabricating calcium-intercalated bilayer graphene C6CaC6 on silicon carbide. We have investigated the structure and electronic states by scanning tunneling microscopy and angle-resolved photoemission spectroscopy. We observed a free-electron–like interlayer band at the Brillouin-zone center, which is thought to be responsible for the superconductivity in 3D GICs, in addition to a large π* Fermi surface at the zone boundary. The present success in fabricating Ca-intercalated bilayer graphene would open a promising route to search for other 2D superconductors as well as to explore its application in devices. PMID:23139407

  13. Ca2+-induced uncoupling of Aplysia bag cell neurons.

    PubMed

    Dargaei, Zahra; Standage, Dominic; Groten, Christopher J; Blohm, Gunnar; Magoski, Neil S

    2015-02-01

    Electrical transmission is a dynamically regulated form of communication and key to synchronizing neuronal activity. The bag cell neurons of Aplysia are a group of electrically coupled neuroendocrine cells that initiate ovulation by secreting egg-laying hormone during a prolonged period of synchronous firing called the afterdischarge. Accompanying the afterdischarge is an increase in intracellular Ca2+ and the activation of protein kinase C (PKC). We used whole cell recording from paired cultured bag cell neurons to demonstrate that electrical coupling is regulated by both Ca2+ and PKC. Elevating Ca2+ with a train of voltage steps, mimicking the onset of the afterdischarge, decreased junctional current for up to 30 min. Inhibition was most effective when Ca2+ entry occurred in both neurons. Depletion of Ca2+ from the mitochondria, but not the endoplasmic reticulum, also attenuated the electrical synapse. Buffering Ca2+ with high intracellular EGTA or inhibiting calmodulin kinase prevented uncoupling. Furthermore, activating PKC produced a small but clear decrease in junctional current, while triggering both Ca2+ influx and PKC inhibited the electrical synapse to a greater extent than Ca2+ alone. Finally, the amplitude and time course of the postsynaptic electrotonic response were attenuated after Ca2+ influx. A mathematical model of electrically connected neurons showed that excessive coupling reduced recruitment of the cells to fire, whereas less coupling led to spiking of essentially all neurons. Thus a decrease in electrical synapses could promote the afterdischarge by ensuring prompt recovery of electrotonic potentials or making the neurons more responsive to current spreading through the network. PMID:25411460

  14. The Puzzlingly Small Ca II Triplet Absorption in Elliptical Galaxies

    NASA Astrophysics Data System (ADS)

    Saglia, R. P.; Maraston, Claudia; Thomas, Daniel; Bender, Ralf; Colless, Matthew

    2002-11-01

    We measure the central values (within Re/8) of the Ca II triplet line indices CaT* and CaT and the Paschen index PaT at 8600 Å for a 93% complete sample of 75 nearby early-type galaxies with BT<12 mag and Vgal<2490 km s-1. We find that the values of CaT* are constant to within 5% over the range of central velocity dispersions 100 km s-1<=σ<=340 km s-1, while the PaT (and CaT) values are mildly anticorrelated with σ. Using simple and composite stellar population models, we show the following: (1) The measured CaT* and CaT are lower than expected from simple stellar population (SSP) models with Salpeter initial mass functions (IMFs) and with metallicities and ages derived from optical Lick (Fe, Mg, and Hβ) indices. Uncertainties in the calibration, the fitting functions, and the SSP modeling taken separately cannot explain the discrepancy. On average, the observed PaT values are within the range allowed by the models and the large uncertainties in the fitting functions. (2) The steepening of the IMF at low masses required to lower the CaT* and CaT indices to the observed values is incompatible with the measured FeH index at 9916 Å and the dynamical mass-to-light ratios of elliptical galaxies. (3) Composite stellar populations with a low-metallicity component reduce the disagreement, but rather artificial metallicity distributions are needed. Another explanation may be that calcium is indeed underabundant in elliptical galaxies.

  15. Focal Ca2+ transient detection in smooth muscle.

    PubMed

    Young, John S; Amos, Robert J; Brain, Keith L

    2009-01-01

    Ca2+ imaging of smooth muscle provides insight into cellular mechanisms that may not result in changes of membrane potential, such as the release of Ca2+ from internal stores, and allows multiple cells to be monitored simultaneously to assess, for example, coupling in syncytial tissue. Subcellular Ca2+ transients are common in smooth muscle, yet are difficult to measure accurately because of the problems caused by their stochastic occurrence, over an often wide field of view, in an organ that it prone to contract. To overcome this problem, we've developed a series of imaging protocols and analysis routines to acquire and then analyse, in an automated fashion, the frequency, location and amplitude of such events. While this approach may be applied in other contexts, our own work involves the detection of local purinergic Ca2+ transients for locating transmitter release with submicron resolution. ATP is released as a cotransmitter from autonomic nerves, where it binds to P2X1 receptors on the smooth muscle of the detrusor and vas deferens. Ca2+ enters the smooth muscle, resulting in purinergic neuroeffector Ca2+ transients (NCTs). The focal Ca2+ transients allow the optical monitoring of neurotransmitter release in a manner that has many advantages over electrophysiology. Apart from the greatly improved spatial resolution, optical recording has the additional advantage of allowing the recording of transmitter release from many distinguishable sites simultaneously. Furthermore, the optical plane of focus is easier to maintain or correct during long recording series than is the repositioning of an intracellular sharp microelectrode. In summary, a method for imaging of Ca2+ fluorescence is outlined which details the preparation of tissue, and the acquisition and analysis of data. We outline the use of several scripts for the analysis of such Ca2+ transients. PMID:19564842

  16. Modulation of intracellular Ca2+ levels by Scorpaenidae venoms.

    PubMed

    Church, Jarrod E; Moldrich, Randal X; Beart, Philip M; Hodgson, Wayne C

    2003-05-01

    The crude venoms of the soldierfish (Gymnapistes marmoratus), the lionfish (Pterois volitans) and the stonefish (Synanceia trachynis) display pronounced neuromuscular activity. Since [Ca(2+)](i) is a key regulator in many aspects of neuromuscular function we sought to determine its involvement in the neuromuscular actions of the venoms. In the chick biventer cervicis muscle, all three venoms produced a sustained contraction (approx 20-30% of 1mM acetylcholine). Blockade of nicotinic receptors with tubocurarine (10 micro M) failed to attenuate the contractile response to either G. marmoratus venom or P. volitans venom, but produced slight inhibition of the response to S. trachynis venom. All three venoms produced a rise in intracellular Ca(2+) (approx. 200-300% of basal) in cultured murine cortical neurons. The Ca(2+)-channel blockers omega-conotoxin MVIIC, omega-conotoxin GVIA, omega-agatoxin IVa and nifedipine (each at 1 micro M) potentiated the increase in [Ca(2+)](i) in response to G. marmoratus venom and P. volitans venom, while attenuating the response to S. trachynis venom. Removal of extracellular Ca(2+), replacement of Ca(2+) with La(3+) (0.5mM), or addition of stonefish antivenom (3units/ml) inhibited both the venom-induced increase in [Ca(2+)](i) in cultured neurones and contraction in chick biventer cervicis muscle. Venom-induced increases in [Ca(2+)](i) correlated with an increased cell death of cultured neurones as measured using propidium iodide (1 micro g/ml). Morphological analysis revealed cellular swelling and neurite loss consistent with necrosis. These data indicate that the effects of all three venoms are due in part to an increase in intracellular Ca(2+), possibly via the formation of pores in the cellular membrane which, under certain conditions, can lead to necrosis. PMID:12727272

  17. Bathymetric Surveys of the Trinity River, CA

    NASA Astrophysics Data System (ADS)

    Matthews, W. V.; Pryor, C. T.

    2012-12-01

    Shallow water (0-5m) bathymetric surveys in alluvial mountain rivers present numerous data collection challenges including highly variable flow depths, rapidly changing topography, turbulent and aerated water in riffles and around large roughness elements, and poor GPS reception. In addition, confined and shallow reaches present access challenges for survey platforms. Recently, nearly 70km of detailed bathymetric surveys were collected along the Trinity River in northwestern CA for the Trinity River Restoration Program. The data collection platform consisted of a 5m jet boat equipped with a multi-transducer hydrographic survey system (or sweep system). The system is capable of collecting data in as little as 0.4m of water and consists of seven transducers, three on each port and starboard collapsible boom and one permanently mounted in the hull of the survey boat. The total swath width is 7.5m, with each transducer evenly spaced at approximately 1.3m apart. Each boom both articulates and collapses, providing flexibility to quickly raise the booms to move upstream under full power or to reduce the boom width in confined areas. A RTK GNSS (GPS+GLONASS) receiver with internal radio for RTK positioning is located directly over the middle transducer and offsets locate the other six transducers. A GNSS heading receiver is used to provide a precise heading for the sweep system. A pitch and roll sensor is placed on the boom just below the GPS antenna and compensates for roll and pitch of the vessel. Depths are sent from the electronics package to a ruggedized laptop running Hypack™ data collection software. Mapping occurred on the falling limb of the Restoration Programs spring flow release. Most data were collected while drifting downstream with the boat matching the water velocity. Data collected along the edges required much greater maneuvering capability and occurred with the boat moving upstream. The boom system allowed data collection up to half the width of the

  18. Estimation of systolic and diastolic free intracellular Ca2+ by titration of Ca2+ buffering in the ferret heart.

    PubMed Central

    Kirschenlohr, H L; Grace, A A; Vandenberg, J I; Metcalfe, J C; Smith, G A

    2000-01-01

    Spectroscopic Ca(2+)-indicators are thought to report values of free intracellular Ca(2+) concentration ([Ca(2+)](i)) that may differ from unperturbed values because they add to the buffering capacity of the tissue. To check this for the heart we have synthesized a new (19)F-labelled NMR Ca(2+) indicator, 1, 2-bis-[2-bis(carboxymethyl)amino-4,5-difluorophenoxy]ethane ('4, 5FBAPTA'), with a low affinity (K(d) 2950 nM). The new indicator and four previously described (19)F-NMR Ca(2+) indicators 1,2-bis-[2-(1 - carboxyethyl)(carboxymethyl)amino - 5 - fluorophenoxy]ethane ('DiMe-5FBAPTA'), 1, 2-bis-[2-(1-carboxyethyl)(carboxymethyl)amino-4-fluorophenoxy]ethane ('DiMe-4FBAPTA'), 1, 2-bis-[2-bis(carboxymethyl)amino-5-fluorophenoxy]ethane ('5FBAPTA') and 1, 2-bis-[2-bis(carboxymethyl)amino-5-fluoro-4-methylphenoxy]ethane ('MFBAPTA'), with dissociation constants for Ca(2+) ranging from 46 to 537 nM, have been used to measure [Ca(2+)](i), over the range from less than 100 nM to more than 3 microM, in Langendorff-perfused ferret hearts (30 degrees C, pH 7.4, paced at 1.0 Hz) by (19)F-NMR spectroscopy. Loading hearts with indicators resulted in buffering of the Ca(2+) transient. The measured end-diastolic and peak-systolic [Ca(2+)](i) were both positively correlated with indicator K(d). The positive correlations between indicator K(d) and the measured end-diastolic and peak-systolic [Ca(2+)](i) were used to estimate the unperturbed end-diastolic and peak-systolic [Ca(2+)](i) by extrapolation to K(d)=0 (diastolic) and to K(d)=infinity (systolic) respectively. The extrapolated values in the intact beating heart were 161 nM for end-diastolic [Ca(2+)](i) and 2650 nM for peak-systolic [Ca(2+)](i), which agree well with values determined from single cells and muscle strips. PMID:10677357

  19. 78 FR 34123 - Notice of Inventory Completion: San Francisco State University NAGPRA Program, San Francisco, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-06

    ... from site CA-PLA-9 in Placer County, CA. This notice is published as part of the National Park Service... site CA-PLA-9 in Placer County, CA, by San Francisco State University personnel in conjunction with... point. The age of site CA-PLA-9 is unknown, but the site is located within the historically...

  20. 8. Credit USAF, ca. 1952. Original housed in the Photograph ...

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

    8. Credit USAF, ca. 1952. Original housed in the Photograph Files, AFFTC/HO, Edwards AFB, California. Oblique low-level aerial view of North Base looking northeast. Based on positions and types of aircraft and automobiles, this photo taken same day as HAER photo CA-170-7. Most temporary structures in this view have been demolished with the exception of the hangars. The concrete foundations remain of many structures, while no trace was found of others. - Edwards Air Force Base, North Base, North Base Road, Boron, Kern County, CA

  1. Electroluminescence in thin-film CaS:Ce

    NASA Astrophysics Data System (ADS)

    Shanker, Virendra; Tanaka, Shosaku; Shiiki, Masatoshi; Deguchi, Hiroshi; Kobayashi, Hiroshi; Sasakura, Hiroshi

    1984-11-01

    We report a double insulated CaS:Ce thin-film electroluminescent (EL) device which emits a bright green EL due to Ce3+ luminescent centers, being characteristic of parity allowed 5d-4f transitions. A brightness level of 500 cd/m2 and emission efficiency of 0.11 lm/W have been obtained under 5-kHz sinusoidal voltage excitation. The CaS:Ce thin film has been fabricated by coevaporation of CaS and sulfur.

  2. Ca4As3 – a new binary calcium arsenide

    PubMed Central

    Hoffmann, Andrea V.; Hlukhyy, Viktor; Fässler, Thomas F.

    2015-01-01

    The crystal structure of the binary compound tetra­calcium triarsenide, Ca4As3, was investigated by single-crystal X-ray diffraction. Ca4As3 crystallizes in the Ba4P3 structure type and is thus a homologue of isotypic Sr4As3. The unit cell contains 32 Ca2+ cations, 16 As3− isolated anions and four centrosymmetric [As2]4– dumbbells. The As atoms in each of the dumbbells are connected by a single bond, thus this calcium arsenide is a Zintl phase. PMID:26870427

  3. Microwave losses of bulk CaC 6

    NASA Astrophysics Data System (ADS)

    Cifariello, G.; Di Gennaro, E.; Lamura, G.; Andreone, A.; Emery, N.; Hérold, C.; Marêché, J. F.; Lagrange, P.

    2007-09-01

    We report a study of the temperature dependence of the surface resistance RS in the graphite intercalated compound (GIC) CaC6, where superconductivity at 11.5 K was recently discovered. Experiments are carried out using a copper dielectrically loaded cavity operating at 7 GHz in a "hot finger" configuration. Bulk CaC6 samples have been synthesized from highly oriented pyrolytic graphite. Microwave data allow to extract unique information on the quasiparticle density and on the nature of pairing in superconductors. The analysis of RS(T) confirms our recent experimental findings that CaC6 behaves as a weakly-coupled, fully gapped, superconductor.

  4. Integrating heterogeneous rules-engine technologies with caGrid.

    PubMed

    Saltz, Joel H; Oster, Scott; Hastings, Shannon L; Langella, Stephen; Ervin, David; Payne, Philip R O

    2007-01-01

    The use of rules-engines spans multiple computational and biomedical domains. Within the NCIs caBIG program, the orchestration of grid-based computational workflow has used the BPEL standard. However, recent strategic planning within caBIG has raised questions about the applicability of BPEL for other rule definition and execution scenarios. In response, we have reviewed the current state of rules-engine technologies, and have formulated an architectural model for the integration of heterogeneous rules-engines with caGrid. PMID:18694196

  5. Anion Permeation in Ca2+-Activated Cl− Channels

    PubMed Central

    Qu, Zhiqiang; Hartzell, H. Criss

    2000-01-01

    Ca2+-activated Cl channels (ClCaCs) are an important class of anion channels that are opened by increases in cytosolic [Ca2+]. Here, we examine the mechanisms of anion permeation through ClCaCs from Xenopus oocytes in excised inside-out and outside-out patches. ClCaCs exhibited moderate selectivity for Cl over Na: PNa/PCl = 0.1. The apparent affinity of ClCaCs for Cl was low: Kd = 73 mM. The channel had an estimated pore diameter >0.6 nm. The relative permeabilities measured under bi-ionic conditions by changes in Erev were as follows: C(CN)3 > SCN > N(CN)2 > ClO4 > I > N3 > Br > Cl > formate > HCO3 > acetate = F > gluconate. The conductance sequence was as follows: N3 > Br > Cl > N(CN)2 > I > SCN > COOH > ClO4 > acetate > HCO3 = C(CN)3 > gluconate. Permeant anions block in a voltage-dependent manner with the following affinities: C(CN)3 > SCN = ClO4 > N(CN)2 > I > N3 > Br > HCO3 > Cl > gluconate > formate > acetate. Although these data suggest that anionic selectivity is determined by ionic hydration energy, other factors contribute, because the energy barrier for permeation is exponentially related to anion hydration energy. ClCaCs exhibit weak anomalous mole fraction behavior, implying that the channel may be a multi-ion pore, but that ions interact weakly in the pore. The affinity of the channel for Ca2+ depended on the permeant anion at low [Ca2+] (100–500 nM). Apparently, occupancy of the pore by a permeant anion increased the affinity of the channel for Ca2+. The current was strongly dependent on pH. Increasing pH on the cytoplasmic side decreased the inward current, whereas increasing pH on the external side decreased the outward current. In both cases, the apparent pKa was voltage-dependent with apparent pKa at 0 mV = ∼9.2. The channel may be blocked by OH− ions, or protons may titrate a site in the pore necessary for ion permeation. These data demonstrate that the permeation properties of ClCaCs are different from those of CFTR or ClC-1, and provide

  6. Credit USAF, ca. 1945. Original housed in the Muroc Flight ...

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

    Credit USAF, ca. 1945. Original housed in the Muroc Flight Test Base, Unit History, 1 September 1942 - 30 June 1945. Alfred F. Simpson Historical Research Agency. United States Air Force. Maxwell AFB, Alabama. View looks north at a hutment typical of several structures erected at the Muroc Flight Test Base (North Base) ca. 1943-1945. Similar structures, Buildings T-61, T-62 and T-63, lie in the distance behind T-40 - Edwards Air Force Base, North Base, Barracks T-40, Second & A Streets, Boron, Kern County, CA

  7. Ca + HF - The anatomy of a chemical insertion reaction

    NASA Technical Reports Server (NTRS)

    Jaffe, R. L.; Pattengill, M. D.; Mascarello, F. G.; Zare, R. N.

    1987-01-01

    A comprehensive first-principles theoretical investigation of the gas phase reaction Ca + HF - CaF + H is reported. Ab initio potential energy calculations are first discussed, along with characteristics of the computed potential energy surface. Next, the fitting of the computed potential energy points to a suitable analytical functional form is described, and maps of the fitted potential surface are displayed. The methodology and results of a classical trajectory calculation utilizing the fitted potential surface are presented. Finally, the significance of the trajectory study results is discussed, and generalizations concerning dynamical aspects of Ca + HF scattering are drawn.

  8. Solution NMR structure of the Ca2+-bound N-terminal domain of CaBP7: a regulator of golgi trafficking.

    PubMed

    McCue, Hannah V; Patel, Pryank; Herbert, Andrew P; Lian, Lu-Yun; Burgoyne, Robert D; Haynes, Lee P

    2012-11-01

    Calcium-binding protein 7 (CaBP7) is a member of the calmodulin (CaM) superfamily that harbors two high affinity EF-hand motifs and a C-terminal transmembrane domain. CaBP7 has been previously shown to interact with and modulate phosphatidylinositol 4-kinase III-β (PI4KIIIβ) activity in in vitro assays and affects vesicle transport in neurons when overexpressed. Here we show that the N-terminal domain (NTD) of CaBP7 is sufficient to mediate the interaction of CaBP7 with PI4KIIIβ. CaBP7 NTD encompasses the two high affinity Ca(2+) binding sites, and structural characterization through multiangle light scattering, circular dichroism, and NMR reveals unique properties for this domain. CaBP7 NTD binds specifically to Ca(2+) but not Mg(2+) and undergoes significant conformational changes in both secondary and tertiary structure upon Ca(2+) binding. The Ca(2+)-bound form of CaBP7 NTD is monomeric and exhibits an open conformation similar to that of CaM. Ca(2+)-bound CaBP7 NTD has a solvent-exposed hydrophobic surface that is more expansive than observed in CaM or CaBP1. Within this hydrophobic pocket, there is a significant reduction in the number of methionine residues that are conserved in CaM and CaBP1 and shown to be important for target recognition. In CaBP7 NTD, these residues are replaced with isoleucine and leucine residues with branched side chains that are intrinsically more rigid than the flexible methionine side chain. We propose that these differences in surface hydrophobicity, charge, and methionine content may be important in determining highly specific interactions of CaBP7 with target proteins, such as PI4KIIIβ. PMID:22989873

  9. Effect of ambient Mg/Ca ratio on Mg fractionation in calcareous marine invertebrates: A record of the oceanic Mg/Ca ratio over the Phanerozoic

    NASA Astrophysics Data System (ADS)

    Ries, Justin B.

    2004-11-01

    The Mg/Ca ratio of seawater has changed significantly over the Phanerozoic, primarily as a function of the rate of ocean-crust production. Echinoids, crabs, shrimps, and calcareous serpulid worms grown in artificial seawaters encompassing the range of Mg/Ca ratios that existed throughout the Phanerozoic exhibit a direct nonlinear relationship between skeletal and ambient Mg/Ca. Specimens grown in seawater with the lowest Mg/Ca (˜1) changed their mineralogy to low-Mg calcite (<4 mol% MgCO3), suggesting that these high-Mg calcareous organisms would have produced low-Mg calcite in the Cretaceous, when oceanic Mg/Ca was lowest (˜1). These results support the empirical evidence that the skeletal chemistry of calcareous organisms has varied significantly over the Phanerozoic as a function of the Mg/Ca of seawater, and that the Mg/Ca of unaltered fossils of such organisms may be a record of oceanic Mg/Ca throughout the Phanerozoic. Mg fractionation algorithms, which relate skeletal Mg/Ca, seawater Mg/Ca, and temperature, were derived from these and other experiments. They can be used to estimate paleoceanic Mg/ Ca ratios and temperatures from fossil skeletal Mg/Ca of the organisms evaluated. Pale oceanic Mg/Ca ratios, recalculated by using the echinoderm Mg fractionation algorithm from published fossil echinoid Mg/Ca, crinoid Mg/Ca, and paleotemperature data, are consistent with other estimates and models of oceanic Mg/Ca over the Phanerozoic.

  10. Retracing diagenetic processes in marine porewaters using Ca isotopes

    NASA Astrophysics Data System (ADS)

    Ockert, C.; Teichert, B. M.; Kaufhold, S.; Gussone, N. C.

    2012-12-01

    Calcium (Ca) isotope ratios of marine organic and inorganic mineral precipitates are used to monitor changes in the oceanic Ca-budget and in paleo-temperature, and serve as a proxy for the trophic level of organisms in the food chain (c.f. Skulan et al., 1997; Zhu et al., 1998). However, during interaction between sediments and porewater, the Ca isotopic composition of marine porewaters might be shifted, bearing the potential to alter the Ca isotope proxy records. While processes, such as partial dissolution of calcareous shells and carbonate recrystallization have been studied (Fantle and DePaolo, 2007; Turchyn and DePaolo 2011), other diagenetic processes such as ion exchange with clay minerals have not been taken into account while studying Ca isotope profiles of porewaters. Nevertheless, first experiments and the investigation of natural porewaters indicate that this process has a significant effect on the Ca isotope composition in marine porewaters. Laboratory experiments aimed to determine if Ca isotope fractionation occurs during Ca adsorption and exchange with ammonium on clay minerals. The results show that Ca adsorption in a seawater environment is associated with fractionation, where light Ca is preferably adorbed. The addition of ammonium to the experimental set up caused partial release of Ca accompanied by isotope fractionation. Based on the results of the experiments, model calculations tested the impact of varying clay mineral type, content and sediment porosity, revealing that ion exchange processes with clay minerals predominantly shift the porewater signal to lighter values. This is in agreement with observations by Teichert et al. (2009), who found a correlation of ammonium-concentration and δ44/40Ca ratios in the porewater of drill core samples from the Cascadia accretionary margin (ODP Leg 204). Calcium isotope ratios of natural marine porewaters of three sites in the North Atlantic (IODP Expedition 303) show that the correlation between

  11. Ca Isotope Fractionation During Gypsum Precipitation in a Sulfidic Cave

    NASA Astrophysics Data System (ADS)

    Fantle, M. S.; Macalady, J. L.; Eisenhauer, A.

    2009-12-01

    In sulfidic caves, limestone dissolution above the water table is assocated with sulfuric acid corrosion and attendant precipitation of CaSO4 crusts. Since sulfuric acid is produced by microbially-mediated sulfide oxidation, such systems present unique opportunities to study the effects of microbial processes on Ca isotope systematics. The current study presents preliminary measurements of the Ca isotopic composition of gypsum, calcite, and water samples collected in and around Grotta Bella cave in the Frasassi cave system (central Italy). The environment sampled in this limestone-hosted cave is situated close to flowing sulfidic groundwater (air [H2S]meas ~3 ppm) and is actively forming gypsum in close association with microbial communities ("snottites") dominated by Acidithiobacillus sp [1]. The pH ranges from >2.3 in gypsum crust accumulating on the cave walls to 0-2 at the surface of snottites, while pH in waters sampled outside the cave is between 7 and 8. The current rate of limestone dissolution is ~0.15 mmol CaCO3/cm2/a [2]. This study reports the Ca isotopic composition (δ44Ca, rel. to bulk Earth) of stream and seep water, limestone, and gypsum samples in and around Grotta Bella. Calcium isotopes were measured on a Finnigan Triton TI thermal ionization mass spectrometer at GEOMAR using a 43Ca-48Ca double spike. Field-acidified stream waters and dissolved gypsum were chromatographically purified using MCI Gel (Biorad) while bulk limestone samples were dissolved in nitric acid and loaded onto single Re filaments without additional purification. The δ44Ca values of stream waters and springs are relatively restricted (~0.2‰) and generally the same as bulk limestone. Actively-precipitating CaSO4 minerals, however, show a range of δ44Ca values from limestone-like to values almost 1‰ lighter than corresponding wallrock. Decreasing δ44Ca values in these gypsum minerals correspond to gradients in pH and mineral grain size. The smallest gypsum grains

  12. Comparative NMR studies on Ca3LiRuO6 and Ca3NaRuO6

    NASA Astrophysics Data System (ADS)

    Chakrabarty, T.; Paulose, P. L.

    2016-06-01

    We report a comparative study of two ruthanate compounds, Ca3LiRuO6 and Ca3NaRuO6 by magnetic measurements, heat capacity and NMR. Ca3LiRuO6 is a weak ferromagnet with a magnetic ordering temperature of 115 K. The 7Li NMR linewidth of Ca3LiRuO6 displays a broad shoulder above the magnetic ordering temperature. Anomalous shoulder of this type is observed in the susceptibility data also. The origin of these phenomena is not clear but could possibly be attributed to low dimensional magnetism. A contrasting magnetic behavior is seen in Ca3NaRuO6, an antiferromagnet with a transition temperature at 87 K. The NMR study shows that the Knight shift is proportional to the magnetic susceptibility. Also, in Ca3NaRuO6, the Knight shift and the linewidth of the spectra change differently compared to Ca3LiRuO6. The heat capacity of both compounds show a λ-type anomaly at respective magnetic transition temperatures. However, in both the systems the entropy change (Δ S) is much less than that of an ordered S  =  3/2 system.

  13. Comparative NMR studies on Ca3LiRuO6 and Ca3NaRuO6.

    PubMed

    Chakrabarty, T; Paulose, P L

    2016-06-15

    We report a comparative study of two ruthanate compounds, Ca3LiRuO6 and Ca3NaRuO6 by magnetic measurements, heat capacity and NMR. Ca3LiRuO6 is a weak ferromagnet with a magnetic ordering temperature of 115 K. The (7)Li NMR linewidth of Ca3LiRuO6 displays a broad shoulder above the magnetic ordering temperature. Anomalous shoulder of this type is observed in the susceptibility data also. The origin of these phenomena is not clear but could possibly be attributed to low dimensional magnetism. A contrasting magnetic behavior is seen in Ca3NaRuO6, an antiferromagnet with a transition temperature at 87 K. The NMR study shows that the Knight shift is proportional to the magnetic susceptibility. Also, in Ca3NaRuO6, the Knight shift and the linewidth of the spectra change differently compared to Ca3LiRuO6. The heat capacity of both compounds show a λ-type anomaly at respective magnetic transition temperatures. However, in both the systems the entropy change ([Formula: see text]S) is much less than that of an ordered S  =  3/2 system. PMID:27157888

  14. Symmetric spike timing-dependent plasticity at CA3-CA3 synapses optimizes storage and recall in autoassociative networks.

    PubMed

    Mishra, Rajiv K; Kim, Sooyun; Guzman, Segundo J; Jonas, Peter

    2016-01-01

    CA3-CA3 recurrent excitatory synapses are thought to play a key role in memory storage and pattern completion. Whether the plasticity properties of these synapses are consistent with their proposed network functions remains unclear. Here, we examine the properties of spike timing-dependent plasticity (STDP) at CA3-CA3 synapses. Low-frequency pairing of excitatory postsynaptic potentials (EPSPs) and action potentials (APs) induces long-term potentiation (LTP), independent of temporal order. The STDP curve is symmetric and broad (half-width ∼150 ms). Consistent with these STDP induction properties, AP-EPSP sequences lead to supralinear summation of spine [Ca(2+)] transients. Furthermore, afterdepolarizations (ADPs) following APs efficiently propagate into dendrites of CA3 pyramidal neurons, and EPSPs summate with dendritic ADPs. In autoassociative network models, storage and recall are more robust with symmetric than with asymmetric STDP rules. Thus, a specialized STDP induction rule allows reliable storage and recall of information in the hippocampal CA3 network. PMID:27174042

  15. 5-Aminolevulinic Acid Thins Pear Fruits by Inhibiting Pollen Tube Growth via Ca2+-ATPase-Mediated Ca2+ Efflux

    PubMed Central

    An, Yuyan; Li, Jie; Duan, Chunhui; Liu, Longbo; Sun, Yongping; Cao, Rongxiang; Wang, Liangju

    2016-01-01

    Chemical fruit thinning has become a popular practice in modern fruit orchards for achieving high quality fruits, reducing costs of hand thinning and promoting return bloom. However, most of the suggested chemical thinners are often concerned for their detrimental effects and environmental problems. 5-Aminolevulic acid (ALA) is a natural, nontoxic, biodegradable, and environment-friendly plant growth regulator. One of its outstanding roles is improving plant photosynthesis and fruit quality. Here, results showed that applying 100–200 mg/L ALA at full bloom stage significantly reduced pear fruit set. Both in vivo and in vitro studies showed that ALA significantly inhibited pollen germination and tube growth. ALA decreased not only cytosolic Ca2+ concentration ([Ca2+]cyt) but also “tip-focused” [Ca2+]cyt gradient, indicating that ALA inhibited pollen tube growth by down-regulating calcium signaling. ALA drastically enhanced pollen Ca2+-ATPase activity, suggesting that ALA-induced decrease of calcium signaling probably resulted from activating calcium pump. The significant negative correlations between Ca2+-ATPase activity and pollen germination or pollen tube length further demonstrated the critical role of calcium pump in ALA's negative effect on pollen germination. Taken together, our results suggest that ALA at low concentrations is a potential biochemical thinner, and it inhibits pollen germination and tube growth via Ca2+ efflux by activating Ca2+-ATPase, thereby thinning fruits by preventing fertilization. PMID:26904082

  16. Reduced junctional Na+/Ca2+-exchanger activity contributes to sarcoplasmic reticulum Ca2+ leak in junctophilin-2-deficient mice

    PubMed Central

    Wang, Wei; Landstrom, Andrew P.; Wang, Qiongling; Munro, Michelle L.; Beavers, David; Ackerman, Michael J.; Soeller, Christian

    2014-01-01

    Expression silencing of junctophilin-2 (JPH2) in mouse heart leads to ryanodine receptor type 2 (RyR2)-mediated sarcoplasmic reticulum (SR) Ca2+ leak and rapid development of heart failure. The mechanism and physiological significance of JPH2 in regulating RyR2-mediated SR Ca2+ leak remains elusive. We sought to elucidate the role of JPH2 in regulating RyR2-mediated SR Ca2+ release in the setting of cardiac failure. Cardiac myocytes isolated from tamoxifen-inducible conditional knockdown mice of JPH2 (MCM-shJPH2) were subjected to confocal Ca2+ imaging. MCM-shJPH2 cardiomyocytes exhibited an increased spark frequency width with altered spark morphology, which caused increased SR Ca2+ leakage. Single channel studies identified an increased RyR2 open probability in MCM-shJPH2 mice. The increase in spark frequency and width was observed only in MCM-shJPH2 and not found in mice with increased RyR2 open probability with native JPH2 expression. Na+/Ca2+-exchanger (NCX) activity was reduced by 50% in MCM-shJPH2 with no detectable change in NCX expression. Additionally, 50% inhibition of NCX through Cd2+ administration alone was sufficient to increase spark width in myocytes obtained from wild-type mice. Additionally, superresolution analysis of RyR2 and NCX colocalization showed a reduced overlap between RyR2 and NCX in MCM-shJPH2 mice. In conclusion, decreased JPH2 expression causes increased SR Ca2+ leakage by directly increasing open probability of RyR2 and by indirectly reducing junctional NCX activity through increased dyadic cleft Ca2+. This demonstrates two novel and independent cellular mechanisms by which JPH2 regulates RyR2-mediated SR Ca2+ leak and heart failure development. PMID:25193470

  17. The role of the Ca2+ binding ligand Asn879 in the function of the plasma membrane Ca2+ pump.

    PubMed

    Rinaldi, Débora E; Adamo, Hugo P

    2009-11-01

    Asn879 in the transmembrane segment M6 of the plasma membrane Ca(2+) pump (PMCA human isoform 4xb) has been proposed to coordinate Ca(2+) at the transport site through its carboxylate. This idea agrees with the fact that this Asn is conserved in other Ca(2+)-ATPases but is replaced by Asp, Glu, and other residues in closely related 2P-type ATPases of different ionic specificity. Previous mutagenesis studies have shown that the substitution of Ala for Asn abolishes the activity of the enzyme (Adebayo et al., 1995; Guerini et al., 1996). We have constructed a mutant PMCA in which the Asn879 was substituted by Asp. The mutant protein was expressed in Saccharomyces cerevisiae, solubilized and purified by calmodulin affinity chromatography. The Asn879Asp PMCA mutant exhibited about 30% of the wild type Ca(2+)-dependent ATPase activity and only a minor reduction of the apparent affinity for Ca(2+). The decrease in the Ca(2+)-ATPase of the mutant enzyme was in parallel with the reduction in the amount of phosphoenzyme formed from Ca(2+) plus ATP. Noteworthy, the mutation nearly eliminated the ability of the enzyme to hydrolyze pNPP which is maximal in the absence of Ca(2+) revealing a major effect of the mutation on the Ca(2+)-independent reactions of the transport cycle. At a pH low enough to protonate the Asp carboxylate the pNPPase activity of Asn879Asp increased, suggesting that the binding of protons to Asn879 is essential for the activities catalyzed by E(2)-like forms of the enzyme. PMID:19761757

  18. Evidence for a Ca(2+)-gated ryanodine-sensitive Ca2+ release channel in visceral smooth muscle.

    PubMed Central

    Xu, L; Lai, F A; Cohn, A; Etter, E; Guerrero, A; Fay, F S; Meissner, G

    1994-01-01

    Although a role for the ryanodine receptor (RyR) in Ca2+ signaling in smooth muscle has been inferred, direct information on the biochemical and functional properties of the receptor has been largely lacking. Studies were thus carried out to purify and characterize the RyR in stomach smooth muscle cells from the toad Bufo marinus. Intracellular Ca2+ measurements with the Ca(2+)-sensitive fluorescent indicator fura-2 under voltage clamp indicated the presence of a caffeine- and ryanodine-sensitive internal store for Ca2+ in these cells. The (CHAPS)-solubilized, [3H]ryanodine-labeled RyR of toad smooth muscle was partially purified from microsomal membranes by rate density centrifugation as a 30-S protein complex. SDS/PAGE indicated the comigration of a high molecular weight polypeptide with the peak attributed to 30-S RyR, which had a mobility similar to the cardiac RyR and on immunoblots cross-reacted with a monoclonal antibody to the canine cardiac RyR. Following planar lipid bilayer reconstitution of 30-S stomach muscle RyR fractions, single-channel currents (830 pS with 250 mM K+ as the permeant ion) were observed that were activated by Ca2+ and modified by ryanodine. In vesicle-45Ca2+ efflux measurements, the toad channel was activated to a greater extent at 100-1000 microM than 1-10 microM Ca2+. These results suggest that toad stomach muscle contains a ryanodine-sensitive Ca2+ release channel with properties similar but not identical to those of the mammalian skeletal and cardiac Ca(2+)-release channels. Images PMID:8159742

  19. Sr/Ca and Mg/Ca in Aragonitic Bivalves: Do They Record Temperature?

    NASA Astrophysics Data System (ADS)

    Gillikin, D. P.; Ulens, H.; Dehairs, F.; Baeyens, W.; Navez, J.; Andre, L.; Keppens, E.; Calmars Group,.

    2003-12-01

    The chemical or isotopic composition of calcareous skeletons have long been recognized as archives of past and present environmental conditions. Oxygen isotopes (d18O) of biogenic carbonates are a powerful proxy of SST, however, although usually dominated by SST, salinity (SSS) also significantly effects the oxygen isotopic signal recorded in the carbonate. This has led researchers to explore new proxies, which are independent of SSS. Generally, Sr/Ca and Mg/Ca of seawater remains unchanged above salinities of 10 and marine animals will commonly live in habitats that do not fluctuate below this salinity. To solve the issue of SSS complicating paleotemperature records, these "new" proxies must be at least as reliable as d18O. If an environmental control is dominant, the proxies should be reproducible between specimens growing under the same field conditions. Both Sr and Mg have been used as paleotemperature proxies in corals and foraminifera, whereas a fewer attempts have been made to use these proxies in bivalves. Some report a clear seasonal periodicity in Sr/Ca profiles of bivalves, which covaries with d18O (i.e., temperature), whereas others have found no clear periodicity. We test the robustness of these proxies by analyzing the shell material from three species of aragonitic clams from around the world using a LA-ICP-MS. Three individuals of M. mercenaria from North Carolina, USA, three individuals of Saxidomus giganteus from Washington, USA and one Arctica islandica from Norway have been analyzed. As expected, there is excellent reproducibility of d18O between specimens (both M. mercenaria and S. giganteus) indicating external environmental conditions control this proxy (i.e. SST and SSS). Preliminary data analysis show that Sr and Mg are not reproducible between specimens from the same site nor do they exhibit a clear seasonal cyclicity, indicating individual metabolic effects (i.e., vital effects) dominate the incorporation of these elements. A. islandica

  20. Using benthic foraminiferal B/Ca to constrain the effect of dissolution on key Pliocene Mg/Ca temperature records

    NASA Astrophysics Data System (ADS)

    White, S. M.; Ravelo, A. C.

    2015-12-01

    The state of the Pliocene tropical Pacific is currently the subject of heated debate. The debate hinges on the veracity of planktic foraminiferal Mg/Ca temperatures from the west Pacific warm pool (WPWP) and the eastern equatorial Pacific (EEP) that show Pliocene WPWP temperatures similar to today but a warmer Pliocene EEP, resulting in a much reduced east-west gradient [Wara et al., 2005]. These findings form the basis of the "permanent El Niño-like state" paradigm of Pliocene climate. However, recent studies using organic biomarker proxies produce temperature records that indicate a WPWP cooling trend since the Pliocene that differs markedly from Mg/Ca-temperature records [O'Brien et al., 2014; Zhang et al., 2014]. Though much of the debate has focused on changes in seawater Mg/Ca, spatial variations in proxy agreement point to dissolution as a key factor. Dissolution, which imparts a cool bias to Mg/Ca temperatures, varies across ocean basins depending on Δ[CO32-], the difference from the carbonate ion concentration needed for calcite saturation. By necessity, dissolution corrections use the modern value of Δ[CO32-] for the entire record, so it is possible that Pliocene proxy discrepancies could stem from varying Δ[CO32-] over time. Here we present benthic foraminiferal B/Ca data (a proxy for Δ[CO32-]) from the EEP and WEP spanning the past 5 Myr, to constrain the effect of dissolution on Pliocene Mg/Ca records. To account for possible changes in seawater B/Ca, we present paired epifaunal-infaunal B/Ca data. Infaunal species are much less sensitive to Δ[CO32-] than epifaunal species, but would still record long-term changes in seawater B/Ca. The true Δ[CO32-] can thus be calculated from the epifaunal-infaunal B/Ca difference [Brown et al., 2011]. Our study is the first to apply this approach downcore; by accounting for long-term changes in seawater, it greatly expands use of the B/Ca proxy and enables a first attempt at correcting for time

  1. 97. HISTORIC PHOTOGRAPH, VIEW OF 'LAPHAM OAK,' NEW CANAAN, CA. ...

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

    97. HISTORIC PHOTOGRAPH, VIEW OF 'LAPHAM OAK,' NEW CANAAN, CA. 1940. FROM PUBLIC WORKS COMMISSIONER'S REPORT. COLLECTION CONNECTICUT STATE LIBRARY AND ARCHIVES. - Merritt Parkway, Beginning in Greenwich & running 38 miles to Stratford, Greenwich, Fairfield County, CT

  2. 4. INTERIOR, FOUNDRY CA. 1919 SHOWING CASTINGS READY FOR CLEANING ...

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

    4. INTERIOR, FOUNDRY CA. 1919 SHOWING CASTINGS READY FOR CLEANING AND FOUNDRY FLASKS TO RIGHT. - Hardie-Tynes Manufacturing Company, Workshop, 800 Twenty-eighth Street North, Birmingham, Jefferson County, AL

  3. Photocopy of ground floor plan, ca. 12939. Plans and renovations ...

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

    Photocopy of ground floor plan, ca. 12939. Plans and renovations required for the 1940-1941 addition are overlaid on the original plan - Stamford Post Office, 421 Atlantic Street, Stamford, Fairfield County, CT

  4. 2. HISTORIC PHOTOGRAPH OF CLINTON AVENUE BRIDGE, CA. 1940. COLLECTION ...

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

    2. HISTORIC PHOTOGRAPH OF CLINTON AVENUE BRIDGE, CA. 1940. COLLECTION CONNECTICUT DEPARTMENT OF TRANSPORTATION. - Merritt Parkway, Clinton Avenue/North Clinton Avenue Bridge, Spanning Merritt Parkway, Westport, Fairfield County, CT

  5. Towards an AC-MOT of CaF

    NASA Astrophysics Data System (ADS)

    Anderegg, Loic; Chae, Eunmi; Ravi, Aakash; Augenbraun, Benjamin; Hemmerling, Boerge; Drayna, Garrett; Hutzler, Nicholas; Collopy, Alejandra; Wu, Yewei; Ding, Shiqian; Ye, Jun; Ketterle, Wolfgang; Doyle, John

    2016-05-01

    Ultra-cold diatomic molecules have rich prospects as candidates to study controlled ultra-cold chemistry, strongly correlated systems and precision measurements. They are also considered as possible qubits in quantum computing and simulation schemes. We report on progress towards loading CaF into a molecular magneto-optical trap (MOT). An AC-MOT will be used to actively remix magnetic dark states via both polarization and magnetic field switching. In order to load a molecular MOT, we have successfully laser slowed a CaF beam to near the expected capture velocity. We describe our AC-MOT apparatus, which is designed to co-trap CaF and Li. We outline our planned study of CaF-Li collisions to explore the feasibility of sympathetically cooling molecules to ultra-cold temperatures.

  6. 3. Photocopy of BUILDING WITH ORIGINAL ROOF BALUSTRADE, taken ca. ...

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

    3. Photocopy of BUILDING WITH ORIGINAL ROOF BALUSTRADE, taken ca. 1860, from A History of the Philadelphia Saving Fund Society 1816-1916, page 64. - Philadelphia Saving Fund Society, 306 Walnut Street, Philadelphia, Philadelphia County, PA

  7. "Before" Main House, photographic copy of ca. 1834 watercolor by ...

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

    "Before" Main House, photographic copy of ca. 1834 watercolor by Thomas U. Walter. Duplicate color view of HABS PA-1248-35 - Andalusia, State Road vicinity (Bensalem Township), Andalusia, Bucks County, PA

  8. 3. Photocopy of architectural rendering, ca. 1902, from Moses King, ...

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

    3. Photocopy of architectural rendering, ca. 1902, from Moses King, Philadelphia and Notable Philadelphians, (1902), page 24 D. - Drexel Institute, Thirty-second & Chestnut Streets, Philadelphia, Philadelphia County, PA

  9. Thermodynamic Optimization of the Ca-Fe-O System

    NASA Astrophysics Data System (ADS)

    Hidayat, Taufiq; Shishin, Denis; Decterov, Sergei A.; Jak, Evgueni

    2016-02-01

    The present study deals with the thermodynamic optimization of the Ca-Fe-O system. All available phase equilibrium and thermodynamic experimental data are critically assessed to obtain a self-consistent set of model parameters for the Gibbs energies of all stoichiometric and solution phases. Model predictions of the present study are compared with previous assessments. Wüstite and lime are described as one monoxide solution with a miscibility gap, using the random mixing Bragg-Williams model. The solubility of CaO in the "Fe3O4" magnetite (spinel) phase is described using the sublattice model based on the Compound Energy Formalism. The effect of CaO on the stability of the spinel phase is evaluated. The liquid CaO-FeO-Fe2O3 slag is modeled using the Modified Quasichemical Formalism. Liquid metal phase is described as a separate solution by an associate model.

  10. 20. Print from copy negative of post card ca. 1910. ...

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

    20. Print from copy negative of post card ca. 1910. (Original in Tippecanoe County Historical Society.) View northeast, south side. - Big Four Depot, 10 South Second Street, Lafayette, Tippecanoe County, IN

  11. A vaccination strategy to SEIR-CA model

    NASA Astrophysics Data System (ADS)

    Almuzakki, Muhammad Zaki; Nuraini, Nuning

    2016-04-01

    A combination between Susceptible-Exposed-Infected-Removed (SEIR) model and Cellular Automaton (CA) called SEIR-CA model has been proposed to simulate spreading diseases through populations. We make an improvement to the parameter which describe the impact of neighborhood in CA system. We also propose a vaccination strategy to the model. Three examples are given to illustrate the model. The first one shows that the previously established SEIR-CA model does not work properly in a population with randomly distributed individuals. After an improvement to the neighborhood impact parameter has been made, the model works properly in a population with randomly distributed individuals and it is shown in the second example. The last example shows the spreading mechanisms with a chosen vaccination strategy. We also show that the vaccination strategy can reduce the number of infected individuals and can suppress the spread of the diseases.

  12. 4. Photocopy of photograph, ca. 1944 (original print on file ...

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

    4. Photocopy of photograph, ca. 1944 (original print on file at U.S. Army Intelligence Security Command, Fort Belvoir, Virginia). VIEW TO SOUTHEAST. - Arlington Hall Station, Building No. 110, 4000 Arlington Boulevard, Arlington, Arlington County, VA

  13. 1. Photocopy of photograph, ca. 1980 (original print on file ...

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

    1. Photocopy of photograph, ca. 1980 (original print on file at U.S. Army Intelligence Security Command, Fort Belvoir, Virginia). AERIAL VIEW OF ARLINGTON HALL STATION. VIEW TO NORTH. - Arlington Hall Station, 4000 Arlington Boulevard, Arlington, Arlington County, VA

  14. 4. Photocopy of photograph, ca. 1944 (original print on file ...

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

    4. Photocopy of photograph, ca. 1944 (original print on file at U.S. Army Intelligence Security Command, Fort Belvoir, Virginia). VIEW TO NORTHEAST. - Arlington Hall Station, Building No. 126, 4000 Arlington Boulevard, Arlington, Arlington County, VA

  15. 4. Photocopy of photograph, ca. 1944 (original print on file ...

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

    4. Photocopy of photograph, ca. 1944 (original print on file at U.S. Army Intelligence Security Command, Fort Belvoir, Virginia). VIEW TO SOUTHEAST. - Arlington Hall Station, Building No. 115, 4000 Arlington Boulevard, Arlington, Arlington County, VA